Dynamics of HBV DNA levels, HBV mutations and biochemical parameters during antiviral therapy in a patient with HBeAg-negative chronic hepatitis B.

Chronic hepatitis B virus (HBV) infection leads to long-term sequelae such as cirrhosis and hepatocellular carcinoma. Antiviral therapy aims at controlling the viral replication and thus, decreasing the likelihood of such complications. In this study, we evaluated the dynamics of biochemical and virological parameters over 10 years of antiviral therapy in a Thai patient with chronic HBeAg-negative HBV infection, who had relapsed after two courses of interferon alfa treatment. Lamivudine administration initially led to a significant reduction in alanine aminotransferase (ALT) and HBV DNA levels, but a subsequent emergence of YIDD mutants caused an ALT flare and a virus breakthrough. A 4-log HBV DNA decrease and normalization of the ALT level were achieved within 3 months of adefovir monotherapy without any relapse during follow-up exceeding 20 months. Thus, careful monitoring during treatment and knowledge of cross-resistance to antiviral salvage therapy are crucial for the management of patients with chronic hepatitis B.

Clinical and virological differences between hepatitis B virus genotypes B and C: a case-control study.

OBJECTIVE: The pathogenic significance of hepatitis B virus (HBV) genotypes is undefined. The aim of this study was to elucidate the differences in clinical and virologicalfeatures between HBV genotypes B and C by conducting a case-control study in Thai patients who were chronically infected with the virus. PATIENTS AND METHOD: HBV genotyping was assessed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) method in stored sera of 470 patients with chronic hepatitis B. Among these, 65 patients with HBV genotype B were enrolled and matched individually to those with HBV genotype C according to sex, age, and distribution of liver disease which included asymptomatic carrier, chronic hepatitis, cirrhosis and hepatocellular carcinoma. RESULTS: Serum alanine aminotransferase (ALT) was significantly higher in patients with genotype C than those with genotype B. Hepatitis B e antigen (HBeAg) was significantly more frequent in genotype C than genotype B patients (50.8 and 30.8%, respectively, p=0.03), but the levels of HBV DNA were comparable between them. Among patients who were positive for HBeAg, the mean age of genotype C patients tended to be older than genotype B patients. CONCLUSION: The present study demonstrated that patients with HBV genotype C had a significantly higher rate of HBeAg, experienced delayed HBeAg seroconversion and exhibited more severe liver disease compared to those with genotype B.

Serum hyaluronan: a marker of liver fibrosis in patients with chronic liver disease.

The aim of this study was to evaluate the clinical significance of serum hyaluronan (HA) as a marker of liver fibrosis in patients with chronic liver disease. Serum HA was measured by an ELISA-based method in 28 patients with chronic hepatitis (CH), 43 patients with liver cirrhosis (LC), 57 patients with hepatocellular carcinoma (HCC) and 60 healthy controls. Mean serum HA concentration in patients with LC was 1,376.80 +/- 2,568.85 ng/ml which was significantly higher than those in patients with CH, HCC and the controls (575.93 +/- 732.58, and 426.36 +/- 687.33, and 117.86 +/- 311.11 ng/ml, respectively). Based on a ROC curve analysis, a cut-off point of 354 ng/ml discriminated between LC and other groups with a sensitivity, specificity and accuracy of 82.4%, 78.2%, and 80.2%, respectively. Mean HA concentrations were correlated with the degree of liver fibrosis, but not the grade of necroinflammatory activity. In patients with LC, the mean serum HA level was significantly increased in the Child C group (3,977.96 +/- 4,906.21 ng/ml) in comparison with the Child B and A groups (1,002.63 +/- 448.55, and 537.90 +/- 424.16 ng/ml, respectively). We conclude that serum HA concentrations reflect the extent of liver fibrosis and severity of cirrhosis. Thus, serum HA can be a diagnostic marker of liver fibrosis and cirrhosis in patients with chronic liver disease.

Comparison of clinical features and survival of patients with hepatitis B- and hepatitis C-associated hepatocellular carcinoma in Thailand.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are leading causes hepatocellular carcinoma (HCC) worldwide. The aim of this study was to determine whether differences do exist between HBV- and HCV-associated HCC in terms of clinical, pathologic features and prognosis among Thai patients. The authors retrospectively reviewed the clinical data of 188 patients with pathologically proven HCC, who were admitted to Chulalongkorn Hospital between January 1997 and December 1999. Of these cases, there were 105 patients (55.9%) with hepatitis B surface antigen (HbsAg) positive, 19 patients (10.1%) with anti-HCV positive, and 2 patients (1.0%) with both markers positive. The authors found that the mean age of patients with HBsAg positive was significantly lower than that of anti-HCV positive (49.2 +/- 12.7 and 58.3 +/- 8.9 years, respectively, p = 0.003). In contrast, the mean serum alpha-fetoprotein level of HBsAg positive group was significantly higher than that of anti-HCV positive group (48,583.6 +/- 109,494.1 and 2,022.7 +/- 4,869.1 IU/ml, respectively, p = 0.001). However, there was no difference between the two groups in terms of the severity of underlying liver disease, tumor histology and morphology, clinical staging, and the overall survival rate of the patients. The authors concluded that, among Thai populations, the majority of clinical features and survival of HBV-associated HCC did not differ from those with HCV-associated HCC.

Caffeine clearance in patients with hepatocellular carcinoma after transcatheter oily chemoembolization treatment.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common neoplasm worldwide, particularly in Asia, with a grave prognosis. Transcatheter Oily Chemoembolization (TOCE) is now universally accepted as the method of choice for the treatment of inoperable HCC. The purpose ofthis study was to evaluate caffeine clearance, a quantitative liver function assessment, in HCC patients before and after treatment with TOCE. METHOD: Both conventional liver function test (LFT) and caffeine clearance were evaluated in twelve patients. Each patient took a 3.5 mg/kg single oral dose of caffeine solution before TOCE, 1 day and 5 weeks after treatment. Blood samples were subsequently collected at 0.5, 1.5, 3, 5, 10 and 24 hours after each dose of caffeine administration and assayed for serum caffeine level by the HPLC technique. Clearance (Cl) was calculated using the equation of Cl = Kel x Vd (Kel = elimination rate constant, Vd = volume of distribution) and half-life was determined using pharmacokinetic analysis. RESULTS: The mean caffeine clearance 1 day after TOCE (0.51 +/- 0.096) and 5 weeks after TOCE treatment (0.43 +/- 0.07) was significantly reduced compared with the mean caffeine clearance before treatment (0.79 . 0.2 ml/min x kg) with the p = 0.06 and p = 0.03, respectively. No significant changes (p > 0.05) in most conventional LFT were observed 5 weeks after treatment. CONCLUSIONS: In the present study, the authors found that caffeine clearance was reduced after TOCE in patients with HCC inspite of no changes in conventional LFT. Thus, the determination of caffeine clearance can serve as a useful parameter for the assessment of hepatic functional reserve in HCC patients post TOCE treatment.

Effectiveness of ranitidine bismuth citrate based triple therapy for treating Helicobacter pylori.

OBJECTIVE: To determine the efficacy, safety and tolerance of a one week regimen of RBC, clarithromycin, and amoxicillin for H. pylori eradication in Thai patients. MATERIAL AND METHOD: Patients who were undergoing endoscopy for dyspeptic symptoms. On the day of endoscopy, three biopsies were taken for H. pylori diagnosis. The patients who had the presence of H. pylori infection by positive from rapid urease test or histologic examination were invited to take part in an open, prospective study. Patients received a combination of RBC 400 mg, clarithromycin 500 mg, and amoxicillin 1 g twice daily for 7 days. Repeated endoscopy was performed to evaluate H. pylori eradication at least 1 month after the end of treatment. Clinical symptoms, side effects and compliance were assessed by interview during the study and at follow-up. RESULTS: Thirty nine patients with H. pylori infection were included. Male and female rates was 27:12 with a mean age of 42.8 +/- 11.4 years (range 21-68). There was a 89.74 per cent eradication rate by intent-to-treat and 94.59 per cent by per-protocol analysis. There were no serious adverse events during the study. Two patients (5.13%) stopped the medication because of side effects. Two patients had failure to eradication after complete treatment. Subjective improvement of the clinical symptoms was found in 92.3 per cent. CONCLUSION: One week's regimen of RBC, clarithromycin, and amoxicillin triple therapy resulted in a relatively high efficacy, safety and tolerance for H. pylori eradication in Thai patients.