Hepatic decompensation associated with lamivudine: a case report and review of lamivudine-induced hepatotoxicity.

We report a case of a 62-yr-old man with chronic hepatitis B virus (HBV)-related cirrhosis who developed hepatic decompensation after being started on lamivudine requiring liver transplantation. Decompensated liver disease while on lamivudine has been previously reported on two occasions, both HIV coinfected patients on a combination of nucleoside analogues. Our patient is alive and well nearly 2 yr after successful liver transplantation.

Hepatitis C in Peru: risk factors for infection, potential iatrogenic transmission, and genotype distribution.

A large seroepidemiologic and genotyping study of hepatitis C virus (HCV) was conducted in Lima, Peru, during the periods of 1986 to 1993 (cohort A) and 1994 (cohort B). Anti-HCV seroprevalence rates were 15.6% (216 of 1,389) and 11.7% (168 of 1,438), respectively. Low rates were seen among volunteer blood donors (1.1% and 0.8%). Anti-HCV rates were much higher among patients undergoing hemodialysis (43.7% and 59.3%), hemophiliacs (60.0% and 83.3%), in those more than 39 years old (18.2% and 26.0%), in females (25.0% and 27.4%), and in less-educated persons (16.9%). Age- and gender-adjusted risk factors in cohort B included blood transfusion history (adjusted odds ratio [AOR] = 29.8), prior organ transplantation (AOR = 9.1) or a history of hepatitis (AOR = 4.9), previous hospitalization (AOR = 3.7), a history of intravenous drug use (AOR = 3.5), prior major surgery (AOR = 2.6), a history of acupuncture (AOR = 2.1), previous dental procedures (AOR = 1.2), and prior medical injections (AOR = 1.04). The most prevalent HCV genotype was type 1 (86%), followed by type 3 (10%) and type 2 (2%). Transmission through unsafe injection-related and medical/dental procedures appears to play an important role in HCV infection among Peruvians.

Hepatitis B virus DNA in persons with isolated antibody to hepatitis B core antigen who subsequently received hepatitis B vaccine.

Serum samples from 133 persons who were positive only for antibody to hepatitis B core antigen (anti-HBc) by enzyme immunoassay (EIA) were retested for seromarkers of hepatitis B virus (HBV) by radioimmunoassay and for HBV DNA by polymerase chain reaction analysis. All persons were subsequently vaccinated with hepatitis B vaccine. HBV DNA was found in only five persons, four of whom remained positive during retesting. Most persons had a primary antibody response with three doses of hepatitis B vaccine. Evidence of HBV DNA was not detected in 96% of persons with isolated anti-HBc by EIA.

Serologic diagnosis of viral hepatitis.

Viral hepatitis has become a difficult field in which clinical and laboratory skills are needed to establish the correct diagnosis and plan for the appropriate therapy. For example, it is no longer enough to diagnose chronic hepatitis B or C. Now, the viral titer or viral genotype must be known. The laboratory test then must be understood in the context of the clinical presentation. This article helps the clinician to acquire such working knowledge. It summarizes available data for hepatitis A, B, C, D, and E. It also includes the recently discovered viral agents, hepatitis G and the hepatitis GB agents.

Evaluation of liver histology, ALT elevation, and HCV RNA titer in patients with chronic hepatitis C.

OBJECTIVE: Hepatic histological evaluation is currently the gold standard to determine the degree of liver injury in chronic hepatitis C. It is unclear whether degree of serum ALT elevation or quantitative hepatitis C virus (HCV) RNA can predict level of histological damage. METHODS: Fifty nine biopsies from 44 patients with chronic hepatitis C were reviewed. The amount of liver damage was quantified using the Histology Activity Index (HAI) and was compared with serum ALT and, in 26 biopsies, quantitative HCV RNA (branched DNA amplification, Quantiplex, Chiron). RESULTS: A statistically significant linear relationship was noted between degree of ALT elevation and amount of liver injury based on HAI score (p < 0.05) although this relationship was not statistically strong (rs = 0.4900). No significant correlation was noted between serum ALT and HCV RNA titer (rs = 0.4044) or between quantitative HCV RNA titer and HAI score (rs = 0.3506). No individual component of the HAI correlated with ALT or HCV RNA. CONCLUSIONS: Although there is a correlation between serum ALT and degree of hepatic injury based on HAI score, this relationship is weak and probably of no clinical use. There is no significant correlation between HCV RNA and serum ALT or HCV RNA and degree of hepatic injury in individual patients. Hepatic histological evaluation continues to be required for clinical assessment of patients with chronic hepatitis C.

Administration of hepatitis A vaccine to a military population by needle and jet injector and with hepatitis B vaccine.

Military personnel are an important target population for hepatitis A immunization. Soldiers are often given vaccines by jet injector and may be required to receive multiple vaccines at one time. Formalin-inactivated hepatitis A vaccine containing 360 ELISA units of antigen was evaluated at Fort Campbell. Volunteers received vaccine at 0, 1, and 6 months as follows: group 1, hepatitis A vaccine by needle; group 2, hepatitis A vaccine by jet injector; group 3, hepatitis B vaccine by needle; and group 4, both hepatitis vaccines by needle in separate arms. Immune response and reactogenicity were evaluated. After two doses, recipients of vaccine administered by jet injector had a higher prevalence of antibody than those who received vaccine by needle (93% vs. 79%). By the 8th month, the vaccine was 100% immunogenic by either route or with hepatitis B vaccine. No interaction between hepatitis A and B vaccines was detected.

Development of a live, oral, attenuated vaccine against El Tor cholera.

Vibrio cholerae El Tor strains from Peru, Bangladesh, and Bahrain were attenuated by deletion of a genetic element that encodes virulence factors and RS1. The B subunit of ctx (ctxB) was reintroduced into the recA gene of the deletion mutants, rendering them unable to recombine with exogenous genetic elements and generating Peru-3, Bang-3, and Bah-3. Fifteen volunteers received one dose of various vaccine strains at 4 x 10(6) to 1 x 10(8) cfu. All strains colonized the gut. A > or = 4-fold rise in vibriocidal titer was observed in 14 volunteers, with titers of > or = 1600 in 13. Peru-3 was the least reactogenic, but 2 of 6 volunteers had loose stools. Peru-14, a filamentous motility-deficient mutant of Peru-3, was well tolerated and colonized 18 of 21 volunteers at doses of 2 x 10(6) to 1 x 10(9) cfu. Also, when 8 Peru-3 or Peru-5 vaccinees, 5 Peru-14 vaccinees, and 8 controls were challenged with 2 x 10(6) cfu V. cholerae El Tor Inaba (N16961), 11 vaccinees were protected compared with no controls. Peru-14 shows promise as a safe, effective, single-dose oral vaccine against El Tor cholera.

A 22-year-old man with a liver mass and markedly elevated serum alpha fetoprotein.

Our patient presented with a large liver mass, an extremely elevated AFP level, and an almost certain diagnosis of HCC. However, extensive evaluation and biopsies failed to demonstrate malignancy, and the available evidence strongly suggests that the patient has an adult polycystic disease without renal involvement, and that the mass was the result of hemorrhage and degenerative changes in one of his cysts. Polycystic diseases can involve only one lobe, as it appears in this case. Only about 10-15% of patients with polycystic disease have symptoms due to the liver disease, while 30-50% have associated renal disease. Thus, our patient is unusual in several respects. However, his liver mass has decreased in size, he feels well, and his biochemical abnormalities have returned to normal. Despite a classic presentation for HCC, this case underscores the necessity for a thorough evaluation, especially for patients without major risk factors for hepatocellular carcinoma.

Serologic diagnosis of viral hepatitis.

The diagnosis of viral hepatitis is complex, particularly when the five leading causative agents belong to different virus families and evoke distinct immunologic response. This article connects known serologic markers to new methods and guides the ordering and interpretation of contemporary laboratory tests.

Recurrent clinical exacerbations of liver disease during the course of infection with hepatitis C virus.

Symptomatic clinical relapses during the course of chronic hepatitis C virus (HCV) infection are uncommon. Furthermore, acute liver dysfunction with elevated bilirubin during alpha-interferon therapy without other apparent coexisting diagnoses is rare. The case of a 31-yr-old man with three clinical exacerbations of HCV infection over an 18-month period is described. The third episode was characterized by rising serum aminotransferase levels on alpha-interferon therapy. The precise cause of this patient's flares is unknown. An immunologically mediated clearance of the hepatitis C virus, mutation of HCV, or infection with different HCV viral strains are the leading possibilities.

Hepatic emergencies in pregnancy.

Although liver disease during pregnancy is a rare event, it can have devastating effects on the mother and the child. This article reviews diseases uniquely associated to pregnancy, such as fatty liver of pregnancy, toxemia, and others. It also details new advances in diseases such as viral hepatitis and pregnancy and intrahepatic cholestasis of pregnancy.

Detection of IgA class antibody to hepatitis E virus in serum samples from patients with hepatitis E virus infection.

A newly developed assay for IgA class antibody to hepatitis E virus (IgA anti-HEV) was used to study 145 serum samples collected during an outbreak of an enterically transmitted hepatitis that occurred in 3 villages in the lower Shebeli region of Southern Somalia between January, 1988 and November, 1989. A total of 52.4% of the afflicted patients were found positive for IgA anti-HEV, and 73.1% of these were also positive for IgM. Both antibodies disappeared during the convalescence period. Similar results were also seen in serum obtained from sporadic cases of acute waterborne hepatitis in Pakistan.

Initial report of a hepatitis investigation in rural Belize.

In spring 1991, Belizian health officials expressed concern about a possible hepatitis outbreak in a banana farming district. A study was designed to identify cases and to address the serological prevalence of hepatitis virus markers. Three populations were studied: (i) persons meeting a clinical case definition for hepatitis; (ii) designated banana workers; and (iii) people in a random sample of households in the community. Information was collected using questionnaires and sera were collected for laboratory testing. This report presents the preliminary results of a study conducted in June 1991. Among people who met the clinical case definition, 24% of 42 tested had immunoglobulin M antibody to hepatitis B virus (HBV) core antigen (anti-HBc IgM). In the worker and household survey populations, 284 and 280 people, respectively, were tested for anti-HBc IgM. In each group, 4% were positive. HBV surface antigen was found in 37% of 43 clinical cases, 18% of workers, and 13% of people in the household survey. Among the 3 study populations, the prevalence of HBV core antibody (anti-HBc) ranged from 73% to 81%. Almost all tested persons had evidence of prior hepatitis A virus infection. Evidence of prior infection with hepatitis viruses A and B was widespread, but an aetiology could not be established for most of the clinical cases. However, the prevalence of hepatitis B markers in this population was very high compared to other reports from the Caribbean.

Solid-phase antibody capture hemadsorption assay for detection of hepatitis A virus immunoglobulin M antibodies.

A solid-phase antibody capture hemadsorption (SPACH) assay was developed to detect hepatitis A virus (HAV)-specific immunoglobulin M (IgM) antibodies in sera from humans recently infected with hepatitis. The assay is performed with microtiter plates coated with anti-human IgM antibodies to capture IgM antibodies from the test sera. HAV-specific IgM antibody is detected by the addition of HAV hemagglutinating antigen and goose erythrocytes. Hemadsorption of erythrocytes to antigen-antibody complexes attached to the solid phase indicate the presence of IgM antibodies. The SPACH assay was compared to a commercial radioimmunoassay and was found to be equally or more sensitive and specific for the detection of HAV IgM antibodies. The SPACH assay is an alternative, rapid assay that doesn't require hazardous substrates or radioactivity for the detection of HAV-specific antibodies.

Recombinant immunoblot assays for hepatitis C in human immunodeficiency virus type 1-infected US Navy personnel.

The prevalence of hepatitis A, B, C, and D viruses was studied in 467 military personnel with human immunodeficiency virus type 1 (HIV-1) infection. Antibody to hepatitis C virus (anti-HCV) by first-generation ELISA was found in 136 (29%). Of sera repeatedly reactive for anti-HCV by first-generation ELISA, two-antigen recombinant immunoblot assay (RIBA) was positive in 41 (32%) and four-antigen RIBA was positive in 55 (41%). Four-antigen RIBA was positive in 33 (30%) of the 109 with an OD on ELISA of < or = 2.0 compared with 22 (81%) of the 27 with an OD > 2.0 (P < .001). Anti-HCV detected by four-antigen RIBA was associated with increasing age, black or Hispanic race, and antibody to hepatitis B core antigen. When patients with hepatitis B surface antigen were excluded, elevated alanine aminotransferase was found in 5 (8%) of 63 with a negative RIBA and 13 (28%) of 47 with a positive RIBA (P = .006). While RIBA was negative in more than half of those with anti-HCV by ELISA, 55 (12%) of these HIV-1 infected personnel had anti-HCV detected by RIBA, which was associated with a strong reaction by ELISA, elevated liver enzymes, coinfection with hepatitis B, minority race, and older age.

Infection of owl monkeys (Aotus trivirgatus) and cynomolgus monkeys (Macaca fascicularis) with hepatitis E virus from Mexico.

Owl and cynomolgus monkeys were inoculated with hepatitis E virus (HEV) to compare disease models and produce antibody and virus. By immune electron microscopy (IEM), all six owl monkeys were shown to have serologic responses manifested by unusually high levels of anti-HEV at 6 months, but only three developed hepatitis. Virus-related antigen in liver (HEV Ag) was detected by immunofluorescence microscopy of biopsies from two of four owl monkeys; one with HEV Ag also had HEV in acute-phase bile (detected by IEM) and feces (detected by infecting another owl monkey). In contrast, cynomolgus monkeys propagated HEV to higher levels and all five had hepatitis. Moderate-to-high levels of HEV Ag correlated with detectable HEV in bile for both species. Thus, the value of using HEV-infected cynomolgus was confirmed. Owl monkeys were shown to be HEV-susceptible and sources of high-level anti-HEV; Sustained anti-HEV in these monkeys may also be useful for understanding immune responses.