Hepatitis Monthly
Volume:11 Issue: 8, Aug 2011

There are seven approved treatments for adults with chronic hepatitis B virus infection in the United States and European countries: interferon-α, pegylated interferon-α, lamivudine, adefovir dipivoxil, entecavir, telbivudine, and tenofovir disoproxil fumarate. At present, two new analogues, entecavir and tenofovir are recommended as the first line therapy by the guidelines of European Association for the Study of the Liver and American Association Study for the Liver Diseases. On the other hand, regarding interferon therapy, use of pegylated interferon-α is recommended as the first line therapy instead of standard interferon-α by both guidelines. Therefore, the main scientific interests and unmet medical needs for treatment of chronic hepatitis B have been narrowed down to long-term efficacy and safety of the two said analogues-entecavir and tenofovir-and combination therapy of pegylated interferon-α with the two analogues. To put it concretely, further studies are needed to assess (1) the long-term efficacy and safety and resistance to entecavir and tenofovir; (2) the efficacy of different durations (24 weeks to 2 years) and lower doses of pegylated interferon-α; (3) the role of combination therapy with two analogues to reduce resistance; and (4) the efficacy and safety of the two analogues with decompensated cirrhosis. Herein, we review the recent available data and results.

A head-to-head comparison of the 72-week and 48-week anti-HCV therapies in slow responders with genotype 1 infection has been performed in several randomized clinical trials (RCTs). This review aimed at summarizing and pooling the results of these studies. RCTs that had evaluated the 72-week vs. 48-week anti-HCV therapy (peginterferon and ribavirin) in slow responders with HCV genotype 1 infection were systematically identified. A meta-analysis was performed using the random effects model. Heterogeneity in results was assessed on the basis of the Q statistics, and publication bias was evaluated by using Harbord's modified test. The end point was set as a sustained virological response (SVR). Data of 1206 subjects were retrieved from 7 studies. A total of 631 patients had received extended therapy. Slow virological responders who received the 72-week therapy had a significantly higher probability of achieving SVR than their counterparts who received the 48-week therapy [RR = 1.44 (95% CI, 1.20-1.73)]. With regard to publication biases, the heterogeneity in funnel plots was not significant (P = 0.19, I2 = 30%, PHarbord = 0.1). Our meta-analysis showed that the 72-week therapy with peginterferon and ribavirin is significantly superior to the standard 48-week therapy in slow responders with HCV genotype 1 infection.

Nearly 350 million persons worldwide are chronically infected with hepatitis B virus (HBV). Ubiquitin (Ub) is a highly conserved small regulatory protein, ubiquitous in eukaryotes, that usually serves as a signal for the target protein that is recognised and degraded in proteasomes. The Ub-mediated processing of antigens is rapid and efficient and stimulates cell-mediated immune responses. Accordingly, Ub-mediated processing of antigens has been widely used in chronic-infection and cancer studies to improve immune response. Many clinical trials have shown that DNA vaccine potency needs to be greatly enhanced. Here, we report a new strategy for designing an HBV DNA vaccine using the ubiquitin (Ub) sequence. The aim of this study was to investigate a novel DNA vaccination, based on the expression of HBV core antigen (HBcAg), fused to Ub to enhance DNA vaccine potency. Mouse ubiquitin fused to the HBcAg gene and cloned into the eukaryotic vector pcDNA3.1 (-). BALB/c mice were immunized with recombinant pUb-HBcAg or pHBcAg DNA vaccine. Lymphocyte proliferation assay, intracellular IFN-γ assay, CTL cytotoxicity assay, and antibody assay were performed to analyze the cellular and humoral immune responses to our DNA constructs. HBcAg was expressed effectively in the COS-7 cells that were transiently transfected with pUb-HBcAg. Strong anti-HBc IgG responses were elicited in mice that were immunized with pUb-HBcAg. The endpoint titers of anti-HBc peaked at 1:656100 on the 42nd day after the third immunization. pUb-HBcAg stimulated greater lymphocyte proliferation and induced higher levels of IL-2 and IFN-γ and a greater percentage of HBcAg-specific CD8+ T cells in mice than pHBcAg. In the CTL assay, the specific lysis rate reached 56.5% at an effector:target ratio of 50:1 in mice that were immunized with pUb-HBcAg. pUb-HBcAg elicits specific anti-HBc responses and induces HBc-specific CTL responses in immunized BALB/c mice. Our results imply that Ub can be used as a molecular adjuvant that enhances the potency of DNA vaccines.

Data on the epidemiology of hepatitis B and C in Bosnia and Herzegovina (B&H) are lacking. To assess the prevalence of hepatitis B surface antigen (HBsAg) and anti-hepatitis C virus (anti-HCV) in blood samples of first time blood donors in a well-defined region of B&H. Our secondary goal was to estimate the prevalence of HBsAg and anti-HCV in the general population of the same region.Patients and We evaluated 8196 blood samples for the presence of HBsAg and/or anti-HCV, adjusted for differences in gender, and used the ratio estimation method to determine the prevalence in the general population. We analyzed 1263 (15.4%) female and 6933 (84.6%) male blood donors (male-to-female ratio: 5.49 to 1). The adjusted prevalence of HBsAg among blood donors was 0.787% (95% CI = 0.535-1.038), while the prevalence of anti-HCV was 0.267% (95% CI = 0.016-0.519). There was no difference in the prevalence of HBsAg or anti-HCV between men and women. We estimate that the prevalence of HBsAg and anti-HCV in the general population is 1.057% to 1.535% and 0.29% to 0.89%, respectively. The prevalence of HBsAg and anti-HCV among blood donors suggests that our region has low endemicity for both hepatitis B and hepatitis C.

Celiac disease (CD) is an autoimmune disease characterized by immune-mediated inflammatory damage of the small intestinal mucosa, precipitated by the ingestion of gluten-containing foods. Since human leucocyte antigen DQ2 (HLA-DQ2) is a marker of nonresponsiveness to hepatits B virus (HBV) vaccine, CD may also be associated with this nonresponsiveness. The aim of this study was to compare the responses to HBV vaccine between children with CD and healthy children. We also investigated the relationship between the patient's responses to hepatitis B vaccine, the clinical presentation of CD, and dietary compliance in the patients.Patients and We recruited 52 children with CD and 20 age- and sex-matched healthy children who received HBV vaccination according to the standard immunization schedule. The production of specific antihepatitis B surface antigen (HBsAg) antibodies was evaluated in all patients and control participants. Subjects with less than 10 IU/L anti-HBs were considered nonresponders to the vaccination. 31 of the 52 patients (59.6%) were female and 21 (40.4%) were male. The mean age of the CD patients was 10.7 ± 4 years (range, 4-18 years). Anti-HBs titers were positive in 32 (61.5%) patients and negative in 20 (38.5%) patients, while they were positive in 18 (90%) of the children in the control group (P < 0.05). We found statistically significant differences between negative anti-HBs titers, clinical presentation of CD, and dietary compliance in patients with CD (P < 0.05). Nonresponsiveness to hepatitis B vaccination was more frequently found in children with CD than in the control group. Therefore, the response to HBV vaccination should be investigated in children with CD, and a different immunization schedule may need to be developed. Further, compliance to the prescribed gluten-free diet (GFD) may improve the immune response to HBV vaccination in children with CD.

Small studies have suggested that nucleos(t)ide analogue therapy (NAT) with reduced hepatitis B immunoglobulin (HBIG) duration may be efficacious in preventing post-liver transplantation (LT) HBV recurrence. This larger study evaluates the use of NAT with short term (< 6 mo) or no HBIG for prevention of post-LT HBV recurrence.Patients and All HBV patients undergoing LT at a university transplant center between 2002 and 2007 were identified retrospectively. Patient demographics, medication regimen, and adverse events were noted. The primary endpoint was HBV recurrence and secondary endpoints were graft and patient survival. 28 study patients were identified. Of these 28 patients, 4 (14%) received no HBIG, 6 (22%) received only inpatient HBIG, and 18 (64%) received inpatient HBIG and outpatient HBIG. 16 of the 28 patients (57%) received combination NAT and 12 patients (43%) received single NAT. At a median time of 15.5 months (range 9-24 months) post-LT, 4 of the 28 patients (14%) had recurrent HBV. Of those patients with recurrent HBV, 3 received both inpatient and outpatient HBIG and 1 received no HBIG. All cases of HBV recurrence were associated with noncompliance. NAT with short-term or no HBIG was efficacious and safe in preventing post-LT HBV. All compliant patients were HBV-free, including 9 patients who received no HBIG or only inpatient HBIG. Additional studies using NAT without HBIG appear justified.

Renal transplant recipients are known to be susceptible to viral infections, with more severe clinical presentations compared to healthy persons. Hepatitis E is generally a self-limited disease, which is caused by hepatitis E virus. Recently, hepatitis E has become more important in organ transplant recipients, because of new findings regarding the potential for chronic infections in this patient group. This study aimed to evaluate the seroprevalence of anti-HEV IgG among kidney transplant recipients in Urmia, in the north-western region of Iran.Patients and 91 patients were selected randomly from amongst patients who had undergone kidney transplantation in Urmia, Iran. Each patient was tested for the presence of anti-HEV IgG antibody using an enzyme-linked immunosorbent assay (ELISA, Dia.Pro; Diagnostic Bioprobes, Italy). 28 subjects (30.8%) were seropositive for anti-HEV IgG. Seropositive patients were generally older than seronegative patients (P = 0.009). There was no correlation between HEV infection and the level of education (P = 0.206), the history of blood transfusion (P = 0.164), or history of pre-transplantation hemodialysis (P = 0.228). There was no significant difference in the serum alanine aminotransferase (ALT) levels of the anti-HEV seropositive and seronegative patients. Multinomial logistic regression analysis indicated no significant relationship between HEV infection and increase in ALT levels, even after controlling for treatment with azathioprine (P = 0.79, OR = 1.12; 95% CI: 0.45-2.76). The anti-HEV IgG antibody has a high prevalence in Iranian kidney transplant recipients, and it is significantly higher in comparison with previous studies in the general population or in hemodialysis patients.

Liver storage diseases are rare biochemical and inherited diseases that affect multiorgan systems. This study was performed to determine the rate of storage diseases and their types in liver pathology specimens of subjects who were referred to a tertiary pediatric center.Patients and Two pathologists evaluated 2216 pathology specimens (stained with hematoxylin and eosin and periodic acid-Schiff) from subjects who were referred to the largest pediatric tertiary referral center in Iran between 1996 and 2007. Baseline data and clinical and laboratory manifestations were retrieved from the patient's files. We identified 117 patients who had storage diseases. A combination of clinical and laboratory findings was used to assess the final diagnosis. Glycogen storage disease (GSD) was observed in 85 of cases, compared with lysosomal storage diseases (LSD) in 31 patients and mucopolysaccharidoses in 1 case. LSD was more prevalent in those aged between 1 month and 1 year, whereas GSD was more frequent in those aged between 1 and 6 years. Most of the patients aged between 1 and 6 years. Most patients with LSD and GSD had unknown types of the disease. The most common known types in the LSD and GSD groups were Niemann-Pick disease and GSD type I respectively. The most common clinical and laboratory manifestation was hepatomegaly and abnormal liver enzymes, respectively. Most of our patients with storage diseases had Gaucher disease. Hepatomegaly and elevated transaminase levels were the most striking finding. However, with regard to the limitations of our methodology, further studies that collect more accurate data are warranted.

Corticosteroids are used widely to treat many types of disease. In general, these drugs are considered safe for the liver; however, recent reports have demonstrated that high-dose methylprednisolone (MT) may cause severe liver injury. Here, we report a case of a 24-year-old female who was given pulsed MT therapy for multiple sclerosis. MT induced icteric hepatitis and impaired liver synthetic function. Hepatotoxicity developed several weeks after drug exposure, and the causal association with MT was confirmed by unintentional rechallenge test. A brief review of the literature on corticosteroid-induced hepatotoxicity is presented.