Natural Liver Cirrhosis Treatment Book

Liver Disease Survivors Guide

Renowned Health Specialist experienced in working with numerous people with liver disorders share with you and: Explains how the liver works and how liver disorders develop in Simple English without Medical Jargon. Shares the facts about cirrhosis of the liver. Explains complications and treatments in simple language. Talks about Nutrition in Liver Disease. Explains Alternative Treatments available. Talks about the latest research developments in liver disease treatment. Shares resources for Liver disease forums and help-lines. Gives you the true in-depth stories from survivors and how they coped with the challenges of liver disorder. Shares touching stories of family members who had to cope with their loved ones suffering from cirrhosis of the liver, and the strategies they used to cope with them. With Liver Disease Survivors Guide, you will discover : Credible information on Liver disease obtained from detailed interviews with specialist doctors, explained in simple language. Healthy steps in dealing with liver disorders. What to do and what not to do while learning to adapt to the liver disorder. Remarkable stories in patients own words. It gives you a real emotional experience of a person with serious liver disorder and how they view the world. Latest research on liver disorders. Best resources and direct links to forums. Direct links to get professional help and identify the best experts in your area. Alternative treatments and therapies available for liver disorders. No medical jargon or difficult language, the book is written in simple and easy to understand language.

Liver Disease Survivors Guide Summary

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Author: Grace Barrera
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Autoantibodies in Overlap Syndrome Between Autoimmune Hepatitis and Primary Biliary Cirrhosis

This overlap syndrome is characterized by the coexistence of clinical, biochemical, or serological features of autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC). In about 5 of patients with a primary diagnosis of AIH, laboratory signs and clinical symptoms of PBC exist. On the other hand, 19 of patients with a primary diagnosis of PBC also have signs of AIH. The overlap of PBC and AIH is characterized by the presence of ANAs in 67 and antibodies against SMAs in 67 . Because patients with an overlap of PBC and AIH respond to corticosteroid treatment equally well as patients with primary AIH, the identification of this variant group by autoantibody characterization is required and contributes to the establishment of an efficacious therapeutic strategy 74, 75 .

Management of Patients with Cirrhosis and Ascites

The most important initial step in treating patients with cirrhosis and ascites is to permit healing of the reversible component of the underlying liver disease. Abstinence from alcohol allows healing of the reversible component of alcoholic liver disease, so that ascites becomes more responsive to medical therapy or may even completely resolve. Positive sodium balance causes ascites formation. To achieve negative sodium balance, sodium output must exceed intake. in the absence of diuretics, many patients with cirrhosis and ascites have almost no urinary sodium excretion. Reducing dietary sodium intake below total output leads to a reduction in fluid volume and weight in these patients. Instituting a low-sodium diet maximizes urinary excretion and fluid loss. Thus, sodium restriction to 2 g (ie, 88 mmol) d is warranted in all patients with cirrhosis and ascites (Bernardi et al, 1993). Ascites may improve with discontinuation of the precipitating agent, such as saline infusions given...

Focal Biliary Fibrosis Cirrhosis

This is a description of the pathology in the liver of CF patients. The scarring around the biliary tree is not generalized, but patchy, and likely occurs to some degree in most patients, although clearly some patients are more affected and go on to an extensive lesion with cirrhosis and consequent portal hypertension. The fibrosis alone does not produce symptoms. Biochemical tests of liver enzymes (aspartate aminotransferase, alanine aminotransferase, GGT, alkaline phosphatase) may, however, be mildly elevated (1.5 to 4 times normal), and if this is sustained for 3 months while the patient is otherwise well, then treatment with ursodeoxycholic acid (20 mg kg d) is started. Once initiated, this would continue as lifelong therapy at most centers. Liver disease, including focal biliary fibrosis, may be entirely silent until a patient presents with cirrhosis. About 15 of patients have or will develop cirrhosis or important liver disease, and liver disease is the third most common cause...

Cirrhosis

In a patient with decompensated cirrhosis, treatment can be extremely challenging with the risk of major adverse events (eg, severe thrombocytopenia, variceal hemorrhage, etc) and further decompensation (eg, worsening hepatic encephalopathy), and should therefore, be handled in liver transplant centers with the requisite experience and infrastructure, and preferably referred for clinical trials until the safety and efficacy data of treatment are established. However, patients with advanced bridging fibrosis or early cirrhosis (Child's class A) can often be treated in the community without major complications. The efficacy of treatment in patients with advanced fibrosis or compensated cirrhosis has been derived mostly from subgroup analysis of larger clinical trials, and suggests that the response is lower than in patients without cirrhosis. The main treatment option for such patients is liver transplant.

Acute Liver Failure

Patients with acute liver failure (ALF) present a variety of unique issues with regard to LT. Because of the acuity of their illness, the luxury of detailed medical and psychosocial testing is not always feasible. When examining these patients, we attempt to make as educated a decision as possible with regards to medical comorbidity. Because the highest priority is supportive care while awaiting LT, we perform only minimal testing in these patients. Moreover, many patients who present with ALF are young with few comorbid conditions. Although we do not perform a transplantation on a known alcoholic who has developed liver failure from acute alcoholic hepatitis, a history of alcohol intake would not necessarily lead to exclusion from transplantation if liver failure was secondary to another cause (acetaminophen, viral, etc). Similarly, use of illegal drugs may have different implications in these patients than someone with chronic liver diseases. At our institution these issues are...

Evidence Based Medicine Approach to Prognosis Prognosis of Hepatitis C

Upon reviewing the abstract and methods sections of the study by Roffi and colleagues (2001), you determine that it meets the validity criteria for a study about prognosis (see Tables 1-6 and 1-7). The sample of patients in this trial was representative of patients with chronic HCV who were sufficiently homogeneous with respect to their risk of objective outcomes, such as cirrhosis, hepatocellular cancer (HCC), and death. Investigators took explicit steps to account for potential confounds, such as age, alcohol and IV drug use, methods of HCV transmission, prevalent cirrhosis, and duration of infection in their analysis. Follow-up was sufficiently long and complete at 1,482 cumulative years, so that important outcomes were unlikely to be missed. The outcomes that were measured were done so in an objective and unbiased manner equally in all patients.

Causes Of Volume Expansioncauses Of Volume Depletion

Secondary renal sodium retention Hypoproteinemia Nephrotic syndrome Protein-losing enteropathy Cirrhosis with ascites Low cardiac output Hemodynamically significant pericardial effusion Constrictive pericarditis Gram-negative sepsis Anaphylaxis Arteriovenous fistula Trauma Cirrhosis

Disease Mapping Modern Developments

Oesophageal cancer three times higher than the rates in their neighbouring districts. The remarkable similarity between the maps showing male mortality from this cancer and those from cirrhosis of the liver led to the hypothesis that some form of alcohol might be causing the oesophageal cancer. The French produce a prodigious variety of alcohol wine in many parts of the country cider in the west beer in the north and east and spirits in the departments of the Nord and Paris. Analysis of the quantities of alcohol consumed by the residents of the various regions of France showed marked variations, with males in Brittany and Normandy having particularly high intakes of alcohol.27 A unique feature of this area of France is the widespread growing of apples and the production of a spirit called calvados, which is made from these apples. Traditionally, farmers were allowed to produce homemade calvados from private stills. In 1960 however, a law was passed limiting the amount of calvados...

Supplemental Reading

Caballeria L, Pares A, Castells A, et al. Hepatocellular carcinoma in primary biliary cirrhosis similar incidence to that in hepatitis C virus-related cirrhosis. Am J Gastroenterol 2001 96 1160-3. Corpechot C, Carrat F, Bonnard AM, et al. The effect of ursodeoxycholic acid therapy on liver fibrosis progression in primary biliary cirrhosis. Hepatology 2000 32 1196-9. Corpochet C, Carrat F, Poupon R, Poupon RE. Primary biliary cirrhosis incidence and predictive features of cirrhosis development in ursodiol-treated patients. Gastroenterology 2002 122 652-8. Dickson ER, Grambsch PM, Fleming TR, et al. Prognosis in primary biliary cirrhosis model for decision making. Hepatology 1989 10 1-7. Gluud C, Christensen E. Ursodeoxycholic acid for primary biliary cirrhosis (Cochrane Review). Cochrane Database Syst Rev 2002 1 CD000551. Guanabens N, Pares A, Monegal A, et al. Etidronate versus fluoride for treatment of osteopenia in primary biliary cirrhosis preliminary results after 2 years....

Etiologies and Prognostic Factors

Worldwide, most cases of HCC occur in areas where viral hepatitis is endemic and develop in a background of cirrhosis. In contrast, in the United States, it is estimated that only 25 of patients with HCC have evidence of hepatitis C virus (HCV) infection, and hepatitis B virus and HCV together account for no more than 40 of HCC cases (ElSerag, 2001). HCC also frequently presents in the setting of severe parenchymal liver disease. Both cirrhosis and fibrosis represent a state of chronic liver injury, which may act as a stimulus for ongoing hepatic regeneration, leading to eventual malignant transformation. The presence of hepatitis, cirrhosis, and fibrosis is also important for post-resection prognosis because several studies have documented an association between cirrhosis, hepatitis status, and tumor recurrence that is presumably due to continued carcinogenesis in the affected liver remnant. In fact, we have previously reported that 5-year survival rates were significantly higher for...

Christian MendezMD Luis MarsanoMD Daniell B HillMD and Craig J McClainMD

Alcoholic liver disease (ALD) remains a major cause of morbidity and mortality worldwide. In the western world, alcohol is the single most significant cause of liver disease, responsible for between 40 and 80 of cases of cirrhosis. In the United States, alcohol was responsible for 44 of deaths from cirrhosis between 1978 and 1988, with endstage liver disease being the sixth leading cause of death in the age group of 45 to 64 years. The mortality rate of this form of liver disease is higher than in many forms of cancer, such as breast, colon, and prostate. In some studies, the mortality from alcoholic cirrhosis is higher than that of nonalcoholic cirrhosis. Although the per capita alcohol consumption has declined in the United States and northern Europe in the last decade, in Latin America and Asia alcohol use has increased. In the United States, almost 14 million people still meet criteria for alcoholism. Among this group, more than 2 million are suspected of having liver disease, and...

Complications of Short Bowel Syndrome

Complications of short bowel syndrome include dehydration (which may result in uric acid nephrolithiasis), generalized malnutrition, electrolyte disturbances, specific nutrient deficiencies, calcium oxalate nephrolithiasis, and cholelithiasis. Those patients with significant malabsorption requiring long term TPN are at additional risk for hepatic steatosis and cholestasis with potential progression to cirrhosis, either acalculous or calculous cholecystitis, metabolic bone disease, nephropathy, and central venous catheter-related problems including infection and occlusion (thrombotic and non-thrombotic).

Indications and Contraindications

Control of acute hemorrhage from esophageal varices not amenable to or failing medical therapy, e. g., pharmacotherapy, balloon tamponade, endoscopic variceal sclerotherapy, in patients with liver cirrhosis and portal hypertension Control of bleeding gastric or intestinal varices Prevention of recurrent variceal bleeding after initial control Complicated Budd-Chiari syndrome

Hepatic Osteodystrophy

The mechanism of metabolic bone disease in patients with liver disease is multifactorial. The liver is a source of factors involved in bone remodeling and these factors are reduced in chronic liver disease. Patients with liver disease have impaired osteoblast proliferation and thus decreased bone formation. The liver is a source of insulin-like growth factor (IGF)-1, which is important in bone remodeling. Animal data suggest that the decrease in IGF-1 in cirrhosis results in decreased bone formation. In humans, however, the correlation between IGF-1 and osteopenia is less clear. OPG is also produced by the liver, and reductions in this may result in increased osteoclast activity. In general cholestatic liver diseases are associated with lower BMD than noncholestatic liver diseases. In particular patients with PBC appear to have decreased BMD but this may also occur because patients are generally older, postmenopausal women. There are also data to suggest that patients with PBC or...

Etiology and Pathophysiology

The observed increase in resistance can be characterized anatomically as presinusoidal (eg, portal vein thrombosis, schistosomiasis), sinusoidal (eg, cirrhosis, primary sclerosing cholangitis, alcoholic hepatitis) or post-sinusoidal (eg, Budd-Chiari, veno-occlusive disease) (Table 117-1). Of note, in those patients with presinusoidal and postsinusoidal portal hypertension, the increased resistance can be either intrahepatic or extrahepatic. Although some of the increased resistance is due to anatomic alterations, such as fibrosis and regenerative nodules, which are irreversible, there are also dynamic elements involving vascular tone. The alterations in vascular tone are mediated by an increase in the endogenous production of endothelin, a potent vasoconstrictor, and a decrease in the intrahepatic production of nitric oxide (NO), a potent vasodilator, leading to alterations in the level of vascular resistance. An additional site of increased vascular resistance is...

Primary Liver Diseases that Lead to Hepatic Insufficiency

End-stage liver disease is the major indication for liver transplantation in pediatrics. Progressive biliary cirrhosis, particularly that due to biliary atresia, is the most common cause of end-stage liver disease in the pediatric population. Parenchymal liver diseases, including chronic active hepatitis with cirrhosis and certain metabolic diseases, are also common (Table 112-1). Cirrhosis is neither a specific disease entity nor a general indication for transplantation. It is an anatomic diagnosis with functional implications. Developing cirrhosis in the course of disease has grave prognostic implications with regard to the prospect of requiring transplantation. However, determining when transplantation should be performed involves estimating the functional reserve of the cirrhotic liver and its potential for supporting life of reasonable quality. Cirrhosis is an indication for immediate liver transplantation when there is evidence of functional hepatic decompensation, such as...

Definition of Noncirrhotic Portal Hypertension

Functional or mechanical obstruction of the above-described circulation (anywhere from the portal venous system to the right atrium) can lead to portal hypertension. Portal hypertension not caused by liver cirrhosis is termed noncirrhotic portal hypertension, though the two can coexist. Noncirrhotic portal hypertension is categorized according to the level of obstruction of the portal blood flow and its drainage, into pre-, peri- and postsinu-soidal and has a large number of causes. The causes of noncirrhotic portal hypertension are listed in Table 118-1. Normally, the pressure within the portal venous system ranges between 5 and 10 mm Hg. Portal hypertension is defined as an absolute portal pressure of more than 10 mm Hg or as a 6 mm Hg difference between hepatic and portal venous pressures (PVPs).

Indications for Therapy

Children with chronic HBV should be examined for possible antiviral therapy with the laboratory tests listed below under a-IFN. Serum a-feto protein, a relatively insensitive marker for HCC should be performed. HCV and human immunodeficiency virus (HIV) should be assessed as well because they are bloodborne pathogens which sometimes coinfect children with HBV. Baseline ultrasound for cirrhosis, HCC, and to mark a site for percutaneous liver biopsy should be performed before initiation of therapy liver biopsy should be performed prior to initiation of therapy. Indications for antiviral treatment in children are similar to those in adults and include the following (1) presence of hepatitis B e antigen (HbeAg) and HBV deoxyribonucleic acid (DNA) in serum, (2) elevated alanine aminotransferase (ALT), and (3) evidence of inflammatory activity in the liver biopsy.

Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC) is a chronic cholestatic disorder of unknown causation that is frequently associated with inflammatory bowel disease (IBD). PSC is characterized by diffuse inflammation and fibrosis of the biliary tree and usually leads to biliary cirrhosis, which can be complicated by portal hypertension and liver failure. The etiology of PSC has remained poorly understood since the earliest description of the disease. The current thinking is that PSC occurs as a consequence of a genetically determined dysregulated immune system, resulting in an uncontrolled inflammatory response in the bile ducts with destruction and fibrosis and, ultimately, biliary cirrhosis. The allo- and or autoantigen(s) that trigger this restricted inflammatory response in the bile ducts are unknown. Putative agents include bacterial antigens absorbed through a diseased bowel mucosa, particularly in patients with underlying IBD, as well as cytotoxic bile acids, viral infections, and...

Porphyria Cutanea Tarda Diagnosis

The major clinical feature in porphyria cutanea tarda (PCT) is fragility of sun-exposed skin which causes the formation of blisters and erosions after minor trauma, particularly on the backs of the hands. Chronic skin damage may lead to scarring and thickening of the skin which resembles scle-roderma. Skin lesions are accompanied by liver abnormalities which vary from mild portal inflammation to cirrhosis. In patients with long standing untreated PCT there is an increased incidence of hepatocellular carcinoma. Neurological symptoms do not occur in PCT. Alcoholism and use of estrogens are precipitating factors of PCT.

Brent A Neuschwander TetriMD

Disorders of the liver characterized by fat accumulation in the absence of excessive alcohol consumption are collectively known as nonalcoholic fatty liver disease (NAFLD). Although the presence of excess amounts of fat as triglyceride in hepatocytes may not always be directly harmful, it is typically associated with progressive liver disease. In fact, in some people, NAFLD is capable of causing cirrhosis and leading to death or liver transplantation. The necroinflam-matory changes associated with progressive liver disease are generally identified pathologically as steatohepatitis, and the pattern of injury and constellation of findings most commonly associated with more severe liver disease is called nonalcoholic steatohepatitis (NASH).

Contraindications

As aforementioned, cirrhosis is a relative contraindication to cholecystectomy because bleeding from the diseased liver parenchyma as the gallbladder is dissected can be difficult to control. This bleeding problem is compounded by portal venous hypertension and coagulation abnormalities from reduced liver synthetic function. In the event that bleeding from the gallbladder fossa cannot be satisfactorily controlled, the only option may be to decrease portal hypertension with a portal-systemic shunt of some sort (usually a TIPS).

Alternative Procedure

Because of the lack of survival benefit and relatively high rate of associated complications, peritoneovenous shunting is not frequently used (4). A third option for the treatment of refractory ascites is the diminution of portal pressures via transjugular intrahepatic portosystemic shunting (TIPS) (3). Placed percutaneously by interventional radiologists as a shunt from the portal vein to the inferior vena cava (IVC), TIPS is replacing paracentesis and peritoneovenous shunting as the treatment of choice for refractory ascites in part because TIPS is the bridge to transplantation for most of these patients who have Child-Pugh Class C cirrhosis. TIPS has worked well because surgical portosystemic shunts are contraindicated in patients with ascites complications associated with the TIPS procedure (in addition to the local and technical ones). Associated complications include significant encephalopathy in 23-30 of patients and shunt occlusion (opposite complications related by virtue of...

Perinuclear Antineutrophil Cytoplasmic Antibodies pANCAs and Antibodies to Asialoglycoprotein Receptor antiASGPRs

Anti-ASGPR is present in all forms of disease 28-30 . Seropositivity is associated with laboratory and histological indices of disease activity, and anti-ASGPRs identify patients who commonly will have a relapse after corticosteroid withdrawal 31, 32 . However, anti-ASGPRs are also found in other liver diseases including alcoholic liver disease, chronic hepatitis B and C, and primary biliary cirrhosis. The development of a commercial assay for application of anti-ASGPRs has been difficult, and their potential as diagnostic and prognostic markers has not yet been realized.

Autoantibodies and Autoantigens in Autoimmune Hepatitis

Autoimmune hepatitis (AIH) represents a chronic, mainly periportal hepatitis upon histology, which is characterized by a female predominance, hypergamma-globulinemia, circulating autoantibodies, and a benefit from immunosuppres-sive treatment. The diagnosis of AIH is based on clinical, serological, and im-munological features as well as on the exclusion of other hepatobiliary diseases with and without autoimmune phenomena. These include disease entities such as chronic hepatitis C, primary biliary cirrhosis, primary sclerosing cholangitis, and the so-called overlap or outlier syndromes. The revised AIH diagnostic score contributes to the establishment of the diagnosis in difficult cases by calculating a probability expressed as a numeric score 11 .

Idiopathic Portal Hypertension

As mentioned above, IPH is a diagnosis of exclusion. In the presence of clear signs of portal hypertension and when clinical history, physical examination, imaging and laboratory studies, and biopsy rule out other causes, only then one can diagnose IPH. Biopsy invariably shows concentric fibrosis around the small portal vein branches without cirrhosis. Some authors report preferential involvement of the left lobe with associated right lobe atrophy. Liver-associated laboratory tests are normal or near normal and serve only to exclude other causes of portal hypertension. Anemia and thrombocytopenia are also common findings in IPH, the latter likely due to the significant splenomegaly that characterizes the disease. It is crucial to properly diagnose IPH from a prognostic and management point of view. With proper management of variceal bleeding and splenomegaly and its associated thrombocytopenia, life expectancy is no different from healthy individuals. Its course is stable over many...

Selection of Candidates for Surgical Resection

The extent of underlying liver disease is a variable known to have a significant effect on operative morbidity and mortality. The presence of steatosis, fibrosis, and cirrhosis is associated with an increased perioperative risk. Studies have shown that only patients with severe fibrosis are at a higher risk for complications and death from liver failure after resection. In one study, 32 of patients with severe fibrosis (cirrhosis) who underwent a right hepatectomy died from liver failure compared with none of the patients with grade 0 to 3 fibrosis (Farges et al, 1999). As a rule, we do not operate on patients who are Child-Pugh class B or C. Similarly, we do not recommend resection for those patients who manifest clinical or radiologic signs of portal hypertension, including splenomegaly, abdominal collaterals, or thrombocytopenia. In fact, the preoperative portal pressure has been found to be an important factor in determining the risk of postoperative liver decompensation in...

Clinical Manifestations Imaging and Histologic Features

When PSC occurs in children, however, the liver disease seems to share features with autoimmune hepatitis. The overlap of PSC and autoimmune hepatitis in adults occurs in 5 of patients. PSC can be identified in patients without symptoms who come into medical attention solely because of abnormal results of function tests. Symptoms such as jaundice, pruritus, abdominal pain, fever, and weight loss or manifestations of portal hypertension in advanced stages of liver disease are uncommon initial manifestations. Physical examination may be unrevealing. Hepatomegaly, splenomegaly, hyperpigmentation, and excoriation can be found, but patients are now coming to medical attention earlier with a diagnosis established before some of the physical findings of more advanced liver disease have developed. Health-related quality of life is significantly impaired among patients with PSC compared with individuals from the healthy population, although it is similar to other liver disease,...

Paul J Thuluvath Md Frcp and Cary H PattMD

Over the past 20 years, liver transplantation (LT) has evolved from an experimental procedure into a successful therapeutic option for patients with end-stage cirrhosis and those with hepatocellular cancer. The recent data from the United Network for Organ Sharing (UNOS) suggest that the 1-year and 5-year patient survival rate has reached close to 95 and 85 , respectively, in many transplantation centers. This remarkable survival rate is due to many factors, including improvements in surgical techniques, better immunosuppression, and, more importantly, better patient selection. When examining a potential candidate for LT, it is imperative to determine whether the recipient is going to benefit from the procedure immediately and in the long term. For instance a patient with Child A (Table 110-1) alcoholic cirrhosis without any major complication may have a comparable 5-year survival with or without transplantation. When the long term complications from immunosuppres-

Psychiatric Comorbidity Alcoholism Mood and Personality

Of particular concern to the gastroenterologist is the high comorbidity between eating disorders and substance abuse, especially alcoholism. The overall rate of all substance use disorders among eating disordered patients was 37 in one study, and rates of alcoholism among bulimics were 40 (Braun et al, 1994). Patients abusing alcohol exhibit high rates of GI comorbidity, and women suffer adverse consequences, such as cirrhosis, from consumption of alcohol more quickly than do men. We recommend screening all eating disordered patients for alcohol abuse behaviors (Redgrave et al,2003).

Diagnosis and Staging

Several clinical staging systems that rely on liver function parameters are often used to guide initial therapy in patients with HCC. The Okuda staging system, which accounts for both liver function and tumor extension, has traditionally been used for predicting the prognosis of patients with cirrhosis and HCC. A new prognostic score proposed by the Cancer of the Liver Italian Program (CLIP) group (2000) includes Child-Pugh stage, tumor F1 Fibrosis score 5 to 6 (severe fibrosis to cirrhosis) is that the cutoff value for tumor size in the prognostic classification was shifted from 2 to 5 cm, and the influence of tumor size was limited only to patients with multiple tumors. All solitary tumors with vascular invasion, regardless of size, are combined with multiple tumors 5 cm and are classified as T2 because of similar prognosis. Multiple tumors 5 cm and tumors with evidence of major vascular invasion are combined and classified as T3 because of a similar poor prognosis. T4 tumors are...

Liver Transplantation

There have been multiple recent studies and reviews concerning liver transplantation in patients with severe alcoholic cirrhosis. There is a well-documented organ shortage for liver transplantation, and there are serious ethical issues concerning this controversial area that have precipitated these studies. HC and ALD are the two major reasons for liver transplantation in the United States. Data clearly demonstrate that patients transplanted for ALD do (short

Liver Disease During Pregnancy

Variable outcomes are seen in pregnant women with cirrhosis and portal hypertension. Significant hepatic decompensation (jaundice, ascites, and encephalopathy) can occur. Preexisting portal hypertension may be worsened by increased total blood volume, possibly increasing the risk of bleeding from esophageal varices. Pregnancy is generally uneventful in patients with chronic hepatitis B or C virus infections. Women with autoimmune hepatitis have had successful pregnancies and should continue to be treated with corticosteroids and or azathioprine. Women with untreated Wilson's disease are generally anovulatory, but can undergo successful pregnancy with following copper chelation treatment. Penicillamine or trientine therapy should be continued in this setting because discontinuation can lead to fulminant liver failure (the potential effects of these medications on the fetus should be discussed with the patient). Alcoholic women with significant liver disease may be anovulatory and thus...

STEP 1Exploration mobilization and resection of the native right hemiliver

After visual and manual exploration of the liver and the entire abdominal cavity, the vascular structures (median hepatic vein and its branches from segments V and VIII) are evaluated by ultrasound with a special emphasis on anatomical variations that may complicate the procedure (i.e., absence of right portal trunk). Next, a wedge biopsy is performed for the evaluation of fibrosis, as the presence of fibrosis or cirrhosis is a contraindication for auxiliary liver transplantation. Parenchymal necrosis is common and its intensity does not necessarily predict the likelihood of recovery.

Th1 versus Th2 Cytokines in Humoral Autoimmunity

During immune responses, all helper CD4+ T (Th) cells produce interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF), but differences in environmental stimulation skews them broadly towards two subtypes bearing distinct patterns of cytokine production (1) Th1 cells, which produce predominantly IL-2, interferon-y (IFN-y), lymphotoxin (LT), and tumor necrosis factor-a (TNF-a) and (2) Th2 cells, which produce IL-4, IL-5, IL-6, IL-9, IL-10, and IL-13 75-77 . This dichotomy has become less clear as recent studies have further detailed the increasingly complex environments of natural immune responses 78, 79 , but nevertheless it has remained of great utility because Th1 cytokines have consistently been associated with cellular immune functions, such as delayed-type hypersensitivity and macrophage activation, while Th2 cy-tokines have been associated with B cell-dependent antibody responses, such as allergy 76, 80 . As such, humoral autoimmune diseases were...

Laparoscopic Cholecystectomy for Expanded Indications

With growing experience, surgeons are now successful in performing laparoscopic cholecystectomy on the majority of patients regardless of presentation. However, several clinical scenarios continue to provide challenging settings for the laparoscopic technique and controversies with regard to methods of treatment. Acute cholecystitis, gallstone pancreatitis, choledocholithiasis, hepatitis or cirrhosis with portal hypertension, previous abdominal surgery, severe obesity, sepsis, and pregnancy are areas where dramatic improvements have occurred. Patients with cirrhosis and portal hypertension remain a challenge for the surgeon to perform any surgical procedure. However, laparoscopic cholecystectomy can be performed safely and effectively in patients with Child's A or B cirrhosis. In addition, increased experience with laparo-scopic lysis of adhesions allows surgeons to successfully complete laparoscopic cholecystectomy in patients who have had previous surgical procedures. Obesity is no...

The Pruritis of Cholestasis

Pruritus is one of the most common complications of cholestasis, but its etiology is unknown. It is a well-recognized manifestation of primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC), but conditions not usually associated with a serum liver profile classic for cholestasis (eg, predominantly increased activity of alkaline phosphatase and y-glutamyl transpeptidase), including liver disease secondary to chronic hepatitis C (HC), can also be associated with pruritus. The pruritus of cholestasis can be severe it is an indication for liver transplantation in cases of intractability.

Liver Resection for Colorectal Metastases

Although most patients with metastases do not have cirrhosis and can tolerate extended resections, increased morbidity can be associated with larger resections, particularly in patients heavily pretreated with chemotherapy. Therefore, an attempt should be made in most cases to preserve as much liver as possible.

Alcohol And The Cardiovascular System

Ethanol has long been recognized as a toxic agent affecting different organ functions both acutely and chronically 6 , A prospective study of middle-aged Swedish males registered for alcohol addiction revealed a two-fold greater increase in the incidence of clinical cardiac events than for liver cirrhosis 7 , Several factors may be responsible for the deleterious effects of alcohol on the myocardium, including (i) a direct toxic effect of ethanol or its metabolites (ii) associated nutritional deficiencies (i.e., thiamine) or (iii) direct toxicity of additives in the alcoholic beverage (i.e., lead or cobalt) 8 ,

Alcohol And The Immune System

Alterations of the immune system due to alcohol consumption have been a focus of multiple studies that have revealed impaired delayed-type hypersensitivity responses and ameliorated host defense against infections. Acute alcohol use has been associated with increased susceptibility to infections, posttrauma immunosuppression, and a decrease in antigen-specific T-cell proliferation response 13,16 , Malnutrition and cirrhosis are two of the conditions that develop with chronic ethanol consumption that affect the efficiency of the immune system to combat infections 11,12 , Ethanol influences the function of lymphocytes, monocytes and polymorphonuclear cells 13-15 ,

Longterm Complications Of Hepatic Resection

Still, the most common late problem encountered by patients who have undergone some form of hepatectomy is a recurrence of the disease that precipitated the need for the original hepatectomy. For example, approx 30 of equivalently selected patients who have undergone either hepatectomy or ablations for colorectal liver metastases will have the first recurrence of their tumor confined to the liver (21-23). Patients who have undergone a hepatectomy for hepatoma usually face not only the risk of recurrence of their tumor, but also the progression of cirrhosis and complications of portal hypertension. Nevertheless, the risk of tumor reappearance in the liver of patients with severely cirrhotic livers is very high (24). Many of these recurrences may really be new tumors arising in the damaged field, but their appearance within 5 yr of successful resection or ablation is unfortunately quite reliable and ultimately lethal.

Interpretation of Abnormal Liver Enzymes

Although the patterns of liver enzyme elevations are not always consistent between patients with similar disease states, there are some general rules that can be applied to interpreting enzymes. Aminotransferase elevations are typically seen with hepatocellular injury and often occur in the setting of normal or near normal bilirubin and alkaline phos-phatase. In almost all liver diseases except those that are alcohol related, the ratio of AST ALT is less than one, until cirrhosis develops when there is often a reversal of this ratio. Alkaline phosphatase elevation as an isolated finding should first be confirmed to be of hepatic origin by evaluating GGT or 5'NT. Once this has been confirmed, the next step is ultrasound or computed tomography scan to assess for biliary tree dilatation or infiltrative process. If the biliary tree is dilated, the next step is endoscopic retrograde cholangiography (ERCP). Although a percutaneous transhepatic cholangiogram can also be performed, the ERCP...

Disease Modifying Therapy

Disease-Modifying Agents in Primary Biliary Cirrhosis ALP alkaline phosphatase BM bone marrow HTN hypertension PBC primary biliary cirrhosis RCT randomized controlled trial UDCA ursodeoxycholic acid. ALP alkaline phosphatase BM bone marrow HTN hypertension PBC primary biliary cirrhosis RCT randomized controlled trial UDCA ursodeoxycholic acid. In patients who progress to liver failure despite treatment, liver transplantation remains the only alternative. Fortunately, patients with PBC tend to do extremely well, with 70 with 5-year survival and 60 with 10-year survival. Although

Causes of Noncirrhotic Portal Hypertension Budd Chiari Syndrome

The clinical presentation of acute Budd-Chiari syndrome includes any combination of ascites, abdominal pain, edema, hepatomegaly and less commonly GI bleeding. Subclinical Budd-Chiari can also be found incidentally during workup of patients with hypercoagulable states. Thus the reported natural history of the disease is skewed towards the most severe forms. In a minority of patients venous outflow obstruction may lead to liver failure and be complicated by encephalopathy, elevated liver function tests, jaundice, and even death. There is also evidence that a small fraction of patients with cryptogenic cirrhosis may have an insidious chronic form of the disease. In the absence of conclusive studies most experts agree on a stepwise approach to the treatment of Budd-Chiari that depends on disease severity. In asymptomatic patients, and when there is no significant liver dysfunction, initial treatment should be limited with emphasis on treating the underlying cause. In the absence of...

Hepatitisassociated antigen See Australia antigen

Anti-HBs does not usually appear until convalescence. HBcAg does not appear in the blood. Anti-HBc appears during the disease and, unlike anti-HBs, persists for years and is a valuable marker of previous infection. HBeAg appears during the incubation period but disappears more rapidly than HBsAg. Persistence beyond 3-4 weeks may herald a chronic infection, which carries risk of hepatic cirrhosis or hepatocellular carcinoma. Not all chronic carriers of Hepatitis B virus develop chronic liver disease. A few infections result in acute hepatic failure probably due to an antigen-antibody reaction. Immune serum globulin (ISG) and hyperimmune globulin (HIG) are effective in providing passive immunity. A plasma-derived vaccine consisting of HBsAg is effective and widely used, especially in developing countries. This has been replaced in most other countries by genetically engineered vaccines derived from HBsAg produced in yeast (Recombivax, Engerovax), which...

Incidence and Etiology

The incidence of FHF is not well defined but has been estimated at approximately 2,000 cases per year in the United States. The various causes of FHF may be grouped into five general categories (Table 109-1). Of note, there is significant geographical variation in the prevalence of various causes of FHF, for example, with drugs and toxins causing most acute liver failure (ALF) in the United States and the United Kingdom, and hepatitis B virus (HBV)causing most cases in some developing countries.

Basuki GunawanMD and Neil KaplowitzMD

Drug-induced liver disease is of great importance because it is the leading cause of acute liver failure (ALF) in the United States. It is also a major reason for withdrawal of drugs during drug development and clinical use. The latter has major medical and economic consequences, as reflected in the recent experiences when bromfenac and troglitazone were withdrawn from the market. Because drug-induced liver disease can mimic the entire spectrum of clinicopathologic features of other acute and chronic liver diseases, it is often challenging to diagnose. Establishing causality is important because the treatment of drug-induced liver disease includes discontinuation of the offending drug.

Maria H SjogrenMD MPH

Once acute hepatitis A is diagnosed, the management of the patient is mainly supportive. There is no specific therapy to accelerate the recovery. In very young patients, acute hepatitis A is a benign disease. It is a reportable infectious disease in the United States with a rate of infection of 4 in 100,000 habitants. The seroepidemiology of the infection is rapidly changing, particularly in the developing world, with increasing portions of the population escaping childhood infection, rendering increasing number of adults susceptible to the infection. Hospitalization rates vary but have been reported as high as 15 in recent outbreaks. Current publications on hospitalized patients due to fulminant hepatic failure cite hepatitis A as a frequent cause of liver failure requiring liver transplant. A 1998 scientific report described the clinical outcome of 256 individuals hospitalized with acute hepatitis A. On admission, 89 had prolonged nausea or vomiting, 26 had a prothrombin time...

Erythropoietic Protoporphyria Diagnosis

The major clinical feature in erythropoietic protoporphyria (EPP) is photosensitivity which usually begins in childhood. Patients report burning, itching, swelling and redness of the skin following sun exposure that varies in length from a few minutes to several hours. Some patients also develop hepatobiliary disease because of the toxic effects of protoporphyrin on liver structure and function. In a small number of patients, probably no more than 5 , this may cause progressive hepatic fibrosis that leads to liver failure and necessitates liver transplantation.

TIPS and Surgical Shunts

TIPS and surgical shunts are considered as salvage therapies to control acute variceal hemorrhage. Ten to 20 of patients will continue to bleed despite endoscopic treatment. TIPS and shunts are extremely effective procedures with control rates approaching 95 . TIPS involves the placement of an expandable metal stent from the hepatic vein, through the liver parenchyma, into the portal vein. Stents are the preferred form of salvage therapy as they can be successfully implanted in almost all patients and decrease the HVPG by half. An alternative to TIPS in Child's A cirrhotics is surgical shunting, which decompresses the portal system by creating a portasystemic anastomosis. Unfortunately, despite their high rate of success in controlling variceal hemorrhage, TIPS and surgical shunts are associated with many significant side effects, including hepatic encephalopathy and worsening liver failure, resulting in higher overall mortality rates.

Indications for the Procedure

As previously mentioned, intestinal transplantation should be undertaken in those cases in which there is a life threatening complication associated with TPN treatment. Ten to 40 of patients with intestinal failure die as a result of these complications within 3 to 5 years. Such complications include cholestatic liver failure, venous thrombosis leading to loss of access, and severe line sepsis. Isolated small intestinal transplantation is also considered in cases where TPN has led to reversible liver injury (Grosfeld et al, 1986). Liver and small bowel grafts are considered in cases of irreversible liver failure. Multivisceral transplantation is undertaken in instances when individual patient characteristics have led to the loss or malfunction of the viscera being replaced (Kato et al, 2002).

Hepatic Encephalopathy of ALF

In acute (fulminant) liver failure, hepatic encephalopathy is always present to same extent, and develops due to a precipitous decrease in hepatic function. It is important to determine whether the abnormal mental status in ALF is due to cerebral edema or if it develops in the absence of increased brain water. Clinical examination and radiological methods are limited tools for making this determination, and in hepatic coma, it is frequently necessary to directly measure the intracranial pressure. The importance of confirming or excluding the presence of cerebral edema or intracranial hypertension lies in the different management strategies. In encephalopathic patients without cerebral swelling, management is not significantly different from that described above for chronic cirrhotic hepatic encephalopathy. In contrast, the presence of cerebral edema requires the use of mannitol therapy, infusion of barbiturates, and preparation for urgent liver transplantation. Dietary protein is...

Surgical Management of Hepatic Metastases

Hepatic metastases occur in about 85 of patients with small intestine NETs within 10 to 20 years. Primary small bowel NETs are most likely to metastasize to the liver (Figure 18-8), followed by primary tumors usually located in the pancreas, rectum, or lung.57 Patients with liver metastases are mainly considered for medical therapy because resection of these metastases is possible in only 10 of cases.59,66 The ideal intervention is a safe procedure (with minimal mortality 3 and low morbidity 20 , avoiding specific complications such as hemorrhage, liver failure, or bile leakage) performed for a functional syndrome not amenable by medical treatment.66 However, the tumor mass must be reduced to 10 to 20 to control the symptoms when cytoreductive hepatic surgery is performed.57 Asymptomatic patients with resectable primary tumor but with liver masses unresponsive to nonsur-gical treatments are also good candidates.67 Recently, new methods have been recommended to treat hepatic metastases...

STEP 7Testing adequacy of mobilization of portal vein and IVC

To determine the adequacy of mobilization of portal vein and IVC, the two vessels are brought together by traction on the umbilical tapes that surround them . It is essential to determine that the two vessels can be brought together without excessive tension. If this cannot be done, it is almost always because the vessels have not been adequately mobilized, and further dissection of the vessels should be undertaken. Resection of part of an enlarged caudate lobe of the cirrhotic liver, recommended by some surgeons to facilitate bringing the vessels together, is associated with some difficulties and, in our opinion, is neither necessary nor advisable.

Indications For Liver Resection

The most common reason tumors are removed from the liver is to attempt a cure for a patient with a malignant neoplasm. Primary hepatocellular cancer, or hepatoma, is the most common malignant solid tumor worldwide. However, it is much less common in the United States. Here, the most common malignant neoplasms of the liver are metastatic deposits from lung, breast, and gastrointestinal (GI) primary sites. Some of these patients can be cured by removing the metastases from the liver. However, they are a highly selected group who have a small number of isolated colorectal or neuroendocrine metastases in the liver. Patients with metastatic lung, pancreatic, breast or gastric cancer are not reliably salvaged by resectional or ablative strategies for the liver metastases. Similarly, a minority of patients with hepatoma can be cured by resection and or ablation because these tumors tend to present at a late stage or in a cirrhotic liver that will not tolerate a resection. Nevertheless, there...

Preoperative Evaluation And Preparation

Coronary Vein Pancreas

The etiology of the portal hypertension should be determined because this has a direct impact on outcome. Patients with nonalcoholic cirrhosis (e.g., postnecrotic cirrhosis, primary biliary cirrhosis) and those with extrahepatic portal vein thrombosis or primary hepatic fibrosis do better, and have an improved survival after the DSRS than alcoholic cirrhotics (17,18). Because prognosis is directly related to liver functional reserve, the Child-Pugh class status should be assessed. Ideally, the nutritional status should be good, there should be no encephalopathy, the serum total bilirubin should be less than 2 mg dL, the serum albumin greater than 3 g dL, there should be no ascites and the prothrombin time should be no longer than 2 sec from the control. Ultrasound assessment of liver volume (between 1000 and 2500 mL) and a functional measurement of the liver reserve by means of the galactose elimination capacity (greater than 250 mg min) will further aid the selection of good-risk...

Types of hepatectomy Resections

Extended Hepatectomy

Although 75 of a normal liver may be resected with a reasonable expectation that enough hepatic function will remain to support regeneration of the hepatic remnant, this percentage is significantly reduced when the liver parenchyma is diffusely diseased. A larger hepatic remnant will be necessary to support regeneration and reduce the risk of fulminant hepatic insufficiency. Typically, when more than 50 of the functional capacity of the liver is removed, the possibility of liver failure becomes a threat. For these reasons, judgments about the advisability of a major resection are based upon both estimates of the normalcy of the residual hepatic cell mass (e.g., no cirrhosis) as well as how much of the functioning tissue will remain after the resection. For example, a right trisegmentectomy may be done relatively safely for a large tumor that has replaced the right lobe and medial segment of the left lobe because most hepatic function will already have shifted to the left lateral...

Complications Of Biliaryenteric Anatomosis

Roux Limb Jejunostomy

Later complications of these operations revolve around progression of the disease that precipitated the need for the original operation (e.g., pancreatic cancer), complications associated with any upper abdominal operation (e.g., wound pains, hernias, adhesive bowel obstructions), and stricture of the biliary enteric anastomosis. Stricture of these anastomoses generally leads to episodes of cholangitis, and even frank obstructive jaundice. In repetitive and neglected cases this can progress to cirrhosis and portal hypertension a development that greatly complicates subsequent therapeutic maneuvers. Although early problems with the anastomosis can presage later failure, recurrence of a benign stricture may take 10 yr to develop (6). So these patients must be followed with periodic checks of their liver function tests (particularly alkaline phosphatase) for years. Whether prolonged perioperative stenting of biliary-enteric anastomoses decreases the chance of later stricture formation is...

Portosystemic anastomoses

A number of connections occur between the portal and systemic circulations. When the direct pathway through the liver becomes congested (such as in cirrhosis) the pressure within the portal vein rises and under these circumstances the porto-systemic anastomoses form an alternative route for the blood to take. The sites of porto-systemic anastomosis include

Extended Left Hemihepatectomy Left Trisectionectomy

Hepatic Trisectionectomy

This procedure should only be performed if the remnant liver (segments 1 9+6+7) provides sufficient liver function. Preoperative assessment of liver function, volumetric evaluation of the expected remnant liver volume and exclusion of liver fibrosis or even cirrhosis are essential.

Extended Right Hemihepatectomy Right Trisectionectomy

Right Hemihepatectomy

The extended right hemihepatectomy (also called right trisectionectomy) includes resection of segments 4-8. For cholangiocarcinoma of the liver hilum (Klatskin's tumor) or carcinoma of the gallbladder, an en-bloc resection including segments 1 and 9 is usually performed. This procedure should only be performed if the remnant liver (segments 2 and 3) provides sufficient liver function. Therefore, preoperative assessment of liver function, a volumetric assessment of the expected remnant liver volume, and exclusion of liver fibrosis or cirrhosis are essential before extended resections.

Ascending Cholangitis Following Portoenterostomy

Extrahepatic biliary atresia is an obliterative cholangiopathy that involves all or part of the extrahepatic biliary tree and, in many instances, the intrahepatic bile ducts. In the U.S.A., from 400 to 600 new cases of biliary atresia are encountered annually (46). The diagnosis is usually suggested by the persistence of jaundice for six weeks or more after birth. Several factors have been considered for the pathogenesis of extrahepatic biliary atresia, including viral infection (e.g., cytomegalovirus) (47), metabolic insults, and abnormalities in bile duct morphogenesis. Although selected patients benefit from prompt diagnosis and Kasai portoenterostomy surgical intervention (48,49) within the first 60 days of life, many ultimately require liver transplantation because of portal hypertension, recurrent cholangitis, and cirrhosis (50).

Measurement of Portal Pressure

Sinusoidal Obstruction Syndrome Sos

Schistosomiasis Precirrhotic stage, primary biliary cirrhosis Alcoholic central sclerosis Endothelitis (liver rejection, radiation injury) Arterioportovenous fistula (traumatic or Olser-Weber-Rendu) Hyperdynamic splenomegaly (infectious or myelodysplastic) Nodular regenerative hyperplasia

Coagulation Disorders

Proper blood clotting depends on normal liver function for two reasons. First, the liver synthesizes most of the clotting factors. Therefore, diseases such as hepatitis, cirrhosis, and cancer that degrade liver function result in a deficiency of clotting factors. Second, the synthesis of clotting factors II, VII, IX, and X require vitamin K. The absorption of vitamin K from the diet requires bile, a liver secretion. Gallstones can lead to a clotting deficiency by obstructing the bile duct and thus interfering with bile secretion and vitamin K absorption. Efficient blood clotting is especially important in childbirth, since both the mother and infant bleed from the trauma of birth. Therefore, pregnant women should take vitamin K supplements to ensure fast clotting, and newborn infants may be given vitamin K injections.

Clinical Features of HH

Those patients who are symptomatic at the time of diagnosis tend to be older than 40 years of age and are predominantly male. Weakness, lethargy, abdominal pain, arthralgias, and loss of libido are common. The arthropathy seen in HFE-associated HH tends to be symmetric and involves multiple joints. Specifically, the proximal inter-phalangeal, metacarpophalangeal, wrist, knee and vertebral joints are most commonly involved. Hepatomegaly and cirrhosis may be present, along with skin pigmentation and clinical diabetes.

Alcoholic versus viral or idiopathic chronic dilated cardiomyopathy DCM

Another clue to the possibility that alcoholics may have a viral pathogenesis for their chronic DCM is a little-known experiment on viral myocarditis in mice. Morin et al. 41 administered Coxsackie B virus to 48 mice. One half received laboratory chow and alcohol and the other half received laboratory chow and sweetened water. At the end of 5 weeks, 80 of the alcohol group showed microscopic cardiac involvement. Only 30 of the non-alcohol group had cardiac lesions (p 0.02). The cardiac involvement in the mice that received the alcohol was not only more frequent but also more severe than in the non-alcohol group 4T . How the damage of a viral attack on the myocardium can be augmented by alcohol is unknown, although there are many possibilities. It has been suggested, for example, that it may be due to the loss of potassium and magnesium from the myocardium or the ability of alcohol to inhibit the active transport of cations across the cell membrane 27,42 , An analogy may be made with...

Jorge A Marrero MD MS and Anna S Lok MD

HCC is currently the fourth most common tumor worldwide. once thought to be rare in the United States, the incidence of HCC has risen from 2.2 per 100,000 persons in 1990 to 3 per 100,000 persons in 1996 to 1998, an increase of 25 during the last 10 years (Davila et al, 2003). Chronic hepatitis C infection has been shown to be the most important factor for the increase in incidence of HCC in the United States, Europe and Japan, whereas chronic hepatitis B infection is the most important etiologic agent worldwide. Cirrhosis remains the most important risk factor for the development of HCC regardless of the etiology, with 5-year probability of developing HCC among cirrhotics around 20 . Thus, cirrhotic patients, particularly those with Child-Pugh class A and B, are the target population for surveillance for HCC. Patients with Child class C cirrhosis should be considered for liver transplantation so the impact of HCC surveillance on survival is less clear, except in the context of...

Acute Delta Hepatitis

Acute delta hepatitis can occur simultaneously with acute hepatitis B (co-infection) or occur in a patient who has an established chronic hepatitis B infection (superinfection). The coinfection is usually self-limited and does not require therapy. The superinfection tends to produce a severe acute attack, in many cases fulminant. Survivors of the acute delta hepatitis have an accelerated path towards cirrhosis and require therapy. Treatment is disappointing high doses of interferon do not eradicate the virus except in rare occasions. Nucleoside analogues like lamivudine have been ineffective in controlling delta hepatitis. Prevention of hepatitis B is important because delta hepatitis cannot survive in the absence of HBV infection. Delta hepatitis infection is rapidly declining because of universal vaccination against hepatitis B.

Colon Varices and Portal Colopathy

Sigmoid Colon

Sharp increases in portal hypertension related to liver cirrhosis or portal vein thrombosis can cause formation of varices throughout the entire colon (Fig. 17.12). Lymphedema is not present. Bleeding is acute and can be controlled with fibrin glue and hemoclips. Long-term prophylactic measures such as lowering

Toxin Mediated Infectious Diarrhea

B. cereus) should suggest either B. cereus or S. aureus food poisoning. Although foodborne disease is almost always self-limited (24 to 48 hours), fulminant liver failure has been reported, and B. cereus may cause a variety of extraintestinal infections (Mahler et al, 1997). Treatment is supportive. Several species of Vibrio other than V. cholerae are capable of causing gastroenteritis the most important of which is V. parahaemolyticus. Others include non-O1 strains of V. cholerae, V. fluvialis, V. hollisae, and V. mimicus. In addition, V. vulnificus is an important cause of sepsis and soft tissue infection in immunocompromised hosts, especially those with cirrhosis or advanced liver disease. Long recognized as a seafood-associated pathogen in Asia, V.para-haemolyticus has emerged as a significant cause of diarrhea in the United States following ingestion of raw or under-cooked shellfish, such as raw oysters (Daniels et al, 2000). As with most types of foodborne gastroenteritis, the...

Nucleotide Reverse Transcriptase Inhibitors Tenofovir Disoproxil Fumerate Viread

The result of several resistant mutations (168,169). However, there are reports that tenofovir can be used to treat HIV-1 strains that are nucleoside-resistant (170). Tenofovir is also active against hepatitis B virus. In one case, an HIV-positive patient with liver cirrhosis secondary to chronic hepatitis B and resistance to lamivudine was treated with tenofovir with significant virologic and histopathologic improvements. This case was so successful that the patient was removed from the liver transplant program and has not had any further hepatic complications (171). Long-term administration of tenofovir (96 weeks), combined with exisiting antiretroviral therapy for patients with preexisting resistance mutations, showed significant and durable reductions in HIV-1 RNA levels (172).

Measuring and Communicating Weak Associations

The abilities to assess weak associations with validity and to appropriately communicate epidemiologic findings to the public are continuing challenges for modern epidemiology. Epidemiology has had great success in identifying the origins (and magnitude) of many public health epidemics. Examples include cigarette smoking lung cancer, asbestos mesothelioma, and alcoholism cirrhosis of the liver. Relative risk estimates for many of these risk factors range from 5 to 20, making their identification and inferences about causation relatively easy. In contrast, for many risk factors currently being studied, it is increasingly difficult to find overwhelming evidence for causality (Gordis 1988). The closer a relative risk estimate comes to unity, the more likely that it can be explained by m thodologie difficulties such as confounding or misclassification, or other sources of bias. New techniques in molecular epidemiology (noted earlier) may prove extremely beneficial in identifying...

Functions of the Liver

We have seen that the liver plays a central role in carbohydrate metabolism. Additional liver functions (table 26.7) were described in previous chapters and will be described later in this chapter. Except for phagocytosis, all of these are performed by the cuboidal hepatocytes described in chapter 25. Such functional diversity is remarkable in light of the uniform structure of these cells. Because of the wide range of functions performed by the liver, degenerative liver diseases such as hepatitis, cirrhosis, and liver cancer are especially life-threatening.

Intrahepatic Cholestasis of Pregnancy

Maternal prognosis is excellent with IHCP and there are usually no hepatic sequelae. Symptoms progress until delivery and then promptly disappear. Jaundice resolves rapidly and serum laboratory tests resolve over weeks to months. Acute liver failure does not occur. IHCP is associated with an increased incidence of primary postpartum hemorrhage (20 to 22 ), likely due to vitamin K deficiency. The incidence of cholelithiasis is also increased.

General Contraindications to Liver Transplantations

Special consideration should be given to the young infant who presents with liver failure. Some of the causes of liver failure in this age group can be treated with medical therapy. For instance, chelation and antioxidant therapy are now used to treat neonatal hemochromatosis. Albeit the rate of survival with medical therapy is only 30 to 40 , but that may be similar to survival after OLT in neonates. Transplantation should be withheld if the candidate has a preexisting condition that will lead to a poor quality of life following transplantation. This applies particularly to the central nervous system (CNS). Congenital malformations or secondary injury to the brain (eg, intracranial hemorrhage or hyperammonemia) often lead to severely impaired children after transplantation. Furthermore, some systemic disorders cause hepatic injury and progressive CNS disease. Alpers' disease is characterized by primary degeneration of cerebral gray matter in association with liver disease and can...

Portal andor Splenic Vein Thrombosis

The presence of thrombus in the portal vein causes obstruction of the venous drainage of much of the GI system. Risk factors include cirrhosis, abdominal sepsis, pan- Cirrhosis The diagnosis of PVT is relatively straightforward once it is suspected. MRI and CT, as well as ultrasound, are usually diagnostic and can provide information regarding the extent of disease as well as its cause. All of these modalities can confirm the presence of varices, splenomegaly, and ascites, as well as cirrhosis. A celiac or mesenteric arterio-gram can be extended to show the venous drainage into the portal vein and diagnose PVT. If required, direct trans-hepatic portal vein percutaneous access can be obtained and a porto-venogram performed. It is important to note that in the absence of liver disease, wedged hepatic pressures are normal, whereas preobstructive pressures (intrasplenic, SMV) are elevated. Laboratory values are usually normal with nonspecific findings, such as hypoal-buminemia and...

Evaluation of Ascites

Physical findings are helpful in determining the etiology of ascites. Vascular spiders, splenomegaly, and engorged abdominal collateral veins suggest cirrhosis. Peripheral edema due to liver disease is usually confined to the lower extremities and may occasionally involve the abdominal wall. Culturing ascitic fluid as if it were blood gives the highest yield. Bedside inoculation of 10 to 20 mL of ascitic fluid into each of 2 culture bottles has become the standard technique, with a detection rate of over 90 . Additional testing on the ascitic fluid includes glucose, lactate dehydrogenase, amylase, triglycerides, bilirubin, and cytology. Ascitic fluid and serum levels of cancer antigen 125 are almost invariably elevated in patients with cirrhosis and ascites and should not be used as surveillance markers for peritoneal carcinomatosis.

Anticentromere Antibodies

ACAs that are relevant for scleroderma diagnosis are directed against the centromere-associated proteins (CENP) CENP-A (17 kDa), CENP-B (80 kDa), and CENP-C (140 kDa). CENP-B is the antigen most commonly targeted by ACAs. Autoantibodies directed against other centromeric proteins (e.g., proteins only transiently associated with the centromere) are not included in the diagnostic-category ACAs. The method of choice for detecting ACAs is indirect immunofluorescence (IIF) using monolayers of tumor cells (usually HEp-2). The number of spots corresponds to the number of chromosomes in interphase nuclei and in the equatorial plane of mitotic cells. If the typical ACA pattern is masked by other autoantibodies, an enzyme immunoassay using recombinant CENP-B protein should be used. ACAs are diagnostic markers for systemic sclerosis with a specificity of 95 (SSc versus other CTD) to nearly 100 (SSc versus normal controls) and a sensitivity of 20-30 in general (reviewed in 42 ). The frequency...

Challa AjitMD and Santiago MunozMD

Hepatic encephalopathy is a neuropsychiatric syndrome consisting of altered neurological function associated with acute or chronic liver disease and portal systemic shunting. Exclusion of other disorders of the central nervous system (CNS) is important to establish the diagnosis. The development of hepatic encephalopathy in a cirrhotic patient indicates decompensation of a previously stable liver disease, or more frequently, it represents the effect of a transient precipitating factor. Hepatic encephalopathy generally implies a poor prognosis its severity is a key component of the Child-Pugh score, an important prognostic system in chronic liver disease. In contrast, onset of hepatic encephalopathy in patients with acute liver failure (ALF), defines a fulminant course and is associated with risk of life threatening complications, including cerebral edema and intracranial hypertension. In spite of the common occurrence of hepatic encephalo-pathy in patients with cirrhosis, there is no...

Treatment of Alcoholism and Alcohol Dependence

Of alcoholism, but can be done by any concerned health care provider. It is important that additional steps be taken to refer the individual for further treatment as soon as he or she is willing to accept the diagnosis. Patients who have developed physical complications of heavy alcohol consumption, such as cirrhosis, pancreatitis, or gastritis, are often more amenable to beginning treatment. The gastroenterologist has an advantage over other providers in being able to state authoritatively that a medical problem is the result of alcoholism. Using this window of opportunity often makes a difference in the likelihood of an individual beginning therapy for alcoholism. As long as appropriate steps are taken to refer the individual, it is not essential for the gastroenterologist to become personally expert in treating alcoholism.

SOS Hepatic Veno Occlusive Disease

SOS is classified as mild (clinical symptoms, no treatment, complete resolution), moderate (clinical symptoms, requires treatment, complete resolution), and severe (death or clinical symptoms that persist for more than 100 days despite optimum treatment). With appropriate treatment, most patients (60 to 75 ) eventually recover. Paradoxically, those who die, die not from liver failure, but rather from cardiac or renal failure. Both unimodal and bimodal forms of the disease have been identified. In unimodal disease, the symptoms appear and progress or resolve as described above. In bimodal disease, initial symptoms abate only to reappear at a later time. Prognosis is worse in bimodal disease. Prevention should be optimized by (1) avoiding SOS causing chemotherapeutic agents if possible and (2) eliminating modulating factors (liver shielding during total body irradiation and adequate treatment of sepsis). Empiric anticoagulation, usually with heparin or low molecular weight heparin, has...

Treatment of Hemochromatosis

Therapy for HH is relatively simple and quite effective. Phlebotomy has been shown to effectively remove excess iron stores without significant side effects. If therapeutic phlebotomy is started before the development of cirrhosis, morbidity and mortality are significantly reduced. Some clinical features of iron overload respond better to phlebotomy than others. Malaise, fatigue, abdominal pain, skin pigmentation, and insulin requirements in diabetic patients tend to improve, whereas arthropathy and hypogonadism are less responsive. Given these findings, early identification and initiation of therapeutic phlebotomy should be the goal. Cirrhosis does not improve with iron reduction therapy. Despite therapeutic phlebotomy, hepatocellular carcinoma (HCC) continues to be a threat in patients who have cirrhosis. In fact, HCC accounts for about 30 of all deaths in HH patients. Orthotopic liver transplantation is a viable alternative for patients who develop decompensated liver disease due...

Orthotopic Liver Transplantation

For those patients whose poor underlying liver function and tumor number or location preclude hepatic resection, we advocate total hepatectomy with orthotopic liver transplantation (OLT). Although the initial series of OLT for HCC reported poor results, the selection criteria for OLT have subsequently undergone major revision, and more recent results have been favorable. Currently, patients with HCC and cirrhosis with three or less tumor nodules up

Secondary Liver Disease

Many children and young adults with cystic fibrosis and biliary cirrhosis have undergone liver transplantation. Initially, there was concern that the use of immunosuppressants might lead to more severe infectious complications in these patients. However, survival appears to be equivalent to that of transplantation performed for primary liver disease. Many patients experience improved pulmonary function, probably as the result of improved strength, but pulmonary infections with Pseudomonas sp and Aspergillus continue to threaten the postoperative course. successful liver transplantation has also been performed in children with destructive cholangitis secondary to Langerhans cell histiocytosis.

Assessment of Severity

Benzodiazepines have been the primary category of drugs used in treating alcohol withdrawal for many years. They are safe and effective, but require monitoring of therapy to avoid unwanted effects such as oversedation. All drugs in this category are effective in both treating and preventing seizures. In recent years, short acting drugs such as lorazepam (Ativan) have been used more frequently. This drug does not accumulate in those patients with chronic liver disease, such as cirrhosis or severe alcoholic hepatitis, although it can precipitate hepatic encephalopathy as easily as other drugs in this category. Diazepam (Valium) and chlordiazepoxide (Librium) have a long track record of use for treating alcohol withdrawal. Both are metabolized to active metabolites, one of which is lorazepam, and have a longer effective half-life than lorazepam. Some protocols for managing withdrawal take advantage of the longer halflife by using a loading dose regimen, which will self-taper over several...

Management of Wilsons Disease Hepatic Disease

For Wilson's disease patients with liver disease, the initial period of treatment with a chelator should range from 2 to 12 months, with close monitoring maintained during this initial period of treatment. For most patients, there is a general trend towards stabilization of hepatic function over the first 8 weeks of therapy. Biochemical parameters of hepatic inflammation and insufficiency should show a trend towards gradual improvement over the next 6 to 12 months, though may improve further for up to about 4 years after the initiation of treatment in some individuals. For those with ascites and edema that respond to the primary treatment of the Wilson's disease, requirements for diuretics decrease with time. Similarly, the need for treatment of encephalopathy, if necessary, may also improve with primary treatment for Wilson's disease. Once stabilization is achieved, then either the chelator can be continued at a reduced dosage, or patients can be maintained on zinc therapy. For those...

Defects of fatty acid metabolism

- CT L-carnitine is essential for the transport of long-chain fatty acids into the Mt for P-oxidation. In primary carnitine deficiency there is increased loss of carnitine into the urine. Secondary carnitine deficiency may be due to Mt disorders, renal failure, muscular dystrophy, chronic myopathy, and liver failure. CT is usually associated with nonsense mutations of the genes encoding OCTN2, a high-affinity sodium-dependent carnitine transporter and SLC22A5, an organic cation transporter.

Tests of Hepatic Function

PT is a very useful marker of hepatic function, and in acute liver failure it can impart prognostic information. Coagulation factors made in the liver include I, II, V, VII, IX, and X. Notably, factor VIII is not made in the liver and can be used to distinguish disseminated intravascular coagulation from liver related abnormalities in bleeding parameters, though this is rarely a clinical dilemma. More importantly, since factor V production is not dependent on vitamin K presence, measurement can be used to distinguish vitamin K deficiency as a cause of prolonged PT from liver disease-related causes. Vitamin K dependent factors are II, VII, IX, and X. Although prolonged PT is not specific for liver diseases, the other causes of prolonged PT, such as consumptive coagulapathy, vitamin K deficiency states, or medication-related causes, are generally simple to rule out. Hence, PT becomes a critical test for liver synthetic function. In fact, the international normalization ratio (INR) is...

Toxic And Metabolic Parkinsonism

One condition in which MRI may suggest the correct diagnosis is manganese intoxication. This is manifested by hyperintensity in T1-weighted images in the pallida, sometimes extending caudally to the substantia nigra. Manganese accumulates in the pallida in many conditions, including liver cirrhosis with portacaval shunt and hepatic encephalopathy (76,77), long-term parenteral nutrition (78), environmental exposure in miners or industrial workers (79), or in other less clear conditions (80). Therefore, demonstration of pallidal hyperintensities in T1-weighted images should prompt investigations of blood manganese concentrations (Fig. 7).

Alcoholic Liver Disease Role Of Free Radicals

Other hand, compounds which inhibit cytochrome P4502E1 such as chlomethiazol or diallyl sulfide 90,91 , also inhibit lipid peroxidation, radical production and result in an improvement ofhepatic morphology. Obviously, the degree of induction of cytochrome P4502E1 is of predominant importance with respect to ALD. It is, therefore, concluded that the ROS produced by this pathway may be especially important. This induction is diet dependent and enhanced with unsaturated fatty acids such as corn oil and low carbohydrates. In addition, iron, an important compound in the production ofROS, plays a significant role. Iron supplementation increases liver disease and administration of an iron chelator decreases ALD. Although, the administration of vitamin E to rodents inhibits ALD to some extent, data in humans are not very encouraging. The approach of administering vitamin E together with selenium and zinc to patients with alcoholic cirrhosis did show an improvement in mortality, but the number...

Family Members Screening for Hemochromatosis

All first degree relatives of patients with HFE-associated HH should be offered screening for HH. Screening of adults should include both a genetic test for HFE mutations and serum iron studies to measure fasting transfer-rin saturation and ferritin. The tested relative is unlikely to have HH if the fasting iron studies are normal and the patient is neither homozygous for the C282Ymutation or a compound heterozygote (C282Y H63D). Alternatively, if the tested relative is either homozygous for the C282Y mutation or is a compound heterozygote with an elevated ferritin or transferrin saturation, then the patient has HH and a therapeutic phlebotomy program should be initiated. Screening of minors raises the potential for genetic discrimination in regards to future insurance and or job candidacy. Therefore, it is appropriate to first perform HFE analysis in the other parent. This may obviate the need to test the children if the other parent has no HFE mutations. Family screening for HFE...

Prevention of a First Variceal Hemorrhage

Patients with cirrhosis should be endoscopically screened for varices so that appropriate therapy can be initiated if varices are present. Because the prevalence of varices increases with the severity of liver disease, screening is based on Child's classification at the time of the diagnosis of cirrhosis. Patients with Child's Class A cirrhosis should be screened when there is evidence of portal hypertension, such as thrombocytopenia (platelets less than 140,000 per mm3), an enlarged portal vein (diameter 13 mm), or evidence of collateral circulation on ultrasound. Screening should occur in anyone with Child's Class B or C cirrhosis at the time of the diagnosis of cirrhosis. If the patient is free from varices at initial screening, follow up endoscopy should be carried out. The timing of follow up will vary with the etiology of the patient's liver disease. Patients with ALD require more frequent screening (every 1 to 2 years), whereas those with cirrhosis due to hepatitis C only need...

Indications and Evaluation

Early in its development, some surgeons limited the use of laparoscopic approach, avoiding patients with acute cholecystitis, gallstone pancreatitis, choledocholithiasis, hepatitis or cirrhosis with portal hypertension, previous abdominal surgery, severe obesity, sepsis, and pregnancy. As surgeons have surpassed the learning curve, the relative contraindications to the laparoscopic approach have been reduced or eliminated. In fact, preoperative concern for gallbladder carcinoma remains the only absolute contraindication to laparoscopic cholecystectomy because of the risk of dissemination of cancer cells by the turbulent flow of gas in the pneumoperitoneum.

Acute Fatty Liver of Pregnancy

Asymptomatic elevations in liver tests may be the only abnormality, but the majority of severe cases present with malaise, fatigue, anorexia, headache, nausea, and vomiting (see Table 120-2). Right upper quadrant or epigastric pain may mimic acute cholecystitis or reflux esophagitis. Within 1 to 2 weeks of onset of symptoms, and within days following clinical jaundice, the disease may rapidly worsen, leading to acute liver failure, with hepatic encephalopathy, ascites, edema, and renal insufficiency. Hallmarks of preeclampsia (hypertension, proteinuria) are seen in over 50 of cases. AFLP is a medical and obstetrical emergency. It is often difficult to distinguish from toxic or viral hepatitis. Patients may progress to fulminant liver failure and death or require liver transplantation. No specific therapy is available. Patients should promptly be admitted to an experienced liver failure unit, since it is impossible to predict which patients will progress to liver failure. The patient...

Figure 111

Osmotic and nonosmotic regulation of antidiuretic hormone (ADH) secretion. ADH is secreted in response to changes in osmolality and in circulating arterial volume. The osmoreceptor cells are located in the anterior hypothalamus close to the supraoptic nuclei. Aquaporin-4 (AQP-4), a candidate osmoreceptor, is a member of the water channel family that was recently cloned and characterized and is found in abundance in these neurons. The osmoreceptors are sensitive to changes in plasma osmolality of as little as 1 . In humans, the osmotic threshold for ADH release is 280 to 290 mOsm kg. This system is so efficient that the plasma osmolality usually does not vary by more than 1 to 2 despite wide fluctuations in water intake 9 . There are several other nonosmotic stimuli for ADH secretion. In conditions of decreased arterial circulating volume (eg, heart failure, cirrhosis, vomiting), decrease in inhibitory parasympathetic afferents in the carotid sinus baroreceptors affects ADH secretion....

Figure 113

Renal disease Congestive heart failure Cirrhosis 1. Intrarenal factors such as a diminished glomerular filtration rate (GFR), or an increase in proximal tubule fluid and sodium reabsorption, or both, which decrease distal delivery to the diluting segments of the nephron, as in volume depletion, congestive heart failure, cirrhosis, or nephrotic syndrome.

Figure 116

Increased but total body water is increased even more than sodium, causing hyponatremia. These syndromes include congestive heart failure, nephrotic syndrome, and cirrhosis. They are all associated with impaired water excretion. Euvolemic hyponatremia is the most common dysnatremia in hospitalized patients. In these patients, by definition, no physical signs of increased total body sodium are detected. They may have a slight excess of volume but no edema 12 . (Modified from Halterman and Berl 12 with permission.)

Statistics

Results of studies about prognosis are usually reported as cumulative incidence rates or survival curves. That is, prognostic studies report the number of events occurring over time. A cumulative incidence rate provides an absolute risk of an outcome over a period of time, whereas survival curves can quantify trends in the risk of an outcome over time. The results of this study indicate that the most common HCV genotypes encountered were type 1b and type 2, and that patients with genotype 1 had a significantly worse prognosis regarding survival and the development of HCC compared with patients with other genotypes. The incidence rates of HCC were 5.9 per person per year for patients with genotype 1a, 4.5 for patients with genotype 1b, and 2.8 in patients with nongenotype 1 HCV. Development of cirrhosis and HCC was significantly greater in the genotype 1b group compared with other genotypes. Treatment with interferon, regardless of total dose or response to therapy, was associated with...

Figure 128

Management of noneuvolemic hyponatremia. Hypovolemic hyponatremia results from the loss of both water and solute, with relatively greater loss of solute. The nonosmotic release of antidi-uretic hormone stimulated by decreased arterial circulating blood volume causes antidiuresis and perpetuates the hyponatremia. Most of these patients are asymptomatic. The keystone of therapy is isotonic saline administration, which corrects the hypovolemia and removes the stimulus of antidiuretic hormone to retain fluid. Hypervolemic hyponatremia occurs when both solute and water are increased, but water more than solute. This occurs with heart failure, cirrhosis and nephrotic syndrome. The cornerstones of treatment include fluid restriction, salt restriction, and loop diuretics 20 . (Adapted from Lauriat and Berl 20 with permission.)

Figure

From a reduction in mean arterial pressure (MAP). Some disorders decrease cardiac output, such as congestive heart failure owing to myocardial dysfunction others decrease systemic vascular resistance, such as high-output cardiac failure, atriovenous fistulas, and cirrhosis. Because MAP is the product of systemic vascular resistance and cardiac output, all causes lead to the same result. As shown in Figures 2-3 and 2-4, small changes in MAP lead to large changes in urinary Na excretion. Although edema-tous disorders usually are characterized as resulting from contraction of the effective arterial volume, the MAP, as a determinant of renal perfusion pressure, may be the crucial variable (Figs. 2-26 and 2-28 provide supportive data). The mechanisms of edema in nephrotic syndrome are more complex and are discussed in Figures 2-36 to 2-39.

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