Clinical Picture, Insulin Resistance, and Adipocytokines Profiles of Nonalcoholic Steatohepatitis (NASH) Patients in Indonesia.

Aim: to know the clinical picture of subjects with NASH in Jakarta, Indonesia and the prevalence of insulin resistance, TNF-a, and adiponectin levels among them. Methods: this was a comparative cross-sectional study between patients with histopathologically confirmed NASH and normal subjects. The population of study was patients with fatty liver without history or significant consumption of ethanol. Patients were consecutively enrolled in the study if the ultrasonography showed fatty liver appearance with or without increased liver transaminases. Results: thirty patients and thirty normal subjects were recruited between February 2005 and January 2006. Median age of the patients was 45 years while the median age of the control group was 32 years. More than 80% of the patients were overweight (BMI 23-25 kg/m2) and obese (BMI > 25 kg/m2). Increased alanine aminotransaminase levels were found in almost two thirds of the patients. Other comorbidities included hypertension, hypertriglyceridemia, and type-2 diabetes mellitus. In patients with NASH, fasting insulin level, insulin resistance, and TNF-a level were significantly higher, whereas adiponectin level was significantly lower than the control group. Conclusion: most of the metabolic syndrome determinants were found in patients with NASH. HOMA-IR and TNF-alpha levels in subjects with NASH are higher than those in controls. Adiponectin levels in subjects with NASH are lower than those in controls. Further epidemiological studies are still needed to elaborate the causal relationship of insulin resistance and cytokine profiles to the development of NASH in Indonesia.

Hepatocarcinogenesis in viral Hepatitis B infection: the role of HBx and p53.

Infection of Hepatitis B Virus (HBV) is a risk factor of chronic active hepatitis (CAH), hepatic cirrhosis and hepatocellular carcinoma (HCC). Infection of HBV may develop to HCC without antecedent hepatic cirrhosis. Pathogenesis of HBV causing malignant changes has not been fully understood. HBx, a protein of HBV, is an activator of transcription process involved in hepatocarcinogenesis. Most of human cancer associated with mutation of p53, a Tumor Suppressor Genes, a protein serves as cellular protection for growth and cell division, which is one of predisposition factor of hepatocarcinoma. Some studies indicate the correlation between mutation / inactivation of p53 and HBV protein x (HBx) in hepatocarcinogenesis. In that process, HBx will suppress p53 function, which will lead to ineffective liver cell division and resulting in HCC.

Genotyping of hepatitis B virus from dried and stored serum on filter paper.

HBV genotype has aclose association with prognosis and therapy as well as for epidemiology study. However, this examination can be done only in large cities that are not practical to send serum sample due to geographical burden and facilities. The aim of this study is to know whether HBV genotype can be determined from dried and stored serum on filter paper and compare the result with sera drawn directly from chronic hepatitis B (CHB) and hepatoma patients. Twenty-three serum samples were obtained from CHB patients. HBV DNA were quantitatively determined with Cobas Amplicor HBM (Roche Diagnostics GmBH, Germany) and dropped on to 3 x 1 cm filter papers. After allowed to dry in a plastic clip, it were put in a closed envelope then stored for 1 week in room condition (27 – 33 oC). DNA extraction were done from the filter papers after a short incubation period and HBV genotypes were determined with PCR and specific primers. For comparison, 20 CHB-Hbe(+) samples and 29 hepatoma samples were drawn directly and not dried. HBV genotype were detected in 18/23 (78.2%) from dried serum samples on filter paper while in sera that were not stored, from CHB-HBe(+) samples, 20/20 (100%) could be determined while from hepatoma patients, 24/29 (82.7%) samples. The proportion of genotype were in line with other reported HBV genotype examination for Indonesia. It is concluded that detection of HBV genotype can be done from dried serum in filter paper and stored for 1 week.

Detection of esophageal varices in liver cirrhosis using non-invasive parameters.

AIM: recent guidelines recommend that all cirrhotic patients without previous variceal hemorrhage undergo endoscopic screening to detect esophageal varices. The aim of this study is to evaluate clinical, laboratory and ultrasound parameters to detect esophageal varices. METHODS: this is a cross sectional study. Fourty seven consecutive cirrhotic patients without history of variceal hemorrhage underwent upper endoscopy. Physical examination, laboratory and ultrasonography to find portal vein diameter and anterioposterior splenic measurement of each patient were also recorded. RESULTS: esophageal varices was detected in 36 of the 47 patients (76.6%). Using bivariate analysis we found that a platelet count of 82,000/ul (90.9% sensitivity; 41.7% specificity), portal vein diameter of 1.15 cm (75% sensitivity; 54.5% pecificity) and an anteroposterior splenic measurement of 10.3 cm (83.3% sensitivity; 63.6% specificity) were predictive factors for esophageal varices in liver cirrhosis. CONCLUSION: our data show that platelet count, portal vein diameter and anteroposterior splenic measurement can be used as non invasive parameters to detect esophageal varices in cirrhotic patients.

Seroepidemiology and risk factors of Hepatitis B and C virus infections among drug users in Jakarta, Indonesia.

The number of drug users is markedly increased in recent times. Data were collected consecutively in Cipto Mangunkusumo Hospital and Mitra Menteng Abadi Hospital in Jakarta. HBsAg were examined using reverse passive hemaglutination assay (RPHA) and anti-HCV with dipstick method; both were from the laboratoium Hepatika, Mataram, Indonesia. In a 5 month period (March - August 1999) there were 203 cases of drug users. Most of them were male ( 185 cases or 91.1%) with a mean age of 21.2 ± 4.3 years. Mean age in starting to use the drug was 18.8 ± 4.0 years. The prevalence of anti-HCV and HBsAg positivity were 74.9% (151 cases) and 9.9% (19 cases), respectively. The prevalence of double infection was 7.4% (15 cases). Injection drug users (IDU) were 168 cases (84%). Extramarital sex was done by 62 cases (30.5%), but only 16 cases (8%) with more than one partner. Tattoo was found in 32 cases ( 15.8%). Multivariate analysis revealed that lDU and tattoo were the risk factors for anti-HCV positivity, with the OR of 9.15 (95% CI 3.28-5.53) and 13.24 (96% CI 1.6 - 109.55), respectively. No significant medical risk factor could be identified for HBsAg positivity. Double infection of HBV and HCV was found in 15 cases (7.4%). We concluded that the prevalence of HBV, HCV infection and double infection of HBV - HCV in drug users were high, with tattoo and injection drug usage as risk factors for hepatitis C virus infection.