Seroepidemiology of hepatitis A virus infection among school children in Delhi and north Indian patients with chronic liver disease: implications for HAV vaccination

BACKGROUND: Universal vaccination against hepatitis A virus (HAV) has been recommended for children because of the changing epidemiological pattern of HAV. Vaccination has also been advised for patients with chronic liver disease as HAV superinfection in these patients can result in severe or even fatal disease. In India, the indications for HAV vaccination are not clear due to contradictory seroepidemiological data in children and lack of data on HAV seroprevalence in patients with chronic liver disease. METHODS: Sera were collected from children studying in two government-run schools and from patients with chronic liver disease attending the Liver Clinic at the All India Institute of Medical Sciences (AIIMS). The sera were tested for anti-HAV antibodies. The incidence of HAV-induced acute hepatitis and acute liver failure at AIIMS over the last 10 years was also assessed. RESULTS: A total of 93.2% (1328/1424) of the school children between 4-18 years of age who were included in the study had anti-HAV antibody in their sera. Eighty percent of the children had antibodies against HAV in their sera by the age of 5 years, whereas all the children above 16 years were positive for anti-HAV antibody. A total of 256 patients with chronic liver disease (94 with cirrhosis of the liver, 160 with chronic hepatitis) were tested for the presence of anti-HAV antibody. Of them, 97.6% (248/254) had anti-HAV antibody in their sera. The annual frequency of HAV-induced acute viral hepatitis and acute liver failure at AIIMS during the last 10 years did not show any change. CONCLUSION: Mass vaccination against HAV is not required in north India because of the presence of protective antibodies against HAV in the majority of the population.     

Seroprevalence of anti-HAV among patients with chronic viral liver disease

AIM:To investigate the current seroprevalence of hepatitis A virus(HAV) antibodies in patients with chronic viral liver disease in Korea.We also tried to identify the factors affecting the prevalence of HAV antibodies. METHODS:We performed an analysis of the clinical records of 986 patients(mean age:49±9 years,714 males/272 females) with chronic hepatitis B virus(HBV) or hepatitis C virus(HCV) infection who had undergone HAV antibody testing between January 2008 and December 2009.RESULTS:The overall prevale...     

Acute hepatitis A and acquired immunity to hepatitis A virus in hepatitis B virus (HBV) carriers and in HBV- or hepatitis C virus-related chronic liver diseases in Thailand

A number of studies have suggested that the clinical course of hepatitis A virus (HAV) infection is more severe in patients with chronic liver disease (CLD). A study was undertaken to determine the impact of acute HAV in asymptomatic hepatitis B surface antigen (HBsAg) carriers (n = 20) and patients with hepatitis B virus (HBV)-(n = 8) or hepatitis C virus (HCV)-related (n = 4) CLD. Disease progression was compared with that in 100 patients with isolated HAV infection. No patient with HAV infection alone developed complications, and all recovered fully. Fulminant or submassive hepatitis occurred in 55% of HBsAg carriers and 33% of patients with HBV- or HCV-related CLD. The mortality rate in HBsAg carriers (25%) was not significantly different from that in the patients with CLD (33%). The seroprevalence of anti-HAV immunoglobulin G in 820 individuals was also determined. Approximately 50% of the individuals had acquired HAV infection between the ages of 21 and 30 years. It was demonstrated that HAV infection may have a more severe clinical course in patients with underlying CLD, particularly among older individuals. Vaccination for such patients should be considered.     

Spectrum of viral hepatitis in thalassemic children receiving multiple blood transfusions.

AIM: To investigate the prevalence of infection with hepatitis viruses in children with thalassemia receiving multiple blood transfusions. METHODS: Sera from 50 children with thalassemia aged 5-15 years (30 boys), who had each received over 80 units of blood, were evaluated for the presence of markers for hepatitis A virus (HAV; IgG and IgM anti-HAV), hepatitis B virus (HBV; HBsAg, and IgG and IgM anti-HBc), hepatitis C virus (HCV; IgG and IgM anti-HCV, and HCV RNA) and hepatitis E virus (HEV; IgG and IgM anti-HEV). IgM anti-hepatitis D virus (HDV) was looked for only in HBsAg or IgM anti-HBc positive sera. RESULTS: No child had evidence of recent HAV or HDV infection. IgG anti-HAV was positive in 12 children. One patient had acute HBV infection. Nine patients were HBsAg-positive. HCV infection was present in 15 cases; six of them were HCV RNA positive, and three had superinfection with hepatitis B. Recent HEV infection was present in 5 cases. CONCLUSION: Thalassemic patients receiving multiple blood transfusions often acquire hepatitis B (20%) and C (30%) infections. Recent hepatitis E infection was documented in 10% in this one-point study.     

HAV and HBV seroprevalence in 1,000 patients with chronic HCV infection in a Tertiary Care Center in São Paulo,Brazil

Background. Patients with chronic HCV infection and superinfection by hepatitis A virus (HAV) or hepatitis B virus (HBV) have higher morbidity and mortality when compared with those without HCV infection. Therefore, HAV and HBV active immunization has become mandatory in this population and hence their serological markers must be determined. The aim of this study was to evaluate the prevalence of serological markers of HAV and HBV infection in patients with chronic HCV.Material and methods. One thousand chronic HCV patients at the University of Säo Paulo School of Medicine were evaluated for the prevalence of serological markers of HAV and HBV infection.Results. Anti-HAV IgG was positive in 92.3% of patients. When stratified by age, anti-HAV IgG was found in 61% of patients between 20-29 years, 70% on patients between 30-39 years, 85% on patients between 40-49 years, 94% on patients between 50-59 years, and in 99% on patients over 60 years of age. Anti-HBc IgG was positive in 244 patients (24%). Stratified by age, in 4.3% of patients between 20-29 years, 17% 30-39 years, 21% 40-49 years, 24% 50-59 years, and in 28% of patients over 60 years. Of the 244 anti-HBc IgG positive patients, 0.8% were HBsAg positive, 8.5% were anti-HBc IgG isolated and 16% were also anti-HBs positive.Conclusions. In conclusion, the prevalence of anti-HAV IgG was similar to the general Brazilian population. However, anti-HBc IgG was higher in our patients, when compared to general population of Western countries, emphasizing the importance of immunization programs for this population.     

Etiology of endemic viral hepatitis in urban North India

This study was carried out to determine the presence of markers of hepatitis viruses in patients with acute liver disease. Coinfection of HAV, HBV, HCV, and HEV was studied. Sera from 306 patients with a clinical diagnosis of acute liver disease were tested for the presence of anti-HAV antibody, HBsAg, anti-HBc antibody, anti-HBs antibody, anti-HCV antibody and IgM anti-HEV antibody by ELISA. Liver function tests were correlated with the presence of infection. Of the 306 cases, 7 (2.3%) had IgM anti-HAV, 9 (2.9%) had IgM anti-HBc, 37 (12.1%) had HBsAg, 84 (27.4%) had anti-HBs, 10 (3.3%) were HCV infected and 63 (20.6%) had IgM anti-HEV. There was no significant difference in the clinical and liver function profiles of infected and uninfected patients. Similarly, no difference was observed in cases coinfected with more than one virus compared with those infected with a single pathogen. HEV had the highest prevalence amongst our cases. There was no difference in the clinical profiles of patients with non-A, non-B, non-C, non-E hepatitis by antibody assays and testing for viremia could be helpful in making the correct diagnosis.     

Acute, hepatitis-A super-infection in HBV carriers, or chronic liver disease related to HBV or HCV

The impact of acute super-infection with hepatitis A virus (HAV) was determined in 20 asymptomatic carriers of the surface antigen (HBsAg) of hepatitis B virus (HBV), eight patients with HBV-related chronic liver disease (CLD), and four patients with CLD related to hepatitis C virus (HCV). For comparison, 100 patients with isolated HAV infection were also studied. The HBsAg carriers and patients with CLD related to HBV or HCV were significantly older than the patients with isolated HAV infection, with mean (S.D.) ages of 43.9 (14.1), 46.4 (16.0), 52.5 (8.6) and 28.4 (10.7) years, respectively (P < or = 0.02). There were no significant between-group differences in the baseline serum concentrations of alanine aminotransferase. All the patients with isolated HAV infection fully recovered. Fulminant or submassive hepatitis occurred in 11 (55%) of the HBsAg carriers and four (33%) of the 12 patients with CLD related to either HBV or HCV. Nine of the 15 patients with severe hepatitis died and the mortality rate among the HBsAg carriers was not significantly different from that among the CLD patients (25% v. 33%; P = 0.15). These fatal cases were all aged > 50 years and were significantly older [59.0 (2.1) years] than the six severe cases who recovered [43.2 (10.7) years] as well as the remaining 17 uncomplicated cases with CLD or HBsAg [40.3 (13.0) years] (P < or = 0.001). The results indicate that acute HAV is rarely fatal in young adults but may be severe and potentially fatal in patients with underlying chronic HBV or HCV infection, especially among the elderly. Vaccination against HAV should be considered for the patients at high risk who are negative for anti-HAV.     

Analysis of serum hepatitis A virus antibody response in different courses of hepatitis A virus infection

Changes in the serum hepatitis A virus anti-body (anti-HAV) response in patients with different clinical courses of HAV infection were examined using immune adherence hemagglutination (IAHA). Anti-HAV was detected 2–6 weeks after the onset of clinical symptoms in patients with the typical course of acute hepatitis A and 1–4 weeks after the onset in those with fulminant hepatitis A. Maximal anti-HAV titers were observed 8–20 weeks after the onset of clinical symptoms, and changes in anti-HAV were similar in the typical and the prolonged course of acute hepatitis A, but maximal antibody titers were higher in the prolonged course. Maximal anti-HAV titers in patients with subclinical HAV infection were significantly lower than titers in patients with the typical and prolonged courses of acute hepatitis A, and in those with fulminant hepatitis A. High titers of anti-HAV remained positive for at least 6 years after infection in patients with clinical infection and for at least 4 years in patients with subclinical infection on follow-up. These findings suggest that the maximum anti-HAV titer correlates with the clinical severity of HAV infection; knowledge of the antibody response should be useful for analyzing the pathogenesis of HAV infection.     

Simultaneous detection of IgM antibodies against the hepatitis A virus and the viral capsid antigen of Epstein-Barr virus in acute hepatitis

The simultaneous detection of IgM antibodies to hepatitis A virus (anti-HAV IgM) and IgM antibodies to viral capsid antigen (anti-VCA IgM) of Epstein-Barr virus (EBV) in patients with acute viral hepatitis has led us to systematically study serological markers of EBV in patients with anti-HAV IgM positive acute hepatitis and to test for anti-HAV IgM in sera of patients with acute hepatitis associated with serological evidence of current primary EBV infection. All patients studied were HBsAg negative and were not drug-addicts, nor homosexuals. In 15 consecutive patients with anti-HAV IgM positive acute hepatitis, anti-HAV IgM and anti-VCA EBV IgM antibodies were simultaneously detected in 9 cases. Of these 9 patients, antibodies to nuclear antigen were positive in 8 cases, antibodies to early antigen were positive in 7 cases and rheumatoid factor was positive in 4 cases. In 5 consecutive patients with acute hepatitis associated with serological evidence of current primary EBV infection, anti-HAV IgM was not detected. Simultaneous presence of anti-VCA EBV IgM, early antigen IgG antibodies and nuclear antigen antibodies in 7 patients with acute hepatitis associated with anti-HAV IgM suggests reactivation of EBV or reactivation of clones secreting antibodies anti-EBV in HAV infections. Furthermore, these results show that anti-VCA IgM only cannot be considered to be a specific marker of early EBV infection in patients with acute hepatitis.     

Seroprevalence of viral hepatitis in an older nursing home population.

OBJECTIVES: To assess the prevalence of current or previous infection with viral hepatitis agents in an older nursing home population. DESIGN: A prospective cohort study. SETTING: Three nursing homes in the greater St. Louis area affiliated with Saint Louis University. SUBJECTS: Older residents admitted to these facilities. MEASUREMENTS: Residents were interviewed and examined for evidence of hepatitis or liver disease. Serum samples were tested for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core and surface antigens (anti-HBc and anti-HBs), antibody to hepatitis A virus (anti-HAV), antibody to hepatitis C virus (anti-HCV), and hepatitis G virus RNA (HGV RNA). RESULTS: Of 329 residents queried, 199 gave consent and were able to participate. The seroprevalence of hepatitis was: HBsAg 0%, anti-HBc 24.1%, anti-HBs 19.5%, anti-HAV 79.9%, anti-HCV 4.5%, and HGV-RNA 10.6%. Frequency of HAV infection increased significantly with age whereas HBV infection correlated with ethnic status and former occupation as a manual worker. A history of blood transfusion was associated with a higher rate of anti-HCV. End stage renal disease, present in 17 patients, was associated with anti-HBc, anti-HCV, and HGV RNA positivity but not with anti-HBs or anti-HAV positivity CONCLUSIONS: The seroprevalence of anti-HCV was surprisingly high in this population residing in skilled nursing facilities, and we recommend that all new patients admitted to this type of institution be screened for anti-HCV. The prevalence of HGV RNA was higher than in the general US blood donor population, but the significance of this finding remains uncertain.     

Prevalence of hepatitis viruses in an anti-human immunodeficiency virus-positive population from Argentina. A multicentre study

The objectives of this study were to investigate the prevalence of infections with hepatotrophic viruses in an anti-human immunodeficiency virus (HIV)-positive population from Buenos Aires and to compare it among the main risk groups for HIV infection. Four hundred and eighty-four consecutive patients attending the HIV outpatients clinic were studied: 359 men and 125 women, median age 29 years (range 16-67 years); 35.5% had presented acquired immune deficiency syndrome (AIDS)-defining conditions. Two hundred and thirty-four patients were intravenous drug users (IVDU), 99 had homosexual and 142 heterosexual preference, seven had received blood transfusions and two had no risk factors. Hepatitis B surface antigen (HBsAg), and antibodies to hepatitis B core antigen (HBcAb) and to hepatitis C virus (anti-HCV) were investigated in all patients; antibodies to HBsAg (HBsAb) and IgG antibodies to hepatitis D virus (anti-HDV) in all HBcAb-positive patients; hepatitis B e antigen and antibodies to HBeAg (HBeAg) in all HBsAg-positive patients; IgG antibodies to hepatitis A virus (anti-HAV) in the first 307 patients; and IgG antibodies to hepatitis E virus (anti-HEV) in the first 91 patients. As control groups, contemporary voluntary blood donors were studied for prevalence of HAV, HBV, HCV and HEV. The percentages of HBcAb, HBsAg, anti-HCV and anti-HEV (58.5, 14.5, 58.5 and 6.6%, respectively) were significantly higher in anti-HIV-positive patients than in control groups (3.2, 0.5, 1.0 and 1.8%, respectively) (P = 0.000). The prevalence of HBcAb was significantly higher in IVDU (72.6%) than in heterosexuals (33.8%) (P = 0.0001) and in homosexuals (59.6%) (P = 0.0189). The percentage of HBsAg was significantly higher in IVDU (19.2%) than in heterosexuals (6.3%) (P = 0.0004). Anti-HCV was significantly higher in IVDU (92.3%) than in homosexuals (14.1%) and in heterosexuals (33.1%) (P = 0.000 in both cases). The prevalence of anti-HDV was relatively low (1.9%). There was no difference in the percentage of anti-HAV between HIV-positive and negative subjects. In conclusion, there is a high prevalence of HBV and HCV infections in HIV-positive patients from our area. Drug use is the main route of transmission, but prevalence of HCV in patients with, probably, sexually acquired HIV infection is also higher than in the control group. The increased prevalence of HEV infection in HIV-positive individuals is another provocative finding that warrants further study.     

Correlation of hepatitis B surface antigen clearance with the route of hepatitis B virus infection

We studied 563 consecutive adults with acute hepatitis B hospitalized from May 1981 to May 1983 and their habitual heterosexual partners. Radio-immunoassays for the detection of serological markers of hepatitis A virus (HAV) and hepatitis B virus (HBV) and enzyme-immunoassay for the detection of IgM antibody to hepatitis B core antigen (IgM anti-HBc) were used. Of the 563 patients, 503 (89.7%) were hepatitis B surface antigen (HBsAg) positive and 60 (10.7%) were HBsAg negative on admission. Absence of HBsAg on admission was observed significantly more frequently in patients infected possibly by the heterosexual route than in the remaining patients (23.3% versus 6.6%; P less than 0.001). This finding was independent of sex. These data show that the route of HBV infection rather than the sex appears to have a more important role in the rapid clearance of HBsAg.     

Hepatitis E in Damascus, Syria

Summary A hospital-based study of acute hepatitis was conducted in Damascus, Syria, from 1995 to 1998. One hundred ninety-three sera from defined acute hepatitis cases were screened by ELISA for IgM anti-HAV, HBsAg, IgM anti-HBc and anti-HCV. Serum samples negative for all markers indicating recent infection by hepatitis A, B, or C were tested for HEV markers. Overall, 47 cases (24.4%) had no detectable hepatitis markers (non-A-E). HAV infection was detected in 71.2% of all viral hepatitis cases. Acute hepatitis B and C constituted 24 and 1.4% of the cases, respectively. Only five cases of acute hepatitis E were noted. Of 47 patients who had non-A-E hepatitis, fifteen (31.9%) tested positive for IgG anti HEV. This study provides indirect evidence that HEV is very likely to be endemic in Damascus, Syria. It reports for the first time the occurrence of hepatitis E in the country, a health problem that should be investigated further.     

Seroprevalence of hepatitis A antibodies among residents of a centre for people with developmental disabilities

Abstract Background: In February 1993,11 cases of hepatitis A virus (HAV) were identified in permanent residents of a centre for young people with developmental disabilities. Aims: To define the extent of the outbreak in the centre, to determine the seroprevalence of hepatitis A antibodies (anti-HAV) in permanent residents, and to ascertain risk factors for serological evidence of HAV infection. Methods: A cross-sectional serological survey of 270 permanent residents, aged eight to 40 years, in a centre for people with developmental disabilities, was conducted in western Sydney. Using a radioimmunoassay technique, sera were tested for anti-HAV (IgM and total antibody). We used logistic regression to determine risk factors for presence of anti-HAV. Results: Blood samples were collected from 259 permanent residents (96%). Serological testing revealed anti-HAV in 128 residents tested (49%). Presence of anti-HAV was associated with living in specific residential units, and with residents' age and length of stay at the centre, but was not associated with reported behavioural factors. Conclusions: More than half of the residents of the centre were susceptible to HAV infection. Behavioural characteristics of the residents and their close contact with each other make HAV transmission difficult to control. HAV vaccine should be promoted in communities at risk, such as those with developmental disabilities. (Aust NZ J Med 1994; 24: 365–367.)     

Coexistence of IgM antihepatitis A virus and IgM antihepatitis E virus in acute viral hepatitis: a prospective, multicentre study in Korea

This study investigated the clinical, serological and molecular characteristics of coexistence of both immunoglobulin M (IgM) antihepatitis A virus (HAV) and IgM antihepatitis E virus (HEV) in acute viral hepatitis using a prospective, multicentre design. Among a total of 771 symptomatic cases with acute viral hepatitis enrolled in a Korean city from September 2006 to August 2008, coexistence of IgM anti-HAV and IgM anti-HEV was found in 43 patients (A+E group; 6%), while the existence of IgM anti-HAV alone was found in 595 patients (A group; 77%) and that of IgM anti-HEV alone in 14 patients (E group; 2%). Clinical data analysis and measurement of IgM and IgG anti-HEV were performed using two different commercial kits, and HAV RNA and HEV RNA were detected in available serum or stool samples. The clinical features of the A+E group were similar to those of the A group. HAV RNA detection rates in the A+E and A group were similar, while HEV RNA was detected only in the stool samples of the E group, not in the A+E group. Comparative testing of anti-HEV using two different ELISA kits showed markedly discordant results for IgM anti-HEV positivity and consistently low positivity for IgG anti-HEV in the A+E group. Coexistence of IgM anti-HEV measured by the Genelabs ELISA kit in the setting of hepatitis A appears to yield false-positive results in nonendemic areas of HEV infection. Diagnosis of hepatitis E using IgM anti-HEV should be made with caution.     

Clinical features of HBsAg-negative but anti-HBc-positive hepatocellular carcinoma in a hepatitis B virus endemic area

BACKGROUND: The presence of antibody to the hepatitis B core antigen (anti-HBc) IgG in serum usually means a past infection of the hepatitis B virus (HBV). The clinical characteristics of patients with hepatocellular carcinoma (HCC), who have only a marker for past HBV infection, were investigated. METHODS: A total of 565 HCC patients were classified according to their markers for HBV and the hepatitis C virus (HCV). The clinical features and the survival rate of hepatitis B surface antigen (HBsAg)(-)/anti-HBc(+) patients were compared to those of HBsAg(+) patients. RESULTS: Four hundred and three patients were positive for HBsAg (B group, 71.3%), 64 were positive for anti-HCV (11.3%), and 90 were negative for both HBsAg and anti-HCV (N group, 15.9%). In the N group, 71 were positive for anti-HBc (PB group, 12.6% of total patients). The clinical characteristics of the PB group were different from those of the B group: age at diagnosis (60.6 +/- 9.6 vs 53.3 +/- 10.6 years, P < 0.001), habitual drinking (59.2% vs 23.6%, P < 0.001), family history of liver disease (9.9% vs 38.9%, P < 0.005), detection with periodic screening (28.2% vs 50.4%, P < 0.001), and elevated alpha-fetoprotein (53.5% vs 76.2%, P < 0.001). In both the PB group and the B group, liver cirrhosis was accompanied by a similar high prevalence (74.6% vs 89.1%). However, there was no significant difference in the cumulative survival rate. CONCLUSIONS: The prevalence of HBsAg(-)/anti-HBc(+) HCC is not rare or more common than that of anti-HCV(+) HCC in Korea, a high HBV endemic area. Although some differences in clinical characteristics may imply a different pathogenesis, chronic HBV infection or habitual drinking may be major contributing factors in the development of HCC in these patients.     

Modern epidemiology of hepatitis A in the north-western region of the Russian Federation

Summary.  The epidemiological features of hepatitis A virus (HAV) infection were studied in eleven territories located in the north-western region of the Russian Federation. The dynamics of HAV infection in Russia and in the region were evaluated during a 17-year period. The age-specific incidence was calculated and 229 305 patients with acute HAV were identified. The analysed database included HA mixed with other viral hepatitis infections: it included information about 8 809 HAV patients. Special attention has been paid to the sero-epidemiological studies conducted in St Petersburg city. These studies included analysis of age-specific incidence in persons 20 years of age and older during 6 years and testing of blood sera from 1 892 healthy persons for IgG anti-HAV. In general there is a trend to reduction of HAV incidence in Russia, and in the north-western region, high indices were registered in some provinces in different years. It was established three types of age-specific incidence distribution: predominated incidence in 3–14 years of age (first type), 15–29 years of age (second type) and uniform distribution in different age groups (third type). It was shown that decrease of HAV incidence in children and young adults lead to the reduction of sero-positivity level in the groups 20+ years of age. These characteristics should be taken in account to define indications for HAV vaccine prophylaxis. HAV infection in 10–13% of cases mixed with acute or chronic hepatitis B and C in the last 15 years in St Petersburg. In the middle of 1990s, HAV mostly mixed with acute viral hepatitis of different aetiology, but in the modern time predominated type of mixture was presented by HAV and chronic HBV and HCV infections. The obtained results are useful for viral hepatitis surveillance and control.     

Influence of GB virus-C/hepatitis G virus infection on the long-term course of chronic hepatitis B

Abstract: Aims/Background: The clinical significance of GB virus-C/hepatitis G virus (GBV-C/HGV) infection in chronic hepatitis B is not well known and its role in the outcome of liver disease was investigated. Methods: HGV-RNA and antibody to HGV (anti-E2) were studied in 125 patients with chronic hepatitis B (41 with multiple hepatitis virus exposure), 82 asymptomatic HBsAg carriers and 103 healthy adults. Results: In chronic hepatitis B, HGV-RNA was more frequent in patients with HDV infection and/or anti-HCV positivity than in those without (29% vs 6%, p<0.0001), mainly in drug addicts (38%). At diagnosis the overall prevalence of any marker (HGV-RNA plus anti-E2) was similar in chronic hepatitis due to HBV alone (17%), in HBsAg carriers (16%) and in healthy adults (17%) and increased to 58% in those exposed to HDV and/or HCV. During 1–11 years of follow-up, HGV infection persisted in 70% of patients with chronic hepatitis B. About 40% of HGV persistently coinfected patients underwent sustained biochemical remission, whereas continuing disease activity was observed in 80% of patients who cleared HGV-RNA. Conclusions: In chronic HBV infection the rate of exposure to HGV is similar to that in healthy adults, except for high risk patients. Long lasting HGV coinfection or anti-E2 seroconversion did not modify the course of chronic hepatitis B.