Hepatitis Monthly
Volume:8 Issue: 3, Summer 2008

Dysfunction of the host immune system in cancer patients can be due to a number of factors, including secretion of tumor-derived immunosuppressive factors or induction of immune tolerance against tumor-specific antigens. Several studies suggest that suppression of tumor-associated antigen reactivates lymphocytes by CD4+ CD25+ regulatory T (Treg) cells. This study was designed to evaluate whether CD4+CD25+ Treg cells in chronic liver disease and hepatocellular carcinoma (HCC) patients exhibit an expanded Treg pool and to correlate it with liver tumor markers and grading. Blood samples were collected from 20 patients with cirrhotic liver disease (CLD), 15 HCC patients and 10 healthy control subjects. Alpha feto-protein (AFP), HBV and HCV antibodies were detected by EIA. HCV was confirmed by immunoblotting and RT-PCR. To evaluate HCC grading, abdominal ultrasound guided liver biopsy was done. Patients were categorized into moderately differentiated (grade II) and poorly differentiated (grade III) groups. Cytometric analysis of CD4+CD25+ Treg cells in PBMCs was performed using anti-CD3, anti-CD4, anti-CD25, anti-CD45RA, and IgG-isotype control (FITC and PE). Both CLD and HCC groups were 80% positive for HCV while only 20% of CLD and 11% of HCC patients were positive for HBV. The mean percentage of CD4+CD25+T cell population demonstrated a highly significant increase in comparing HCV to HCC patients [2.47±0.66 vs. 8.96±1.38 (P<0.001)] and when comparing both group to controls [1.15±0.5 (P<0.01)]. Nine HCC patients were in grade II while 6/15 were in grade III. Their mean CD4+CD25+ T cells percentage was 9.12±1.52 and 8.73±1.33, respectively. A negative correlation was found between mean CD4+CD25+ T cells percentage and AFP serum level in HCC patients (r=-0.923) while Treg cells with patients tumor grades (II and III) (r=0.474 and 0.582, respectively). CLD showed a significant correlation with AFP level (r= 0.962). Tumor specific Treg cells may limit the efficacy of anti-tumor response. Treg cells correlate properly with the unique marker AFP and with tumor grades. Better understanding of the underlying mechanism of Treg regulation or of the strategy for controlling Treg cells may lead to effective HCV immunotherapy and enhancing immunity against cancer.

Insulin-like growth factor-I (IGF-1) is a liver-derived humoral factor, which has important anabolic and metabolic actions. Low serum concentrations of IGF-1 have been reported in patients with chronic liver disease, especially cirrhosis and hepatocellular carcinoma and metastatic liver cancer. The aim of our study was to evaluate any possible relationship between intensity of liver metastases on serum IGF-1 concentrations. Serum IGF-1 were measured by ELIZA (III) in10 patients with uninodular or multinodular liver metastases and extension |£50% (group A) and 10 patients with multinodular or massive liver metastases and extension > 50% (group B) of liver size without liver failure. Serum IGF-1 concentration was significantly lower in the more sever metastatic group (group B) than the less sever metastatic group (group A) (121.40 ± 52.08 vs. 210.30 ± 42.59 ng/ml, respectively; P < 0.001). Our findings suggest that the states of serum IGF-1 levels in patients with metastatic liver cancer may be a helpful finding for determining the severity of metastasis to the liver

Hepatitis B virus (HBV) DNA level is used as a criterion for antiviral therapy in patients with chronic hepatitis B (CHB). However, the relationship between serum HBV-DNA level with liver histology remains controversial. The objective of this study was to determine the relationship between HBV-DNA load with liver histopathology in patients with CHB. The study was conducted between October 2003 and May 2007 in the Department of Hepatology of Bangabandhu Sheikh Mujib Medical University. 209 consecutive patients with CHB were studied. The liver histology was graded by Knodell''s criteria. 175 (83.5%) of patients were male; the patients had a mean±SD age of 26.6±8.4 years, had a mean±SD HBV DNA level of 6.9±1.6 log10 copies/mL, necro-inflammatory score of 6.8±3.2 and fibrosis score of 1.7±1.2. Eight-one (38.8%) patients were HBeAg-negative. There was no correlation between the HBV-DNA load and either of necro-inflammatory activity or fibrosis. Eight (9.9%) patients in HBeAg negative group and 2 (1.6%) in HBeAg positive group had DNA level below the recommended level of treatment but had significant pathology. HBV-DNA load does not have any correlation with the histological abnormalities and fibrosis in liver and the lowest level of HBV-DNA to start the treatment requires reconsideration.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of increased liver enzymes. According to statistical reports, 20%-40% of Western population and 5%-30% of the population of Pacific and Asian countries are afflicted with this disease. The prevalence of NAFLD is higher in hyperlipidemic, diabetic and obese people. Considering the high prevalence of NAFLD and its complications and lack of consensus on its treatment, we were motivated to study the efficacy of silymarin on this disease. In this randomized clinical trial, 50 patients including 32 men (64%) and 18 women (36%) were divided into case and control groups. The mean age of case group was 40.3 and for control group was 39.9 years. All patients had elevated liver enzymes and had increased liver echogenicity (lipid accumulation) on sonography. The case group was treated with one tablet containing 140 mg silymarin per day for two months and the control group was treated in the same manner with placebo. Before and after the study, weight, body mass index (BMI) and liver transaminases levels were measured for each patient. The difference between the mean weight and BMI measured before and after the study was not statistically significant in both case and control groups. But the mean ALT and AST levels deceased from 103.1 to 41.4 and 53.7 to 29.1 IU/mL, respectively in case group which was statistically significant (P<0.001 & P<0.001). In the control group, the decrease in mean ALT and AST, with decrease of 7.8 and 2.2 IU/mL, respectively, was not statistically significant. Considering the significant drop in liver enzymes following administration of silymarin, it seems that after conducting similar studies in order to determine the appropriate doses and treatment periods, this cheap and easy to access drug can be prescribed for treatment of NAFLD.

Non-alcoholic steatohepatitis (NASH) is reported to be present in 49-86% of patients with type-II diabetes mellitus (DM). Risk factors for the development of NASH in DM are not clear. This prospective analysis was planned to define the chronological relation between DM and NASH as well as to define risk factors for the development of NASH in DM. In a 3-year study, all consecutive NASH patients (n=100, age= 42.8±4.6 years, M: F=4.2:1) were evaluated for the presence of DM, at baseline and during three monthly follow-up. In NASH patient with DM (group A, n=27, age=39.3±5.2 years, M: F=4.4:1), risk factors such as obesity, central obesity, dyslipidemia and family history of chronic liver disease were evaluated for comparative analysis. Similar number of consecutive patients of DM without evidence of liver disease (group B, n=27, age=45.9±5.6 years, M: F=3:1) were analyzed for similar parameters. Among 100 patients with NASH, 27 (27%) patients had DM of whom, DM was preexisting in 13 (48.1%), was diagnosed at baseline in 11 (40.7%) and was diagnosed during follow-up in 3 (11.1%) patient. On statistical analysis (group A vs. group B), none of the risk factors were found to be statically significant: obesity (77.7% vs. 70.3%), central obesity (88.8% vs. 92.5%), dyslipidemia (51.8% vs. 44.4%), hypolipoproteinemia (7.4% vs. 3.7%), family history of chronic liver disease (7.4% vs. 0%), family history of DM (62.9% vs. 66.6%), hypertension (18.5% vs. 14.8%), ischemic heart disease (7.4% vs. 11.1%), cerebrovascular disease (3.7% vs. 0%) and hyperuricemia (11.1% vs. 14.8%). DM does not always precede NASH, but may follow NASH in some patients. Risk factors like obesity, central obesity, dyslipidemia and family history do not predict the development of NASH in diabetic patients.

More than 35% of Iranians have been exposed to hepatitis B virus (HBV) and almost 3% are chronic carriers. Knowledge of HBV-related diseases and its chronicity, and insufficient knowledge about the transmission routes are predisposing factors for occurrence of psychological disorders among these patients. Self-administered CHQ28 questionnaire was used to find the prevalence of psychiatric disorders among 100 HBV carriers. We found depression in 30%, anxiety in 6%, functional impairment in 6%, and somatic abnormalities in 8% of HBV carriers. 36 patients had at least one psychiatric disorder. The prevalence of psychiatric disorders among HBV carriers is higher than that of community. Psychiatric consultation after screening along with continuous education of patients and their families may improve this condition. Physical, psychological, spiritual and social support to HBV carriers is therefore of paramount importance.

Hepatitis C virus (HCV) is known to be responsible for both hepatic and extrahepatic diseases. Mixed cryoglobulinemia, Sjögren syndrome, and chronic polyarthritis are the most documented rheumatologic extrahepatic manifestations of HCV infection. The most frequent and clinically important extrahepatic endocrine manifestations of chronic HCV infection are thyroid disorders and type 2 diabetes mellitus. From a meta-analysis of the literature, a significant association between HCV infection and thyroid autoimmunity and/or hypothyroidism as well as a high prevalence of thyroid cancer have been reported. The pattern of thyroid disorders observed in HCV infected patients is characterized by the presence of elevated circulating anti-thyroid peroxidase antibodies with increased risk of hypothyroidism. Several clinical epidemiologic studies have reported that HCV infection is a risk factor for type 2 diabetes. The type of diabetes manifested by subjects with chronic HCV infection is not of the classical type 2 diabetes; in fact, HCV-related diabetic patients are leaner than the classical diabetic patients, and have a significantly lower LDL-cholesterol, and both systolic and diastolic blood pressure. Furthermore, patients with mixed cryoglobulinemia (mixed cryoglobulinemia) and chronic HCV infection with type 2 diabetes have more frequently non-organ-specific-autoantibodies than non-diabetic patients with mixed cryoglobulinemia and those with chronic HCV infection. Based on the above-mentioned findings, it has been hypothesized that diabetes in HCV infection may have an immune-mediated pathogenesis. In patients with chronic HCV infection, we found an increased risk of carotid artery plaque and carotid intima-media thickening. These findings suggested a possible role for chronic hepatitis C in the pathogenesis of carotid artery remodelling. Recently, high prevalence rates of anti-HCV antibodies were shown in patients with hypertrophic cardiomyopathy or dilatated cardiomyopathy; association with myocarditis has also been suggested. Many studies have linked the Th1 immune response with HCV infection, autoimmune thyroid disorders and diabetes. These findings suggest that a possible common immunological Th1 pattern could be the pathophysiological basis of the association.

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the insulin resistance syndrome and thus a frequent cause of elevated liver enzymes. The term "insulin-resistance associated hepatic iron overload syndrome (IR-HIOS)" has been coined to describe the frequent association of hepatic steatosis with increased levels of serum ferritin, normal or slightly elevated transferrin saturation and mild hepatic iron deposition. There is mounting evidence that increased iron stores in insulin resistance are associated with an unfavorable course of the disease and an increased prevalence of associated conditions such as diabetes, hypertension or cardiovascular disease. Iron depletion via phlebotomy has been demonstrated to improve several aspects of the insulin-resistance syndrome. Multiple interactions have been observed between molecules of iron and glucose metabolism. On a molecular level, impaired iron export has been demonstrated to be the principal mechanism of iron accumulation in fatty liver disease. Obesity-related inflammation, low ferroxidase activity associated with low copper bioavailability and decreased expression of the iron export molecule ferroportein have so far been identified as contributors to increased iron accumulation in human NAFLD.

Combined factor V and VIII deficiency (CF5F8D) is a rare hemorrhagic disorder. Treatment of patients with blood products has been associated with infections with blood-borne viruses. Due to absence of any survey on status of blood borne viruses in individuals with CF5F8D, we tried to address this question. Among 25 known cases, 24 individuals were assessed for hepatitis B and C viruses (HBV & HCV), human T lymphotropic virus type one (HTLV-I) and human immunodeficiency virus type1/2 (HIV1/2) using enzyme linked immunosorbent assay method. In the group under survey, 2 cases (8.3%) were positive for anti-HCV. There was no infection with HBV, HTLV-I and HIV. Hepatitis C is a major health problem in CF5F8D, as in hemophiliacs, and may need more attention from manufacturers of blood products and more careful pre-transfusion screening of blood products for anti-HCV.

Plagiarism is substantially duplicating another article without acknowledgement. Academic scientists, commercial or political motivations are the main probable reasons for this detrimental problem. We introduce a case of plagiarism in Hepatitis Monthly and present some valuable ways to tackle this complicated problem since we believe that prevention of duplicate publication can be achieved through increasing editors'' awareness and reviewers'' knowledge.