Clinical and virological characteristics of hepatitis B or C virus co-infection with HIV in Indonesian patients

Hepatitis virus-related liver disease increases substantially the mortality rate of patients with HIV on highly active antiretroviral therapy (HAART). Therefore, early diagnosis of hepatitis B virus (HBV) and hepatitis C virus (HCV) is important. However, the prevalence of HBV and HCV infection in Indonesian patients infected with HIV is unknown. Therefore, this study examined the molecular and clinical characteristics of HBV and HCV in 126 patients infected with HIV, mostly on HAART, at Dr. Sardjito Hospital, Yogyakarta, Indonesia. The rates of triple infection, HIV/HCV co-infection, HIV/HBV co-infection, and mono-infection were 4.8%, 34.1%, 3.2%, and 57.9%, respectively. Seven HCV genotypes were detected, with genotypes 1a, 1b, 1c, 3a, 3k, 4a, and 6n found in 23 (52%), 1 (2%), 4 (9%), 5 (11%), 7 (16%), 3 (6%), and 1 (2%) patients, respectively, indicating multiple modes of transmission. HBV-DNA was detected in 2/10 patients with hepatitis B surface antigen; both patients were HAART naive. Univariate analysis revealed that male sex, higher education level, injection drug use, sexual contact, alanine aminotransferase ≥40 IU/L, and aspartate aminotransferase-to-platelet ratio index > 0.5 were associated with HCV co-infection. In multivariate analysis, injection drug use (OR: 26.52; 95% CI: 3.52-199.54) and alanine aminotransferase ≥40 IU/L (OR: 6.36; 95% CI: 1.23-32.89) were independently associated with HCV co-infection. HCV co-infection was common among Indonesian patients infected with HIV, particularly among injecting drug users, and was a risk factor for disease progression of HIV.     

Hepatitis B and hepatitis C co-infection in patients with HIV. Reviews in Medical Virology 11(4): 253-270

The original article to which this Erratum refers was published in Reviews in Medical Virology 11(4): 253-270     

Fibrosis progression in chronic hepatitis C patients with occult hepatitis B co-infection.

Occult hepatitis B virus (HBV) infection in individuals without hepatitis B surface antigen (HBsAg) can be identified in hepatitis C virus (HCV) infected patients. However, its role in fibrosis progression remains uncertain. This retrospective study compared the fibrosis progression (defined as fibrosis progression by at least one stage) and progression to severe fibrosis (fibrosis stage 3 or 4) in HCV patients with occult HBV infection. Occult HBV infection was diagnosed by the detection of HBV DNA in the serum of 74 consecutive anti-HCV positive patients by PCR. Thirty-one patients (41.9%) had occult HBV infection. All 74 patients had a median of 2 (range 2-3) liver biopsies. The median time between the first and last liver biopsy was 57.7 (range 15.0-132.8) months. Eleven of the 31 patients with occult HBV infection compared with 12 of the 43 patients without occult HBV infection had fibrosis progression (35.5% versus 27.9%, respectively, p=0.608). Six of the 31 patients with occult HBV infection compared with 8 of the 43 patients without occult HBV infection developed severe fibrosis (19.4% versus 18.6%, respectively, p=0.946). In conclusion, chronic HCV patients with occult HBV co-infection does not seem to progress more than patients without occult HBV infection. However, more large-scale studies are needed before a definite conclusion can be obtained.     

Hepatitis B vaccination in patients with chronic hepatitis C.

The aim of the study was to evaluate the safety, immunogenicity, and possible therapeutic effect of hepatitis B vaccine in patients with chronic hepatitis C. The subjects studied included three groups: group I, 26 patients with chronic hepatitis C who were susceptible to hepatitis B virus infection; group II, 35 healthy subjects who were susceptible to both hepatitis B and hepatitis C virus infection; and group III, 30 patients with chronic hepatitis C receiving no hepatitis B vaccination as controls. Three 20 microg/dose of recombinant hepatitis B vaccines were given to subjects of groups I and II in months 0, 1, and 6. Blood samples from the subjects were collected before and 1 month after each dose of vaccination for serological testing. The subjects of groups I and II had similar antibody to hepatitis B surface antigen (anti-HBs) response rates after the first (30.8% vs. 17.1%), second (61.5% vs. 60.0%), and third (88.5% vs. 91.4%) doses of vaccination. Also, their geometric mean titers of anti-HBs did not differ much when vaccination completed in 7 months (360 vs. 581 mIU/ml). During vaccination period, patients with chronic hepatitis C demonstrated no significant change of serum cytokines and HCV RNA levels, but significantly lowered ALT levels after three doses of vaccination. Hepatitis B vaccination is safe and immunogenic in patients with chronic hepatitis C. It did not significantly affect their levels of HCV RNA, but tended to lower ALT levels.     

Hepatitis C genotypes in patients with dual hepatitis B and C virus infection

In patients with chronic hepatitis B and C virus (HBV, HCV) infection, an inverse relationship in the replicative activity of the two viruses has been reported. In the present study the genotype of HCV was evaluated in 34 consecutive cases found with hepatitis B surface antigen (HBsAg) and anti-HCV in the serum, in order to identify its possible influence in determining the pattern of HBV/HCV interaction. Nineteen patients were HCV-RNA positive and could be genotyped: 8 were infected by HCV-1 (3 by HCV-1a and 5 by HCV-1b), 10 by HCV-2, and only 1 by HCV-3. Among these, 3 were HBV-DNA positive, compared to 10 of 15 HCV-RNA-negative patients (P = 0.003), and all 3 were coinfected with HCV-2. Mean alanine aminotransferase (ALT) levels were similar between patients infected with HCV-1 and HCV-2. Among 7 patients with cirrhosis 5 were infected by HCV-2, while 6 of 12 of those without cirrhosis had HCV-1 infection. In conclusion, HBV replication was inhibited more efficiently by HCV-1 than by HCV-2. Cirrhosis was frequently found in patients with dual HBV and HCV-2 infection. © 1996 Wiley-Liss, Inc.     

Hepatitis B and D genomes in hepatitis B surface antigen negative patients with chronic hepatitis C

Hepatitis B and hepatitis D viral genomes were tested by nested polymerase chain reaction in the serum and liver of 69 hepatitis B surface antigen (HBsAg) negative, anti-hepatitis C virus (HCV) positive patients (47 with HCV RNA and 22 without HCV RNA). Serum hepatitis B virus (HBV) DNA-was detected in 49% of the patients with HCV-RNA and in 64% of those without HCV-RNA. Furthermore, intrahepatic HBV-DNA was found in four of five (80%) of the biopsies analysed. Delta genome was found in 72% and 73%, respectively, of the anti-HCV positive patients with or without HCV-RNA. In addition, intrahepatic delta virus genome was detected in another four liver biopsies studied. In the group of patients with HCV-RNA, the simultaneous presence of hepatitis B and D genomes was statistically higher in transfused patients than in drug addicts, or in those with an unknown infection route (P < 0.001). These results show a high percentage of B and D genomes in HBsAg negative patients with anti-HCV, irrespective of the presence or absence of the HCV genome. However, the clinical implications of this finding should be examined in future studies. © 1995 Wiley-Liss, inc.     

Hepatitis B and hepatitis C in emergency department patients.

BACKGROUND. Infections with hepatitis B virus (HBV), hepatitis C virus (HCV), and the human immunodeficiency virus type 1 (HIV-1) are common in inner-city populations, but their frequency and interrelations are not well established. METHODS. During a six-week period, excess serum samples were collected, along with information on risk factors, from all adult patients presenting to an inner-city emergency department. The samples were assayed for hepatitis B surface antigen (HBsAg) and antibodies to HCV and HIV-1. RESULTS. Of the 2523 patients tested, 612 (24 percent) were infected with at least one of the three viruses. Five percent were seropositive for HBV, 18 percent for HCV, and 6 percent for HIV-1. HCV was found in 145 of the 175 intravenous drug users (83 percent), 36 of the 171 transfusion recipients (21 percent), and 5 of the 24 homosexual men (21 percent). Among black men 35 to 44 years of age, the seroprevalence of HCV was 51 percent. HBsAg was present in 9 percent of those whose only identifiable risk was possible heterosexual exposure. At least one viral marker was found in about 30 percent of the patients who were actively bleeding or in whom procedures were performed. Testing for HIV-1 alone would have failed to identify 87 percent of the patients infected with HBV and 80 percent of those infected with HCV. CONCLUSIONS. In a population of patients in an inner-city emergency room, HBV, HCV, and HIV-1 are all highly prevalent. However, routine screening for HIV-1 alone would identify only a small fraction of the patients who pose risks of severe viral infections, including HBV and HCV, to providers.     

Management of hepatitis B and C in HIV co-infected patients

Morbidity and mortality from co-morbid hepatitis B (HBV) and hepatitis C (HCV) infection in HIV co-infected patients are increasing; hence, the management of HIV and HBV or HCV co-infected individuals is now one of the most challenging clinical management issues. Less than 10% of all HIV-infected patients show markers of chronic HBV infection. Hepatitis B in HIV co-infected patients is characterized by high levels of HBV replication and a high risk for cirrhosis. Treatment of HBV with lamivudine (3TC) remains the best treatment option at this time. Initial results of studies of adefovir or tenofovir, however, demonstrate good antiretroviral efficacy, even in patients with 3TC-resistant HBV. In Europe, it is estimated that approximately 30% of HIV-infected individuals are co-infected with HCV. HIV accelerates HCV liver disease especially when HIV-associated immune deficiency progresses. Within 10-15 years of initial HCV infection, 15-25% of patients who are co-infected with HIV develop cirrhosis compared with 2-6% of patients without HIV infection. With the introduction of pegylated interferon in combination with ribavirin, promising treatment options have become available for HIV/HCV co-infected patients leading to early virological response rates of approximately 50%. The high number of HIV/HCV and HIV/HBV co-infections, as well as the much more unfavorable course of HBV and HCV in these patients, underlines the need to establish treatment strategies for HBV and HCV in HIV co-infected individuals.     

Hepatitis B and hepatitis C among institutionalized psychiatric patients in Taiwan

To investigate the seroprevalence of hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (anti-HCV) in a psychiatric institution in Taiwan, where hepatitis B virus (HBV) is hyperendemic, a total of 780 patients with psychiatric disorders were studied. Enzyme-linked immunosorbent assays (ELISA) were used for testing HBsAg and anti-HCV. The prevalence of HBsAg was higher than that of anti-HCV among these patients (18.1% vs. 6.8%, P < 0.0001). The HBsAg carrier rate in these patients was consistent with that of the general population, with a trend for HBsAg carrier rate to be lower in the aged and in females. In contrast, the prevalence of anti-HCV was higher in these patients than in general population. Anti-HCV positivity was found more frequently in patients who had received blood transfusion previously (24% vs. 6.4%, P < 0.05). The majority (92%) of patients with positive anti-HCV did not have a history of apparent parenteral exposure. The prevalence of anti-HCV increased significantly with duration of the psychiatric disorder. The prevalence of anti-HCV also tended to increase with duration of hospitalization but without reaching statistical significance. These findings suggest that these institutionalized psychiatric patients contract hepatitis B, as does the general population in Taiwan, and they should be considered as a specific risk group for hepatitis C infection. © 1993 Wiley-Liss, Inc.     

Hepatitis C viremia in HIV/HCV-coinfected patients: lower levels in presence of chronic hepatitis B

Complex reciprocal interactions between hepatitis C (HCV) and hepatitis B (HBV) viruses (HBV) have been reported. We examined the influence of HBV on HCV RNA titers in 376 HCV/HIV-coinfected patients (30 were also HBsAg positive). Regression analyses identified negative HBsAg and male sex as factors associated with HCV RNA values >500,000 IU/mL.     

Hepatitis B virus genotypes and lamivudine resistance mutations in HIV/hepatitis B virus-coinfected patients

BACKGROUND: Differences in subtypes, hepatitis B early antigen (HBeAg)-negative variants, and drug resistance mutations all seem to influence the clinical and therapeutic outcome in patients with chronic hepatitis B virus (HBV) infection. Information available on the prevalence and distribution of distinct HBV variants in HIV-positive patients is scarce. METHODS: All HIV-infected patients with persistent serum hepatitis B surface antigen and detectable HBV viremia were identified in a reference HIV clinic located in Madrid, Spain. HBV load, subtypes, precore (PC) and basal core promoter (BCP) variants, and lamivudine (LAM) resistance mutations were analyzed. RESULTS: A total of 81 HBV/HIV-coinfected patients (4.1%) were identified in a population of 1968 HIV-positive patients. Plasma specimens with detectable HBV viremia could be obtained from 62 subjects, and this was the study population that underwent further virologic characterization. HBV genotype distribution was as follows: A (n = 27), D (n = 27), E (n = 1), F (n = 2), and G (n = 3). Two patients had mixed HBV genotypes (A/E and A/F). HBV subtype A was predominant (74%) among patients infected through sexual contact, whereas HBV-D was most frequent (74%) among intravenous drug users (P < 0.001). PC/BCP mutants were more frequent in patients with HBV-D than in those with HBV-A (63% vs. 18%; P < 0.01). Median time on LAM was 40 months; patients with HBV-A tended to show LAM resistance mutations more often (53% vs. 44%) and to develop them earlier (35 vs. 45 months) than patients with HBV-D. The dual L180M + M204V/I mutant was the predominant resistance pattern, although a triple rt173V + 180M + 204V, which acts as a vaccine escape mutant, was found in 1 individual. In the multivariate analysis, patients with LAM resistance mutations were significantly more frequently HBeAg-positive and older than individuals with wild-type HBV. Hepatitis-delta was recognized in 13 (21%) of these 62 HBV viremic patients, with no association with specific HBV variants. CONCLUSION: Risk transmission group, age, and positive serum HBeAg are the main determinants of distinct HBV virologic variants, including HBV genotypes and LAM-resistant mutants, in HBV/HIV-coinfected patients.     

Effect of interferon on GB virus C and hepatitis C virus in hepatitis patients with the co-infection

Of 74 patients who were infected with hepatitis C virus (HCV) and received interferon, 12 (16%) were positive for RNA of GB virus C (GBV-C). RNA of GBV-C was determined in sera from the co-infected patients retrospectively, and the effect of interferon on GBV-C was compared with that on HCV in them. Titers of both GBV-C and HCV RNAs decreased during interferon in all of them. Two patients lost both GBV-C and HCV RNAs and remained clear until 6 months after treatment with interferon, while 2 lost RNA for GBV-C only and 2 for HCV RNA alone. Low pre-treatment RNA titers of GBV-C and HCV correlated with the efficacy of interferon in clearing. Alanine aminotransferase returned to normal only in the patients who lost HCV RNA, regardless of the persistence or loss GBV-C RNA. These results indicate that the response to interferon of GBV-C is comparable to but independent of that of HCV and that the persistence of GBV-C would not prevent the normalization of aminotransferases in response to interferon in patients with chronic hepatitis C. J. Med. Virol. 52:156–160, 1997. © 1997 Wiley-Liss, Inc.     

Hepatitis C virus RNA in patients with chronic hepatitis C

Reviews recent data on the detection of genome and replicative HCV RNA in patients with chronic hepatitis C by PCR and in situ hybridization. Discusses the results of HCV RNA detection in the liver, lymphocytes, serum, and other organs and tissues and notes the relationship between the incidence of RNA and activity of the pathological process. Analyzes the results of HCV RNA detection after IFN treatment. Discusses the role of HCV RNA in the pathogenesis of hepatitis C.     

Lamivudine resistance mutations in European patients with hepatitis B and patients co-infected with HIV and hepatitis B

Evaluation of resistance pattern in patients with chronic hepatitis B. Retrospective study of hepatitis B virus (HBV) resistance mutations in patients found viraemic after first-line treatment. HBV viral load was determined by a real-time polymerase chain reaction and the substitutions in HBV-DNA were studied by polymerase sequencing test. First line treatment had failed in 12 out of 33 patients (36%) receiving anti-HBV drugs. The 12 patients with persistent viraemia were all lamivudine (LAM) experienced and 7 had a polymerase sequencing test available. LAM substitution mutations L180M + M204V/I were found in six out of seven cases, with an accompanying V173L mutation in three cases. These mutations were also related with changes in HBsAg. The use of potent drugs in the first line anti-HBV therapy may reduce the resistance mutations in the future.