The interactions among hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis delta virus (HDV) were studied by measuring HBV-DNA and HCV-RNA levels and by determining the influence of viral genotypes and mutations in HBV basal core promoter (BCP) and precore regions. We included 65 consecutive patients, 25 HBV/HCV, 18 HBV/ HDV, and 22 HBV/HCV/HDV. Controls consisted of 55 patients with chronic HBV and 55 with chronic HCV infection. HBV-DNA and HCV-RNA levels were lower in coinfections than in single infections (P < .05). HBV/HCV coinfection was associated with lower HBV viremia (8.2 ؋ 10 4 copies/ mL) and lower HCV-RNA levels (7 ؋ 10 5 IU/mL), than the corresponding control group (P < .05), with more marked decrease in HBV replication (P < .05). Moreover, in HBV/ HCV coinfection and in triple coinfection we observed an inverse relationship between HBV-DNA and HCV-RNA levels (P < .05). HBV/HDV coinfection was associated with lower HBV viremia (2.5 ؋ 10 4 copies/mL) than that found in HBV infection (P < .05). Patients with triple coinfection showed lower HBV-DNA and HCV-RNA levels than control groups (P < .05). Prevalence of precore mutations was lower in HCV coinfections (P < .05). No significant association was observed between HCV-RNA levels and HBV precore mutations, BCP mutations or HBV genotypes, or between HBV-DNA levels and HCV genotypes (P < .05). In conclusion, HCV exhibited stronger inhibitory action in the reciprocal inhibition seen in HBV/HCV coinfection. HDV was the dominant virus in HBV/HDV coinfection and in triple coinfection, and had a greater unfavorable influence on HCV than on HBV replication. The reciprocal inhibition of viral replication seemed to be little influenced by the inherent genomic factors studied. (HEPATOLOGY 2001;34:404-410.)Hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis delta virus (HDV) are the most common causes of chronic liver disease. All 3 viruses are transmitted by exposure to infected blood and it is not unusual to find patients coinfected with HBV and either HCV or HDV, or with all 3 viruses. 1 Although the phenomenon of viral interference in mixed infection has been described previously, the interplay between these viruses and the mechanisms regulating this interplay are not completely defined, and it is not clear which is the strongest in terms of mutual replicative suppression. 2 Studies in dual HBV and HCV infection have yielded conflicting data, with some reports suggesting that HCV possesses the strongest suppressing effect 3,4 and others attributing the dominant role to HBV. 5,6 Moreover, an alternative replicative dominance, probably because of mutual interference, has also been suggested. 6,7 In HBV and HDV dual chronic infection, evidence from animal experiments and human clinical studies indicates that HBV replication diminishes as a result of HDV superinfection. 8 Finally, contrasting results regarding viral replication have been observed in triple infection. In this context, early studies reported serologic and immunohistologic fi...

No abstract

The precore-core gene of hepatitis B virus (HBV) was directly sequenced from serum samples of 42 patients with chronic B hepatitis (19 hepatitis B e antigen [HBeAg]+ and 23 anti-HBE+). Viral genotypes were determined by comparison with 11 reference sequences and by restriction analysis. Genotype A was identified in 16 cases, genotype D in 24 cases, and other genotypes in 2 cases. Precore mutations, mainly M1 (stop at codon 28), were differently distributed among the viral genotypes: 3 cases (18.8%) with genotype A and 18 cases (75%) with genotype D. In sequences with precore mutants, the encapsidation signal was more stable (negative stabilization energy) than in sequences without precore mutants. In genotype A, the M1 mutation coexisted with a second mutation (C-->T at position 1858 in codon 15), and both mutations were paired in the secondary structure of the RNA encapsidation signal, which justified the rare presence of precore mutants in this genotype. The analysis showed different distribution of mutations depending on the viral genotype; patients with genotype D were more likely to have persistent HBV infection by selection of precore mutants. Multiple amino acid substitutions were detected in the core region, mainly in two subsequences that have been previously described as epitopes (flanked by codons 11 to 27 and 74 to 83); the presence of these mutations was significantly related to the presence of precore variants which abolished the expression of HBeAg.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term changes in the frequency and outcome of hepatitis delta virus (HDV) infection have seldom been analysed. This retrospective, longitudinal study includes 398 consecutive hepatitis B surface antigen (HBsAg)-positive patients with anti-HDV antibodies who attended our institution between 1983 and 2008. At enrolment, 182 patients had acute and 216 chronic hepatitis. Patients were grouped into two periods. Those who attended between 1983 and 1995 and those between 1996 and 2008. The former group was significantly younger, mainly intravenous drugs users, and had a greater incidence of acute HDV and HIV and HCV coinfection. Patients with acute HBV/HDV coinfection cleared both infections in 90% of cases, while all patients with HDV superinfection evolved to chronic disease. One hundred and fifty-eight patients with chronic HDV were followed for a median period of 158months. Seventy-two per cent of the patients remained stable, 18% had hepatic decompensation, 3% developed hepatocellular carcinoma, and 8% cleared HBsAg. Liver-related death was observed in 13% of patients and mainly occurred in patients from the first period (P=0.012). These results indicate an outbreak of HDV at the end of the 1980s and the beginning of the 1990s, with a large number of acute HDV cases affecting predominately young, male intravenous drug users. Currently, patients with chronic HDV disease are older, and factors associated with worse prognosis include the presence of cirrhosis and age at the time of diagnosis.

Although the efficacy of hepatitis B vaccines in patients under chronic hemodialysis treatment has been well documented, the persistence of immunity in this population remains largely unknown. In this study we have followed 60 hemodiaysis patients up to 3 years after primary hepatitis B vaccination (four doses of recombinant hepatitis B vaccine; Engerix B, 20 mg/dose) to evaluate the persistence of immunity (as indicated by serum levels of antibody to hepatitis B surface antigen – anti-HBs – higher than or equal to 10 mlU/ml). Four-ty-four (73%) patients developed anti-HBs levels above 10 mlU/ml after vaccination; the remaining 16 (27%) vaccinees were considered nonresponders and were given a booster dose that again failed to elicit an immunoresponse. After 3 years of follow-up, 18 out of 44 (41 %) responders had no detectable anti-HBs levels in the serum (antibody loss occurring within 8 and 12 months in 3 cases, within 1 and 2 years in 13, and within 2 and 3 years in 2 other cases). When compared with the responders that lost their antibodies during the follow-up period, those who remained immunoreactive 3 years after vaccination was initiated were younger and had higher anti-HBs levels at 8 months of follow-up. Two hepatitis B virus infections were detected among nonresponders during the follow-up period. Based on these data, we conclude that patients undergoing chronic hemodialysis therapy not only have lower response rates to hepatitis B vaccination than healthy adults, but also that these are frequently transient. We then recommend for this population (1) anti-HBs testing soon after vaccination and (in case of response) every 6 months thereafter and (2) to give a booster dose to primary responders whenever their antibody levels decrease below 10 mlU/ml.

No abstract

Lamivudine combined with hepatitis B immune globulin (HBIg) is the standard of care for preventing the recurrence hepatitis B virus after liver transplant. To determine the risk of hepatitis B virus (HBV) recurrence after early withdrawal of HBIg in patients receiving lamivudine maintenance therapy, 20 patients receiving a course of HBIg and lamivudine after transplantation and long-term maintenance therapy with lamivudine and 9 patients receiving HBIg and lamivudine indefinitely were analyzed. The survival rate was 90% after a mean follow-up of 83 months. The HBV recurrence rate was 14% with a mean period of 91 months free from HBV recurrence. Both groups had similar HBV recurrence rates, 15% for the combination and 11% for lamivudine alone. Four patients, 3 of whom were noncompliant with therapy, experienced posttransplant HBV recurrence. Patients who adhere to long-term prophylaxis with lamivudine after early withdrawal of HBIg have a low risk of HBV recurrence, similar to those who receive combination prophylaxis.

Alpha-1-antitrypsin (α1-AT) deficiency is mainly evaluated in the diagnostic process of chronic obstructive pulmonary disease (COPD). Around 95% of individuals with severe α1-AT deficiency carry the PI*ZZ genotype. Little is known about the epidemiology of the remaining deficient α1-AT variants, which are called 'rare' due to their low prevalence. The retrospective revision of 3511 α1-AT deficiency determinations performed in Barcelona from 1998 to 2010 detected 1.6% of cases with rare α1-AT alleles, a rate similar to those reported in other European studies. Among these variants, PI*I and PI*Mmalton represented 54% of cases. Hence, the so-called 'rare' α1-AT alleles may not be rare as has been assumed. It would be of interest to implement simple allele-specific molecular biology methods to study the most prevalent rare variants in each region. Augmentation therapy is recommended in patients with emphysema and PI*ZZ genotype, but there is little evidence regarding the implications of rare variants on therapy.