The natural course of hepatitis B and hepatitis C virus infection

Chronic hepatitis B and hepatitis C virus infections maintain a significant risk for the development of liver cirrhosis and hepatocellular carcinoma and cause a considerable morbidity in the population. Among patients with chronic HBV infection and histologically confirmed hepatitis the annual incidence of liver cirrhosis is 2%. The risk for hepatocellular carcinoma in chronic HBsAg carriers is elevated about 40-230 fold. 20-30% of patients with chronic HCV infection will develop cirrhosis over 20-30 years. Hepatocellular carcinoma evolves yearly in about 3% of patients with chronic HCV infection and cirrhosis, whereas HCV-carriers without cirrhosis usually do not develop hepatocellular carcinoma. The high incidence of serious sequelae warrants a regular surveillance of chronic virus carriers.     

Loss of HBsAg with interferon-alpha therapy in chronic hepatitis D virus infection

Previous studies have demonstrated that demographic characteristics of subject populations influence both the incidence of periodontal diseases and various aspects of host responses to periodontal bacteria. In this study we analyzed the components of the subgingival microflora from individuals with adult periodontitis, early onset periodontitis, gingivitis, and periodontal health as a function of gender and race (black and white). Clinical categories were analyzed individually so that there were no differences in the clinical characteristics of the sampled sites. No significant differences were noted in the subgingival microflora between males and females. When either the first two bacterial samples from each subject or all bacterial samples taken from each subject were included in the analysis, it was found that Porphyromonas gingivalis was more significantly associated with black subjects in the adult periodontitis group. When all samples were considered in the analysis, it was found that Peptostreptococcus anaerobius was associated with black subjects in the adult periodontitis group, while Fusobacterium nucleatum was associated with white subjects in both the adult periodontitis and early onset periodontitis groups. Thus a limited number of important bacterial components of the subgingival microflora are influenced by the race and diagnosis of the subject group.     

The prevalence of antibodies to the hepatitis A virus in Owambo children

The prevalence of hepatitis A virus infection, in a population as well as the age at which it is usually acquired reflect the prevailing socio-economic conditions and standards of public hygiene. Infection occurs equally in both the sexes. Black Africans are known to have a high prevalence of hepatitis A virus infection and do acquire the infection early in life. This study documents the age-specific prevalence in Owambo children and confirms an equal sex distribution.     

The elimination of hepatitis B virus infection: changing seroepidemiology of hepatitis A and B virus infection in Okinawa, Japan over a 26-year period

Serial changes in hepatitis A virus (HAV) and B virus (HBV) markers were determined from 1970 to 1996 in healthy Japanese residents of a rural area of Okinawa, Japan. All 190 serum samples taken in 1970, 791 in 1980, 708 in 1988, and 523 in 1996 from residents 0 to more than 60 years of age were tested for antibody to HAV (anti-HAV), antibody to hepatitis B core antigen (anti-HBc), and hepatitis B surface antigen (HBsAg). The age-adjusted prevalences of anti-HAV and anti-HBc decreased significantly from 83.9% and 74.9%, respectively, in 1970 to 39.7% and 36.6%, respectively, in 1996. In residents < or = 29 years of age, the prevalences of anti-HAV and anti-HBc decreased significantly from 65.3% and 83.8%, respectively, in 1970 to 0.7% and 8.2%, respectively, in 1996. The age-adjusted HBsAg prevalence decreased significantly from 8.2% in 1980 to 4.1% in 1988. These results indicate that exposure to HAV and HBV infections among Okinawa residents less than 29 years of age is decreasing, probably because of improvements in socioeconomic conditions since 1970. Infection with HBV may be eliminated there in the near future.     

Chronic hepatitis B virus infection in south Auckland

AIM: Previous studies have identified high prevalence rates of hepatitis B infection in New Zealand Maori, Pacific Island and Asian populations within New Zealand. However, the true impact of chronic hepatitis B virus (HBV) infection on health resources has not been evaluated. This study was designed to determine the incidence of serious sequelae of chronic HBV infection in a high prevalence community. METHODS: All patients treated for HBV-related conditions at Middlemore Hospital from January 1995 to January 1997 were identified through discharge coding and laboratory records. Demographic characteristics and laboratory results, including liver function tests, hepatitis serology and liver histology were recorded. Number of admissions, average length of stay and survival were calculated from Casemix data. RESULTS: During the study period, 215 patients were referred for management of hepatitis B infection, of whom 179 had persistently elevated aminotransferases. Forty six percent of patients were hepatitis B 'e' antigen (HBeAg) negative, and 21% of these had delta co-infection (all Samoan). Liver biopsy was performed in 87 patients with raised aminotransferases. No features of chronic hepatitis were found in 5%, mild chronic hepatitis in 30%, moderate to severe chronic hepatitis in 44% and cirrhosis in 22%. Fifty five patients were admitted to hospital during the two year period with an HBV-related diagnosis, with an average length of stay of 12.2 days compared to 4.9 days for all other medical and surgical admissions during this period (p < 0.001). Twenty eight of the 55 subsequently died, 20 from hepatocellular carcinoma. CONCLUSIONS: Chronic hepatitis B infection is associated with significant morbidity and mortality in Maori, Pacific Islanders and Asians living in South Auckland. Screening of these high risk populations with vaccination of noninfected individuals should reduce the incidence of these serious sequelae and eventually lead to eradication of HBV.     

Patterns and prevalence of hepatitis C virus infection in posttransfusion non-A, non-B hepatitis

Improved serologic and polymerase chain reaction (PCR)-based tests for hepatitis C virus (HCV) infection provided an opportunity to reexamine a posttransfusion follow-up study done from 1969 to 1972. A total of 213 cardiac surgery patients was prospectively followed after receiving an average of 18 units of blood, 24% of which was from paid donors. Serial sera were tested for antibody to recombinant DNA-derived C100-3 and capsid polypeptides; selected cases were also tested against synthetic peptides derived from different regions of the HCV sequence. PCR and RIBA II immunoblot assays were done on selected sera. Each of 55 probable and 5 of 11 possible hepatitis cases who were seronegative before transfusion seroconverted. Anti-HCV seroconversion also occurred in 6 (4%) of 148 subjects without hepatitis. Among subjects followed > 1 year, PCR positivity persisted in 14 (82%) of 17. If the results of this study can be generalized, all bloodborne non-A, non-B hepatitis may be due to HCV.     

Alpha interferon therapy in children with chronic active hepatitis B and delta virus infection

Two children with chronic hepatitis B virus and delta virus infection were treated with alpha interferon. Both tolerated the therapy without complications, and one demonstrated clearance of the infection and development of immunity.     

Variations of hepatitis B virus core gene sequence in Western patients with chronic hepatitis B virus infection

Heterogeneity of the hepatitis B virus (HBV) core gene has been reported to be associated with the presence of active liver disease in Japanese patients with chronic HBV infection. This study evaluated the significance of HBV core gene heterogeneity in Western patients with chronic HBV infection. The hepatitis B virus precore/core gene from 45 patients (inactive:active liver disease ratio 16:29) was amplified from serum by polymerase chain reaction (PCR). Gel electrophoresis was employed to detect large deletions. The PCR amplicons from 13 patients (all HBV serotype adw but with a different spectrum of liver disease) were cloned and sequenced. Hepatitis B surface antigen (HBsAg) serotypes were tested by enzyme immunoassay (EIA) and hepatic expression of HBV antigens was assessed by immunohistochemistry. The HBV core gene was amplified from the serum of all 45 patients. Three patients had mixed infection with both precore mutant and wild-type HBV and all three had active liver disease. No patient had a large deletion of the HBV core gene. Hepatitis B virus core gene sequence variations were more common in the midcore region and there was no difference in the number of silent and missense substitutions between those with inactive and active liver disease. There was no correlation between the nucleotide or encoded amino acid substitutions and the clinical and biochemical parameters, including the subsequent response to interferon-alpha therapy (n = 37) or hepatic HBV antigen expression. Variation of the HBV core gene was not found to be preferentially associated with active liver disease in Western patients with chronic HBV infection. The pattern of hepatitis B core gene variation is in accord with the genomic organization of HBV.     

Hepatitis B virus infection, hepatitis B vaccine, and hepatitis B immune globulin

Hepatitis B virus (HBV) infection is a major health problem in the United States; in 1995, approximately 128,000 cases occurred. Transmission of HBV occurs primarily by blood exchange (eg, by shared needles during injection drug use) and by sexual contact. Persons infected early in life are much more likely to become chronically infected than those infected during adulthood: as many as 90% of infants infected perinatally develop chronic infection and up to 25% will die of HBV-related chronic liver disease as adults. Clinical signs of acute hepatitis occur in about 50% of infected adults but in only 5% of infected preschool-aged children. In the United States, hepatitis B vaccine is currently made by recombinant DNA technology using baker's yeast. Preexposure vaccination results in protective antibody levels in almost all infants and children (> 95%) and healthy adults younger than 40 years of age (> 90%). The most common adverse event following administration of hepatitis B vaccine is pain at the injection site, which occurs in 13% to 29% of adult and 3% to 9% of children. A comprehensive hepatitis B vaccination policy is now recommended that includes (1) routine infant vaccination; (2) catch-up vaccination of 11- to 12-year-olds who were not previously vaccinated; (3) catch-up vaccination of young children at high risk for infection; (4) vaccination of adolescents and adults based on lifestyle or environmental, medical, and occupational situations that place them at risk; and (5) prevention of perinatal HBV infection.     

Antibody-negative chronic hepatitis C virus infection in immunocompetent children

Two new pyrrolidine alkaloids, broussonetines G and H, were isolated from the branches of Broussonetia kazinoki SIEB. (Moraceae). Broussonetines G and H were formulated as 2 beta-hydroxymethyl-3 alpha, 4 beta-dihydroxy-5 alpha-(1-hydroxy- 6:10;10:13-diepoxytridecyl)-pyrrolidine (1) and 2 beta-hydroxymethyl-3 alpha, 4 beta-dihydroxy-5 alpha-(1-hydroxy- 5:9;9:13-diepoxytridecyl)-pyrrolidine (2), respectively, by spectroscopic methods. 1 and 2 inhibited beta-glucosidase, beta-galactosidase and beta-mannosidase.     

Prevention and control of hepatitis B virus infection in Singapore

Hepatitis B virus (HBV) accounted for 24% to 54% of the reported acute viral hepatitis cases in Singapore from 1982 to 1996. The prevalence of HBV infection, as indicated by the presence of markers of HBV, increased from 9.3% in children below 5 years of age to 54.6% in adults above 55 years. The overall hepatitis B surface antigen (HBsAg) prevalence was 5.7% for males and 3.4% for females, with the highest rate among the Chinese. About 39% of the HBsAg carriers were hepatitis B 'e' antigen positive. The main mode of transmission during the first year of life was perinatal, with 43% of the babies born to HBsAg-positive mothers developing the carrier state. Horizontal transmission within the infected household was significantly associated with sharing of personal and household articles. Based on the findings of seroprevalence surveys in various population groups and clinical trials on the safety, immunogenicity and efficacy of various doses and schedules with the plasma-based and yeast-derived hepatitis B vaccines in newborn babies, a national childhood hepatitis B vaccination programme was formulated and implemented in phases, starting with babies born to carrier mothers on 1 October 1985 and finally extending to all newborns on 1 September 1987. The hepatitis B prevention and control programme has been successful. During the period 1994 to 1996, more than 90% of children completed the full schedule of immunisation by below one year of age, and 85% had evidence of vaccination at school entry at age six. Follow-up of 2 cohorts of vaccinated children showed that perinatal transmission has been reduced by 80% to 100%. Horizontal transmission has also declined through other public health measures. The efficacy of the hepatitis B vaccine and the adequacy of reduced doses in the long-term protection of chronic carrier state have been shown in children and adults. The incidence of acute hepatitis B has declined from 10.4 per 100,000 in 1985 to 4.8 per 100,000 in 1996. There is a noticeable reduction in HBsAg prevalence in selected population (school children, national servicemen and antenatal women). The age-standardised incidence rate of primary liver cancer among males had also dropped from 27.8 per 100,000 per year during 1978 to 1982 to 19.0 per 100,000 per year during 1988 to 1992.     

Immunoglobulin- and hepatitis B surface antigen-specific circulating immune complexes in chronic hepatitis B virus infection

24 consecutive AIDS patients with wasting, and who had never received anabolic therapies, were evaluated to determine their profile of sex hormones and whether transformation of testosterone (T) to the nuclear androgen, dihydrotestosterone (DHT), was impaired. Eleven (46%) patients had normal testosterone and DHT (group I), 10 (42%) had normal testosterone but low DHT (group II), and 3 (12%) had low testosterone and low DHT (group III). Age, prior opportunistic complications, symptoms, serum albumin, hemoglobin levels, and CD4 lymphocyte counts were similar in the groups. DHT was significantly lower (22.2 +/- 6.8 microg/dl) in group II compared with group I (50.8 +/- 15.3 microg/dl). The ratio of T/DHT, a measure of the conversion of testosterone to DHT, in group I was 15.1 +/- 3.5, which was within the range for eugonadal young men. In group II, the ratio was 22.3 +/- 1.5, indicating a defect in generation of DHT. Patients in group II had lost 9.2 +/- 3.5 kg compared with 5.6 +/- 2.6 kg in group I (p = .015). Thus, a syndrome of low DHT with normal testosterone was associated with significantly greater weight loss than in patients with normal testosterone and DHT. Further studies are needed to clarify whether low DHT is a result of AIDS wasting or is causally related to weight loss and whether androgen therapy in the form of DHT could reverse some of the metabolic changes associated with AIDS wasting.     

Interferon-alpha treatment of chronic hepatitis C virus infection in children

The leukotrienes (LT) LTD4 and LTB4 have been shown to cause bronchoconstriction and neutrophil accumulation, respectively, in horse lungs. Such changes are characteristic of the equine allergic respiratory disease, chronic obstructive pulmonary disease (COPD). To further investigate the role of these putative mediators in the pathogenesis of equine COPD the effect of a 5-lipoxygenase inhibitor, fenleuton, on antigen-induced changes in horses with this condition has been examined. Six horses with COPD underwent a series of four antigen challenges, one month apart, with placebo pre-treatment on three occasions and fenleuton (4 days oral dosing 5 mg/kg) pre-treatment on one occasion. Three horses received fenleuton prior to the second challenge and three horses received the drug prior to the fourth antigen challenge. Changes in radiolabelled neutrophil distribution, lung function and peripheral leucocyte counts were monitored on each occasion for 7 h following the start of antigen challenge. Antigen challenge caused an increase in radioactive counts over the lungs and a decrease in peripheral leucocyte count. Neither response was affected by fenleuton pre-treatment. Mean maximal changes in pleural pressure (delta Pplmax) and respiratory rate were also unaffected by fenleuton pre-treatment. However, in the two horses which responded to antigen-challenge with a particularly marked increase in delta Pplmax (> 15 cm H2O), prior administration of fenleuton reduced the response by 64 and 63%. These results suggest that 5-lipoxygenase inhibitors warrant further investigation as bronchodilators in equine COPD.     

Ganciclovir treatment of active hepatitis B virus infection in a heart transplant patient

We report a 51-year-old woman with alopecia caused by sarcoidosis. The lesion enlarged within 4 years and only repeated biopsies enabled the diagnosis. The medical work-up revealed that the patient had asymptomatic pulmonary involvement. Scarring alopecia is a rare complication of sarcoidosis and biopsy from the active margin may lead to the diagnosis.