Abnormal liver function test results are related to metabolic syndrome and BMI in Taiwanese adults without chronic hepatitis B or C.

BACKGROUND: Metabolic syndrome (MS) is considered a cause of abnormal deposition of fat into hepatocytes, which might be associated with hepatic steatosis or abnormal liver function. OBJECTIVE: The aim of this study was to explore the factors associated with MS and the relationship between MS and abnormal aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) levels in Taiwanese subjects without chronic hepatitis B (CHB) or C (CHC). SUBJECTS: We enrolled 2539 Taiwanese adults without CHB or CHC (age range: 16-88 years old) and investigated the factors related to MS using the NCEP-ATP (National Cholesterol Education Program-Adult Treatment Panel) III criteria; body mass index (BMI) was measured using Asia-Pacific criteria. RESULTS: The prevalence rate of MS in Taiwanese adults without CHB or CHC was 16.9% using the modified ATP III criteria and 15.4% using the International Diabetes Federation criteria. Males had a significantly higher prevalence rate than females (P<0.001), and subjects with MS were significantly older and had significantly higher BMI values and AST, ALT and GGT levels (all P<0.001). In univariate analyses, the abnormality of liver function test results were related to gender, level of fasting sugar, systolic blood pressure, triglyceride, high-density lipoprotein, BMI and MS (all P<0.05). Multivariate analysis showed that the male gender, a higher BMI value and MS were related to abnormal liver function test results. The cutoff value for ALT in relation to MS is 31 IU l(-1) for male and 18 IU l(-1) for female. CONCLUSION: The prevalence of MS in Taiwanese adults without hepatitis B or C was found to be high, and MS and BMI were identified as being related to abnormal liver function test results in these adults.

Bacterial infection and neutropenia during peginterferon plus ribavirin combination therapy in patients with chronic hepatitis C with and without baseline neutropenia in clinical practice.

BACKGROUND: Peginterferon-alpha-based therapy frequently leads to neutropenia. It remains unclear whether neutropenia is associated with bacterial infection in chronic hepatitis C (CHC). AIM: To evaluate the risk of bacterial infection and neutropenia in patients with CHC treated with peginterferon-alpha/ribavirin. METHODS: In all, 207 patients with CHC with (group A, n = 30) and without (group B, n = 177) baseline neutropenia were treated with peginterferon-alpha/ribavirin. RESULTS: Group A had significantly higher rates of moderate (<750 cells/microL) and severe (<500 cells/microL) neutropenia than group B (70.0% and 26.7% vs. 20.3% and 8.5% respectively, both P < 0.0001). The sustained virological response rate was similar between patients with and without neutropenia, at baseline or during treatment. Bacterial infection occurred in 4.3% of patients. Group A and patients with lower baseline neutrophil counts had substantially higher rates of bacterial infection. Patients with cirrhosis had significantly higher rates of infection during combination therapy than those without cirrhosis (15%, 3 of 20 vs. 3.2%, 6 of 187, P = 0.045). Nadir neutrophil counts were not correlated to infection episodes. CONCLUSIONS: Bacterial infection during peginterferon-based therapy for CHC was associated with comorbidity of cirrhosis, but not with neutropenia, whether at baseline or during treatment. Neutropenic CHC patients might be treated safely with close monitoring.

Antinuclear antibody is associated with a more advanced fibrosis and lower RNA levels of hepatitis C virus in patients with chronic hepatitis C.

AIMS: Positive serum antinuclear antibody (ANA) is present in a number of patients with chronic hepatitis C virus (HCV) infection. This study aimed to evaluate the prevalence of ANA in patients with chronic hepatitis C (CHC) and to elucidate its clinical implications in virological and histological characteristics of CHC infection. METHODS: A total of 614 CHC patients were enrolled in this prospective, hospital-based study. The serum levels of aspartate aminotransferase, alanine aminotransferase and ANA, and HCV genotype, HCV RNA level, and histological activity index scores for liver histopathology, were determined. RESULTS: The prevalence of positive ANA (titre >1:40) was 35.0%. Women had a significantly higher prevalence than men (41.2 vs 31.0%; p = 0.012). Patients positive for ANA were significantly older (mean (SD), 53.7 (10.5) vs 49.7 (11.3) years; p<0.001) and had higher mean (SD) alanine aminotransferase levels (186.9 (178.8) vs 155.50 (113.5) IU/l; p<0.001) and lower mean (SD) HCV RNA levels (5.2 (0.9) vs 5.4 (1.0) log IU/ml; p = 0.048) than those without ANA. Among 447 patients undergoing liver biopsy, those positive for ANA had a significantly higher mean (SD) fibrosis score (2.0 (1.3) vs 1.5 (1.1); p<0.001) and a higher frequency of F3-4 (69/187, 36.9% vs 50/260, 19.2%; p<0.001) than those negative for ANA. Multivariate logistic regression analyses showed that advanced fibrosis, lower HCV RNA levels and age were significant factors related to positive ANA. CONCLUSION: ANA is associated with a more advanced liver fibrosis and lower serum HCV RNA level in patients with CHC.

Sustained virological response to interferon reduces cirrhosis in chronic hepatitis C: a 1,386-patient study from Taiwan.

BACKGROUND: The long-term benefits of interferon-based therapy on preventing cirrhosis at non-cirrhotic stage in chronic hepatitis C patients are not fully clarified. AIM: To evaluate the effectiveness of interferon-based therapy regarding to cirrhosis prevention in non-cirrhotic chronic hepatitis C patients. METHODS: A total of 1386 biopsy-proven, non-cirrhotic chronic hepatitis C patients (892 received interferon-based therapy and 494 untreated) were enrolled. RESULTS: Fifty-six untreated and 51 treated (24 sustained virologic responders and 27 non-responders) patients developed cirrhosis during a mean follow-up period of 5.0 (1-16) and 5.1 (1-15.3) years, respectively. The annual incidences of cirrhosis in untreated and treated groups were 2.26 and 1.11% (non-responders: 1.99%, sustained responders: 0.74%), respectively. The 15-year cumulative incidence of cirrhosis was significantly lower in treated (9.9%) than untreated patients (39.8%, P = 0.0008, log-rank test). The 14.5-year cumulative incidence of cirrhosis was significantly lower in sustained responders (4.8%) compared with non-responders (21.6%, P = 0.0007) and untreated patients (36.6%, P < 0.0001). The difference was not significant between non-responders and untreated controls. Cox proportional hazards regression showed sustained virologic responders and younger age were independent negative factors for cirrhosis development. CONCLUSION: A sustained virologic response secondary to IFN-based therapy could reduce cirrhosis development in chronic hepatitis C patients.

Associations of tumour necrosis factor alpha promoter polymorphisms at position -308 and -238 with clinical characteristics of chronic hepatitis C.

The aim of this study was to investigate the association between G vs A transitions in the promoter region of the tumour necrosis factor (TNF) alpha at positions -308 (TNF308.2) and -238 (TNF238.2) and clinical features of chronic hepatitis C (CHC). These two promoter TNF-alpha variants were determined in 250 biopsy-proven CHC patients by polymerase chain reaction amplification, followed by the Restriction Fragment Length Polymorphism (RFLP) method. The distribution of -308 and -238 TNF-alpha promoter genotypes were TNF308.1/TNF308.1: 187 (74.8%), TNF308.1/TNF308.2: 57 (22.8%) and TNF308.2/TNF308.2: 6 (2.4%), respectively, and TNF238.1/TNF238.1: 247 (98.8%) and TNF238.1/TNF238.2: 3 (1.2%). The frequencies of the TNF308.2 and TNF238.2 promoter alleles were 13.8% and 0.6%. Increased TNF308.2 allele copy numbers were significantly associated with increased frequency of lower pretreatment hepatitis C virus (HCV) RNA levels (<800 000 IU/mL; P = 0.031) and severe fibrosis stage (F3-F4; P = 0.006) and higher mean fibrosis score (P = 0.007). The higher cytokine production (with one or two TNF308.2 alleles) was correlated significantly with lower pretreatment HCV RNA levels with a lower mean HCV RNA level (P = 0.024) and increased frequency of lower pretreatment HCV RNA levels (<800 000 IU/mL; P = 0.017). Stepwise logistic regression showed that higher fibrosis score and low HCV RNA levels were independently related to the TNF308.2 allele [odds ratio (95% CI): 1.385 (1.127-1.702) and 0.698 (0.488-0.990)]. We conclude that inheritance of the TNF-alpha promoter genotype at the position -308 appears to be associated with variability in severity of fibrosis and viral load in chronic HCV infection.