M.-L. Yu

621 A simple non-invasive index for predicting long-term outcome of chronic hepatitis C after interferon-based therapy

Changes in hepatic fibrosis after interferon-based therapy may be important in determining the long-term outcome of chronic hepatitis C (CHC). The use of liver biopsy for posttreatment assessment is not a viable option as a routine follow-up procedure. This study evaluated the predictive value of a simple noninvasive index, the aspartate aminotransferase (AST)-to-platelet ratio index assessed 6 months after end of treatment (APRI-M6). We evaluated APRI-M6, platelet-M6, AST-M6, and alpha-fetoprotein-M6 of 776 CHC patients with interferon-based therapy as well as the parameters at baseline of 562 untreated patients who were evaluated to predict the risk of hepatocellular carcinoma (HCC) and mortality, during a mean follow-up period of 4.75 (1.0-12.2) and 5.15 (1.0-16) years, respectively. Based on analysis of receiver operating characteristics (ROC) and using optimized cutoff point, the APRI-M6 and platelet-M6 had superior prediction models for long-term outcome with area under the curve of 0.870-0.875 and 0.824-0.847, respectively, and accuracy of 78%-81% and 76%-78%, respectively, for interferon-based-treated patients. The predictive values of all 4 parameters were poor in untreated patients. In subgroup analysis, the APRI-M6 provided a more consistent prediction ratio than platelet-M6 for sustained responders and cirrhosis-free subgroups; both parameters had similar prediction power for nonresponders and were unsatisfactory in patients with cirrhosis. According to Cox proportional hazards analysis, cirrhosis and APRI-M6 were the 2 most important factors for predicting HCC. In conclusion, APRI-M6 can accurately predict the long-term outcome of patients subjected to interferon-based treatment. Nevertheless, the data needs further validation, particularly since the predictive accuracy for patients with cirrhosis is low.

Viral hepatitis and proteinuria in an area endemic for hepatitis B and C infections: another chain of link?

Background and objectives.  Virus hepatitis may lead to nephropathy as one of its multiple extrahepatic manifestations. Proteinuria by dipstick, a simple test in practice, is a useful and cardinal sign of underlying renal abnormalities. The aim of this study was to elucidate the impact of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections on the occurrence of proteinuria amongst adults.

Sustained virological response to interferon reduces cirrhosis in chronic hepatitis C: a 1386‐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.

Hepatic focal nodular hyperplasia: findings on color Doppler ultrasound

Abstract.Background: We assessed the color Doppler ultrasound (US) findings in focal nodular hyperplasia (FNH). Methods: Seven FNH lesions were imaged with color Doppler US and hepatic angiography. Results: In four lesions, color Doppler demonstrated a central stellate vascular appearance which correlated with central feeding artery with spoke-wheel sign angiographically. Except for one lesion, color Doppler US imaging correlated with angiographic findings. Conclusions: Color Doppler US is capable of demonstrating the typical findings of a central feeding artery and stellate vascular pattern in many cases of FNH.

The role of thyroid autoantibodies in the development of thyroid dysfunction in Taiwanese chronic hepatitis C patients with interferon‐alpha and ribavirin combination therapy

Summary.  To investigate the role of thyroid autoantibodies in the development of thyroid dysfunction among chronic hepatitis C (CHC) patients receiving interferon‐alpha (IFN‐α) plus ribavirin (RBV) combination therapy, 95 Taiwanese naïve patients with baseline euthyroidism were enrolled. They were treated with IFN‐α2b, 6 million units thrice weekly, plus RBV 1000–1200 mg daily for 24 weeks. Thyroid function, anti‐thyroglobulin and antiperoxidase autoantibodies were tested at enrolment (M0), at the end‐of‐treatment (M6) and 6 months after end‐of‐treatment (M12). The percentages of thyroid autoantibodies were 8.4%, 11.6% and 9.5%, at M0, M6 and M12 respectively. Fourteen (14.7%) patients developed thyroid dysfunction at M6 or M12. Thyroid dysfunction occurred during treatment in five (62.5%) of the eight patients with baseline thyroid autoantibodies, which was significantly higher than nine (10.3%) of 87 patients without baseline thyroid autoantibodies (P = 0.0001). Among 14 patients who developed thyroid dysfunction, four (80.0%) of five patients with baseline thyroid autoantibodies recovered at M12, in contrast to two (25%) of eight without baseline thyroid autoantibodies recovered at M12 (P < 0.05). In conclusion, thyroid autoantibodies, either occurred before or during IFN‐α plus RBV combination therapy, carry a high prediction of subsequent thyroid dysfunction. There also exists difference in the clinical manifestations of thyroid dysfunction in CHC patients treated with combination therapy.

Serum insulin-like growth factor-II as a serologic marker of small hepatocellular carcinoma

Objective Alpha-fetoprotein (AFP) is not a useful tumor marker for diagnosis of small hepatocellular carcinoma (HCC). There is over-expression of insulin-like growth factor (IGF)-II in HCC tissue. This study investigates the diagnostic application of IGF-II in small HCC. Material and methods Serum levels of IGF-II and AFP were determined in 41 patients with small cirrhotic HCC (≤3 cm), 41 sex- and age-matched patients with cirrhosis alone (LC), and 41 healthy adults. The optimal cut-off values for diagnosing HCC were determined with receiver operating characteristics (ROC) curve. Results Both IGF-II and AFP levels in HCC were higher than those in LC patients or controls (each p=0.0001). The IGF-II levels in LC patients were lower than those in controls (p=0.001). In HCC patients, multivariate analysis indicated that that both IGF-II (odds ratio, 4.54; 95% confidence interval, 2.15–9.55; p=0.0001) and AFP (odds ratio, 1.05; 95% confidence interval, 1.01–1.08; p=0.003) were found to be associated with an increased risk of presence of HCC. The optimal cut-off values of IGF-II (4.1 mg/g prealbumin) and AFP (50 ng/ml) were determined with ROC curves. The sensitivity, specificity, and diagnostic accuracy values for IGF-II were 63%, 90%, and 70%, respectively. Those for AFP were 44%, 95%, and 70%, respectively. Determination of both markers in parallel significantly increase the diagnostic accuracy (88%) and sensitivity (80%), with a high specificity (90%). Conclusions Serum IGF-II level can be used as an independent serologic marker or a complementary tumor marker to AFP for diagnosis of small HCC.

Serum Insulin-Like Growth Factor-II and α-Fetoprotein as Tumor Markers of Hepatocellular Carcinoma

To evaluate the diagnostic application of serum insulin-like growth factor-II (IGF-II) and α-fetoprotein (AFP) levels in hepatocellular carcinoma (HCC), IGF-II and AFP were determined in 100 cirrhotic patients with HCC, 100 sex- and age-matched patients with cirrhosis alone and 50 healthy controls. The results indicated that IGF-II and AFP levels in patients with HCC were higher than in those with cirrhosis alone (p = 0.0001). There is an inverse correlation between IGF-II and logAFP (r = –0.410, p = 0.0001) in patients with HCC. Multivariate analysis indicated that IGF-II and AFP were closely associated, in a dose-related fashion, with the presence of HCC. Receiver operating characteristic curves were used to determine the optimal cutoff values of IGF-II (4.5 mg/g prealbumin) and AFP (100 ng/ml), respectively. Both IGF-II and AFP show a high specificity and positive likelihood ratio. The sensitivity was 42.0% for IGF-II and 73.0% for AFP. Determination of both markers in parallel significantly increased the diagnostic accuracy (96.5%) and sensitivity (97.9%), with a high specificity (95.1%) and positive likelihood ratio (19.9). In conclusion, IGF-II and AFP may be used as complementary tumor markers to discriminate HCC from cirrhosis.

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

Summary.  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.

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 γ-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‐α–based therapy frequently leads to neutropenia. It remains unclear whether neutropenia is associated with bacterial infection in chronic hepatitis C (CHC).