Surface protein mutations in chronic hepatitis B patients who received hepatitis B vaccine therapy.

OBJECTIVE S: The aim of this study was to determine the correlation between vaccine therapy and appearance of mutations in hepatitis B surface antigen (HBsAg)-positive chronic hepatitis B virus (HBV) patients. MATERIALS AND METHODS: 16 patients received the HBV vaccine and another 16 individuals from the control group did not. The surface gene was amplified and directly sequenced from samples prior to vaccination and six months after the third dose. RESULTS: Only one patient lost HBsAg. 48 and 44 amino acid mutations were found before and after vaccine therapy in the vaccine group respectively, 51 of which (55.4%) occurred in immune epitopes: 5 were in B cell, 21 in T helper (Th), and 25 in cytotoxic T-lymphocyte (CTL) epitopes. In the control group, 35 and 41 amino acid substitutions were found before and after therapy, respectively. 32 (42%) of 76 amino acid changes occurred within immune epitopes. There were no differences in age, gender, and duration of chronicity in both patient and control groups in terms of the frequency and the patterns of mutations. CONCLUSION: In chronic carriers who already had HBsAg variants selected by the host-immune response, any immune stimulation by the vaccine had no effect on the chronic state of these patients or selected any remarkable escape mutants. Newer strategies should be considered based on third generation or the use of DNA vaccines or new adjuvants.

Epidemiology of hepatitis B, hepatitis C, and human immunodeficiency virus infecions in patients with beta-thalassemia in Iran: a multicenter study.

BACKGROUND: Though regular blood transfusion improves the overall survival of patients with beta-thalassemia, it carries a definite risk of infection with blood-borne viruses. We carried out this multicenter study to provide epidemiologic data on hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infection among Iranian beta-thalassemic patients. Moreover, HCV infection-associated risk factors were investigated in this population. METHODS: Seven hundred and thirty-two patients with beta-thalassemia major or beta-thalassemia intermedia, selected from five provinces of Iran including Tehran (n = 410), Kerman (n = 100), Qazvin (n = 95), Semnan (n = 81), and Zanjan (n = 46), were enrolled in this study. Using ELISA, their sera were tested for HBsAg, HBcAb, HBsAb, HCVAb, and HIVAb. The positive HCVAb results were confirmed by RIBA-2nd generation. RESULTS: The study sample consisted of 413 males and 319 females, with a mean +/- SD age of 17.9 +/- 9.0 years. One hundred forty-one (19.3%) patients were HCVAb positive; 11 (1.5%) were HBsAg positive. No one was HIVAb positive. Univariate analysis showed that beta-thalassemia major (P = 0.01), older age (P = 0.001), longer transfusion duration (P = 0.000), HBsAg seropositivity (P = 0.03), and higher serum ferritin level (P = 0.002) were significantly associated with a higher prevalence of HCV. Furthermore, the prevalence of HCV infection dropped significantly after the implementation of blood donors screening (22.8% vs. 2.6%; P = 0.000). Using multivariate analysis, beta-thalassemia major (P = 0.002), age (P < 0.001), serum ferritin level (P < 0.001), as well as consumption of unscreened blood (P = 0.003), were independent factors associated with HCV infection. CONCLUSION: The prevalence of HCV infection is much higher among Iranian beta-thalassemic patients as compared with HBV and HIV infections. Routine screening of donated blood for HCV is highly recommended.

Effect of oral naltrexone on pruritus in cholestatic patients.

AIM: To determine the efficacy and potential complications of oral naltrexone used in the treatment of pruritus in cholestatic patients and to compare them with other studies. METHODS: Thirty-four enrolled cholestatic patients complaining of pruritus were studied. In the initial phase, pruritus scores during day and night were evaluated. Subsequently, patients were given a placebo for one week followed by naltrexone for one week. In each therapeutic course (placebo or naltrexone) day and night pruritus scores were distinguished by a visual analogue scale (VAS) system and recorded in patients' questionnaires. RESULTS: Both naltrexone and placebo decreased VAS scores significantly. Naltrexone was more effective than placebo in decreasing VAS scores. Both day and night scores of pruritus decreased by half of the value prior to therapy in thirteen patients (38%). Daytime pruritus improved completely in two patients (5.9%), but no improvement in the nighttime values was observed in any patient. Sixteen patients (47%) suffered from naltrexone complications, eleven (32%) of them were related to its withdrawal. Complications were often mild. In the case of withdrawal, the complication was transient (within the first 24-28 h of therapy) and self-limited. We had to cease the drug in two cases (5.9%) because of severe withdrawal symptoms. CONCLUSION: Naltrexone can be used in the treatment of pruritus in cholestatic patients and is a safe drug showing few, mild and self-limited complications.

Effects of indomethacin on viral replication markers in asymptomatic carriers of hepatitis B: a randomized, placebo-controlled trial.

OBJECTIVES: Previous studies have suggested some benefits of nonsteroidal antiinflammatory drugs (NSAIDs) use in patients with chronic viral hepatitis. We evaluated potential effects of indomethacin in asymptomatic carriers of hepatitis B surface antigen (HBsAg). DESIGN: Randomized, placebo-controlled, double-masked clinical trial. METHODS: One hundred and twelve patients who were confirmed to be HBsAg carriers for at least 6 months and had normal liver function tests, normal abdominal sonography, and no sign of cirrhosis were randomly assigned into two groups. One group (56 participants, mean age (+/-SD) 31.7 (+/-9.6) yr, 29 male, mean serum alanine aminotransferase (ALT) (+/-SD) 24.9 (+/-9.2)) received indomethacin capsules (25 mg) three times daily and the other group (56 participants, mean age (+/-SD) 33.8 (+/-10.2) yr, 33 male, mean serum ALT (+/-SD) 24.5 (+/-8.7)) took placebo capsules with identical package and appearance. All participants were under treatment for 6 months and were followed 3 months thereafter. Statistical analyses were performed both by intention-to-treat and on-treatment methods. RESULTS: Nine participants in the indomethacin group (16%) and 8 in the placebo group (14%) did not complete the trial. HBsAg seroconversion did not differ by treatment group (2 subjects in each group became seronegative). Hepatitis B virus DNA (HBV-DNA) became negative in sera of 7 participants in the indomethacin group but only in 1 in the placebo group (intention-to-treat p= 0.06; on-treatment p= 0.03). Seroconversion of HBeAg to anti-HBe occurred only in 5 participants in the indomethacin group (intention-to-treat p= 0.06; on-treatment p= 0.03). Adverse events included one case of hepatotoxicity and two cases of gastritis in the indomethacin group and one suspected gastritis in the placebo group. CONCLUSIONS: We suggest use of indomethacin only in the subgroup of asymptomatic HBsAg carriers who have detectable HBV-DNA or HBeAg in their sera.

Clinical and histological features of nonalcoholic steatohepatitis in Iranian patients.

BACKGROUND: Although several studies have been performed on risk factors and natural course of NASH, it seems that NASH tends to be more than a disease confined to strict boundaries. The objective of this study was to assess the clinical and paraclinical features and risk factors for non-alcoholic steatohepatitis (NASH) patients in an Iranian population METHODS: Patients with histologically confirmed NASH who had elevated liver aminotransaminases, negative serologic markers of viral or autoimmune hepatitis and no findings in favor of metabolic liver disease were enrolled. A careful history was taken regarding alcohol intake. RESULTS: 53 patients consisting of 32 male and 21 female entered the study. The mean age was 37.8 +/- 11.3 years. Twenty-six patients (55.3%) were overweight, 15 (31.9%) obese, 40 (75.5%) dyslipidemic, and three patients (5.7%) were diabetic. Liver biopsy showed mild steatosis in 35.7%, moderate steatosis in 53.6%, and severe forms in 10.7%. In 80.2% of patients, portal inflammation was present, and 9.4% had cirrhosis. The amount of increase in liver enzymes bore no relationship with fibrosis, portal inflammation, and degree of steatosis. CONCLUSIONS: The patients in our study showed a male predominancy and were somewhat younger than other studies.

The efficacy of furazolidone-based quadruple therapy for eradication of Helicobacter pylori infection in Iranian patients resistant to metronidazole-based quadruple therapy.

BACKGROUND: Furazolidone has recently shown promising efficacy in H. pylori eradication and has replaced metronidazole in different eradication regimens especially in countries, like Iran, with high prevalence of metronidazole resistance and where clarithromycin is expensive and hardly available. This study tries to determine the efficacy of a quadruple therapy based on furazolidone as a second line treatment. MATERIAL/METHODS: 90 consecutive patients with a prior history of H. pylori infection who had failed to respond to a 14 day course of metronidazole-based quadruple therapy were included to take a two week quadruple therapy consisting of furazolidone, bismuth subcitrate, amoxicillin and omeprazole. Eradication was described as negative 14C-urea breath test, 4 to 6 weeks after end of the treatment. RESULTS: 89 of 90 patients completed the treatment course. The total eradication rate was 70/89 (78.7%). 35/49 (71.4%) of male patients and 35/40 (87.5%) of female patients had successful eradication. Eradication rate did not have any significant relationship with patient's sex (p>0.05). All patients had at least one upper GI endoscopy before the treatment by which they were categorised into three groups: duodenal ulcer (DU, 78.9%), gastric ulcer(GU, 11.1%) and non-ulcer dyspepsia (NUD, 10%). Eradication rates was different in these groups, but not significantly (p>0.05). Eradication rate was significantly lower in smokers (p<0.05, OR=3.12). CONCLUSIONS: Furazolidone can replace metronidazole successfully in those patients who have failed to respond to metronidazole-based quadruple therapy and it is well tolerated. We recommend it, especially in countries where clarithromycin is expensive or not available.