Hepatitis Monthly
Volume:9 Issue: 4, Autumn 2009

To investigate the efficacy and safety of a gemcitabine plus oxaliplatin combination regimen and a floxuridine plus oxaliplatin combination regimen used in transcatheter arterial chemoembolization for patients with inoperable hepatocellular carcinoma (HCC). From October 2005 to October 2008, 122 chemonaïve patients with newly diagnosed, inoperable HCC were randomized into a gemcitabine plus oxaliplatin combination regimen group (GO group) or a floxuridine plus oxaliplatin combination regimen group (FO group). The GO group was treated with 1,600 mg of gemcitabine and 200 mg of oxaliplatin, and the FO group was treated with 1,000 mg of floxuridine and 200 mg of oxaliplatin. Both groups were treated with glutin and iodolipol as the embolic agent in the transcatheter arterial chemoembolization (TACE). The progression-free survival, the median survival period, and the median time to progress had no significant difference between the two groups. However, there was a significant difference in the incidence of grade 3/4 thrombocytopenia between the two groups (P = 0.002). Grade 3/4 hematologic toxicity was observed only in the GO group. One patient (1.7%) with grade 3/4 leukopenia and 6 patients (10%) with grade 3/4 thrombocytopenia were observed. A multivariate analysis revealed that the Eastern Cooperative Oncology Group (ECOG) scores and portal vein thrombosis were the only independent prognostic factors that affected progression-free survival. The floxuridine plus oxaliplatin combination regimen was tolerated better than the gemcitabine plus oxaliplatin combination regimen used in TACE.

Hepatitis E virus (HEV) infection causes an acute, self-limiting hepatitis that is associated with high mortality, especially in pregnant women. Our previous clinical experiences indicated that there was a high prevalence of hepatitis A virus (HAV) among school-age children in the city of Ahvaz (in the southwest of Iran). Due to the fact that HEV is transmitted generally by the same route as HAV, the present study was performed to determine the seroprevalence of HEV among school-age children in Ahvaz. In a cross-sectional study, the seroprevalence of anti-HEV antibodies was determined in sera from 566 children aged 6-15 years by enzyme-linked immunosorbent assay (ELISA). The study population included 257 (45.4%) males and 309 (54.6%) females. Anti-HEV antibodies were detected in 48 children (8.5%; 95% CI, 6.3-11.1). The seroprevalence of HEV was not statistically different between males and females or between different age groups. HEV is relatively prevalent in children that live in the southwest of Iran, and further studies are needed to investigate the seroprevalence of HEV in other age groups.

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver condition that is characterized by significant hepatic lipid deposition with or without necroinflammation and fibrosis. Researchers have proposed that oxidative stress may play a role in pathogenesis of NAFLD, and there is challenging evidence for the efficacy of antioxidant agents in its treatment. Therefore, we tried silymarin as an antioxidant in a randomized controlled trial for a group of patients with NAFLD. During an 18-month period, a placebo-controlled study was conducted among patients with nonalcoholic steatohepatitis (NASH) referred to the Ahvaz Jundishapour University Hospital (AJSUH) and Hepatitis Clinic from 2007 to 2008. Based on sonography findings and elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels or liver biopsy, we selected 100 NASH patients who were referred to our center for management of liver disease. Patients who had positive viral markers and other hepatic diseases and patients who had ingested ethanol or drugs known to produce fatty liver disease within the previous 6 months were excluded from the study. Patients were randomized to two groups: Group A received a placebo, and Group B received treatment with 280 mg of silymarin. Treatment was continued for 24 weeks, and cases were evaluated every 4 weeks in the outpatient clinic. A total of 100 subjects who met the inclusion and exclusion criteria were included in the analysis. Group A (50 cases, 29 males and 21 females) and Group B (50 cases, 28 males and 22 females). The mean age was 39.0 ± 10.70 years for Group A and 39.28 ± 11.117 years for Group B. The age range for both groups was 20 to 50 years. The mean serum ALT levels in the silymarin group were 113.03 and 73.14 IU/mL before and after treatment, respectively (P = 0.001). ALT normalization (ALT < 40) was observed in 18% and 52% of patients in Groups A and B, respectively (P = 0.001). AST normalization (AST < 40) was observed in 20% of cases in the placebo group and 62% of cases in the silymarintreated group (P = 0.0001). No significant side effects were reported in our cases. Silymarin treatment appears to be significantly effective in biochemical improvement and decreasing transaminases levels in patients with NAFLD.

Chronic liver diseases could lead to cirrhosis and related complications. Histological diagnosis by liver biopsy has long been the gold standard for assessing the degree of fibrosis and diagnosis of cirrhosis, but it is an invasive procedure with inherent risk and sampling variability. The aim of this study was to assess the ability of the artificial neural network (ANN) to predict the presence or absence of cirrhosis in patients with chronic hepatitis B by using routine laboratory findings. 114 chronic hepatitis B patients who were admitted between 1996 and 2006 at Loghman Hakim hospital and the Tehran Hepatitis Center were evaluated. The disease was confirmed by hepatitis B virus (HBV) DNA, liver biopsies, and biochemistry values, which were obtained from all of patients. Back propagation ANN analyses were carried out by training the networks with the data. The patients were divided into two groups. The first group (92 patients) included two thirds of the cirrhotic patients (12 patients) and two thirds of the non-cirrhotic patients (80 patients) in a randomized rout. Ascitis, edema, pruritus, splenomegaly, and hepatomegaly were present in 26.3%, 31.6%, 21.1%, 63.2%, and 0% of cirrhotic patients, respectively, and 0%, 0%, 3.2%, 2.4%, and 0.8% of non-cirrhotic patients, respectively. The sensitivity, specificity, and positive and negative predictive ANN values in comparison with liver biopsy in the diagnosis of cirrhotic patients due to chronic HBV were 71.43%, 84.45%, 71.43%, and 95%, respectively. In chronic hepatitis B patients, if the ANN value of certain laboratory manifestations is negative, there will be a 95% chance of having a negative liver biopsy.

Most studies on the prevalence of transfusion-transmissible infections (TTIs) have been done on preselected blood donors. There is paucity of information on the prevalence of these TTIs in the general population in Port Harcourt, Nigeria. A total of 1,500 apparently healthy individuals aged 17-50 years consisting of 701 (46.7%) males and 799 (53.3%) females were tested for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) using Determine and Genie II HIV-1/HIV-2, Clinotech hepatitis B surface antigen (HBsAg), and HCV kits. Prevalence rates of 1.7%, 2.1%, and 0.1% were obtained for HIV, HBV, and HCV, respectively. A breakdown of HIV prevalence gave HIV-1 (1.1%), HIV-2 (0.27%), and HIV-1 /2 (0.33%). From the 1,500 subjects tested, 357 (23.8%) belong to the Ijaw, 408 (27.2%) to Ikwerre, 201(13.4%) to Ogoni/Eleme, 75 (5.0%) Ekpeye and 459(30.6%) belong to the other ethnic groups. Other ethnic groups accounted for the highest prevalence of HIV and HBsAg. Youths aged 21 to 30 constituted the highest number of HIV and hepatitis infections. Of the 23 subjects positive for HIV, 16 (1.2%) had HIV-1, 4 (0.3%) had HIV-2, and 5 (0.5%) had the HIV-1/2. Of the 1,500 subjects tested, 0.2% had HIV and HBV co-infection. Chi-square analysis indicated that age was a risk factor for the transmission of the three transmissible infections (P < 0.01, P < 0.05, and P < 0.05 for HIV, HBsAg, and HCV, respectively). Gender had an influence on HIV and HBsAg (P < 0.05). There was also a positive association between the ethnic groups and the TTIs (χ2 = 18.136, P < 0.01 for HIV; χ2 = 2.785, P < 0.05 for HBsAg; and χ2 = 2.411, P < 0.05 for HCV). The 0.1% prevalence of HCV in this study occurred exclusively among nonnatives. This study has provided epidemiological data on some transfusion-transmissible viral infections in Port Harcourt and has identified some risk factors associated with it. To ensure safety in blood-transfusion practices, selection and screening of donors within the high-risk groups, especially individuals 21 to 30 years old, should be thorough and in accordance with the approved safety guidelines.

Hepatitis G virus (HGV) has a worldwide distribution, and the prevalence rates among blood donors and high-risk groups are different. The purpose of this study was to assess the frequency of the HGV infection in blood donors as a blood borne pathogen and in high-risk groups (multitransfused patients), such as thalassemic, hemophillic, and hemodialysis patients. 400 Iranian (Tehran Blood Transfusion Center, 2004) blood donors were tested for HGV RNA by a reverse transcriptase chain reaction (RT-PCR) method. The participants were negative in blood screening tests for hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (anti- HCV), human immunodeficiency virus (HIV) Ag/Ab, and Rapid Plasma Reagin (RPR). HGV RNA positivity was surveyed in 40 thalassaemic, 16 hemophilic, and 46 hemodialysis patients by RT-PCR. To assess the frequency of infection, the prevalence of HGV RNA positive cases per 100 donors/patients with 95% confidence intervals (95% CI) were calculated. P values were estimated with chi-square tests. 19 (4.8%; 95% CI: 2.9-6.5%) out of 400 blood donors samples were HGV RNA positive. The prevalence of HGV infection was 5.28% (13 out of 243) in repeat donors, 4.12% (4 in 99) in lapsed donors, and 3.50% (2 out of 58) in first-time blood donors. The combined prevalence of HGV infection in these groups of patients was 16 (15.7%; 95% CI: 8.3-23.1%) out of 102 samples. HGV RNA frequency was 1 out of 40 (2.5%; 95% CI: 1.8-3.2%) thalassemic patients, 15 out of 46 (32.6%; 95% CI: 16.8-48.4%) hemodialysis patients, and 0 out of 16 hemophilics patients. The prevalence of HGV RNA in the high-risk population was 15.7% and nearly 3 times more than blood donors (4.8%). These data indicate the possibility of parenteral transmission of HGV, especially by transfusion of blood and blood components. Decisions to screen blood supplies for a transfusion-transmitted infection agent should be based on sufficient benefits for recipients.

Hepatitis B virus (HBV) and hepatitis D virus (HDV) infections are major health problems in Iran. Preliminary reports indicate that HDV infection, a satellite virus of HBV, exists in this area. However, its prevalence in patients with different types of liver diseases has not been studied in detail. This study was carried out to determine the seroprevalence of HDV among individuals who tested positive for hepatitis B surface antigen (HBsAg) in a southwestern province of Iran. In this cross-sectional study a total of 1,725 consecutive patients with HBV liver diseases attending the Ahwaz JundiShapur University Hospitals (AJSUH) and Hepatitis Clinics from 2002 to 2008 were included. We performed tests for HBV and HDV serum markers, using commercially available enzyme-linked immunosorbent assay kits. Patients were split into two groups according to their HDV antibody (anti-HDV) status (HDV positive or negative). The collected data were coded, and the statistical analyses were conducted. The mean age of the patients was 37 ± 13/8 years. There were 1,157 males and 568 females. Of the 1,725 patients with HBV liver disease, 150 were found to be reactive for anti-delta antibodies, yielding an overall HDV seroprevalence of 11.5%. Anti-HDV was found in 3.59% of patients with inactive chronic hepatitis, 45.5% of patients with chronic active hepatitis, and 43.2% of cirrhotic and hepatocellular carcinoma patients (P < 0.001). A higher proportion of individuals testing positive for antibodies to HDV were observed among males (72%) than among females (28%). The patients without HDV infection were younger than anti-HDV-positive/HBsAg-positive patients (P < 0.01). HDV infection was common in patients with HBV in our community. All HBV patients should be screened for HDV infection. The results indicate that HDV co-infection was related to the severity of the liver disease. More studies designed to elucidate HDV''s epidemiology are needed.

The duration of protection provided by hepatitis B (HB) vaccine is still unknown but can be estimated indirectly by measuring the anamnestic immune response to booster doses of the vaccine. We searched electronic databases and conference databases up to December 2008. We also screened reference lists of articles and contacted the authors and vaccine manufacturers for additional references. We included randomized and nonrandomized studies assessing the anamnestic immune response to the booster of HB vaccine in healthy participants 5 years or more after initial vaccination. The meta-analysis included 34 studies with 53 intervention groups and 4,479 individuals. The protective antibodies induced by initial vaccination waned over time; however, nonprotected vaccinees who had lost their antibodies to hepatitis B surface antigen (anti-HBs) over time responded strongly to the booster dose. The seroprotection rate of HB vaccine after the primary vaccination was 98.00% [95% confidence interval (CI): 95.32%, 99.52%] after 5 years, 96.88% [95% CI: 94.61%, 98.50%] after 6-10 years, 88.80% [95% CI: 79.84%, 95.08%] after 11-15 years, and 85.12% [95% CI: 82.18%, 88.20%] after 16-20 years. According to these findings, the protection provided by HB vaccine is dependent on immune memory rather than anti-HBs titer; therefore, recommendations for booster doses should be based on immune memory instead of the persistence of antibody. In addition, a full course of HB vaccination can induce a long-term and strong serologic immunity against hepatitis B virus infection. Nonetheless, the decreasing trend of seroprotection during the first and second decades after immunization indicates that the long-term immunity induced by HB vaccine may diminish over time. This issue raises the possibility of the need for a booster dose, although universal revaccination does not seem necessary during the first and second decades after primary vaccination in healthy individuals with normal immune status who had fully responded to a complete course of the vaccine.

Hepatitis D virus (HDV) infection is a major concern among hemodialysis (HDi) subjects, particularly the hepatitis B surface antigen (HBsAg) positive patients; in HBsAg-positive subjects HDV can be transmitted at serum dilutions as high as 10-11 (1) and HBsAg-positive HDi patients stand therefore a very high risk of becoming infected with HDV through blood contamination of the hemodialysis machinery or through transfusions. Despite the importance of the problem studies of HDV in HDi are limited, the reported frequency of HDV infection among HDi patients is different throughout the world and there is no definite standard protocol to manage disease in these patients. The following represent important issues when considering HDV infection among HDi subjects: 1) High risk of HDV/ hepatitis B virus (HBV) transmission due to chronic transfusion or blood exchanges during dialysis 2) High mortality and morbidity rates 3) difficulties in the diagnosis of HDV in HDi patients 4) Irreversible complications 5) Uncertain methods for treatments. Clearly the absence of a definite standard protocol for effective management of HDV infection in HDi subjects stems from limited research on this matter. As HDV infection in HD patients has been largely neglected globally, in order to gain knowledge on this issue we carried out a world-wide investigation to determine the magnitude as well as the disease burden of HDV infection among HDi subjects with the ultimate goal to provide guidelines to manage HDV infection in this setting. We reviewed all the related studies on "HDV and hemodialysis" "renal failure" by searching the MEDLINE. Forty-seven manuscripts were retrieved in total. After a preliminary evaluation, we found only 18 articles that seemed relevant. These articles were analyzed in detail and the relevant data were gathered and summarized.

A 35-year-old man was referred to our center because of low grade fever, vomiting, yellow sclera, and tenderness in the upper-right quadrant of his abdomen. Laboratory tests showed a white blood cell (WBC) of 7100/µL, a platelet of 184,000/µL, an erythrocyte sedimentation rate (ESR) of 4 mm/h, an alanine aminotransferase (ALT) of 525 U/L, an aspartate aminotransferase AST of 142 U/L, a total bilirubin level of 4.23 mg/dL, and a direct bilirubin level of 3.16 mg/dL. Viral hepatitis markers, immunoglobuline M antibody to cytomegalovirus (anti-CMV IgM), Ebstein-Barr virus (EBV) IgM, and immunologic markers of autoimmune hepatitis were negative. The patient was diagnosed with acute hepatitis. Alkaline phosphatase was in the normal range throughout the course of the disease. Because of the patient''s occupation as a butcher and his history of eating semi-cooked sheep testes, serologic tests of brucellosis were conducted; the tests came out positive. We were concerned about the hepatotoxicity of standard regimens; therefore, we started treatment with streptomycin and ciprofloxacin regimens. Although liver enzyme had fallen and fever discontinued, the total and direct bilirubin concentrations in the patient''s serum both increased in spite of using 2 weeks of the abovementioned drug regimen. The elevation of bilirubin could have been due to drug hepatotoxicity. Alternatively, a regimen containing ciprofloxacin may have not have been efficient enough and may have had effects on the direct bilirubin concentration. Fortunately, within 8 weeks, progressive recovery was noticed. Brucellosis should be considered in the differential diagnosis of fever and hepatitis for those who live in endemic areas, especially if his/her job was at high risk for acquiring brucellosis. We recommend taking a careful occupational and behavioral history for patients with acute hepatitis syndrome. We assumed that ciprofloxacin was not suitable for brucella hepatitis treatment and also it may cause liver damage. The most appropriate treatment is a standard regimen containing doxycycline.