Hepatitis Monthly
Volume:10 Issue: 4, Autumn 2010

Hepatocellular carcinoma (HCC) is a well known consequence of chronic liver diseases (CLD). The aim of this study was to extract the HCC risk incidence in Kerman province, located in southern part of Iran and compare the data with other parts of the country. All medical records regarding the HCC were collected through the hospital based and/ or outpatient services in public or private centers. The records of all oncology, radiotherapy and pathology centers in Kerman province were actively searched between 1999 and 2006. Annual incidence of HCC around the country was calculated, using the national cancer registry database provided by the Health Ministry of I.R. Iran during 2005-2006. Using the stata version 8, the crude and age-sex standardized annual incidence risks were computed. The crude annual incidence of HCC per 100,000 persons in Kerman and Iran was 0.522 (95%CI: 0.238-0.88) and 0.199 (95%CI: 0.167-0.234) respectively. The age and sex-adjusted annual incidence of HCC in Kerman and Iran were 0.7 (95%CI: 0.4-1.1) and 0.2 (95%CI: 0.2-0.3) per 100,000 persons respectively (p<0.01). The mean age of patients in Kerman was around 5.5 years less than other parts of Iran (56.17 ± 18.32 years versus 61.68 ± 14.62 years; P=0.004). Generally the incidence of HCC is not so much high in Iran; however the higher incidence of HCC in Kerman and also lower age of onset mandates further research to detect its risk factors in this part of country.

AIM Since hepatitis C virus (HCV) core protein (Core), protein kinase R (PKR) and signal transducer and activator of transcription 3 (STAT3) all play a relevant role in the pathogenesis of HCV persistent infection and hepatocellular carcinoma (HCC), and PKR could interact with Core. Here we further investigate the associations among Core and STAT3 and PKR, and and the domains of them involved in the interactions. Methods Expression levels of HCV Core, PKR, eukaryotic initiation factor 2 (eIF-2α), phosphorylated eIF-2α (p-eIF-2α), STAT3 and phosphorylated-STAT3 (p-STAT3) were compared between Huh-7 and replicon cell-Huh-7 cells harbouring selecting full-length of genotype 1b HCV genomes. Co-immunoprecipitation and glutathione S-transferase (GST) pull-down assay were done among PKR, STAT3 and Core. Results HCV could induce the expression of STAT3 and the activity of PKR (p-eIF-2α). Either of Core, STAT3 and PKR can interact with one another. The N-terminal 1-126 amino acid (aa) of HCV Core contributed to Core/STAT3 interaction and only the full-length of PKR binds to STAT3 and p-STAT3. Conclusions These findings suggest that Core, PKR and STAT3 can interact with each other. Core plays its function through both of PKR and STAT3; or Core binding to STAT3 and activating STAT3 might be due to Core/PKR interaction. The distinct interactions among them might play an important role and provide a new molecular mechanism in the pathogenesis of HCV persistent infection and HCV-related HCC

An impaired lipid metabolism is often found in patients with chronic liver diseases. The aim of this study was to determine lipid profiles in patients with cirrhosis and control subjects and to relate the findings to the severity of the cirrhosis. This study was a descriptive-analytical research. 50 patients with cirrhosis were considered as «case» and matched non-cirrhotic admitted patients were regarded as «control». A questionnaire was used containing personal characteristics, etiology of cirrhosis, pathologic criteria of CHILD and MELD and lipid profile (total cholesterol, LDL, HDL and triglyceride). Data were analysed using SPSS software. In patients with cirrhosis, there was a significant decrease in triglyceride, total cholesterol, LDL and HDL serum levels compared with controls (mean 82 vs. 187, 138 vs. 184, 80 vs. 137 and 40 vs. 44, respectively; all p<0. 05). Comparison of lipid profile with pathologic progression of cirrhosis revealed that with the exception of TG, serum level of lipids diminishes linearly with progression of liver damage (ANOVA, p < 0. 05). The decreases in the levels of serum total cholesterol, LDL and HDL in patients with cirrhosis were related to the increasing severity of cirrhosis.

We aimed to evaluate the effectiveness of nucleoside analogues such as lamivudine, adefovir, entacavir and tenofovir in the patients with chronic hepatitis B who failed to respond to Interferon therapy and develop relapses. A total of 73 patients with hepatitis B who were followed up in hepatitis outpatient clinic in our hospital, subsequently received nucleoside analogues therapy were evaluated retrospectively. The biochemical and virologic response rates were evaluated in 3rd and 12th months and our results were compared with naive patients. There were 29 (39.7%) HBeAg positive and 44 (60.3%) HBeAg negative patients and their mean age were 35.8 (±13.4) years. Thirty-three, 18, 13 and 9 of them received entacavir, tenofovir, lamivudine and adefovir treatment, respectively. In HBeAg negative patients; the early biochemical response and virologic response in 3rd and 12th months were detected as 91% and 98%; as 93% and 73%, respectively. In HBeAg positive patients the early biochemical response and virologic response in 3rd and 12th months were 83% and 97%; as 90% and 48%, respectively. In chronic hepatitis B therapy for those patients nucleoside analogues can be preferred. There are disadvantages such as risk for developing resistance during therapy, reduced HBeAg seroconversion compared to interferons and therapy's ambiguous duration. In our study, in HBeAg negative patients who received nucleoside analogues, in one year of lamuvidin therapy a lower biochemical response was detected compared to other therapies, whereas in HBeAg positive patients in one year of tenofovir therapy the virologic response was higher than other therapies.

To investigate the prevalence and patterns of Precore (PC) and Basal Core Promoter (BCP) mutations and their clinical significance in patients with genotype D chronic hepatitis B infection in Fars Province, Southern Iran. From January 2007 to March 2008, 44 patients with chronic hepatitis B infection, referred to the hepatology clinics affiliated with Shiraz University of Medical Sciences, were evaluated. All Patients were HBe Ag negative and HBe Ab positive. BCP and PC mutations in these patients were determined to be correlated, by means of clinical phenotype and laboratory tests. The mean age of patients was 37.21± 10.54 years. Twenty-seven patients (61.4%) had no mutations, while 17 patients (38.6%) had mutations in the PC and BCP regions. The mean serum alanine aminotransferase (ALT) level in mutation-free patients was 59.74±55.86 IUL, while patients with PC and BCP mutations had a serum ALT level of 71.35 ± 59.49 IUL. The mean serum aspartate aminotransferase (AST) level in patients with mutations was higher than in patients without mutations (59.53±41.35 IUL vs.40.65±25.21 IUL). There was no statistically significant difference between the two groups in terms of age, sex, and liver enzyme levels (P > 0.05). Fourteen out of the 44 patients (31.8%) had mutations in the PC region G 1896A, and 17 patients (38.6%) had mutations in the BCP region. This study revealed a high prevalence of PC and BCP mutations in southern Iran. Although no statistically significant difference was noted in liver enzymes, those with mutations had higher liver enzymes in comparison with mutation- free patients.

Currently, vaccination is the most effective protective tool against hepatitis B virus (HBV) infection. Some studies have shown that positive results of hepatitis B virus surface antigen (HBsAg) test could be seen after vaccination. The aim of this study was to compare the incidence of positive results of HBsAg test after vaccination with two different hepatitis B recombinant vaccines. In this clinical trial study 62 healthy adult volunteers were randomly allocated to vaccinate with Engerix-B or Hepavax-Gene hepatitis B recombinant vaccine. Blood samples were drawn 1, 3, and 5 days after vaccination and tested for HBsAg using two different ELISA kits (Behring and Mega). HBsAg test was positive in 5, 3, and 2 participants of Engerix-B group in the 1st, 3rd, and 5th day after vaccination respectively using Behring ELISA kite; the test was positive only in one subject in Hepavax-Gene group in the 5th day after vaccination. No positive result was seen in any groups when Mega ELISA kite was used to test the specimens. Conclusion Our results showed transient HBsAg antigenemia after vaccination against hepatitis B. This condition depends on the type of vaccine and HBsAg diagnostic test.

Previous studies have demonstrated the dominance of genotype D/ayw in patients with hepatitis B virus infection in Turkey. The aim of the present study is to report for the first time, to identify genotype A2/adw2 of hepatitis B virus, in a patient who is a hepatitis B carrier in the inactive carrier state in Turkey. Hepatitis B virus DNA isolated from the serum sample was amplified by polymerase chain reaction. The polymerase gene segment of hepatitis B virus was directly sequenced. The distance matrix/UPGMA comparison was used for phylogenetic analysis and the genotype of the virus was identified accordingly. The subgenotype and subtype of hepatitis B virus were also detected. The genotyping of the patient revealed that the isolated hepatitis B virus was genotype A2/adw2. Inconsistently with the previous data from Turkey, although identification of A2/adw2 of hepatitis B virus is the first case. This data suggests that the transmission of another genotype except genotype D/subtype ayw of hepatitis B virus is possible in Turkey.

One of the extra-hepatic manifestations of hepatitis B virus (HBV) is polyarteritis nodosa (PAN). It may involve mediumand small-sized arteries in any organ. Coexistence of these two disease conditions may be life threatening, thus, both conditions should be treated. Herein, we report on a patient with severe PAN. The patient was an 18-year-old man with multiple progressive wounds in skin, who referred to Baqiyatallah Hospital. Skin biopsy showed vasculitis compatible with PAN. He had been treated with low dose prednisolone and lamivudin for three years; however, his condition deteriorated and ulcers in his leg became life-threatening. The hepatitis B Viral load was 17,000,000 copy/mL. The wound developed a superimposed resistant bacterial infection. He was then treated with two antiviral drugs (lamivudin 100 mg/day plus adofovir 10 mg/day), high dose cyclophosphamide (750 mg once monthly) and prednisolone (60 mg/day for one month). After six months, the viral load dropped to 100,000 copy/mL; the wounds were also improved. We concluded that high viral load of HBV associates with severity of PAN. We recommend combination therapy with two antiviral agents plus high dose immunosuppressive drugs until both disease conditions resolve remarkably.