Hepatitis Monthly
Volume:9 Issue: 2, Spring 2009

Iran is a vast country with a population of different ethnic backgrounds. Therefore, a wide variation in the frequencies of hepatitis C virus (HCV) genotypes is expected to occur. To address this issue, 116 serum samples from HCV RNA-positive carriers representing different parts of Iran were collected from 2000-2005 and were tested by restriction fragment length polymorphism (RFLP) method. 1a, 1b, and 3a were the predominant genotypes circulating throughout the country with an overall prevalence rate of 61.2%, 13.8%, and 25%, respectively. The rate of HCV genotypes did not differ significantly in relation to demographic characters and risk factors. Sequence analysis of the core region from 16 HCV isolates representative of all genotypes confirmed the RFLP results, except for one sample, which submitted as a new subtype 3. The predominance of genotypes 1a and 3a in our population is in agreement with available data collected from blood donors and patients in Iran. Considering the even distribution of genotype 1a indicates that it has been presented and circulated in our community for a long time.

Hepatitis C virus (HCV) infection is treated with alpha interferon (IFN-α). The mechanisms by which IFN-α suppresses HCV replication are not well-known; only limited benefits are achieved with the therapy because the virus in turn, directs some mechanisms to resist the host IFN-α response. The present study was undertaken to determine the therapeutic effects of IFN-α 2b and to measure the serum level of antibody against IFN-α 2b (anti-IFN-α 2b) after treatment with IFN-α 2b in patients with chronic hepatitis C. The levels of HCV antibody (anti-HCV), HCV-RNA and anti-IFN-α 2b immunoglobulin G (IgG) in serum of 94 patients with chronic hepatitis C who were treated with IFN-α 2b (three 3-MU injections per week for 3 months), were measured in different courses of treatment. The total negative rates for anti-HCV and HCV-RNA were 33% (31/94) and 38% (36/94) in patients treated with IFN-α 2b, respectively. The rates for those treated with routine medications were 10% (4/40), 15% (6/40), respectively (P<0.01). After the first, second and third course of treatment with IFN-α 2b, the negative rates of anti-HCV, HCV-RNA in serum were 0% (0/94), 15% (14/94) and 21% (20/94), 23% (22/94) and 33% (31/94), 38% (36/94), respectively. After the treatment with IFN-α 2b, the total positive rate of anti-IFN-α 2b IgG was 5% (5/94). There was no significant difference between the two treatment groups (P>0.05). Among them, after treatment with IFN-α 2b for three, six and 12 months, the positive rates of anti-IFN-α 2b IgG were 0% (0/94), 2% (2/94), 5% (5/94), respectively. The productive ability of anti-IFN-α2b IgG was similar during the different courses of treatment with IFN-α 2b (P>0.05). IFN-α 2b has curative effect for patients with chronic hepatitis C and its therapeutic efficacy is better than that of routine treatments. Although IFN-α 2b has certain antigenicity, anti-IFN-α 2b IgG production is seen in only a few of patients during the course of treatment; the restrain effect of anti-IFN-α 2b IgG on the further treatment with IFN-α 2b is weak.

Thyroid dysfunction has been reported in patients with chronic viral hepatitis B and C before and after Alpha Interferon (IFNα) therapy and a high prevalence of anti hepatitis C virus (anti­-HCV) antibodies in patients with autoimmune thyroiditis has been shown. The aim of this study was to determine the rate of thyroid dysfunction in hepatitis B virus (HBV) and HCV infected patients during IFNα therapy and to compare them. In this prospective study, many patients with hepatitis B and C who had undergone IFNα therapy were studied. Eighteen cases of HBV and fifty-eight cases of HCV entered the study. Thyroid weight measurement, thyroid functional test and anti-thyroid antibodies assay were performed when the study initiated and were repeated after two, four and six months. Thyroid dysfunction was not seen in the HBV group. Only 6 (10.3%) cases of thyroid dysfunction were seen in HCV group (5 hypothyroidism and 1 thyroiditis). Four cases of them had positive levels of Tpo Ab before IFNα therapy. In the HBV group, only 1 (5.5%) patient had positive levels of Tpo Ab. However, at the end of the study, 3 (16.7%) patients had positive levels of Tpo Ab. In the HCV group, at the beginning of the treatment, 8 (13.8%) patients had Tpo Ab; but at the end of study, 14 (24.1%) cases became positive. During the IFNα therapy, mean weight of thyroid gland in both HCV and HBV groups were significantly increased (P<0.005, P<0.001, respectively). There were not any relationships between Tg Ab levels and duration of IFNα therapy. Patients with HCV are more susceptible to thyroid dysfunction during IFNα therapy than patients with HBV. As a result, screening of thyroid gland function and Tpo Ab titers in all patients with HCV before and during IFNα therapy may be necessary. However, this needs further studies in HBV patients.

Diagnostic modalities for hepatocellular carcinoma (HCC) as markers, sonography, and CT have contributed to the early detection of HCC but are still not sensitive enough. Human telomerase RNA subunit (hTERT-mRNA) has been identified in many cancers and claimed to be reactivated in HCC. To investigate hTERT-mRNA in the peripheral blood of HCC and chronic liver disease (CLD) patients and correlate its level with alpha feto protein (AFP), the serological marker for HCC. The study was conducted on 44 patients selected from the National Liver Institute. Patients included Group I (22 patients diagnosed to have HCC), Group II (22 patients with CLD), and 12 apparently healthy volunteers as controls (Group III). All selected individuals were subjected to history taking, a clinical examination, abdominal sonography and laboratory investigations as liver function tests (LFTs), cell blood count (CBC), hepatitis viral markers, AFP, and real-time polymerase chain reaction (PCR) Quantitative detection of -mRNA expression, encoding for telomerase catalytic subunit. There was a significant elevation of AFP levels in the HCC group compared to both the CLD and control groups (P < 0.00, P < 0.001). The mean hTERT-mRNA expression in HCC patients was significantly higher than both CLD patients and controls (P < 0.001, P < 0.001). hTERT-mRNA was correlated with AFP and tumor size (P < 0.05, P < 0.001). The AFP cutoff level (185 ng/ml) resulted in a 63.6% sensitivity, a 85.3% specificity; a 89.3% positive predictive value (PPV) level, a 76.2 % negative predictive value (NPV) level and a 83.4% accuracy for HCC prediction. The hTERT-mRNA cutoff level (112.5 copies/ml) showed a 77.3% sensitivity, a 97.1% specificity, a 98% PPV level, a 79.2 % NPV level, and an accuracy of 84% for HCC prediction. Combining hTERT-mRNA and AFP increased diagnostic accuracy to 90.5%. Both markers had a 84.1% sensitivity, a 86.4% specificity, a 86.4% PPV level, and a 88.3 % NPV level. hTERT-mRNA is thought to be superior to AFP in CLD patients and could be a marker for the early diagnosis of HCC. Combined hTERT-mRNA and AFP would augment early detection and successful follow-up of HCC patients.

Approximately 2-3% of the world population are infected with Hepatitis C Virus (HCV), which is the single most common indication for liver transplantation. This study aimed to determine the hepatitis C viral genotypes in HCV and Human Immunodeficiency Virus (HIV)/HCV positive patients in southern Iran. During 2004-2005, 273 patients who were infected with HCV were enrolled. Out of them, 250 subjects accepted blood sampling, and RNA extraction was undertaken for 238 subjects. Specific and nested polymerase chain reaction (PCR) - restriction fragment length polymorphisms (RFLPs) were performed to determine viral infection and genotype analysis. Liver enzymes including ALT and AST and the correlated risk factors were also determined. HCV-RNA was detected in 238 subjects. 50 had HIV/HCV co-infection, among whom 88%, 92% and 56% had positive a history of intravenous drug use, being in prison, and tattooing, respectively. 188 subjects showed HCV mono-infection, among whom 14.36% had major thalassemia and 37.76%, 16.48%, 3.72%, 2.65% and 29.25% had a history of being in prison, dental visits, hemophilia, hemodialysis and tattooing, respectively. Of 50 subjects with HIV/HCV co-infection, 40% were genotype la, 34% genotype 3a, and 26% genotype 1b, and one of the patients had mixed infection with 1b/3a. Among 188 subjects with HCV mono-infection, 44.1% were genotype la, 42.0% genotype 3a, and 13.8% genotype 1b. ALT and AST levels in all genotypes were compared. This study showed that Genotype 1a, followed by 3a and 1b, were the most prevalent types in both groups. No other genotypes were detected, but mixed infection with 3a/1b was observed in one of the HIV/HCV co-infected patients. HCV genotype had no correlation with mode of transmission or liver enzyme abnormalities.

Recently, many studies have reported that the plasma concentrations of natural anticoagulants, such as Antithrombin-III (AT-III), are altered in patients with chronic liver disease. In addition, the changes in the synthesis of AT-III occur in liver tissue and are associated with the extent of chronic hepatitis and cirrhosis. In this study, we analyzed the plasma level of АТ-III and serum activity of aminotransferase in 60 participants: 20 patients with chronic hepatitis, 20 patients with cirrhosis, and 20 healthy individuals (controls). Low levels of AT-III and elevated levels of aminotransferase activity were associated with both chronic hepatitis and cirrhosis. We found that among patients with elevated gamma glutamyl transferase (GGT) activity and chronic liver disease, the level of АТ-III in plasma was significantly lower in patients with chronic cirrhosis than in patients with chronic hepatitis (P < 0.05) and the level of АТ-III in plasma was lower in patients with liver disease in comparison to healthy participants (P < 0.001). The level of AT-III in patients with chronic liver disease may be used as a non-invasive factor for the laboratory diagnosis of cirrhosis.

Hepatitis C virus (HCV) has contaminated almost 170 million people worldwide. The HCV genotype is a good predictor of response to antiviral therapies and prognosis. In this study, we tried by using real-time polymerase chain reaction (RT-PCR) and melting curve analysis, to identify the HCV genotype isolated from affected patients. Using PCR and enzyme-linked immunosorbent assay (ELISA), serum sample of 310 suspicious patients with HCV were screened. Applying QIAamp Viral RNA Mini-kit, the viral RNA was collected from serum samples of 160 positive patients. Using one-step RT-PCR protocol, genotypes of the isolated HCV were specified according to the temperature melting (Tm) ranges. The frequency distribution of the 5 detected HCV genotypes (i.e., 1a/b, 2a/c, 4, 2b, and 3a) in 160 cases, were as follows: 77 (48.12%) were genotype 3a; 35(21.87%) had genotype 2b; 19 (11.87%) were 2a/c; 16 (10.0%) were 4; and 13 (8.12%) had genotype 1a/b. The most common HCV genotype in West Azerbaijan province in the Northwest of Iran is type 3a. We therefore concluded that it is possible to used PCR for routine HCV genotyping.

Hepatitis B virus (HBV) infection has been shown to induce several extra-hepatic lesions, especially through deposition of immune complexes in different organs, and renal involvement is one of the most important of them. The association between chronic HBV infection and glomerular diseases was first described by Combes et al. in 1971, and since then, overwhelming observations have been reported in the literature by authors from all over the world. HBV-related nephropathy is one of the HBV infection manifestations that has provoked high sensitivities around the world, most especially in terms of the management and treatment of the infection and the renal involvement. In this literature review, we tried to address all important issues related to HBV associated nephropathies.

Prevention of vertical transmission of hepatitis B virus (HBV) is extremely important because HBV infection in early life usually results in a chronic carrier state. The objective of this study was to assess the prevalence of HBV markers among pregnant women in the Middle Black Sea Region in Turkey. Between March 2003 and May 2004, 2654 women in the first trimester of pregnancy who attended the Samsun Maternity and Women''s Disease and Pediatrics Hospital pregnancy fallow-up clinics were enrolled into this study. Blood samples were taken and tested for hepatitis B surface antigen (HBsAg) by enzyme-linked immunosorbent assay (ELISA). Hepatitis B e antigen (HBeAg), antibody against hepatitis B e antigen (anti-HBe), hepatitis B surface antibody (anti-HBs), and total hepatitis B core antibody (anti-HBc) tests were studied for only HBsAg positive cases. HBsAg was found positive in 56 (2.1%; 95% CI: 1.6%-2.7%) and negative in 2598 (97.9%) women. Serological markers of HBV could be investigated in 40 HBsAg-positive cases. HBeAg and anti-HBe were found positive in 5 (12.5%; 95% CI: 2.3%-22.8%) and 31 (77.5%; 95% CI: 64.6%-90.4%) cases, respectively. In all the 40 patients, anti-HBc was found positive and anti-HBs was negative. Despite routine vaccination introduced in the Turkey national program, we suggest that pregnant women be routinely investigated for HBV infection. In this way, feto-maternal transmission of HBV may be reduced that might play an important role to break the cycle of HBV infection in Turkey.

Hepatitis B infection is a serious public health problem worldwide. It has been shown that the levels of antibody to hepatitis B surface antigen (anti-HBs) decrease after vaccination. The main objective of this study was to assess the level of anti-HBs among children after primary vaccination against hepatitis B virus (HBV) in Tehran, Iran. The study was conducted in four selected healthcare centers in Tehran during a 6-month period from September 2005 to March 2006 in Tehran. Blood samples collected from 165 healthy, 1- to 5-year-old children who had been vaccinated against HBV were tested for anti-HBs using enzyme-linked immunosorbent assay (ELISA). Approximately 47.9 % of the cases were male. Among the cases, the minimum and maximum titers of hepatitis B surface antibodies (HBsAb) were zero and 1000 m IU, respectively. The mean level of HBsAb titer in this study was 232.64 m IU, with a standard deviation of 278.711 m IU. The results showed that HBsAb titer may decrease over time after vaccination. Finally, along with prevention and control strategies, ongoing investigation and monitoring of antibody levels against HBV in children and other age ranges is recommended.

Wilson''s disease, caused by a deficient cellular copper export system, is transmitted as an autosomal recessive inherited disorder and results in copper accumulation in liver and other organs, particularly in brain. Acute hepatic failure and severe Coombs'' negative hemolysis may occur in the course of the disease which has a poor prognosis and most patients do not survive the crisis. Only liver transplantation has been recommended as an effective medical intervention. Herein, we presented a 25-year-old woman with impaired consciousness, acute hepatic failure and hemolysis who was treated with plasmapheresis and albumin replacement. Beside improvement in medical condition, serum copper and hemolysis decreased significantly and renal function was preserved. We concluded that plasmapheresis may be a life saving intervention during fulminant hepatic failure of Wilson''s disease.