Hepatitis Ebook

Alternative Hepatitis C Treatments

The therapeutic goals of Natural treatment for Hepatitis C are as follows: Decrease iral load Normalize liver enzyme levels. Enhance/regulate immune system function. Strengthen and promote healthy liver function. Protect the liver, prevent further damage. Virological response; i.e. viral clearance, viral reduction or elimination of the virus. Starve the virus by limiting levels of iron. Optimizing cellular levels of glutathione in the body, making detoxification of the liver possible and enhancing the immune system. Stimulate regeneration of the damaged liver cells. Use of antioxidants to combat the effects of free-radicals generated by the virus. Reduce inflammation. Slow viral replication. Replace all of the inflammation-damaged liver cells. Regulate immune function/prevent auto-immune problems. Cancer preventative measures. Reverse fibrosis to prevent and improve cirrhosis

Alternative Hepatitis C Treatments Summary


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Evidence Based Medicine Approach to Prognosis Prognosis of Hepatitis C

You are the attending in a busy liver clinic. The gastroenterology fellow has just seen a 25-year-old male with chronic hepatitis C (HCV). The patient has liver enzymes that are two to three times the normal level, an elevated HCV RNA, and an HCV genotype of 1b. The fellow expresses a desire to treat the patient aggressively with interferon-based therapy because he has a worse prognosis than patients with other HCV genotypes. When you ask him to justify his comment, he produces a recent article by Roffi and colleagues in which the influence of HCV genotype on the clinical outcome of liver disease was assessed in 2,307 patients with chronic HCV (Roffi et al, 2001). 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...

Prevention and Treatment of Acute Hepatitis C

There are no vaccines available to prevent acute hepatitis C. The only way to effectively prevent it is to eliminate exposure to risk factors. No firm recommendation can be made for postexposure prophylaxis for hepatitis C. Study results are equivocal. Some experts recommend administration of Ig (0.06 mg kg) after a bonafide percutaneous exposure. The immunoglobulin should be administered as soon as possible. However, work in animal models (chimpanzees) has shown a lack of protectiveness when animals that received prophylaxis with immunoglobulin were challenged with HCV. Moreover, available data show that in humans the neutralizing antibody evoked after infection with HCV is short lived and does not protect against reinfection. Passive immunoprophylaxis for hepatitis C appears to be inefficient. To date, there is no effective vaccine against HCV infection, possibly because of the extensive genetic and antigenic diversity among HCV strains, the absence of natural immunity after...

Hepatitis and cholestasis

Abnormal liver biochemistry and or hepatomegaly are common clinical problems although frank jaundice is uncommon. With the multiple therapies being used in treatment and prophylaxis, a drug-induced hepatitis must always be considered in a patient with AIDS and abnormal liver function tests. The differential diagnosis is wide and may involve the use of serology, abdominal ultrasound, ERCP, and liver biopsy. These latter two diagnostic procedures are clearly invasive and would not be indicated unless treatment of opportunistic infection, malignancy or biliary strictures was contemplated. In the absence of dilatated bile ducts on ultrasound, liver biopsy usually shows a granulomatous hepatitis caused by atypical mycobacteria. HIV infection may alter the natural history of hepatitis B infection in a number of ways. The response rate to hepatitis B vaccination is lower in HIV-infected recipients. Immunodeficiency may favour the establishment of chronic infection following acute infection...

Hepatitisassociated antigen See Australia antigen

Hepatitis A virus (HAV) Type species of the genus Hepatovirus. Virion diameter 27-29nm, density in CsC1 1.32-1.34 g ml, sedimenting at 160S in sucrose. The genome RNA is positive-sense, 7.48kb in length, with a VPg protein covalently attached at the 5' end, and poly A at the 3' end. There is a single open reading frame encoding a polyprotein of 2235 amino acids. The virus replicates in various primate cell cultures after adaptation, usually without cyto-pathic effects. Causes enterically transmitted 'short incubation' hepatitis (less than 6 weeks) in humans. The virus is present in the feces during the prodromal phase of the disease but usually disappears about the time jaundice appears. Chronic carriers of the virus are not seen and the virus does not cause progressive liver disease. Epidemics of hepatitis A are usually due to water- or food-borne infection. Antibodies may be demonstrated by CFT, immune adherence, hemagglutination and radioimmunoassay. They appear soon after the...

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 . Since the first description of AIH in 1950 by Waldenstrom 12 , serological findings have attracted considerable attention not only for the diagnosis of this chronic liver disease but also as a means to study and eventually to understand its...

Table 3 ACS Recommendations for Preventing Transmission of Hepatitis54

Surgeons have the same ethical obligations to render care to patients with hepatitis as they have to render care to other patients. On the basis of current information, surgeons infected with HCV have no reason to alter their practice but should seek expert medical advice and appropriate treatment to prevent chronic liver disease.

Problemsspecial considerations Viral hepatitis

Viral hepatitis accounts for 40 of all liver disease associated with pregnancy. It is thought that pregnant women might be more susceptible to viral hepatitis because of their relatively immunosuppressed state. Hepatitis A is highly contagious and spread by the faecal-oral route. The incidence in pregnancy is unknown since many infections are mild, but is thought to be low in the UK. Hepatitis B is thought to infect up to 1 50 pregnant women in UK inner cities, in which there is a large immigrant population. It is readily spread by contact with blood and body fluids. Women who are known to have been exposed to intravenous drug use or to have had multiple sexual partners should be assumed to be at high risk of having hepatitis B, and appropriate precautions should be taken. Prostitutes are at particularly high risk, since many are using illegal drugs and working as prostitutes to fund their drug habit. Pregnant women have been screened for hepatitis B in the UK since 2000. There is a...

Autoantibodies and Autoantigens Associated with Autoimmune Hepatitis Type

AIH type 2 is a rare disorder that affects up to 20 of AIH patients in Europe but only 4 in the United States 33, 34 . The average age of onset is around 10 years, but AIH type 2 can also occur in adults, especially in Europe. In AIH type 2, patients are not only younger but also more frequently display an acute onset of hepatitis with a more severe course and rapid progression than do patients with AIH types 1 or 3. 13.4 Autoantibodies and Autoantigens Associated with Autoimmune Hepatitis Type 2 295

Autoantibodies Frequently Associated with Autoimmune Hepatitis Type

AIH type 1 represents the most common form of AIH (80 of all cases), mainly occurring between the ages of 16 and 30 years. The clinical course is usually not fulminant and an acute onset is very rare. It is characterized by the presence of antinuclear antibodies (ANAs) and or anti-smooth muscle antibodies (SMAs). The target autoantigen(s) of type 1 autoimmune hepatitis are largely unknown but consist of multiple nuclear proteins including centromeres, ribonucleoproteins, and cyclin A as well as smooth muscle actin 13-17 . How- 13.3 Autoantibodies Frequently Associated with Autoimmune Hepatitis Type 1 293

Prevention of Hepatitis B

The hepatitis B vaccine was first licensed in the United States in 1981 and is recommended for both pre- and postexposure prophylaxis. Hyperimmune globulin (HBIG) is a passive immunization that provides temporary protection and is indicated in certain postexposure situations. HBIG contains high concentrations of HB antigens, whereas regular immunoglobulin (like the one used for hepatitis A passive immunization) is prepared from plasma with varying concentrations of HB antigens. In the United States, HBIG has an HB antigen titer 1 100,000 by radioimmunoassay. TABLE 105-2. Passive and Active Immunization of Subjects at Immediate Risk of Developing Acute Hepatitis B Virus Infection TABLE 105-2. Passive and Active Immunization of Subjects at Immediate Risk of Developing Acute Hepatitis B Virus Infection TABLE 105-3. Immunization Schedule for Hepatitis B Vaccine in Adults and Children TABLE 105-3. Immunization Schedule for Hepatitis B Vaccine in Adults and Children HB hepatitis B. HB...

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 .

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.

Hepatitis GB viruses See GB viruses

Hepatitis infectiosa canis virus Synonym for Canine adenovirus. hepatitis non-A non-B virus In the mid-1970s, when diagnostic tests were established for Hepatitis A and Hepatitis B viruses, it became clear that much transfusion-related hepatitis was not caused by either virus. The term 'non-A non-B' was used together with a diagnosis of exclusion to describe the agent(s) responsible for this disease. See Hepatitis C, E, F, G and GB viruses. Hepatovirus A genus in the family Picornaviridae comprised of one species Hepatitis A virus, with two strains, human hepatitis A virus and simian hepatitis A virus. There is one tentative species in the genus, avian encephalomyelitis-like virus. Virions are stable, resistant to acid pH and elevated temperatures. There are a large number of strains of Hepatitis A virus which differ by less than 20 in genome RNA sequence homology, but there is little sequence similarity with other picornaviruses. The viruses cause hepatitis and gastroenteritis, with...

Inclusion body hepatitis IBH of chickens

Inclusion body hepatitis (IBH) of psittacine birds A usually fatal disease of budgerigars and parrots with gross liver lesions first described by Pacheco and Bier in 1930 following an epizootic in parakeets, and also known as Pacheco's disease. Often appears in captive birds following movement or delays in transit. The disease is caused by psittacid herpesvirus 1.

Hepatitis B neuropathy

Symptoms The symptoms in Hepatitis B neuropathy are most commonly similar to those of Hepatitis B neuropathy is very rare and, when present, occurs in the setting of chronic active or chronic persistent Hepatitis B. Examination reveals symmetrical sensory loss and weakness with areflexia. The weakness can be profound affecting all 4 extremities. In rare cases, patients have weakness and sensory loss in multiple named nerves. Diagnosis There is hematologic evidence of chronic active or chronic persistent hepatitis

Viral Hepatitis

Both hepatitis B and hepatitis C are important causes of chronic hepatitis and hepatitis B has been linked to hepatocellular cancer. Hepatitis C virus (HCV) is a positive-strand RNA virus and is the major infectious agent responsible for causing chronic hepatitis. Presently, there is no vaccine for HCV infection. There have been recent advances in drug therapy for this disease using a combination of Ribavirin with IFNa 39 however, there is still need for improved sustained therapy. Lieber and colleagues have demonstrated that adenoviral-mediated gene transfer of hammerhead ribozymes directed against a conserved region of the plus strand and minus strand of the HCV genome were efficient at reducing or eliminating the respective plus- or minus-strand HCV RNAs expressed in cultured cells and from primary human hepatocytes obtained from chronic HCV-infected patients. Another therapeutic approach has been to locally upregulate innate antiviral immunity. Toward this end Aurisicchio and...

Acute Hepatitis C

Unlike HBV, acute hepatitis C frequently progresses to chronic infection in approximately 80 of infected individuals when acquired as a result of blood transfusion. Early therapy had been advocated for acute hepatitis C because of its propensity to develop into a chronic infection. However, recent reports show that hepatitis C acquired through nontransfusional factors, such as intravenous contamination or sporadic hepatitis C may become chronic with lesser frequency in 40 to 50 of the cases. The new epidemiological data have important implications on the timing of therapy and is discussed further below.

Acute Hepatitis B

Acute hepatitis B carries the possibility of becoming a chronic infection in 1 to 5 of susceptible adults and 90 of neonates born to HBV-carrier mothers if the neonate does not receive prophylaxis at birth (Table 105-2). If the infection does not become chronic, it is benign in the majority of infected individuals, although some develop acute liver failure. The contribution of hepatitis B to the development of ALF has traditionally been larger than hepatitis A. In early studies in US populations, hepatitis B accounted for 18 to 34 of the ALF cases, whereas hepatitis A was a rare contributor of ALF in the United States. The decline of viral hepatitis as a cause of ALF is mainly due to the control of hepatitis B virus (HBV) infection through preventive measures that include education and general immunization. In the 1970s the rate of HBV in ALF cases was reported as 34 , in the 1980s it was reported as 19 , in the 1990s as 10 , and in recent years it dropped off to 7 . As in acute...

Acute Hepatitis E

Outbreaks of acute hepatitis E have been reported in Mexico, India, Pakistan, Nepal, Afghanistan, and other countries, but not in the United States. However, sporadic cases of acute HEV have been reported in the United States. The acute infection resembles acute hepatitis A and it is distinguished from it only with appropriate serological tests. Most cases have a benign clinical course and require only supportive therapy. However, fulminant cases and mortality have been described during epidemics. Pregnant women appear to be at higher risk of fulminant hepatitis E compared to nonpregnant women or men. Passive immunization is not available for hepatitis E and no specific therapy exists interferon-based therapy has not been tried. Prevention is best done by better sanitation and water purification. An experimental vaccine has been prepared, phase II studies are promising and there is hope that a phase III study will show acceptable safety and efficacy.

Hcvhiv Coinfection

Special consideration for HCV HIV co-infection is warranted, because up to 30 of HIV infected individuals are co-infected with HCV, and nearly all studies indicate that HIV accelerates progression of HCV to cirrhosis and liver failure. Preliminary studies indicate the safety of peginterferon and ribavirin to be comparable to HCV mono-infected patients, despite some early concerns about fatigue, anemia, and depression. Ribavirin should not be co-administered with didanosine because of increased tox-icity. Often, initiation of high active antiretroviral therapy in HCV HIV co-infected patients will lead to a HCV disease flare from immune reconstitution injury or drug toxicity.

Breaches in Reprocessing Protocol

This report documented patient-to-patient transmission of the hepatitis C virus during colonoscopy due to failure to clean the endoscope's suction and biopsy channels using a brush as reprocessing guidelines emphasize. In addition, this report indicated that high-level disinfection of the colonoscope was ineffective because the colonoscope was immersed in 2 glutaraldehyde for only 5 minutes, guidelines recommending an immersion time of no less than 20 minutes not withstanding. This report also indicated that, although mechanically cleaned using a detergent, the biopsy forceps, like the colonoscope, were immersed in 2 glutaraldehyde and not steam sterilized as reprocessing guidelines recommend. (Also contributing to the possibility for disease transmission, the intravenous (IV) lines and needles used on patients discussed in this report were changed, but the syringes used to administer the IV medications were reused and not disposable and single use...

Supplemental Reading

Bronowicki P, Venard V, Botte C, et al. Patient-to-patient transmission of hepatitis C virus during colonoscopy. N Engl J Med 1997 337 237-40. Centers for Disease Control and Prevention. Bronchoscopy-related infections and pseudoinfections New York, 1996 and 1998. MMWR 1999 48 557-60. Cheung RJ, Ortiz D, DiMarino AJ. GI endoscopic reprocessing practices in the United States. Gastrointest Endosc 1999 60 362-8.

Autoantibodies and Organspecific Autoimmunity 291

13.2 Autoantibodies and Autoantigens in Autoimmune Hepatitis 292 13.3 Autoantibodies Frequently Associated with Autoimmune Hepatitis Type 1 292 13.4 Autoantibodies and Autoantigens Associated with Autoimmune Hepatitis Type 2 294 13.5 Autoantibodies and Autoantigens Associated with Autoimmune Hepatitis Type 3 296 13.7 Autoantibodies in Overlap Syndrome Between Autoimmune Hepatitis and Primary Biliary Cirrhosis 297

Avian type C oncovirus group

Avihepadnavirus A genus of the family Hepadnaviridae containing only viruses which infect birds. The type species is Duck hepatitis B virus. The only other confirmed species in the genus is Heron hepatitis B virus, but Ross's goose hepatitis B virus may also be a member.

Measuring The Epidemic

Figure 1.5 The monthly infection rate (solid line) and monthly AIDS incidence (squares) in San Francisco, as estimated by Bacchetti (1990). The plot of HIV prevalence rate (percent) for homosexual and bisexual men participating in hepatitis B vaccine trials in San Francisco (triangles) is derived from data in Hessol, Lifson, O'Malley, et al. (1989). Figure 1.5 The monthly infection rate (solid line) and monthly AIDS incidence (squares) in San Francisco, as estimated by Bacchetti (1990). The plot of HIV prevalence rate (percent) for homosexual and bisexual men participating in hepatitis B vaccine trials in San Francisco (triangles) is derived from data in Hessol, Lifson, O'Malley, et al. (1989).

Familial Hypercholesterolemia

Capillaries Transcytosis

Endothelial cells also imbibe insulin by receptor-mediated endocytosis. Insulin is too large a molecule to pass through channels in the plasma membrane, yet it must somehow get out of the blood and reach the surrounding cells if it is to have any effect. Endothelial cells take up insulin by receptor-mediated endocytosis, transport the vesicles across the cell, and release the insulin on the other side, where tissue cells await it. Such transport of a substance across a cell (capture on one side and release on the other side) is called transcytosis32 (fig. 3.23). Receptor-mediated endocytosis is not always to our benefit hepatitis, polio, and AIDS viruses trick our cells into engulfing them by receptor-mediated endocytosis.

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

TK Sreepada Rao David Roth

Infection with hepatitis B virus (HBV) may be associated with a variety of renal diseases. In the past, HBV was the major cause of viral hepatitis in patients with end-stage renal disease (ESRD). Introduction of rigorous infection-control strategies has led to a remarkable decline in the spread of HBV infection in dialysis units. Physicians also are increasingly recognizing the association between chronic hepatitis C virus (HCV) infection and glomerular disease, both in native kidneys and renal allografts. Liver disease caused by HCV is a major factor in morbidity and mortality among patients with ESRD treated with dialysis and transplantation. The first part of this chapter focuses mainly on issues related to HCV infection. The second part of this chapter examines the renal complications in patients with human immunodeficiency virus (HIV) infection.

Detection Of Circulating Cryoglobulins And Determination Of Cryoprecipitate

Ized events might induce the shift to abnormal proliferation of a clone of B cells, producing a monoclonal IgM rheumatoid factor. Thus, a type II MC is induced that can be considered a lym-phoproliferative disorder. It has been suggested that the IgMk produced by this permanent clone of B cells has affinity for the glomerular matrix and can deposit, in the glomerulus together with the IgG to which it binds in the blood, IgG that probably acts as an anti-HCV antigen antibody. not clear, and this group of mixed cryoglobulinemias was called essential 2,3 . As indicated in Figure 9-4, it now is evident that most essential mixed cryoglobulinemias are associated with hepatitis C virus infection.

Giuseppe DAmico Franco Ferrario

Up to the end of the 1980s, the cause of about 30 of both type II and III mixed cryoglobulinemias (MC) in patients was not known, and this subgroup of patients were referred to as having essential mixed cryoglobulinemia. Essential mixed cryoglobulinemia was characterized clinically by systemic signs, mainly purpura, arthralgias, and fever, together with hepatic, neurologic, and renal symptoms. During this decade, antibodies against hepatitis C virus (HCV) antigens and HCV RNA (which is a marker of active viremia) have been detected in the serum of up to 90 of these patients. Hepatitis C virus can infect B lymphocytes and stimulate them to synthesize the cryoprecipitating polyclonal rheumatoid factors responsible for type III MC. In some patients with this polyclonal B-cell activation, additional but as yet uncharacter-

Membranoproliferative Glomerulonephritis

The first, known as membranoproliferative (mesangiocapillary) glomerulonephritis type I, is a primary glomerulopathy most common in children and adolescents. The same pattern of injury may be observed during the course of many diseases with chronic antigenemic states these include systemic lupus erythematosus and hepatitis C virus and other infections. In membranoproliferative glomerulonephritis type I, the glomeruli are enlarged and have increased mesangial cellularity and variably increased matrix, resulting in lobular architecture. The capillary walls often are thickened with double contours, an abnormality resulting from peripheral migration and interposition of mesangium (A). Immunofluorescence discloses granular to confluent granular deposits of C3 (B), immunoglobulin G, and immunoglobulin M in the peripheral capillary walls and mesangial regions. The characteristic finding on electron microscopy is in the capillary walls. C, Between the basement membrane and...

Hepacivirus replication occurs in association with the ER

Hepatitis C virus (HCV) is closely related to the flaviviruses, and its importance as a human pathogen has generated great interest in its mechanism of replication. Until, recently infection models have not been available to study the replication complex of HCV, and the studies discussed here have focussed on the expression of the entire polyprotein from replicons (Egger et al., 2002 Gosert et al., 2003). However, the recent production of a HCV that replicates efficiently both in vivo and in cell culture (Lindenbach et al., 2006 Wakita et al., 2005 Zhong et al., 2005) will expand the possibilities for studying and understanding the viral replication cycle. HCV replication is thought to occur on membranes derived from the ER as all studies of NSPs have found them localized to this organelle (Dubuisson et al., 2002 Hugle et al., 2001 Kim et al., 1999 Wolk et al, 2000). Studies have also identified a ''membraneous web'' of membrane vesicles of 85-nm diameter associated with the ER and a...

GB agents See GB viruses

GB viruses Isolated from a surgeon (George Barker) with acute non A-non B hepatitis, by injection of his serum into marmosets (tamarins) of Saguinus sp which then developed hepatitis. Could be serially passed in marmosets. Immunologically and structurally distinct from the Hepatitis A, B, C and E viruses. Two GB viruses (GBV-A and GBV-B) were isolated recently by representational difference analysis and molecular cloning from the serum of an infected marmoset, and have been shown to be new members of the Flaviviridae associated with GB agent hepatitis. A third virus, GB virus C, was identified in human sera by reverse-transcription and polymerase chain reaction using consensus primers based on the GBV-A, GBV-B and Hepatitis C helicase gene, and appears to be identical to Hepatitis G virus. For this reason the virus is usually called GB virus C Hepatitis G virus. Although GBV-C HGV has not been shown to cause hepatitis it seems to be able to infect liver as well as spleen cells without...

Liver Kidney Microsomal Antibodies

Indirect immunofluorescence first led to the description of autoantibodies reactive with the proximal renal tubule and the hepatocellular cytoplasm in 1973 38 . These autoantibodies, termed LKM-1, were associated with a second form of ANA-negative AIH. Between 1988 and 1991, the 50-kDa antigen of LKM-1 autoantibodies was identified as CYP2D6, which belongs to the CYP superfam-ily of drug-metabolizing proteins located in the endoplasmic reticulum (ER) 39-42 . LKM-1 autoantibodies recognize a major linear epitope between amino acids 263 and 270 of the CYP2D6 protein 43 . These autoantibodies inhibit CYP2D6 activity in vitro and are capable of activating liver-infiltrating T lymphocytes, indicating the combination of B- and T-cell activity in the autoimmune process involved 44, 45 . In addition to linear epitopes, LKM-1 autoantibodies have also been shown to recognize conformation-dependent epitopes 46 . However, the recognition of epitopes located between amino acids 257 and 269 appears...

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). II Acute and chronic hepatitis b. Chronic hepatitis HBV, HCV, autoimmune, idiopathic a. Idiopathic neonatal hepatitis HBV hepatitis B virus HCV hepatitis C virus TPN total parenteral nutrition.

Paul J Thuluvath Md Frcp and Cary H PattMD

The improvement in outcome and better awareness has resulted in an increasing demand for LT in the United States over the past 10 years. However, the increase in organ demand has exceeded the supply resulting in longer waiting periods and higher death rates on the waiting lists. Approximately 10 to 20 of patients on the LT list die each year without receiving an organ in a timely fashion. Transplantation physicians have responded to this increased demand by developing several strategies, including the use of older donors, grafts from hepatitis C (HCV) positive donors or those with previous hepatitis B infection (positive HBV core immunoglobulin G antibody), grafts from nonheart-beating donors, domino transplantation (livers from patients with familial amyloid polyneuropathy transplanted into older recipients), split liver grafts, and, more recently, live donor liver transplantation (LDLT). There is also ongoing research in the field of xenotrans-plantation, artificial liver support...

Liver Disease Patients

Studies evaluating the frequency of HFE mutations and abnormalities in iron metabolism have been done in groups of patients with porphyria cutanea tarda (PCT), nonalcoholic steatohepatitis (NASH), chronic hepatitis C (HC), and alcoholic liver disease (ALD). In PCT, about half the patients have mutations in HFE and it is well known that this disorder responds favorably to iron reduction therapy by phlebotomy. Accordingly, all patients with PCT should have HFE mutation analysis and serum iron studies performed. In ALD, it appears that HFE mutations are not responsible for the mild degrees of secondary iron overload that are occasionally seen in this disorder. Also, there is no clear benefit by phlebotomy therapy in patients who have ALD with our without abnormalities in iron metabolism. In patients with chronic HC, about a dozen studies have been performed looking at HFE mutations and parameters of iron metabolism. Almost all studies have shown the same prevalence of HFE mutations in...

Maria H SjogrenMD MPH

Acute viral hepatitis has generally been of minimal medical interest because it has been viewed as a mild illness where observation and supportive therapy have been the expected management. However, with the advent of safe and effective vaccines and effective medical therapies, the concept of management of acute hepatitis is changing. In addition, variations in epidemiology and an increase in costs associated with liver transplants are compelling clinicians and regulators to have a more comprehensive approach and to prevent or treat early in an attempt to prevent complications of chronic liver disease. The purpose of this chapter is to review the current status of management and prevention of hepatitis A, hepatitis B, hepatitis C, hepatitis D, and hepatitis E. Acute Hepatitis A 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....

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.

Estimated Exposure Risks

In addition to laboratory and clinicians' reports there are also data on the prevalence of hepatitis C, hepatitis B, and HIV from the Unlinked Anonymous Prevalence Monitoring Programme Survey of HIV and Hepatitis in Injecting Drug Users. Overall HIV infection remains relatively rare among IDUs in the UK although there is evidence of ongoing and possibly increased transmission. The prevalence of HIV among IDUs has remained substantially higher in London than the rest of the country. Needle- and syringe-sharing increased in the late 1990s, and since then has been stable, with around one in three IDUs reporting this activity in the last month. The sharing of other injecting equipment is more common, whilst few IDUs wash their hands or swab injecting sites prior to injecting. Over 4,000 reported cases of HIV occur in the population of intravenous drug users and this accounts for 6.5 per cent of HIV diagnosis up to 2003.

Specific Medical Therapy Table 1095

Hepatitis B Autoimmune hepatitis Amanita intoxication Budd-Chiari syndrome Wilson's disease HSV hepatitis CMV hepatitis Lymphomatous infiltration of liver Ischemic hepatitis Pregnancy-related FHF should be treated with early delivery along with administration of corticosteroids to foster maturation of the fetal lungs. Copper chelation is very effective for chronic Wilson's disease, but rarely effective in fulminant Wilson's in which liver transplantation is usually the only option. Other potentially beneficial but unproven therapies include high dose corticosteroids for fulminant autoimmune hepatitis, and lamivudine (and or adefovir), acyclovir, or ganciclovir for FHF secondary to HBV, HSV, or CMV infection, respectively. In all of these situations, specific therapy should not delay evaluation and listing for transplant in suitable candidates.

Interpretation of Abnormal Liver Enzymes

Chronic viral infections, such as hepatitis B (HB) or HC, and fatty liver disease are the most common causes of persistently elevated enzymes. Again, enzymes rarely rise above 300 U L in these settings. HC is the most common chronic hepatotropic infection in Western countries, is asymptomatic, and ALT can range from normal to 10-fold above normal values. HB affects 400 million worldwide and can also present with a spectrum of aminotransferase abnormalities ranging from normal levels to the thousands (U L). Nonalcoholic fatty liver disease is increasingly recognized even in those without the classic risk factors of obesity and diabetes mellitus. Steatosis may develop from medication use, including corticosteroids, amiodarone, and tamoxifen. There is more evidence lately that steatosis may not cause significant enzyme elevations. The typical pattern of enzyme elevation is AST ALT ratio of less than one, with numbers sometimes as high as fivefold the upper limit of normal. Unfortunately,...

Liver Transplantation

And long term) as well as patients transplanted for HC or other types of liver disease. However, alcoholic hepatitis clearly is not an indication for liver transplantation at the current time. Virtually all centers require that alcoholic patients undergo formal psychiatric examination and treatment before transplantation. Many centers impose a six month rule of abstinence before being considered for orthotopic liver transplantation however, most centers also show some flexibility with this rule. It is unusual for ALD alone to be the cause of graft failure. The majority of patients with ALD are not listed for liver transplantation for multiple reasons including continued alcohol consumption, improvement of liver function with abstinence, lack of interest, etc. Patients with ALD appear to have a higher incidence of certain malignancies of the upper airway and upper digestive tract. Therefore, these patients should be screened for these processes prior to transplantation and monitored...

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.

Problemsspecial considerations

The differential diagnoses at initial presentation include pre-eclampsia, acute viral hepatitis, drug-induced hepatitis, cholestasis of pregnancy and biliary tract disease. Pruritus is uncommon in acute fatty liver and is highly suggestive of cholestasis. Clinical examination the mother is usually, but not invariably, jaundiced. Although she may complain of abdominal pain it is unusual to find marked liver tenderness on examination, and this finding is suggestive of viral hepatitis or HELLP syndrome. If presentation occurs late, all the stigmata of acute liver failure may be present, including hepatic encephalopathy, disseminated intravascular coagulation (DIC) and renal failure. The prognosis is poor if the disease presents in this advanced state. Laboratory findings serum alanine and aspartate transaminases levels are increased, but not as high as in viral hepatitis. Bilirubin is increased. Platelet counts fall, and there may be giant platelet formation. Prothrombin time is...

Preoperative Investigation and Preparation for the Procedure

Alcohol consumption and alcohol withdrawal syndromes, hepatitis and hepatotoxic medications Variceal bleeding, ascites, hypersplenism, hepatic encephalopathy, jaundice, nutritional status, signs of portal hypertension (e.g., caput medusa) ALT, AST, bilirubin, alkaline phosphatase, albumin, coagulation profile (PT, INR, platelets), tumor markers and serologies (e.g., hepatitis), when indicated. Electrolyte and acid-base profile

CPE See cytopathic effect

CR 326 virus A strain of Hepatitis A virus. Isolated from patients in Costa Rica by the injection of serum or extracts of clotted blood into white moustached marmosets, Saguinus mystax. Can be serially passed in marmosets, causing hepatitis. Human convalescent serum neutralizes the virus.

Dosage And Administration Guidelines For Vaccines Available In The United States

Infants born to HBsAg-posltlve mothers (immunization and administration of 0.5 mL hepatitis B Immune globulin Is recommended for Infants born to HBjAg mothers using different administration sites) within 12 hours of birth administer vaccine at birth repeat vaccine dose at 1 and 6 months following the initial dose

Bis[2diethylaminoethoxyfluoren9one hydrochloride See tilorone hydrochloride

Differentiation The differentiation of specialized functions particular to a cell type by expression of tissue-specific genes. Certain viruses require such tissue-specific expression in order to infect, e.g. via specific cell receptors, or to replicate - for some viruses no in vitro cell culture system exists that provides the functions necessary to support their replication (e.g. papillomaviruses, Hepatitis B).

Canine adenoviruses 1 and 2 CAdV1 and

-2) Two serotypes of Canine adenovirus, a species in the genus Mastadenovirus. A natural infection of dogs, often silent, but in puppies there is often fever, vomiting and diarrhea with up to 25 mortality. There is cutaneous edema, ascites, hemorrhages into the viscera and hepatitis. Also a cause of laryngotracheitis (kennel cough). In foxes there is acute encephalitis and hemorrhage into the brain. Spread of infection is from the respiratory tract and urine. Experimentally, dogs and foxes may be infected by any route. Bears, coyotes, wolves and raccoons are susceptible. Virus replication with CPE occurs in cultures of dog, ferret, raccoon and pig cells. Hemagglutination is reported. A modified live vaccine, attenuated by passage in pig kidney cell cultures, produces solid immunity following a single dose in dogs of any age. The complete DNA sequence of canine adenovirus 1 has been determined. There was little identity to human adenoviruses in the early region genes, more in the late...

Fever In The Returning Traveller Definition

The last three months however, certain illnesses such as hepatitis, tuberculosis (TB), malaria and amoebic liver abcess can take longer than this to manifest themselves, so this should be taken into consideration in anyone with a history of foreign travel in the last six months. viral hepatitis

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.

Arthur H Cohen Richard J Glassock

Many glomerular diseases may be associated with acute and chronic infectious diseases of bacterial, viral, fungal, or parasitic origin. In many instances, the glomerular activators are transient and of little clinical consequence. In other instances, distinct clinical syndromes such as acute nephritis or nephrotic syndrome may be provoked. Some of the more important infection-related glomerular diseases are illustrated here. Others diseases, including human immunodeficiency virus and hepatitis, are also discussed in Volume IV.

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,...

Diagnosis Antimitochondrial Antibodies

The identification of antimitochondrial antibodies (AMAs) as the serologic hallmark of PBC greatly improved the diagnostic sensitivity and specificity of this disease. These nonorgan-, nonspecies-specific antibodies are directed at the 2-oxoacid dehydrogenase enzymes located on the inner mitochondrial membrane. Using sensitive enzyme-linked immunosorbent assay or immunoblotting, AMAs can be detected in 95 of patients with histologic and clinical features of PBC, and they are rarely associated with any other clinical condition. They may occasionally be found in otherwise clear-cut autoimmune hepatitis but, fortunately, are not seen with any other chronic cholestatic liver diseases. Along with AMAs, other laboratory features of PBC include elevation of serum alkaline phosphatase and y-glutamyl transpeptidase, a pattern typical of anicteric cholestasis, an elevated immunoglobulin (Ig)M, and high total cholesterol.

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...

Protection Against Other Liver Diseases

Patients with chronic HBV infection should be counseled to minimize alcohol use, although the safe level of consumption has not been defined. It is important that patients be advised to have household and sexual contacts tested for both HBsAg and HBsAb to identify both those who are infected and require further examination, and those who are susceptible to infection. Until HBsAb is documented in sexual partners, either via natural infection or vaccination, safe sex techniques must be employed. Hepatitis A (HA) vaccination is advised in all patients with chronic liver disease. Generally, screening for HA antibody is not cost effective before vaccination but may be in selected patients with a high likelihood of prior HA infection, such as those born in developing countries.

Of Acute Renal Failure

Ultrasonography, computed tomography, or magnetic resonance imaging Consider need for additional blood tests Vasculitis glomerulopathy human immunodeficiency virus infections, antineu-trophilic cytoplasmic antibodies, antinuclear antibodies, serologic tests for hepatitis, systemic bacterial endocarditis and streptococcal infections, rheumatoid factor, complement, cryoglobins Plasma cell disorders urine for light chains, serum analysis for abnormal proteins Drug screen level, additional chemical tests Consider need for evaluation of renal vascular supply

Trinidad donkey virus A strain of

Trisodium phosphonoformate An antiviral agent. A pyrophosphate analog that is a non-competitive inhibitor of the viral DNA polymerase. Inhibits both herpesviruses and Hepatitis B virus. Used to treat cytomegalovirus infections of the eye effective against acyclovir-resistant viruses. Synonym foscarnet. TT virus (TTV) A non-enveloped single-stranded circular DNA virus, genome length about 3.8kb, which is unclassified. Named from the initials (TT) of a patient who developed non-A, B, C, D, E or G transfusion-related hepatitis. Representational difference analysis of DNA was originally used to isolate a clone from serum comparing before and after transfusion. Using specific primers to screen sera by PCR it was found that more than 90 of some human populations are infected, and the virus is distributed world-wide. However, multiple variants are found in the human population, and also in non-human primates. It seems likely that transmission may occur by the fecal-oral route as well as...

Malignant catarrhal fever of European cattle See Alcelaphine herpesvirus

Lang) serotype 2 (strain D5 Jones) and serotype 3 (strain Dearing). Cause benign infections in humans worldwide, only rarely associated with mild respiratory or enteric symptoms. In experimental mice, MRV can cause diarrhea, runting, oily hair syndrome, hepatitis, myocarditis, myositis, pneumonitis, encephalitis and neurological symptoms. This mouse model has been widely used to investigate the molecular basis of viral pathogenesis even though reovirus is not a significant human pathogen.

California rabbit fibroma virus See Rabbit fibroma virus

Callitrichid hepatitis A highly fatal disease of captive marmosets and tamarins, caused by infection with the arenavirus Lymphocytic choriomeningitis virus (LCMV). The zoo animals become infected by contact with LCMV-infected newborn mice (pinkies) provided as food for the primates. There is no evidence to suggest that spread of the disease occurs between primates.

Treatment Of Adolescents

When treating adolescents there are some important considerations the patient's age and weight can affect the dose of the drug for example, the dose of hepatitis B vaccine is different for under-15s from the dose for adults. Some drugs may have particular side-effects, making them unsuitable for teenagers for example, doxycycliney's effects on teeth and bone development. The dosing and administration of treatment should be carefully considered so that

Reports of Health Events

For some public health purposes, however, effective action requires additional detail on each case. For this reason, supplemental data collection systems have been developed for some of the diseases involved in the NNDSS. Such supplemental systems are sometimes less comprehensive in terms of the population represented but provide more detailed information on characteristics of the occurrence of disease (CDC 1991). For example, cases of hepatitis are reported weekly to NNDSS for publication in the Morbidity and Mortality Weekly Report (MMWR). In addition, the Viral Hepatitis Surveillance Project collects data on specific risk factors for different types of viral hepatitis in selected geographic areas. These data have been used to evaluate the importance of behavior associated with sexual activity and drug use as risk factors for transmitting hepatitis type B and to target educational and vaccination programs. Other uses of data may require the ability to identify the patient whose case...

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.

Antinuclear Antibodies

Screening determinations of ANAs are routinely performed by indirect immunofluorescence on cryostat sections of rat liver, kidney, and stomach as well as on HEp2 cell slides. Most commonly, a homogeneous or speckled immunofluorescence pattern is detectable in all three tissues. The most precise definition of an ANA pattern is obtained using HEp2 cells, a cell line derived from laryngeal carcinoma with prominent nuclei. ANAs represent the most common autoanti-bodies in AIH and occur in high titers, usually exceeding 1 160. However, the titer does not correlate with disease course, disease activity, prognosis, progression, requirement of transplantation, or disease reoccurrence after transplantation. Furthermore, ANAs are not specific for autoimmune hepatitis and can also be detected in other autoimmune disorders such as systemic lupus erythemato-sus. In the future, more refined techniques using recombinant nuclear antigens and immunoassay formats may enable the identification of...

GFV1 virus See goldfish virus

Gianotti-Crosti syndrome A self-limited childhood skin disease (papular acroder-matitis) associated with Hepatitis B virus or parvovirus B19 infection and usually accompanied by lymphadenopathy and anicteric hepatitis. Lesions usually persist for about 3 weeks and do not recur. Prevalent in Italy and Japan.

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

Expression of soluble scFv and Affinity chromatography

Construction of murine scFv fragments by PCR. (A) Amplification of variable heavy and light chain gene from hybridoma cells producing antibody specific to hepatitis B surface antigen. M marker, lanes 1-2 present the PCR products of variable light chain gene using different forward primers for amplification of K light chain and lane 3 present the amplified VH product. (B) scFv fragment was constructed using jumping-PCR-assembly techniques to join heavy-chain and light-chain variable domains with flexible polypeptide (Gly4Ser)4 linker. The assembled products of two reactions were 750 bp that indicated by an arrow. Figure 1. Construction of murine scFv fragments by PCR. (A) Amplification of variable heavy and light chain gene from hybridoma cells producing antibody specific to hepatitis B surface antigen. M marker, lanes 1-2 present the PCR products of variable light chain gene using different forward primers for amplification of K light chain and lane 3 present the amplified...

Mouse leukemia virus See Murine leukemia virus

MS-1 virus A strain of Hepatitis A virus in the genus Hepatovirus. Originally identified as one of two hepatitis-inducing viruses in the Willowbrook State School for the Mentally Handicapped. The other virus, MS-2, was Hepatitis B. MS-1 was demonstrated in the sera of hepatitis patients by inoculation into normal human volunteers, in whom the disease could be passaged by the fecal-oral route with a relatively short incubation period of about 4 weeks compared to MS-2 virus. Murid herpesvirus 1 (MuHV-1) The type species of the genus Muromegalovirus. A P-herpesvirus with a genome DNA 235 kb in length G+C is 59 . Probably a ubiquitous silent infection of wild mice but present in a minority only of laboratory stocks. Young uninfected mice can be infected by any route, the virus localizing in the salivary glands, in which tissue alone is serial passage possible. Large doses of virus given i.p. will kill mice in 4-7 days. Small doses produce focal hepatitis. Infection of pregnant mice causes...

Delgadito virus See Cao Delgadito virus

Delta agent Synonym for Hepatitis delta virus. delta antigen A nuclear antigen, first described in 1977, that by 1980 was characterized as Hepatitis delta virus. delta virus Synonym for Hepatitis delta virus. Deltavirus A genus containing a single species, Hepatitis delta virus. Virions are spherical, 36-43 nm in diameter, with an inner nucleocapsid of 19 nm containing the circular negative sense single-stranded RNA genome, about 1.7 kb in length. The genome structure and catalytic activities resemble those of viroids and satellite viruses found in plants, but are unique and distinct from all other known animal viruses.

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...

Metabolic Miscellaneous Etiologies

Included in this group are FHF secondary to Wilson's disease (see Chapter 124, Management of Wilson's Disease ), autoimmune hepatitis, Reye's syndrome, and pregnancy-related ALF from acute fatty liver of pregnancy, hemolysis, abnormal liver enzymes and low platelets(HELLP) syndrome, or hepatic rupture (see Chapter 133, Biliary Strictures and Neoplasms ). FHF may be the first clinical manifestation of Wilson's disease. Indeed, Wilson's disease should be considered in any young patient with unexplained FHF, particularly when

The Nidovirus replicase is generated from two polyproteins

The Nidovirales order comprises the Arteriviridae, Coronaviridae, and Roniviridae families. The replicase gene is composed of two open reading frames termed ORF1a and ORF1b. ORF1b is generated from a frameshift in 1a, and both reading frames encode complex polyproteins processed by viral proteases (Gorbalenya et al., 2006 Ziebuhr, 2006). The arterivirus ORF1b encodes NSPs 9-12, including the RdRp (NSP9) and helicase (NSP10). The ORF1b, however, lacks hydrophobic domains able to target the replicase to membranes. Interestingly, the hydrophobic domains necessary for membrane targeting are encoded by ORF1a in NSP2, 3, and 5, suggesting that ORF1a proteins produce a scaffold to locate the viral replication-transcription complex to membranes (Fig. 1D) (Pedersen et al., 1999 van der Meer et al., 1998). A similar strategy is used by CoV, for example mouse hepatitis virus (MHV) and severe acute respiratory syndrome-CoV (SARS-CoV) (Prentice etal., 2004a,b), where transmembrane domains are...

Membrane rearrangements can be induced by expression of nonstructural proteins

Membrane rearrangements have been studied by expressing individual, or combinations, of picornavirus proteins in cells. Most of this work has involved studies of Poliovirus proteins, and membrane rearrangements are reported for the 2B, 2C, 2BC, 3A, and 3AB proteins. Poliovirus 2B causes fragmentation of the Golgi complex (Sandoval and Carrasco, 1997). The 2BC and 2C proteins lead to vesiculation and tubulation and sometimes myelin-like swirls of ER-derived membranes (Aldabe et al., 1996 Cho et al., 1994). Similar structures are induced by 2C and 2BC of hepatitis A virus (Teterina et al., 1997). Expression of the Poliovirus 3A protein causes swelling of ER cisternae (Doedens et al., 1997) and the disappearance of vesicles budding from the ER, while the 3AB protein also induces myelin-like swirls of ER (Egger et al., 2000). The membrane rearrangements induced by expression of single proteins do not, however, mirror those observed in infected cells, and since myelin-like modifications to...

Production Of Recombinant Proteins In B Subtilis And Other Bacilli

A wide variety of recombinant proteins have been produced in B. subtilis cells, both from prokaryotic and from eukaryotic origin (Table 6.7). Expression was achieved either intracellularly or extracellularly using the promoters and signal sequences described above. The first description of using B. subtilis cells for the expression of recombinant proteins occurred by Hardy et al. (1981) who expressed the hepatitis B core antigen and the major antigen of foot and mouth disease virus intracellu-larly. The group of Palva developed the first vectors allowing secretion of foreign proteins into the growth medium (Palva et al., 1982). They fused b-lactamase to the signal sequence of an a-amylase derived from

Comparison of Multiplexed Assays

The majority of the clinically useful autoantibody tests have been cleared by the FDA for in vitro use to help diagnose autoimmune diseases. These include those to help diagnose connective tissue diseases such as RA, SLE, SS, SSc, and PM DM gastrointestinal diseases such as celiac disease, Crohn's disease, and ulcerative colitis autoimmune liver diseases such as PBC and autoimmune hepatitis types I and II autoimmune vasculitides such as Wegener's granuloma-tosis and Goodpasture's syndrome autoimmune endocrine diseases such as Hashimoto's thyroiditis and Graves' disease and autoimmune coagulation disorders such as antiphospholipid syndrome. Examples of clinically useful autoantibody tests that have not been cleared by the FDA include antibodies to help diagnose pernicious anemia, autoimmune skin-blistering diseases such as pemphigus and pemphigoid, and some autoimmune neurological diseases. Auto-

Human endogenous retroviruses HERV

Human hepatitis A virus (HHAV) human hepatitis A virus (HHAV) See Hepatitis A virus. Human herpesvirus 1 (HHV-1) Type species of the genus Simplexvirus in the subfamily Alphaherpesvirinae. The genome DNA has been completely sequenced for the 17syn+ strain, and consists of about 150kb with a G+C of 67 . The DNA is infectious and has two components, L and S, each of which is bracketed by internal repeats. Primary infection is common in young children, often sub-clinical, but occasionally with acute stomatitis. The virus can pass along nerves and become latent in ganglia from whence it can be reactivated by non-specific stimuli (fever, sunlight, menstruation) to cause lesions, often around the mouth. Rarely, the virus may cause acute hepatitis, kerato-conjunctivitis or meningo-encephalitis. Vaccination has not been successful but treatment of kerato-conjunctivitis and skin lesions with locally applied acyclovir ointment is beneficial. In cases of encephalitis, neonatal herpes or...

Rifampicin See rifamycin

Cattle are less seriously affected. Herdsmen and slaughtermen often become infected and develop a biphasic illness which is usually mild, although retinal damage may occur. Buffalo, camels and antelopes may be naturally infected and die. Infection is mosquito-borne, but contact infection probably also occurs. Large mosquito-borne epizootics occurred in 1977-78 in Egypt, in 1987-88 in East Africa. Absent for a decade, it returned to Egypt in 1993. Then in 1999 a large outbreak began in the Kingdom of Saudi Arabia and Yemen, the first outbreak ever recorded outside the African continent, with more than a thousand human cases and more than 150 deaths by the end of 2000. Control is by protection from mosquitoes and by vaccination of livestock with formalin-ized or attenuated vaccines. Mice die of hepatitis when infected experimentally. Guinea pigs, ferrets and young dogs can also be infected, but birds are resistant. Virus replicates in cultures of chick, rat, mouse...

Aminoglycoside Antibiotics As Rna Binders

Stimulated by these intriguing observations suggesting aminoglycosides to be potent RNA binders, we and others started exploring this family of antibiotics for their potential to bind various other RNA targets.12 Over the course of the past decade, numerous discoveries have established aminoglycosides as universal RNA binders. These antibiotics have been found to bind the hammerhead ribozyme,29 human hepatitis delta virus ribozyme,30 and RNase P,31 as well as HIV-1 TAR32 and even transfer RNA.33 Additionally, multiple binding sites for aminoglycosides were discovered on small and large RNA molecules.34 Aminoglycosides are therefore rather promiscuous RNA binders, a phenomenon that can be rationalized by a model suggesting structural electrostatic complementarity. 35'36 While these naturally occurring antibiotics are unlikely to display the necessary selectivity to become therapeutically relevant antivirals,37 they provide a solid foundation for the potential development of more potent...

Contagious pustular stomatitis of sheep virus Synonym for Orf virus

Gastroenteritis virus and Turkey coronavirus, but is O-glycosylated in mouse hepatitis virus and Bovine coronavirus. Replication involves synthesis of a complementary (negative) strand RNA of genome length that acts as a template for synthesis of a 3' co-terminal nested set of 5-7 subgenomic mRNAs which have a capped 5' terminus and are 3' polyadenylated. Only the 5' unique region of each mRNA appears to be translationally active. Viruses mature by budding through the endo-plasmic reticulum and Golgi membranes, not at the plasma membrane. Coronaviruses infect birds and many mammals, including humans, especially the respiratory tract, gastrointestinal organs and neurological tissues. Murine hepatitis virus

Introduction And Historical Overview

Some studies were based on periodic screening of individuals for HIV antibody. Thus, the date of seroconversion could be determined up to an interval defined by the latest screening test that was negative for HIV infection and the earliest screening test that was positive. Examples of these studies include cohorts of hemophiliacs who were patients at hemophilia treatment centers (National Cancer Institute Multicenter Hemophilia Cohort Study (Goedert, Kessler, Aledort, et al. 1989)) and a cohort of homosexual men in San Francisco enrolled in a study of hepatitis B vaccine (Hessol, Lifson, O'Malley, 1989). Sera obtained from periodic follow-up visits on these cohorts had been stored in the 1970s and 1980s. Statistical problems that arise because of the uncertainty in the dates of seroconversion are discussed in Section 4.5. who are closely monitored for evidence of infection and then followed to detect onset of AIDS. A number of such studies got underway in 1984-1985 including the San...

PCR See polymerase chain reaction

Penciclovir A drug related to acyclovir which is selectively phosphorylated by the HSV thymidine kinase and inhibits replication of herpesviruses such as VZV and CMV as well as HSV. It is licensed as a cream for use against oral herpes. Because it was not effective orally, the 6-deoxydiacetyl ester derivative famciclovir was developed as an orally delivered prodrug of penciclovir and is now licensed for treatment, especially of herpes zoster infections in immunosup-pressed patients. It is also effective against hepatitis B.

Far East Russian encephalitis virus

Farnesylation The addition of three iso-prene units (farnesyl group) to a protein. The farnesyl group is specifically attached to proteins that have the C-ter-minal motif CAAX, and is believed to play a role in membrane attachment. This modification is essential for virion formation of Hepatitis delta virus.

Drug Induced Osteoporosis Glucocorticoids

If glucocorticoids cannot be avoided, in certain cases the clinician may choose a safer glucocorticoid alternative. Budesonide in a controlled ileal release (CIR) preparation (Entocort) is effective for mild to moderate ileal and right-sided colonic CD. This preparation is associated with fewer steroid-related side effects and less adrenocortical gland suppression. A prospective study of 98 steroid-naive patients treated with prednisolone versus CIR-budesonide found that patients had a significantly greater drop in BMD with prednisolone treatment compared with CIR-budesonide (-1.04 versus -3.84 , p .0084) (Schoon et al, 2002). Thus, whenever possible CIR-budesonide should be considered for the patient with CD. For patients with distal colonic IBD, topical rectal steroids in short courses ( 2 weeks) do not increase bone turnover in patients, but long term therapy with these agents does result in bone loss (Robinson et al, 1998). By contrast, however, oral budesonide therapy in patients...

Mild Moderate Acute Crohns Colitis

Although debate continues regarding the role of aminosalicylates for the treatment of mild-moderate CD, there is good evidence that sulfasalazine is efficacious for the treatment of colonic CD. There is less substantial evidence for alternative mesalamine agents. Nevertheless, the aminosalicylates are advocated as a first line therapy for mild-moderately active CD. The use of sulfasalazine in divided doses of 3 to 6 g d, supported by the National Cooperative Crohn's Disease Study (NCCDS), is compromised, in up to 25 of patients, by side effects attributable to the sulfapyridine carrier molecule, such as headache, nausea, GI upset, and, in males, a transient reduction in number and motility of sperm. Rare but more serious hypersensitivity reactions include hemolytic anemia, neutropenia, rash, and hepatitis. In contrast to UC, where alternative azo bond delivery systems such as olsalazine and balsalazide are effective alternatives, in Crohn's colitis these agents have not been shown to...

Selection of Candidates for Surgical Resection

Although there is a general consensus that the extent of safe resection is limited mainly by the size and function of the residual liver after resection, there are emerging data regarding what minimal volume of residual liver is sufficient to avoid postoperative liver failure. Based on volumetric studies, we feel that a liver remnant volume of 20 is the minimal safe volume that can be left following extended resection in patients with a normal underlying liver. In a diseased liver (cirrhosis or hepatitis), we use 40 of the total liver volume as the cutoff for the minimally safe liver remnant. CT can now provide an accurate, reproducible method for preoperatively measuring the volume of the future liver remnant (FLR). We routinely measure the FLR directly by three-dimensional CT volumetry. The ratio of the measured FLR volume to the total estimated liver volume is determined using a formula that is derived from the association between total liver volume and body surface area (BSA), as...

Phocid distemper virus See Phocine distemper virus

Phocid herpesvirus 1 (PhoHV-1) A species in the genus Varicellovirus isolated from harbor seals, Phoca vitulina, during an outbreak of pneumonia and focal hepatitis in a seal orphanage in the Netherlands in which half the seals died. Subsequently, related viruses were isolated from harbor seals in Germany and the USA, and from the European grey seal, Halichoerus grypus. Synonym harbor seal herpesvirus.

Nearestneighbor base frequency analysis

Neural spread Dissemination of virus infection by spreading along peripheral nerves. Plays an essential role for viruses such as rabies, herpes simplex and pseudorabies viruses, which do not generally spread by viremia. Other viruses such as polio, reovirus and mouse hepatitis may utilize both viremia and neural spread to disseminate infection.

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.

Susceptibility To Skin Cancer

In the prevalence survey in the BFD-endemic area, both hepatitis B virus (HBV) chronic infection and liver dysfunction indexed by an elevated serum level of alanine transaminase were associated with an increased prevalence of skin cancer (Hsueh et al., 1995). The multivariate-adjusted odds ratio was 6.6 for HBV surface antigen carriers with liver dysfunction compared with non-carriers with normal liver function. It was hypothesized that liver dysfunction may reduce the methylation of inorganic arsenic in the liver and thus increase the deposition of inorganic arsenic in the skin. The detailed mechanism needs further elucidation.

Challenges In Genomic Analysis

Although blood can be used directly in PCR, there is clearly a need for simpler, noninvasive, and more cost-effective means of sample collection, DNA extraction, and genetic diagnosis in general. There are several disadvantages of using blood. First, blood collection can be very inconvenient, because genetic testing often involves analysis of multiple family members. Furthermore, drawing blood can be uncomfortable for the patient and, most important, the handling of blood samples can increase the chances of infection by blood-borne pathogens such as HIV and hepatitis. To date, a variety of alternative sources of DNA have been used for genetic testing including finger-prick blood samples, hair roots, as well as the use of cheek scrapings and oral saline rinses as a means of collecting buccal epithelial cells. The oral saline rinse is perhaps the most extensively used nonblood-based sampling technique. However, it still involves liquid sample handling and requires an additional...

Clinical Implications

The health care impact of chronic HCV infection appears to be increasing due to the increased prevalence of patients with infection for more than 20 years. Chronic HC infection is now estimated to be the leading cause of end-stage liver disease necessitating liver transplants in the United States.

Virologic Assessment of Response

Baseline reference HCV RNA (viral titer and genotype) is best measured just before starting treatment to determine optimal treatment duration and regimen, and to establish a baseline to determine later treatment end-points. 2. Early virologic response can be assessed after 12 weeks of therapy. Failure to achieve a decline in HCV RNA levels of at least 2 logs by week 12 predicts an extremely low likelihood of a sustained virologic response with further treatment (negative predictive value 98 ). 4. Sustained virologic responses is performed at the end of 6 months of observation following completion of treatment, and appears to be the gold standard for long term loss of serum HCV RNA.

Preparation of ASODNs

Resuspend morpholino AS-ODN HCVm330-354 (5'-GAUUUGUGCUCAU GAUGCACGGUCU-3') that exactly complements HCV 1b genotype IRES sequences spanning nt 330-354 and a random mismatch oligonucleotide, RDMm330-354 (5'-UUGGGCCUGUAGUCCAUAUCAGGUU-3'), were distilled deionized sterile (cell culture-grade) H2O at a final concentration of 100 M, filter sterilize, aliquot, and freeze at -20 C.

Flaviviruses can modulate the secretory pathway

Newly synthesized MHC proteins from the ER. Increased TAP expression is mediated by increased transcriptional activity of p53 and can be induced in liver HepG2 cells by expression of the HCV core capsid protein alone (Herzer et al., 2003 Momburg et al., 2001). While the capsid core protein is able to increase cell surface expression of MHC class I through increase expression of TAP1, expression of the HCV polyprotein has been shown to slow the movement of proteins through the secretory pathway of host cells (Konan et al., 2003). The rate of delivery of MHC class I to the plasma membrane in cells infected with HCV was reduced three- to fivefold relative to cured control cells. Expression of the precursor NS4A-B was found to reduce ER-to-Golgi traffic two- to threefold (Konan et al., 2003), while the other NS proteins of HCV including NS4A and NS4B, individually or combined, were unable to interfere with the trafficking pathway. NS4B alone induces a membraneous web in cells (Egger et...

Pretransplantation Examination

If no obvious contraindications are identified on the initial clinical visit, recipients undergo comprehensive examination by the transplantation team. The diagnostic workup includes pulmonary function tests, an electrocardiogram, chest radiograph, echocardiogram, and routine blood tests, as well as serology for human immunodeficiency virus, HBV, HCV, cytomegalovirus, and syphilis. Patients over 50 years of age, those with a history of diabetes, hypertension, or family history of cardiac disease, undergo a dobutamine stress echocardiogram or thallium scan. If there is a clinical suspicion of CAD, we recommend coronary arteriogram and carotid duplex. In order to evaluate the hepatic vascular anatomy, three-dimensional computed tomography scan or magnetic resonance imaging is done. Angiogram is performed only in the presence of portal vein thrombosis to determine the extent of thrombosis. Candidates for LDLT undergo similar tests and examination as the cadaver transplantation recipients.

The importance of virus specific CD4 Tcells

Replication after transplantation (43), and with the resolution of HCV viremia (78). The characterization of CD4+ T-cell populations specific for viral antigens represents a major challenge in human immunology. There is a substantial gap in our knowledge between CD8+ T-cells and CD4+ T-cells. This is in part due to the apparent complexity relative to the nature of these cells. On the basis of the pattern of cytokines produced, CD4+ T-cells have been divided into distinct functional subpopulations T helper-0 (Th-0) cells , Th-1 cells and Th-2 cells in addition, there are subsets of CD4+ T-cells that have regulatory - suppressing functions, or also cytotoxic potential. A further difficulty relates to the lack of tools adapted to their detailed study. Current approaches to study virus specific CD4+ T-cells rely on particular functions of the cells, such as proliferation and cytokine (often IFN-y) production. This way, it is possible to detect CD4+ T-cell activity specific for most human...

Preoperative Evaluation And Preparation

Mesenteric Caval Shunt

Preparation of patients for elective surgery involves improving their nutritional status, optimizing cardiopulmonary function, and medical control of ascites when this is present. Electrolyte abnormalities should be corrected and abstinence from alcohol is encouraged. Patients with active liver disease, e.g., alcoholic hepatitis, and chronic active hepatitis have an increased mortality (16), and should not undergo surgery until this has been stabilized. A liver biopsy may be necessary to assess for disease activity. Perioperative antibiotics are given to reduce the risk of infection and prophylactic H2 blocker therapy is recommended for 4-6 wk. Significant coagulopathy is corrected with fresh frozen plasma and vitamin K before surgery.

Effects of Maternal Medication

Fetal Hydantoin Syndrome

During pregnancy, the average fetus is exposed to four physician-prescribed and five self-prescribed drugs. Every drug administered or taken by a pregnant woman presents the mother with both risks and benefits. The risks include the drug's potential as a teratogen or as a cause of toxicity in the fetus. Most human teratogens affect the embryo during a very narrow period of early development as illustrated by the time (24 to 33 days gestation) during which the fetus is susceptible to limb reduction defects caused by thalidomide. Several human teratogens, such as alcohol, androgens, cocaine, diphenylhydantoin, radiation, tetracycline, valproic acid, and warfarin have serious side effects beyond the period of organogenesis. These effects may include cell deletion, vascular disruption, necrosis, physiologic decompensation, organ pathology, and intrauterine growth retardation. Drugs taken in the third trimester may not have teratogenic effects, but may be toxic to the fetus. Some examples...

Options for Hormonal Therapy

Flutamide, a very potent antiandrogen that is also used to treat prostate cancer, can be used in the treatment of acne, hirsutism, and androgenic alopecia 52 . It can be given in doses of 250 mg twice daily, in combination with an OC. Fatal hepatitis is a concern with this drug, and liver function tests should be followed 53 . The hepato-toxicity associated with flutamide seems to be dose- and age-dependent 54 . Low dose (62.5-125 mg) has been reported to be safe and effective 55 .