Significant hepatic histopathology in chronic hepatitis B patients with serum ALT less than twice ULN and high HBV-DNA levels in Indonesia.

OBJECTIVE: To study the prevalence of significant hepatic histopathology in chronic hepatitis B (CHB) patients with alanine aminotransferase (ALT) ≤ twice upper limit of normal (ULN) and its association with age, HBeAg status, hepatitis B virus (HBV)-DNA level and viral genotype. METHODS: A prospective study was conducted over a 3-year period in treatment-naive CHB patients with ALT ≤ twice ULN. Patients with a history of acute flare hepatitis, use of alcohol and hepatotoxic drugs, hepatitis C, hepatitis D and human immunodeficiency virus (HIV) co-infection were excluded from the study. Hepatic histopathology was assessed according to the METAVIR scoring system. RESULTS: A total of 145 patients were recruited, 81 (55.9%) of whom were male. The patients' mean age was 41.50 ± 10.74 years (range 16-70 years). Significant hepatic inflammation was found in 59.3% of these patients, and significant hepatic fibrosis was found in 62.1%, the latter being associated with hepatitis B e antigen status, ALT levels and serum HBV-DNA, but not with their age group or viral genotype. Significant hepatic fibrosis was found in 24 of 35 CHB patients (68.6%) who were previously considered in an immunotolerance phase. CONCLUSIONS: The prevalence of significant hepatic histopathology in CHB patients with serum ALT levels ≤ twice ULN is high. Delayed antiviral treatment can be harmful.

Diagnostic accuracy of transient elastography (FibroScan) versus the aspartate transaminase to platelet ratio index in assessing liver fibrosis in chronic hepatitis B: the role in primary care setting.

BACKGROUND: A non-invasive method to assess liver fibrosis by measuring liver stiffness with transient elastography (TE) has been recently introduced. The role of TE among chronic hepatitis B (CHB) patients in starting antiviral therapy in the primary care setting is still controversial because of its high cost. The AST to platelet ratio index (APRI) could be a much cheaper alternative. OBJECTIVES: This study compares the diagnostic accuracy of TE and APRI in assessing liver fibrosis in CHB patients. PATIENTS AND METHODS: A cross-sectional study in CHB patients intending to start antiviral treatment. Liver fibrosis was staged according to the METAVIR scoring system. Liver stiffness was measured by TE performed on the same day with liver biopsy, while APRI was calculated as follows: APRI=(AST/upper limit of normal)×100/platelet count (10(9)/l). Cutoff levels of liver stiffness and APRI were calculated by using the receiver operating characteristic curve to detect significant liver fibrosis, defined as fibrosis stage F2 or more. RESULTS: 117 patients were enrolled in the study; their mean age was 40.6±10.97 years. The median liver stiffness was 5.9 kPa (2.5-48 kPa) and the median APRI was 0.239 (0.09-2.73). The cutoff level of liver stiffness was 5.85 kPa for ≥F2 with an AUC of 0.614, 60.3% sensitivity, 63.6% specificity, 73.3% PPV, 49.1% NPV and a LR+ of 1.66. The APRI cutoff level was 0.235 for F≥2 with an AUC of 0.693, 64.4% sensitivity, 70.5% specificity, 78.3% PPV, 54.4% NPV and a LR+ of 2.18. Both methods gave comparable diagnostic accuracy. CONCLUSION: APRI is a useful marker to screen liver fibrosis in the primary care setting when TE is not available.

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma.

INTRODUCTION: The Asian Pacific Association for the Study of the Liver (APASL) convened an international working party on the management of hepatocellular carcinoma (HCC) in December 2008 to develop consensus recommendations. METHODS: The working party consisted of expert hepatologist, hepatobiliary surgeon, radiologist, and oncologist from Asian-Pacific region, who were requested to make drafts prior to the consensus meeting held at Bali, Indonesia on 4 December 2008. The quality of existing evidence and strength of recommendations were ranked from 1 (highest) to 5 (lowest) and from A (strongest) to D (weakest), respectively, according to the Oxford system of evidence-based approach for developing the consensus statements. RESULTS: Participants of the consensus meeting assessed the quality of cited studies and assigned grades to the recommendation statements. Finalized recommendations were presented at the fourth APASL single topic conference on viral-related HCC at Bali, Indonesia and approved by the participants of the conference.

Alpha-fetoprotein gene polymorphisms and risk of HCC and cirrhosis.

BACKGROUND: Elevated level of alpha fetoprotein (AFP) is found in approximately 60% of hepatocellular carcinoma (HCC) cases. Other liver diseases including cirrhosis and chronic hepatitis are related with an increased level of AFP. The regulation of AFP gene expression has been relatively less studied although the gene has been suggested to play a role in HCC development. This study aimed at identifying genetic variations in AFP that might be associated with the presence of HCC and cirrhosis among ethnic Indonesians. METHODS: Direct DNA sequencing was carried out to sequence AFP promoter, exons, and 3' untranslated region (UTR) in DNA samples isolated from 119 HCC, 119 cirrhosis and 105 control subjects. For each sample serum AFP level was determined and association studies with single nucleotide polymorphisms (SNPs) and haplotypes were performed. RESULTS: In this study we identified 47 SNPs in the AFP gene. Statistically significant associations with HCC and cirrhosis were detected for six individual SNPs in the AFP promoter, AFP intron 1 and intron 2 (rs6834059, rs3796678, rs3796677, rs3796676, rs28532518 and rs4646038). Furthermore, we identified two SNPs in AFP intron 7 and 3'UTR, rs2298839 and rs10020432, which are associated with increased risk of cirrhosis. CONCLUSION: Genetic variants in the AFP gene may be associated with HCC and cirrhosis risk for ethnic Indonesians.

Hepatitis B virus subgenotypes and basal core promoter mutations in Indonesia.

AIM: To identify the distribution of hepatitis B virus (HBV) subgenotype and basal core promoter (BCP) mutations among patients with HBV-associated liver disease in Indonesia. METHODS: Patients with chronic hepatitis (CH, n = 61), liver cirrhosis (LC, n = 62), and hepatocellular carcinoma (HCC, n = 48) were included in this study. HBV subgenotype was identified based on S or preS gene sequence, and mutations in the HBx gene including the overlapping BCP region were examined by direct sequencing. RESULTS: HBV genotype B (subgenotypes B2, B3, B4, B5 and B7) the major genotype in the samples, accounted for 75.4%, 71.0% and 75.0% of CH, LC and HCC patients, respectively, while the genotype C (subgenotypes C1, C2 and C3) was detected in 24.6%, 29.0%, and 25.0% of CH, LC, and HCC patients, respectively. Subgenotypes B3 (84.9%) and C1 (82.2%) were the main subgenotype in HBV genotype B and C, respectively. Serotype adw2 (84.9%) and adrq+ (89.4%) were the most prevalent in HBV genotype B and C, respectively. Double mutation (A1762T/G1764A) in the BCP was significantly higher in LC (59.7%) and HCC (54.2%) than in CH (19.7%), suggesting that this mutation was associated with severity of liver disease. The T1753V was also higher in LC (46.8%), but lower in HCC (22.9%) and CH (18.0%), suggesting that this mutation may be an indicator of cirrhosis. CONCLUSION: HBV genotype B/B3 and C/C1 are the major genotypes in Indonesia. Mutations in BCP, such as A1762T/G1764A and T1753V, might have an association with manifestations of liver disease.

Diagnostic value of a group of biochemical markers of liver fibrosis in patients with non-alcoholic steatohepatitis.

OBJECTIVE: The objectives of this study were to investigate the use of non-invasive biochemical markers to evaluate the severity of liver fibrosis in patients with non-alcoholic steatohepatitis (NASH). METHODS: This was a cross-sectional study of patients with histopathologically confirmed NASH between January 2005 and December 2006. The patients' characteristics were recorded and the body mass index was calculated for each patient. All patients underwent ultrasound-guided liver biopsy and a fibrosis assessment was performed using the Brunt criteria. The non-invasive laboratory markers measured were insulin resistance, tumor necrosis factor (TNF-alpha), type IV collagen and hyaluronic acid (HA). RESULTS: Thirty patients were recruited, of whom 18 (60%) were men. Their mean age was 45 +/- 13.9 (18-71) years. About 83% of patients had fibrosis stage 1-2. In bivariate analysis, age, TNF-alpha and type IV collagen concentrations showed a weak but significant correlation with the fibrosis stage. When the patients were grouped into mild fibrosis (stages 1-2) and advanced fibrosis (stages 3-4), the mean concentrations of HA and type IV collagen were significantly higher in those with advanced fibrosis than those with mild fibrosis (180.8 +/- 49.63 vs 543.6 +/- 360.45 ng/mL; for HA; P = 0.026 and 125.3 +/- 32.11 vs 288.0 +/- 171.22 ng/mL for type IV collagen; P = 0.010). CONCLUSION: Our study showed that the degree of liver fibrosis was significantly correlated with age, TNF-alpha and type IV collagen concentrations. The level of HA and type IV collagen could differentiate between mild (F1-2) and advanced fibrosis (F3-4).