Hepatitis Monthly
Volume:10 Issue: 2, Spring2010

In this editorial I will present some unanswered questions about hepatitis D virus (HDV) infection and some further discussion; everybody is asked to send us their comments.

. Hepatitis G virus/GB virus-C (HGV/GBV-C) is a newly identified member of the Flaviviridae family. Its clinical significance in chronic hepatitis C infection remains controversial. There is a geographical difference in the distribution of GBV-C in the world. The frequency of GBV-C infection among hepatitis C virus (HCV) infected patients varies. The aim of the current study was to determine the prevalence and genotypes of GBV-C among Iranian patients infected with chronic HCV.. Infection with GBV-C was surveyed in 71 chronic confirmed hepatitis C infected patients. These samples were collected at the Digestive Disease Research Center (DDRC) of Shariati Hospital, Tehran, Iran from January to October 2007. The 5’-UTR region of GBV-C RNA was detected using a novel in-house touchdown nested reverse transcription polymerase chain reaction (RT-PCR), the products were sequenced and the results were aligned and phylogenically analyzed.. Of the 71 HCV-infected patients, 31 (43.6%) were found positive for GBV-C RNA. Sequencing and phylogenic analysis showed that the samples were Genotype 2 of GBV-C.. It seems that there is a high rate of GBV-C infection among Iranian patients infected with chronic HCV. In comparison with the six reference genotypes, it was observed that all the samples were categorized in Genotype 2 of GBV-C, prevalent in North America, Africa and in European countries.

To compare several non-invasive methods of fibrosis assessment in chronic hepatitis C virus (HCV) infection (platelet count, the APRI score, the Forns score, the Lok score, FIB-4, Transient Elastography [TE]), versus percutaneous liver biopsy (LB).. Our study included 150 patients with chronic HCV infection in which LB, liver stiffness measurement (LSM) by means of TE and biological tests needed for calculating the scores (according to the classic formulas) were performed in the same session.. The best test for predicting significant fibrosis (F ≥ 2 Metavir) was LSM with AUROC-0.773, followed by APRI (AUROC-0.763), Forns (AUROC-0.744), platelet count (AUROC-0.732), Lok (AUROC-0.701) and FIB-4 (AUROC-0.669), but the differences were not statistically significant (P > 0.05). For excluding cirrhosis, all the tests had excellent NPV (>97%). The best test for predicting cirrhosis was LSM (AUROC-0.979), significantly better than platelet count (AUROC- 0.899, P = 0.022) and than FIB-4 (AUROC-0.839, P = 0.042), otherwise the differences were not statistically significant (P > 0.05). All of the non-invasive tests were statistically significantly correlated (P < 0.0001) to the severity of fibrosis: APRI r=0.570; Forns r=0.540; Lok r=0.4843; FIB-4 r=0.4171; platelet count r=-0.4842.. LSM by means of TE seems to be more sensitive than APRI, Forns, Lok and FIB-4 scores and than platelet count for the prediction of significant fibrosis, but the differences are not statistically significant. The APRI score and Forns scores correctly identified most (71%) of the patients having, or not having, significant fibrosis. LSM was the best method for predicting cirrhosis, but all the evaluated tests had excellent predictive value (AUROCs 0.839-0.979).

. The treatment of chronic hepatitis B (CHB) is a challenging problem today, and previous study has shown that oxidative stress causes the collective pathophysiological conditions of many hepatopathies, so other new therapeutic approaches are needed. Hence, in this study the paraclinical and oxidative stress parameters of the efficacy of N-acetyl cysteine (NAC) as an antioxidant in the treatment of CHB have been evaluated.. In this double-blind placebo-controlled clinical trial study, 43 patients with CHB were enrolled in 2008 in Tehran, Iran. The patients were randomly assigned to receive either 1200 mg/day NAC or a placebo for 45 days. Paraclinical tests and oxidative stress parameters were measured on experimental day 0 and on day 45.. Liver function tests, i.e. alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels were not significantly different in the NAC group and in the placebo group. A reduction in catalase (CAT) activity and an increase in glutathione concentration were statistically significant in the NAC group (P < 0.05).. According to our results, oral NAC is not an effective adjuvant treatment for patients with CHB, but further research with a larger population is needed for the evaluation of the effectiveness of NAC in these patients.

. Viral hepatitis is a serious complication among intravenous drug users (IDUs). The objectives of this study were to determine the seroprevalence of hepatitis B and C viruses (HBV and HCV), and associated risk factors among IDUs at a teaching hospital in Ahvaz, southwest Iran.. Medical records of 333 IDUs hospitalized from 2002 to 2006 at Razi Hospital, which is affiliated to Ahvaz Jundishapur University of Medical Sciences, were reviewed. Cases meeting the criteria for a diagnosis of viral hepatitis infection were included in this study. Patients’ characteristics, clinical and laboratory findings were extracted. Data of cases with hepatitis virus infection (HVI), called the HVI group and without HVI, called the NHVI group, were compared, using the chi-square test for qualitative variables and the t-test for quantitative variables. Differences with a P < 0.05 were considered significant.. Out of a total of 333 IDUs, 115 (34.5%), mostly male, with a mean age of 24.8±6.2 had HVI. More than 65% had a history of imprisonment. The mean duration of IDU was 4.5±1.6 years for the HVI group and 1.8±0.4 years for the NHVI group (P < 0.05). 85% of the HVI group and 45% of the NHVI group shared injection equipment (P < 0.05). 103 patients (30.9%) had HCV and 12 (3.6%) had HBV infection. There was a significant difference in age, duration of drug abuse, time spent in prison, sharing injection equipment, history of surgery, blood transfusion, packs of cigarettes per year and human immunodeficiency virus (HIV) co-infection between the two groups (P < 0.05).. HVI in IDU population is a prevalent complication, and is associated with heavy smoking (high number of packs of cigarettes per year), sharing injection equipment, long duration of drug usage, long duration of prison stay, HIV co-infection, history of surgery, blood and blood products transfusion. Older age, longer duration of IDU and imprisonment put the cases at higher risk of acquiring HCV in comparison to HBV.

. The determination of the prevalence of cardiopulmonary complications at a liver transplant center in Iran.. Ninety-nine patients (61 male and 38 female) with a mean age of 36.5 (15-66) years with proven cirrhosis were enrolled in this study. Patients with primary cardiac disease, current smokers, those with sepsis, hepatocellular carcinoma, recently ruptured esophageal varices and chronic pulmonary or renal diseases were excluded from the study. Sixty-nine patients had ascites. Forty-four patients had grade C Child-Pugh classification. All patients were evaluated for respiratory function by chest X-ray (CXR), room air arterial blood gas, simultaneous pulse oximetry, cardiac echocardiography and spirometry.. Sixty-one patients (66.1%) had a widened alveolar-arterial O2 difference (> 20 mmHg); 14 (14.1%) had hy- poxemia; 6 (6.1%) had mean pulmonary arterial pressure (MPAP) = 25-40 mmHg; 12 (12.1%) had tricuspid regurgita- tion; pleural effusion and lung restriction were detected in 4 (4%) and 50 (50.5%), respectively. P(A-a)O2 was nega- tively associated with pulmonary hypertension (P < 0.03) and tricuspid regurgitation (P < 0.005). Portal hypertension and portal vein thrombosis were detected in 91 and 8 patients, respectively.. A widened alveolar-arterial oxygen difference was common in our patients, but hypoxemia occurred in 14% of patients. Portopulmonary hypertension was preponderant in those patients of male gender.

Backgrounds and Hepatitis Delta Virus (HDV) is a defective ssRNA virus requiring the provision of hepatitis B virus (HBV) for packaging of new HDV virions. Since the epidemiological features of HDV in this part of Iran seem to be unknown, the aim of this research was to determine the seroprevalence of HDV of hepatitis B surface antigen positive (HBsAg+) in blood donors, injecting drug users, hemophiliacs, hemodialysis and thalassemic patients in the city of Tabriz in northwestern Iran.. The numbers of patients who were screened in the years 2006-2007 were 100 hemodialysis patients, 165 blood donors and 90 intravenous drug users, or a total of 355 patients who were HBsAg+ and randomly selected at the Tabriz Regional Educational Blood Center. Anti-HDV antibodies (IgM), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in serum samples were measured.. Eight of the hemodialysis patients (8%), 3 of the 165 blood donors (1.8%) and 9 intravenous drug addicts (10%) were HDV-IgM antibody-positive. Out of 152 serum samples collected in the hemophiliac population, only 11 samples were HBsAg+ (7.23%), and anti-HDV IgM antibodies were detected in just 2 cases. Also out of 112 thalassemic patients’ sera specimens, only 2 samples was HBsAg+, and HDV-IgM antibodies were negative. The seropositivity of anti- HDV antibodies was 6.01%. The study of serum ALT levels in HBV-positive and HDV-positive patients showed obvious elevation in more than 95% of cases.. The results show the endemicity of HDV infection in Tabriz. HDV infection in Iran could be controlled by nationwide HBV vaccination.

The epidemiology and risk factors for hepatitis C virus (HCV) infection in developing countries where intravenous drug use (IDU) is uncommon its poorly understood. This study therefore aims to determine the prevalence of HCV and its associated risk factors among pregnant women in Calabar municipality.. A total of 506 out of 716 antenatal care (ANC) patients seen at the General Hospital, Mary Slessor Avenue, Calabar between August and November 2005 and the University of Calabar Teaching Hospital (UCTH) between October and November 2005 were evaluated for their HCV status using the One Step HCV Test kit (Binomial diagnostics, UK), with reference to the subjects'' demographic and behavioural risk factors.. HCV prevalence was determined to be 0.4% (2/506) and was only seen in women aged 38 years and over. Histories of blood transfusion, surgery, involvement in polygamous marriage, sharing of a toothbrush and female circumcision were all non-significant risk factors for the infection.. This study reveals a low HCV prevalence among pregnant women in Calabar municipality with no identifiable risk factor. The study calls for a re-evaluation of the transmission modes of HCV especially in developing countries where intravenous drug use is rare.

Two types of peginterferon, alpha-2a (PEG-IFN-α2a) and 2b (PEG-IFN-α2b), are approved for the treatment of hepatitis C infection. Several high-quality studies have compared the efficacy of these two types of interferon, but it seems that any of these trials had inadequate statistical power on their own to find even a tiny difference between these two medicines. We pooled the available data in the literature to find any small difference between these two medicines.. In a systematic review of the literature, randomized controlled trials comparing the use of PEG-α2a vs. 2b were assessed. The DerSimonian and Laird method was employed to run meta-analysis. The end points were virological responses.. In 7 randomized controlled trials, 3518 patients were randomized to receive PEG-IFN-α2a + ribavirin (n=1762) or PEG-IFN-α2b + ribavirin (n=1756). Early virological response (EVR), early treatment response (ETR), and sustained virological response (SVR) were greater for patients treated with PEG-IFN-α2a. Odds Ratios (ORs) were 1.38 (95% confidence interval [CI] 1.11-1.71), 1.67 (95% CI 1.24-2.24), and 1.38 (95% CI 1.02-1.88) respectively. In the subset of naïve patients with genotype 1/4 and 2, ORs of SVR were 1.38 (95% CI 1.02-1.88) and 4.06 (95% CI 1.67-9.86) respectively. PEG-IFN-α2a had significantly higher rate of neutropenia OR=1.50 (95% CI 1.25-1.79) but pooled OR for withdrawal rates was not significant [OR=0.78 (95% CI 0.47-1.29)].. PEG-IFN-α2a with similar safety is more effective than PEG-IFN-α2b. A longer duration of maximum serum concentration compared with PEG-IFN-α2b (168 vs. 48-72 h.) yields a greater SVR and higher neutropenia in PEG-IFN- α2a recipients.

.Chronic hepatitis C (CHC) is one of the commonest infectious diseases of the liver and may lead to cirrhosis or hepatocellular carcinoma. Combination therapy with pegylated interferon (PEG-IFN) and Ribavirin is the treatment of choice for CHC. Combination therapy is thought to act by means of antiviral mechanisms and immunomodulation. Thyroid dysfunction is the most common autoimmune adverse effect associated with combination therapy; hypothyroidism is more common than hyperthyroidism. Antithyroid antibodies and female sex have a predictive value in the development of interferon induced thyroid disease (IITD). Patients with CHC should be informed of the possibility of side effects on the thyroid gland. Screening for antithyroid antibodies and thyroid function tests should be performed in patients with CHC before the commencement of antiviral treatment, and during and after it. This article reviews different aspects of IITD, including its pathogenesis, clinical manifestations, association with treatment regimens and treatment response and the outcome of thyroid dysfunction.

.Hepatitis B virus (HBV) strains, resistant to at least two anti-HBV agents from different subclasses of nucleos(t)ide analogues (NUCs) without a cross-resistance profile, are defined as multidrug-resistant. However, there are limited in vivo data for resistance to multiple NUCs. In this study, we report the case of the emergence of a multidrug-resistant HBV strain in a Turkish patient receiving sequential therapy. Polymerase gene mutations of HBV were detected using direct sequencing, line probe assay and clonal analysis. Twelve months after the start of lamivudine (LAM) therapy, virological breakthrough occurred (4.2E+07 IU/ml) and the rtM204V variant was detected in the patient’s sera: adefovir (ADV) was added to the therapy. ADV therapy was continued as monotherapy for 11 months, until the occurrence of clinical breakthrough i.e. alanine aminotransferase (ALT) 60 IU/L, and emergence of drug resistance to ADV (rtN236T). At that time, switch therapy was resumed with ADV + entecavir (ETV) in combination for 5 months. In the 18th month of the ETV monotherapy, direct sequencing showed reduced susceptibility to ETV (rtL180M+rtM204V). Currently, ETV + tenofovir (TDF) are being used as antiviral treatment and the HBV DNA load has decreased substantially (<1.0E+02 IU/ml). In conclusion, we have detected an HBV strain with multidrug-resistance, which had a very fast course of development. Patients with a multidrug-resistant profile should be more frequently followed up both by direct sequencing and line probe assay, for the detection of possible novel HBV variants and low level mutants present in the viral population, in case of the sudden emergence of drug resistance.