J.-F. Tsai

Effect of hepatitis C and B virus infection on risk of hepatocellular carcinoma : a prospective study

To assess whether there is an additive effect between chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection on the development of hepatocellular carcinoma (HCC), 400 consecutive cirrhotic patients were followed prospectively with periodic abdominal ultrasound examination and measurement of serum alpha-fetoprotein (AFP) level every 4 months. During a follow-up of 1185 person-years, 80 (20%) patients developed HCC, with an annual incidence of 6.8%. The annual incidence was 2.0% in patients negative for hepatitis B surface antigen (HBsAg) and antibodies to HCV (anti-HCV), 6.6% in patients with HBsAg alone, 7.0% in patients with anti-HCV alone and 13.3% in patients co-infected with HBV and HCV. There was a positive linear trend in the annual incidence of HCC among patients without either marker, patients with single viral infection and patients with dual viral infection (P[for trend] < 0.0001). Coxs proportional hazard model indicated that HCV/HBV co-infection [hazard ratio (HR), 6.41; 95% confidence interval (CI), 1.80-22.80], anti-HCV alone (HR, 3.74; 95% CI, 1.07-13.07) and HBsAg alone (HR, 4.06; 95% CI, 1.23-13.34) were independently risk factors of HCC. In conclusion, there is an additive and independent effect modification of HCV and HBV infection on HCC development.

Associations between hepatitis C viremia and low serum triglyceride and cholesterol levels: A community-based study

BACKGROUND/AIMS To evaluate the association of virologic status with serum cholesterol and triglyceride levels in individuals with hepatitis C virus (HCV) infection. METHODS We conducted a large scale community-based study enrolling 11,239 residents in an area endemic for hepatitis B virus (HBV) and HCV infection in southern Taiwan. Overall, 703 (6.3%), 1,536 (13.7%), 84 (0.7%) and 9,084 (80.8%) subjects were sero-positive for anti-HCV antibody (anti-HCV), hepatitis B surface antigen (HBsAg), and both anti-HCV and HBsAg, and negative for anti-HCV and HBsAg, respectively. RESULTS By multivariate logistic analyses, the independent factors significantly associated with elevated serum cholesterol level were older age, female, negative for diabetes, anti-HCV or HBsAg and elevated triglyceride levels. The independent factors significantly associated with elevated serum triglyceride level were male, positive for diabetes, negative for anti-HCV or HBsAg, higher body mass index (BMI) and elevated cholesterol levels. Of 642 anti-HCV-positive subjects that have HCV RNA tested by standardized automated qualitative PCR assay, 478 (74.5%) were positive for HCV RNA. By multivariate logistic analyses, the independent factors associated with elevated serum cholesterol level were female, elevated serum triglyceride levels, negative for diabetes or HCV RNA. The independent factors associated with elevated serum triglyceride levels were elevated serum cholesterol levels, positive for diabetes, higher BMI and negative for HCV RNA. Diabetes, lower cholesterol and triglyceride levels were independent factors associated with positive HCV RNA. CONCLUSIONS Based on the result of this large scale community study, HCV viremia appears to be associated with lower serum cholesterol and triglyceride levels which implies that HCV itself might play a significant role on serum lipid profile of patients with chronic HCV infection.

Elevated urinary transforming growth factor-beta1 level as a tumour marker and predictor of poor survival in cirrhotic hepatocellular carcinoma.

To assess the clinical relevance of transforming growth factor-beta1 (TGF-beta1) in hepatocellular carcinoma (HCC), urinary TGF-beta1 and serum alpha-fetoprotein (AFP) were determined in 94 patients with cirrhotic HCC, 94 age- and sex-matched patients with cirrhosis alone and 50 healthy adults. TGF-beta1 level in HCC was higher than in cirrhosis alone or in healthy controls (each P = 0.0001). There is an inverse correlation between TGF-beta1 and AFP levels (r = -0.292, P = 0.004). Significantly higher TGF-beta1 level was found in HCC patients with worsening Child-Pugh stages, diffuse HCC, tumour size > 3 cm, multilobular tumour and AFP < or = 20 ng ml(-1). TGF-beta1 level decreased after complete treatment with transcatheter arterial chemoembolization (P = 0.0001). The median survival in HCC patients with raised TGF-beta1 was shorter than those with normal TGF-beta1 (P = 0.018). Multivariate analysis indicated that TGF-beta1 and AFP were significantly correlated with the presence of HCC. In addition, TGF-beta1 could be used as a diagnostic marker for HCC, particularly in tumours with low AFP production. In conclusion, elevated urinary TGF-beta1 level is a tumour marker and predictor of poor survival for cirrhotic HCC.

Betel quid chewing as a risk factor for hepatocellular carcinoma : a case-control study

The role of betel quid chewing in the aetiology of hepatocellular carcinoma (HCC) was evaluated in a case–control study including 263 pairs of age- and sex-matched HCC patients and healthy controls. Serum hepatitis B surface antigen (HBsAg), and antibodies to hepatitis C virus (anti-HCV) were determined, and standardized personal interview conducted using a structured questionnaire. Multivariate analysis indicated that betel quid chewing (odds ratio (OR), 3.49; 95% confidence interval (CI), 1.74–6.96), HBsAg (OR, 16.69; 95% CI, 9.92–28.07), anti-HCV (OR, 38.57; 95% CI, 18.15–81.96), and educational duration of less than 10 years (OR, 1.71; 95% CI, 1.05–2.78) are independent risk factors of HCC. In addition, there was an additive interaction between betel quid chewing and chronic infection with either hepatitis B virus (synergy index, 5.37) or hepatitis C virus (synergy index, 1.66). Moreover, risk on HCC increased as duration of betel quid chewing increased, or amount of betel quid consumed (each P for trend < 0.0001).

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.

Additive effect modification of hepatitis B surface antigen and e antigen on the development of hepatocellular carcinoma

To assess the role of hepatitis B e antigen (HBeAg) and its interaction with hepatitis B surface antigen (HBsAg) on the development of hepatocellular carcinoma (HCC), this case-control study included 361 age- and sex-matched pairs of patients with histologically proven HCC and healthy control subjects. HBsAg, HBeAg and antibody to HBeAg (anti-HBe) were detected by radioimmunoassay. Antibodies to hepatitis C virus (anti-HCV) were detected by second-generation enzyme immunoassay. The prevalences of HBeAg (20.2%), HBsAg (80.3%) and anti-HCV (29.5%) in cases were higher than in controls (1.9%, 20.7%, and 2.7% respectively; each P < 0.0001). Using patients negative for HBsAg, HBeAg and anti-HBe as a referent group, univariate analysis indicated that HBsAg alone or HBsAg and HBeAg were risk factors for HCC (P for trend < 0.0001). Calculation of incremental odds ratio indicated that there was additive interaction between HBsAg and HBeAg. Multivariate analysis indicated that HCC development was strongly associated with the presence of HBeAg (odds ratio, 8.1; 95% confidence interval, 2.4-27.1), HBsAg (odds ratio, 68.4; 95% confidence interval, 20.5-227.8) and anti-HCV (odds ratio, 59.3; 95% confidence interval, 13.6-258.4). In conclusion, HBsAg, HBeAg and anti-HCV are independent risk factors for HCC. There is additive and independent effect modification between HBsAg and HBeAg on the development of HCC.

Frequency of raised alpha-fetoprotein level among Chinese patients with hepatocellular carcinoma related to hepatitis B and C.

Antibody to hepatitis C virus (anti-HCV) was found to be an independent risk factor for hepatocellular carcinoma and raised serum alpha-fetoprotein (AFP) level. In addition, the frequency of raised AFP in patients with anti-HCV was higher than in those without (91.5% vs 65.2%, P = 0.0001).

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.

Clinical evaluation of serum alpha-fetoprotein and circulating immune complexes as tumour markers of hepatocellular carcinoma.

To evaluate the diagnostic application of serum alpha-fetoprotein (AFP) and circulating immune complexes (CICs), AFP, 3% polyethylene glycol (PEG)-CICs, 4% PEG-CICs, and C1q-CICs were determined in 101 patients with cirrhosis alone, 101 sex-matched and age-matched cirrhotic patients with hepatocellular carcinoma (HCC) and 54 healthy controls. Multivariate analysis indicated that AFP (odds ratio 1.014; 95% confidence interval 1.004-1.024) and 3% PEG-CICs (odds ratio 1.011; 95% confidence interval 1.005-1.017) are associated, in a dose-related fashion, with an increased risk for HCC. A receiver operative characteristic (ROC) curve was used to determine the optimal cut-off values of AFP (120 ng ml-1) and 3% PEG-CICs (310 micrograms aggregated IgG equivalent ml-1). The area under ROC curve was 0.875 for AFP and 0.812 for 3% PEG-CIC. Both AFP and 3% PEG-CICs show a high specificity (100%) and positive likelihood ratio. The sensitivity was 65.3% for 3% PEG-CICs and 67.3% for AFP. Determination of both markers in parallel significantly increase the diagnostic accuracy (92.1%) and sensitivity (84%), with a high specificity (100%) and positive likelihood ratio (> 84). In conclusion, both 3% PEG-CICs and AFP are independent risk factors of HCC, and may be used as complementary tumour markers to discriminate HCC from cirrhosis. Determination of 3% PEG-CICs should be performed in cirrhotics negative for AFP to improve detection of HCC.

Hepatitis C Virus Infection among Patients with Chronic Liver Disease in an Area Hyperendemic for Hepatitis B

BACKGROUND The prevalence of hepatitis C virus (HCV) infection was assessed in patients with non-alcoholic chronic liver disease (CLD). METHODS Antibody levels to HCV (anti-HCV) were assessed in 100 pairs of CLD patients and healthy controls. RESULTS The prevalence of anti-HCV was higher in patients (26.0%) than in controls (2.0%; p = 0.0001). The patient group with anti-HCV was older (p = 0.0001) and had more smokers (p = 0.034), fewer hepatitis B surface antigen carriers (p = 0.0001), and more patients with active liver disease (p = 0.023) and a history of blood transfusion (p = 0.026). Multivariate analysis showed that anti-HCV (odds ratio, 8.1; 95% confidence intervals, 3.7-17.6) was strongly associated with CLD. CONCLUSIONS HCV infection is a risk factor of non-alcoholic CLD, and HCV causes more severe hepatocellular damage than HBV.