Hepatitis Monthly
Volume:9 Issue: 3, Summer 2009

Hepatitis B virus infection is still a major public health concern all over the world, and much research must be carried out on the various aspects of this issue. Since infection with hepatitis B virus in pregnant mothers is a threat for both mother and her fetus, this study was performed to determine the relationship between maternal HBsAg carrier status and perinatal outcome. A retrospective case-control study was performed on 450 carriers of hepatitis B surface antigen (HBsAg) pregnant women and compared to 450 controls. Both groups were matched for age, parity, and body mass index (BMI). When compared to the control group, patients with HBsAg displayed significantly higher incidence of gestational diabetes mellitus (GDM) (7.7% vs. 2% P=0.001), increased hospitalization period after delivery (22.9% vs. 3.33%, P<0.0001), preterm labor at less than 37 weeks (10.9% vs. 2.67%, P<0.0001), pregnancy induced hypertension (13% vs. 2.89%, P<0.0001), and preterm premature rupture of membranes (3.55% vs. 1.1%, P=0.03). Also, the incidence of macrosomy (6.67% vs. 2.22%, P=0.02), intrauterine fetal death (5.56% vs. 0.44%, P=0.001), still birth (2.89% vs. 0.44%, P=0.005), and NICU admission (25.78% vs. 2.22%, P<0.0001) in the carrier mothers were higher. HBsAg carriers have increased risk of hospitalization period after delivery, preterm labor, gestational hypertension, preterm premature rupture of membranes. In addition higher incidence of macrosomy, intrauterine fetal death, still birth, and NICU admission were observed. Therefore our results showed HBsAg carrier mothers have increased maternal and neonatal complications.

Liver biopsy remains the gold standard to assess hepatic fibrosis, including for those with chronic hepatitis B. The search for a novel, non-invasive alternative to liver biopsy to assess hepatic fibrosis continues. The serum aspartate-aminotransferase-to-platelet ratio index (APRI) has been shown to correlate with the degree of hepatic fibrosis in patients chronically infected with hepatitis C virus (CHC). The aim of this study was to investigate whether the same also applies in cases of chronic hepatitis B (CHB). One hundred and eleven consecutive patients who tested positive for hepatitis B surface antigen (HBsAg) for more than 6 months in our unit from July 2006 to June 2007 were included in the study. For all of the patients, platelet count, aspartate aminotransferase (AST), hepatitis B e antigen (HBeAg) by enzyme-linked immunosorbent assay (ELISA), hepatitis B virus (HBV) DNA by polymerase chain reaction (PCR), and percutaneous liver biopsy were tested for. APRI was calculated for every patient using the formula, AST x UNL x 100 / platelet count x 109/L. Patient characteristics, including APRI, were compared between those with a fibrosis? 2 and those having a fibrosis < 2. AST level was found to be higher in those with significant fibrosis (HAI-F > 2) and the proportion of HBeAg-positive patients was higher in those with a fibrosis ³ 2 (39%) compared to those with a fibrosis < 2. Only 3 patients out of 111 had an APRI > 1.5 and all of them had a fibrosis < 2. Liver biopsy remains the gold standard for assessment of fibrosis in chronic hepatitis and cirrhosis related to Hepatitis B infection. AST level was seen to differ among two groups, but no difference was seen for platelet counts. Although APRI has been shown to have good predictive value for significant fibrosis in patients with chronic hepatitis C infection, it does not appear to be of use in predicting fibrosis in patients with chronic hepatitis B infection.

Hepatitis B vaccination has been part of the EPI of Iran since 1993. To extend HBV immunization to 25-year-old adolescents, HBV mass vaccination has been planned for adolescents born from 1989 to 1992. The first 3-round campaign in Iran covered 1989-born adolescents and was implemented in 2007. This study was conducted to estimate vaccination coverage of the campaign using administrative data at the provincial level. To assess the campaign vaccination coverage we divided the number of adolescents vaccinated in the campaign by the total number of 17-year-old adolescents who resided in a given province. For the number of vaccinated cases we used administrative data as reported from universities of medical sciences and for the basic population we used the data from the last national population census (2007). After the 3 rounds of the campaign, a total of 3,983,291 doses of vaccine were administered. At the end of the third round, 70.0% (from 44.2% to 96.1% in various provinces) of the target population received full doses of the HBV vaccination. Moreover, 74.5% (51.3% to 99.9% in various provinces) received at least two doses and 78.3% (from 52.9% to 100% in various provinces) received at least one dose of the vaccine. Nineteen out of 30 provinces achieved acceptable full-dose coverage of higher than 70%. Low coverage (less than 50%) was reported from 3 provinces. Vaccination coverage was significantly higher in girls compared with boys (83.3% vs. 68.7% for full-dose coverage; P<0.001). In addition, vaccination coverage was significantly higher in rural areas than urban areas (84.1% vs. 68.7% for full-dose coverage; P<0.001). The campaign reached acceptable coverage in the majority of the provinces. Higher coverage for women and rural areas, two known vulnerable populations in most health care systems, was attained within the campaign.

Hepatitis delta virus (HDV) is an RNA virus that can lead to severe acute, and chronic forms of liver disease using the helper function of the hepatitis B virus. HDV strains are categorized into three genotypes and eight clades, which distribute geographically. The prevalence rate of HDV infection varies from 2.4 to 10 percent in blood donors for chronic liver disease in Iran. The aim was to find out the phylogenetic background of samples isolated in Tehran. A molecular phylogenetic analysis in some samples has been conducted in Iran previously. However, the number of cases did not cover the whole country. In addition, based on the restriction in the number of cases, we studied 26 samples. In this study, a phylogenetic distribution of 26 Iranian isolates was determined using a neighbor-joining method. The revealed that all isolates belonged to Genotype I (Clade 1). It is shown that our finding is in concordance with previous studies in Iran. It can be concluded that the strain of HDV being spread in Iran belongs to Genotype 1. This study is in concordance with previous studies in Iran.

Hepatitis B virus (HBV) infection is an important public health problem. Hepatitis B vaccine induces protective response in the majority of vaccinated persons. In our country, we do not have any evaluation for the efficacy of each type of vaccines used in adult and our objective was therefore to evaluate the efficacy of vaccines. In a randomized double-blind clinical trial 347 military personnel and their family in Kashan city, central Iran, were studied during August 2007 to April 2008. Participates who did not have history of HBV vaccination were included in this study. Five-mL blood samples were taken from each person and tested for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb) and total hepatitis B core antibody (HBcAb). If the test results were negative, they were then divided into two groups and vaccinated with either recombinant Cuban or Korean vaccine. One month after the latest vaccine dose, we assessed the antibody to hepatitis B surface antigen (anti-HBs Ab) titer. 347 subjects (207 men, 140 women) were studied. All participants were more than 15 years old. The mean±SD age of participants was 32.3±7.2 years. The mean±SD titer of anti-HBs Ab was 253.6±95.4 MIU/mL in Cuban group and 315.7±163.5 in Korean vaccine group (P<0.001). The Korean vaccine induced a higher titer of antibody in ages less than 40. Four (2.3%) subjects in the Cuban and 2 (1.1%) in the Korean vaccine group did not develop protection. The Korean vaccine induces more protection and higher titer in subjects aged less than 40 years than the Cuban vaccine. Therefore, we believe that the Korean hepatitis B vaccine is a better choice in comparison to the Cuban vaccine for prevention of hepatitis B virus infection and mass vaccination in our country.

Hemodialysis (HD) patients seem to be at considerable risk of acquiring HBV infection. This study was carried out to determine the seroprevalence of hepatitis B virus (HBV) infection in hemodialysis patients living in the province of Tehran and to investigate the association between viral hepatitis B and the probable risk factors for HD patients. From June to August 2005, this study was done on the entire HD population of the province of Tehran (2630 patients; 1505 males and 1125 females, mean age: 53.4 years). Social and demographic data, date of onset of HD, length of time receiving HD services, history of a kidney transplant, multiple sex partners, and other probable risk factors were evaluated. Blood samples were tested for liver enzyme levels as well as human immunodeficiency virus (HIV) 1, HIV 2, hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis C antibody (anti-HCV). A total of 64 patients were HBsAg positive (2.4%). The male-to-female ratio was 45/19 for HBsAg-positive patients and 1462/1104 for the remaining patients (P = 0.03), respectively. Except for nationality (P < 0.001), previous kidney transplants (P < 0.001), age (P < 0.001), and transient HD (P < 0.001), no association was found between HBV infection and probable risk factors. Common erythropoietin administration, blood testing for transfusion purposes, implementation of universal precaution in dialysis units as well as the use of dedicated machines for HBV-infected patients has led to a decreasing trend of HBV infection. Periodic surveillance of HBV infection among patients undergoing hemodialysis is strongly recommended.

There is no overall estimate of hepatitis C infection (HCV) in Iran. We reviewed all of the published and unpublished evidence related to HCV infection in Iran in order to accurately estimate the prevalence of HCV infection in the Iranian general population to inform future health system programs. In this systematic review, all papers, medical congresses, HCV-related reports, projects of Iranian research centers and medical universities, reports from the Deputy for Health Affairs (published or unpublished), and online theses about HCV in Iran were included. We selected descriptive and analytic cross-sectional studies and surveys related to the prevalence of HCV infection in the Iranian general population between 2001 and 2008 that have sufficiently declared objectives, proper sampling methods with identical and valid measurement instruments for all study subjects and proper analysis methods regarding sampling design and demographic adjustments. We used a survey data analysis method to estimate the national prevalence rate. From the 6,431 studies we investigated, eight eligible studies reported a prevalence of HCV infection in the general population. They were from six (out of 30) provinces, in which about 43 percent of the country''s population lives. We calculated that the HCV infection prevalence rate in Iran is 0.16% (95% confidence interval [CI]: 0%-0.59%). In comparison with similar studies, the prevalence of HCV infection in Iran is low. This might be a result of having prevention programs for high-risk groups and strict blood screening programs.

To investigate the clinical charcteristics and treatment response of patients with chronic coinfection of hepatitis B virus (HBV) and hepatitis C virus (HCV). The study included nine consecutive patients with chronic HBV/HCV coinfection. Diagnosis was performed by liver biopsy and/or clinical and laboratory evaluation. Six patients received 48 weeks of pegylated interferon (Peg-IFN) monotherapy or combination therapy with Peg-IFN plus ribavirin according to the dominant virus. The dominant infection was hepatitis C in six cases. Of the four patients who completed the treatment and follow-up period, only one had a sustained viral response (SVR) to HCV, but unfortunately, this was accompanied by a reactivation of HBV-DNA without flaring of hepatitis. No patient had an HBV-DNA response. Another two patients are still in the follow-up period. One of these patients had an undetectable level of HCV-RNA, and the other had an undetectable level of HBV-DNA at baseline. At the end of treatment, both HBV-DNA and HCV-RNA were negative in these patients. The HBV-DNA-negative patient showed a transient HBV-DNA positivity after clearance of HCV-RNA. In the majority of HBV/HCV coinfected cases in our sample, HCV was the dominant virus. Currently, the standard treatment regimens are not effective for clearance of HBV and/or HCV. HCV clearance may induce HBV reactivation without flaring of hepatitis.

The aim of this study was to evaluate infants'' immune response to the hepatitis B virus (HBV) vaccination. This was a cross-sectional descriptive study carried out on 215 infants 7-12 months of age in the Golestan province in northeastern Iran in 2006. These children had already received the complete three-dose vaccination against hepatitis B. The serumal levels of hepatitis B surface antigen antibody (anti-HBs), hepatitis B core antibody (anti-HBc), and hepatitis B surface antigen (HBsAg) were determined using enzyme-linked immunosorbent assay (ELISA). Of all 215 participants, 55.3% were males. All of them were 7-12 months old. Eighty-six percent of the studied cases responded positively to the vaccination. The response rate for males was lower than the rate for females (P = 0.34). We found that non-response to HBV vaccination is an important issue in our area. Further studies are needed to assess the influence of major factors such as the vaccination procedure, the type and site of inoculation, and vaccine preservation and transportation.

Hepatitis E virus (HEV) is mainly the causative agent of waterborne epidemics, but some authors have found that patients on chronic hemodialysis have an increased risk of exposure to HEV. We conducted this study to reveal HEV seroprevalence in hemodialysis patients as a specific group in Iran, and to evaluate age, duration of hemodialysis, and the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in them. The presence of immunoglobulin G antibodies to HEV(anti-HEV IgG) was measured by enzyme-linked immunosorbent assay (ELISA) in the patients'' sera. Both ALT and AST serum levels were measured. The duration of hemodialysis and the age and sex of the participants were obtained from the medical records of patients, and the data were made into quantitative variables, which were expressed as mean ± standard deviation (SD). 43 patients (29 males and 14 females) enrolled in this study. 3 of these patients (7% of the sample) were HEV antibody positive (2 males and 1 female). The mean levels of AST and ALT in all of the studied patients were 22.3 ± 23.3 IU/L and 21.3 ± 27.6 IU/L, respectively. An association between HEV positivity and duration of hemodialysis was revealed by our results, but there was no significant association between HEV antibody positivity and patient age. All 3 patients who were positive for anti-HEV antibody in our study also had elevated liver enzymes. The finding that HEV infection was associated with elevated liver enzymes in patients who were on chronic hemodialysis may indicate that hemodialysis is a route for HEV transmission, and more controlled studies are needed to explore this association in Iran.

Clinical resistance to lamivudine (LAM) can lead to exacerbation and high-level cross-resistance to all L-nucleotides in chronic hepatitis B patients, but the underlying reasons for this remain unclear. This study aimed to compare the clinicopathological features of LAM-resistant and LAM-responsive patients and tried to detect the tissue levels of Glutathione S-transferas pi (GSTpi) in the naive biopsies of both groups to find possible risk factors of LAM resistance. Patients with naive biopsies and successful LAM therapy for one year were included as controls (n = 25), and patients who interrupted their LAM regimen during clinical relapse (n = 16) were considered cases. Clinicopathological characteristics of patients and GSTpi levels were compared between the two groups by an immunohistochemical analysis. Although no significant difference was detected between tissue levels of GSTpi in cases and controls, statistical tests showed a significant role of prior interferon-alpha (IFN-a) (P = 0.024, odds ratio [OR] = 5.25) therapy and higher HAI scores (P = 0.05, OR = 4.08) of naive biopsy samples and emphasized their roles as two relative risk factors for LAM resistance. Half of the cases showed higher HAI scores (> 6) whereas only 19% of controls showed the same pattern. A higher rate of LAM withdrawal was detected in patients with a history of IFN therapy (P = 0.024), and a history of IFN therapy was considered to be a possible risk factor of LAM withdrawal (OR = 5.21). Higher HAI scores were also detected in patients with a history of INF therapy (P = 0.041, OR = 4.8), and a history of INF therapy was considered to be a possible risk factor of tyrosine-methionine-aspartate-aspartate (YMDD) mutation (OR = 3.83). This study has introduced two possible new predictive markers of LAM resistance in chronic hepatitis patients, which should be confirmed in future studies with larger groups to optimize the best pharmacotherapy regimens in chronic hepatitis B patients and may help physicians reduce the risk of adverse drug reactions.