Hepatitis Monthly
Year:2011 | Volume:11 | Issue:9 (38)|Papers Count:14

Only 20% of patients with chronic hepatitis C (CHC) progress to cirrhosis. Progressive fibrosis is the hallmark of an unfavorable course and is related to several factors such as male gender, contracting the disease at an older age, features of the metabolic syndrome, iron overload, ethanol abuse, and co-infection with hepatitis B or human acquired immunodeficiency viruses. However, the course of the disease is highly variable from individual to individual. Liver biopsy remains the gold standard for evaluating necroinflammation (grade) and fibrosis (stage) in CHC; however, this pre-eminence is currently being examined due to its intrinsic risks and limitations. Liver biopsy is an invasive procedure that carries a risk of complications, although rarely severe.The biopsy provides a very small specimen of liver tissue and has both a significant rate of sampling error, especially when the cylinder obtained is less than 25 mm in length, and interobserver variability. The risk-benefit ratio of liver biopsy is insufficient to maintain it as a firstline procedure, and new and non-invasive criteria for the evaluation of liver fibrosis are urgently needed.

Hepatitis D virus (HDV) infections remain a worldwide health problem. However, the clinical impact of these infections is often underestimated, and therapeutic options for the infections are often unexploited. Gulsun et al. have addressed both these issues in the paper “Treatment of chronic hepatitis D; a 9 years retrospective analysis” published in this issue of Hepatitis Monthly.The present study was conducted in Diyarbakir, Eastern Turkey, where chronic hepatitis D is one of the most prevalent liver diseases. HDV causes liver failure due to cirrhosis and hepatocellular carcinoma in a significant proportion of hepatitis B surface antigen (HBsAg) carriers.Over 8 years, The authors enrolled 46 patients with florid hepatitis D. These patients showed the typical features of HDV infections; most of them were young adult men with concomitant hepatitis B virus (HBV) infections that were positive for the antibody to hepatitis B antigen and not for the HBe antigen.

Hepatitis C remains as an important health problem worldwide. Hepatitis C treatment, especially among patients infected with HCV genotype 1 who are considered difficult to treat, is a high priority for health policy-makers. PegInterferon alfa instead of Interferon and ribavirin combination therapy has been accepted as the standard treatment regimen for hepatitis C patients; however, only 50% of patients infected with HCV genotype 1 achieve a sustained virological response. Published data from various clinical trials of protease inhibitors suggest that new therapeutic regimens may increase the chances of a successful response in patients infected with HCV genotype 1. Triple therapy that includes boceprevir has been shown to result in high rates of sustained virological response in both naive and experienced patients with HCV genotype 1 infection. In this review, we have summarized the results obtained with this new regimen and have attempted to provide a guideline for the treatment of patients in Iran, with emphasis on cost and the occurrence of adverse events.

Hepatitis B is one of the most frequent post-transfusion infections. Occult hepatitis B infection (OBI) is a form of hepatitis B infection in which, despite the presence of HBVDNA in the serum and hepatocytes of the carrier, HBsAg is absent. In addition to the risk of transmission through the transfusion of infected blood, reactivation of hepatitis B in OBI patients and recipients of their blood can lead to cirrhosis, hepatic cancer, and reactivation of viral replication in the carrier. Therefore, effective assays to assess and screen for OBI in blood donors are of paramount importance and require urgent attention. Recently, several investigations in various regions of Iran have reported OBI in blood donors. In response, there has been a drive to apply more specific, sensitive, and accurate methods for the detection of HBV, which should become an obligatory screening process for all blood transfusion services. In this review, we address the progression of occult hepatitis B and the common problems associated with occult hepatitis B worldwide. Finally, we reflect on the research and screening that is being performed in Iran to deal with this problem.

Background: The p16 tumor suppressor gene is an important negative regulator of the cell cycle. Inactivation of p16, especially via promoter hypermethylation, has been found in numerous human cancers such as breast, lung, colorectal, and liver.Objectives: To determine the role of epigenetic methylation in p16 regulation in Iranian patients with hepatocellular carcinoma (HCC).Patients and Methods: The methylation pattern in the p16 gene promoter was analyzed by bisulfite direct sequencing in 43 paraffin-embedded formalin-fixed tissues from patients with HCC. In addition, normal specimens from liver graft donors were used as the control group.Results: The bisulfite direct sequencing showed heterozygous hypermethylation in 13.9% of individuals with HCC. Homozygous methylation within the GC-box IV was detected in another 58.1% of the patients.Conclusions: It is proposed that methylation, but not necessarily hypermethylation, may play a role in the down-regulation of the p16 gene promoter at least in some Iranian patients with HCC.

Background: Hepatitis C is a global health concern that represents a major cause of liver disease and socioeconomic burden. Currently, there is no vaccine that protects against this infection or drug that treats it effectively. The current treatment for hepatitis C virus (HCV) infection does not produce a sustained virologic response. Therefore, discovery and identification of a new drug for HCV treatment is a high priority.Camel milk is a traditional medicine that could improve the control of HCV.Objectives: To assess the potential effect of casein purified from camel milk on HCV cellular infectivity in a tissue culture model.Materials and Methods: Casein was purified from defatted camel milk to electrophoretic homogeneity. PBMCs and HepG2 and HeLa cell lines were used. Three kinds of experiments were conducted. HCV was directly interacted with casein and then mixed with different cell types, casein was incubated with the cells and then exposed to HCV, and the HCV pre-infected cells were treated with casein at different concentrations and time intervals. Non-infected cells were used to assess cytotoxicity and the apoptosis effect of casein.Results: Direct interaction of casein (with or without a-lactalbumin) with neither the virus nor the cells prevented HCV cell entry. However, casein with a-lactalbumin induced a cytotoxic effect in HepG2 and HeLa cell lines but not in human naïve leukocytes.At all concentrations tested, casein with a-lactalbumin could induce apoptosis in both infected and non-infected HepG2 cells.Conclusions: Camel milk casein (with or without a-lactalbumin) did not demonstrate any anti-HCV activity. However, the cellular apoptotic cascade was initiated in HepG2 and HeLa cells treated with casein (with a-lactalbumin) but not in naïve leukocytes.

Background: Chronic delta hepatitis is the most severe form of viral hepatitis, for which interferon administration is the only available treatment. However, the efficacy of interferon treatment is affected by the dose and duration of treatment, and relapse rates are high.Objectives: In this study, we sought to evaluate the efficacy of treatment with pegylated interferon and observe the relapse rates of delta hepatitis after treatment.Patients and Methods: Forty-six patients with chronic delta hepatitis were retrospectively studied between January 2002 and December 2010. Patients were evaluated for biochemical, virological, and histological responses. They were then followed-up for at least 1 year after discontinuation of the treatment.Results: All the 46 patients in the study received PEG-IFN therapy. Of the 46 patients, 25 were treated with PEG-IFN for 1 year and 21 were treated for 2 years. Sixteen patients (34.7%) showed a biochemical response, 27 (58.6%) showed a virological response, and 39 (84.7%) showed a histological response. Sustained virological and biochemical responses were achieved in 41% and 47.8% of the patients, respectively. Sixteen (84.2%) patients of the 19 with high levels of hepatitis delta virus RNA (HDV RNA) (HDV RNA level>1 × 105) and 10 (71.4%) of the 14 patients with high titers of hepatitis B surface antigen (HbsAg) (HbsAg>102 IU/mL) at the beginning of the treatment showed relapse after treatment.Conclusions: We found no significant differences between 1-year and 2-year treatments.However, the relapse rate was lower in the 2-year treatment group. Higher HDV RNA and HbsAg levels before treatment were associated with higher relapse rates. Younger age was a significant factor in predicting response.

Background: There are little data on the prevalence of serological markers of hepatitis B and hepatitis C viruses in pregnant women in Iran.Objectives: This study was designed to determine the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection among pregnant women in Lorestan, west of Iran.Patients and Methods: Serum samples of 827 pregnant women who lived in rural (36.8%) and urban areas (63.2%) of Lorestan were collected during 2007-2008. Data were obtained through questionnaires. Samples were first screened for anti-HCV and anti-HBc by ELISA. Those who were positive for anti-HBc were tested for HBsAg.Results: Anti-HBc was found in 28 of 827 pregnant women (overall prevalence, 3.4%; 14 of 523 in urban areas, 2.7%; 14 of 304 in rural areas, 4.6%). Of the 28 positive samples, 6 (0.7%) were positive for HBs-Ag. Only 2 samples (0.2%) were anti-HCV-positive.Conclusions: These results underscore the need for prenatal screening for HBV infection in pregnant women and treatment of newborns from HBsAg-positive mothers.More studies are needed to identify risk factors of HCV infection and highlight the importance of HCV screening and treatment programs.

Background: The purpose of the present study is to investigate the association of nonalcoholic fatty liver disease (NAFLD) with the doppler waveform pattern of hepatic veins and portal vein doppler indices.Objectives: This assay may be useful in evaluating the natural course of NAFLD and monitor treatment efficacy on follow-up.Patients and Methods: This case control study was performed in 31 patients with NAFLD and 31 normal healthy adults who served as the control group. The patients presented with elevated liver enzymes levels (ALT/AST) and hyperechogenic livers in the B-mode ultrasonography examination. Eleven patients had a liver biopsy. After an 8-hour fast, B-mode and duplex doppler ultrasonography were performed, and the waveform patterns of the right hepatic vein, portal vein diameter, grade of fatty liver, portal vein pulsatility index (VPI), and mean flow velocity (MFV) were measured.Results: VPI and MFV values were 0.42 ± 0.92 and 17.27 ± 5.34 cm/second, respectively, in the control group and 0.25 ± 0.50 and 12.82 ± 4.32 cm/second in patients with NAFLD (P <0.01). The frequency of abnormal hepatic vein doppler waveform patterns (biphasic or monophasic) was significantly higher in patients with NAFLD (55.2%) versus control subjects (3.2%) (P<0.001). There was no correlation between the degree of fat infiltration and VPI (P=0.714), MFV (P=0.911), or hepatic vein waveform pattern (P=0.197). We found no correlation between liver enzyme levels and MFV or VPI. However, the rate of abnormal hepatic vein was higher in patients with enzyme levels that exceeded twice the normal value (P=0.05).Conclusions: Patients with NAFLD have a high rate of abnormal hepatic vein doppler waveform patterns, and decreased VPI and MFV are suggestive of reduced vascular compliance in the liver. Elevated liver enzymes levels do not influence VPI or MFV, but patients with abnormal enzymes have higher rates of abnormal hepatic vein doppler waveform patterns.

Background: Hepatitis E virus (HEV) infection is a significant public health concern and has been identified as a zoonotic infection.Objectives: Since no reports have characterized the epidemiological and genotypic features of HEV infections in Macaca mulatta (rhesus macaques) from Yunnan, China, where swine HEV infections are endemic, we aimed to investigate these characteristics.Materials and Methods: Seroepidemiological and molecular characterization of HEV in both Macaca mulatta and pigs from the Yunnan province of China were conducted using enzyme-linked immunosorbent assay (ELISA) and reverse transcription-nested PCR (RT-nPCR). Four hundred and eighty-two stool samples (320 from Macaca mulatta and 162 from pigs) and 92 serum samples (all from Macaca mulatta) were collected for the detection of HEV RNA and anti-HEV antibodies (IgG/IgM).Results: Thirty-three rhesus macaques (35.87%) were positive for HEV IgG. Of these, 3 were also positive for HEV IgM. Four different strains of swine HEV RNA were detected in pigs; however, we failed to detect any in Macaca mulatta.Conclusions: Results indicate that Macaca mulatta may not be a natural reservoir of HEV.

Background: Viral hepatitis caused by hepatitis B virus (HBV) is a leading cause of acute and chronic liver diseases worldwide.Objectives: In Italy, a mandatory vaccination policy was introduced in 1991 and was established for all newborns and 12-year-old individuals. In 2004, vaccination of 12-yearold adolescents was discontinued, and that of infants was maintained.Patients and Methods: We evaluated the seroprevalence of HBV markers in 806 individuals, who were vaccinated at birth or at 12 years of age, to assess the effectiveness of the national policy against HBV.Results: The overall prevalence of anti-HBs antibodies was 90.32% (95% confidence interval [CI]: 88.28–92.36%); 2.23% (95% CI: 1.21–3.25%) of the subjects were positive for both antibodies to HBsAg (anti-HBs) and antibodies to hepatitis B core antigen (anti-HBc), whereas 5.83% (95% CI 4.21–7.45) of the subjects were negative for all markers tested.Further, 1.61% (95% CI: 0.74–2.48%) of the subjects were positive for hepatitis B surface antigen (HBsAg).Conclusions: Our data provide additional evidence that HBV vaccination can confer long-term immunity when performed at birth and when performed for healthy adolescents; moreover, the results show the effectiveness of the application of a national vaccination strategy.

Dear Editor: We read with great interest the article by Malaguarnera et al. in this issue of Hepatitis monthly, in which the safety and efficacy of rosuvastatin plus interferon and ribavirin were evaluated in a randomized controlled trial. Sustained viral response was observed in 40% of the standard-care group and 51% of the triple-therapy group, and this was associated with improvement of steatosis and fibrosis without causing side effects. Despite the importance of this study, we think that the clinical implications extracted from this study deserve further evaluation. In particular, we question some components of the study design.

Dear Editor: We read with interest the article by Abu El Makarem MA et al. (1) entitled, “Platelet count/bipolar spleen diameter ratio for the prediction of esophageal varices: The special Egyptian situation.” This study evaluated noninvasive predictors of esophageal varices in cirrhotic patients by multivariate logistic regression and receiver operating characteristic (ROC) curve analysis. However, in our opinion, some aspects of the statistical analysis could be clarified. The first issue concerns the ROC analysis.The full area under the ROC curve (AUC) is a measure of the performance of the diagnostic test because it reflects the test performance at all possible cutoff levels.The AUC lies in the interval [0.5, 1], and the larger area, the better performance. A perfect test has an AUC of 1.0, whereas random chance gives an AUC of 0.5 (2, 3). In Abu El Makarem MA et al.’s paper, the AUC for age is 0.33, which is less than 0.5. Therefore, we think that something might have gone wrong when the authors performed the ROC analysis with the SPSS software. Because both the univariate analysis and multivariate logistic regression identified age as a valuable predictor of varices, older patients experienced a higher risk having varices. We presume that the AUC for age may be 0.67 (1-0.33) rather than 0.33. The second issue has to do with the odds ratio. The odds ratio refers to a ratio of the odds of the outcome occurring in one group divided by the odds of the outcome occurring in the other group with a 1-unit increase in x (4). The odds ratio for age was 1.205 in Abu El Makarem MA et al.’s (1) paper, but no statement such as “for a one year increase in age” was mentioned.

Sirli et al.'s (1) effort to compare several noninvasive methods of fibrosis assessment in chronic hepatitis C virus (HCV) infection is commendable. Their study evaluated several simple serological tests for the prediction of fibrosis in chronic HCV infection: number of platelets, the aspartate aminotransferase–platelet ratio index (APRI test), the Forns score, the Lok score, and the FIB-4 score. They also compared these tests to liver stiffness measurement (LSM) by transient elastography (TE) and to the current “gold standard”: liver biopsy (LB). They concluded that LSM was the best method for predicting cirrhosis, but all the evaluated tests had excellent predictive value (1). We have to keep in mind that LSM failure can occur in 2%-10% of patients, and this is generally related to obesity, especially with the use of the M probe.