Hepatitis Monthly
Year:2011 | Volume:11 | Issue:6 (35)|Papers Count:15

Soon after introducing recombinant hepatitis B virus (HBV) vaccine, universal neonatal vaccination became the corner stone of the preventive measures for this potentially life threatening infection (1-3). By 2006 more than 177 out of 193 member states of world health organization (WHO) introduced HBV vaccination in their national infant immunization programs (1). Following a complete series of vaccination during neonatal period, protective antibody level raises in more than 95% of infant’s blood test up to 18 months after vaccination (3-5).The effectiveness of this strategy has been shown by several investigators in reducing the incidence of HBV carrier rate and probably cirrhosis and hepatocellular carcinoma (1, 2, 5-7).

Blood transfusion is a life-saving component of health care systems. Nevertheless, it can also be a quick and easy method of exposing patients to risks, particularly the transmission of infectious agents to recipients.Despite substantial improvements in the safety of transfusion services worldwide, the presence of paid and replacement blood donors are still of cause concern for ensuring sustainable safe blood donations.Although the Eastern Mediterranean region consists of a heterogeneous group of countries that vary in their levels of development, they all share common concerns regarding blood safety. In the region, concerns regarding the spread of Hepatitis B and C through blood transfusion continue to exist.Therefore, there is an urgent need for further improvements in both organization and safety measures of blood transfusion activities in the region. Although establishing a centralized blood transfusion system might not be achievable in the short term in some of the countries in the region, the implementation of centralized test kit procurement, data collection, and donation testing could be considered feasible approaches.

Hepatitis C virus (HCV) infection is one of the most common indications for liver transplantation worldwide. Because of the existing organ shortage, adult-to-adult living donor liver transplantation (LDLT) has become an important method of expanding the donor pool to meet the ever-increasing need. However, despite advantages such as the quality of the hepatic graft and the timing of the transplant, the exact role of LDLT in the treatment of HCV is still unclear. In this review, we aim to address some of these issues in an effort to highlight both the advantages and disadvantages, as well as to identify the main challenges, of using LDLT for treating patients with HCV infection.

The plasma of patients with hepatitis C contains chromosome-damaging substances, the so-called “clastogenic factors” (CFs), as this is the case for other chronic inflammatory diseases and after radiation exposure. These endogenous clastogens, formed as a consequence of increased superoxide production by inflammatory cells, can be detected with cytogenetic methods, as they are used for exogenous clastogens. The long-lived, autosustained DNA-damaging effects of CFs are risk factors for the development of cancer and leukemia. In hepatitis C, the highest clastogenic scores has been observed in patients with hepatocellular carcinoma. In agreement with the link to inflammation, clastogenic score are correlated with necro-inflammatory scores in liver biopsies. Antioxidant therapy with a powerful superoxide scavenger resulted in normalization of clastogenic scores and significant decreases in aminotransferase levels, but did not influence the virus load. Preliminary results of our study on a limited number of patients suggest that pre-treatment with antioxidants may improve the outcome of interferon/ribavirin treatment. A comparison of a three-month treatment with either interferon alone or the antioxidant alone, yielded similar results for reduction of ALT levels, but only complete normalization of clastogenic scores for the antioxidant. Further studies have to be conducted to see whether a combination of an antiviral agent with an appropriate antioxidant would allow to reduce interferon and its side effects. Combination of antioxidants with IFN/RIBA was also reported by other authors with discordant results. The CF-test can be useful in clinical trials for the choice of the appropriate antioxidant.

Background: Hepatitis B virus infection is a global health problem and vaccine-preventable disease, but the duration of the effects of HBV vaccination in infants is unknown.Objectives: The aim of this trial, which comprised children who had received 3 doses as part of the universal HBV immunization program and no additional doses, was to investigate anti-HBs titers and HBsAg status after 9 years.Patients and Methods: We performed a descriptive, cross-sectional field research study.The study sample, based on sociodemographics and minimum seroprevalence, was analyzed based on 10.00%±1.50 (95% confidence interval) (1150 individuals); trial was realized in a total of 1279 children (623 females and 656 males). Anti-HBs titers were measured by micro-EIA (Dia Sorin-Italy); titers<10 IU/mL were negative, 10-49 IU/mL were low-positive, and>50 IU/mL were high-positive. For anti-HBs titers below protective levels, HBsAg was measured by micro-EIA.Results: In approximately half of the children (48.5% in those living in semiurban areas and 42.3% in urban areas), antibody titers were below protective levels.Conclusions: Mass HBV vaccination, which was implemented in Turkey in 1998, significantly decreases HBsAg positivity in childhood. Nevertheless, it might be necessary to administer a booster dose after 8-9 years in children, especially those in low socioeconomic areas or in whom irregular/insufficient immunization is suspected.

Background: Intermittent clamping (IC) of the portal triad is an effective method of protecting the liver from ischemia-reperfusion injury (IR). In clinical practice, this method is employed during a resection, but its mechanism is still not clear.Objectives: To evaluate the effect of IC on rat liver and determine its mechanisms.Materials and Methods: Wistar rats were submitted to 60-min IC (cycles of 12-min clamping followed by 4-min reperfusion), and the samples were collected after 1, 6, and 72 hrs of reperfusion. We determined the serum activity of alanine aminotransferase (ALT), and measured the concentration of TNF-a, malondialdehyde (MDA) and myeloperoxidase (MPO) in liver homogenates. The apoptosis of hepatocytes was evaluated immunohistochemically.Results: When compared to the IR rats, the activity of ALT decreased in the IC group in all periods of observation (the highest decrease of ~48% after 1 hr of reperfusion).When compared to the IR group, a statistically significant decrease (p<0.05) in the TNF-a concentration (~33%) in the IC rats occurred only after 1 hr of reperfusion, and it was accompanied by a decrease in the MPO concentration after 1 and 6 hrs of reperfusion.IC reduces the effects of reactive oxygen species (ROS) activity, which has been confirmed by a statistically significant decrease in MDA concentration by 25%–35% in all studied periods. The limitation of hepatocytes apoptosis due to IC occurs in the early (~26%; p<0.05) and late (~45%; p<0.01) phases of reperfusion.Conclusions: The use of IC in early phase of reperfusion brings about a decrease in TNF-a release, which can be related to liver injury due to neutrophil infiltration and apoptotic cell reduction. It seems that the reduction of lipid peroxidation may also limit the liver injury.

Background: Non-alcoholic fatty liver disease (NAFLD) has been recognized as the most common cause of chronic liver disease worldwide. It occurs in patients who do not consume alcohol in large amounts. Alanine aminotranferase (ALT) and aspartate aminotransferase (AST) are indicators of hepatocellular injury.Objectives: To determine correlation between histopathologic specifications of NAFLD in patients with little or no history of alcohol consumption and the serum level of ALT.Patients and Methods: In a cross-sectional study carried out in two gastroenterology and hepatology clinics in Tehran, Iran, the medical records of those who had undergone liver biopsies between years 2005 and 2009 were reviewed. Clinical and laboratory information of biopsy-proven cases of NAFLD were obtained from 147 eligible medical records.The histopathologic, demographic, and laboratory data of the participants were also collected. Two groups of patients according to their serum ALT level (cutpoint of 35 U/L) were defined. The quantitative pathologic grade of the biopsy specimens was determined based on Brunt scoring system.Results: We studied 147 NAFLD patients including 127 men (86.4%) and 20 women (13.6%) with a mean±SD age of 41.4±11.2 years. Considering serum ALT, the mean±SD quantitative grade of hepatosteatosis was 1.50±0.67 and 1.74±0.73 (p=0.136); advanced fibrosis (consisted of grade III and cirrhosis) was found in 4.5% (1/22) and 5.6% (7/125) of patients (p=0.327).Conclusions: We found that using the cut-off value of 35 U/L for serum ALT level, it has little contribution to predict NAFLD severity.

Backgroud: Hepatitis E virus (HEV) and caliciviruses are enteric pathogens of humans and animals, and pigs have been considered an important reservoir of these viruses.Objectives: The aim of this study is to determine the infection rates of HEV and caliciviruses (sapovirus [SaV] and norovirus [NoV] ) in different age groups of pigs in Guizhou province, China, and characterize the strains that are prevalent in this mountainous area.Materials and Methods: A total of 209 stool samples from healthy pigs of different ages were collected from 6 pig farms in Guizhou province from May to June 2009 and tested for HEV, SaV, and NoV by reverse-transcription polymerase chain reaction (RT-PCR).Results: The overall prevalence of porcine HEV and porcine SaV was 6.7% (15/209) and 1.0% (2/209), respectively. No NoV was detected. The prevalence rates of porcine HEV infection were 15.4% in piglets aged<1 mon (4/26), 6.8% in piglets aged between 1 and 4 mon (3/44), 12.5% in piglets aged » 4 mon (6/48), and 1.1% in sows aged between 6 and 14 mon (2/91). Porcine SaV was detected only in piglets (7.7%, 2/26). All 10 HEV isolates belonged to genotype 4, clustering with a human HEV strain (AF103940) from an adjacent province.Conclusions: This is the first report on the existence of porcine SaV in swine in Guizhou province, China. The clustering of the porcine HEV isolates with a human strain suggests cross-species transmission between swine and humans in this area.

Background: Extracts of milk thistle (MT), Silybum marianum, have been used as medical remedies since the time of ancient Greece. Methotrexate is a potentially hepatotxic drug.Objectives: To clarify the hepatoprotective effects of MT on methotrexate.Materials and Methods: From January 2010 to April 2010, 30 male rats were recruited into three 10-rat subgroups in Tabriz University of Medical Sciences. Normal saline was injected intraperitoneally in the first group (A; the controls); intraperitoneal methotrexate plus oral MT extract were administered to the second group (B) and intraperitoneal methotrexate alone was given to the third group (C). Pre- and post-interventional measuring of serum parameters were carried out every 15 days. After six weeks, the rats were decapitated and histopathological evaluation of liver was done.Results: Serum liver enzymes (AST, ALT), alkaline phosphatase, total and direct bilirubin, creatinine and BUN were measured on days 0, 15, 30, 45. They were significantly higher in the group C, comparing with other two groups. Serum albumin was the least in group C animals as well. There were no significant differences between groups A and B. The mean±SD fibrosis score using semi-quantitative scoring system (SSS) was 1.25±0.46, 1.40±0.52 and 6.70±0.82, in groups A, B and C, respectively (p<0.001).Conclusions: MT extract can effectively prevent methotrexate-induced liver dysfunction and fibrosis in rats.

Background: There is growing evidence suggesting that interleukin-18 (IL-18) plays a crucial role in viral clearance and disease pathogenesis, and that single nucleotide polymorphisms (SNPs) within the gene may influence its production.Objectives: To investigate the potential association of two polymorphisms (137G/C and 607C/A) in the promoter region of the IL-18 gene with the risk of HBV recurrence after liver transplantation (LT) in Han Chinese patients.Patients and Methods: IL-18 promoter genotyping was performed by the snapshot technique in 125 patients with HBV-related end-stage liver disease (ESLD) receiving LT in our center from 2004 to 2008.Results: Among the study samples, no significant association between the IL-18 promoter polymorphisms (137G/C and 607C/A) or haplotypes and HBV recurrence after LT was found.Conclusions: The polymorphisms (137G/C and 607C/A) in the promoter region of the IL- 18 gene may not play a key role in HBV recurrence after LT in Han Chinese population, and may not be suitable predictors for HBV recurrence in clinical practice.

We read with great interest the article, “efficacy of hepatitis B vaccine in those who lost hepatitis B surface antigen during follow-up” by Taheriet al. published in Hepatitis Monthly (1). In this article, the authors assessed the efficacy of HBV vaccine in those who lost their HBsAg without seroconverssion to anti-HBs antibody with no detectable anti-HBs antibody and HBV DNA in their sera.They reported that nearly 24% of chronic HBsAg-positive subjects who lost their HBsAg responded to HBV vaccine and the remaining cases need to be followed for occult HBV infection (OBI).

The article “efficacy of hepatitis B vaccine in those who lost hepatitis B surface antigen during follow-up” published recently in Hepatitis Monthly (1), described the efficacy of HBV vaccine in chronic HBV patients who had been found negative for HBsAg and HBV DNA in sera. The manuscript was highlighted by an Editorial in the same issue.

In patients with chronic liver disease (CLD), liver biopsy is currently an indispensable reference method to assess inflammatory activity and fibrosis stage and thus to estimate prognosis and guide management decisions in such patients. Given that the presence of advanced fibrosis is a predictor of nonresponse, the decision (1) to begin antiviral therapy in cases of chronic viral hepatitis is highly influenced by the stage of liver fibrosis.For example, in chronic hepatitis C (CHC) patients, the stage of liver fibrosis is a predictor of response to interferon based treatment. Despite these premises, liver biopsy has several disadvantages, including poor patient compliance, sampling error, limited usefulness for follow up, and poor intra- and interobservation agreements.

We read with interest the article by Taheriet al. regarding the efficacy of Hepatitis B vaccine in those who lost Hepatitis B surface antigen (HbsAg) during follow up (1).As the authors mentioned, a protective anti-HBs level developed in 24% of chronic HBsAg-positive subjects who had already lost their HBsAg after hepatitis B vaccination, and the remaining cases need to be monitored for occult HBV infection. Subjects with no response after hepatitis B vaccination may have low levels of HBsAg or have immunologic tolerance to hepatitis B vaccination and no ability to produce anti-HBs antibody as reported previously.

Without downgrading the histological assessment of liver fibrosis, efforts are being made to develop accurate and reliable non-invasive indices as alternatives to liver biopsy. Previously proposed panels of liver fibrosis usually include 2 to 7 blood markers. The majority of publications were concerned with liver fibrosis among patients with chronic hepatitis C (CHC).