Publications (74) View all
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Article: Synergistic Effects of Family History of Hepatocellular Carcinoma and Hepatitis B Virus Infection on Risk for Incident Hepatocellular Carcinoma.
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ABSTRACT: BACKGROUND: & Aims: Little is known about the effects of family history of hepatocellular carcinoma (HCC) on hepatitis B progression or risk of HCC. We examined how family HCC history, and presence or stage of hepatitis B virus (HBV) infection, affect risk for HCC. METHODS: We performed a population-based cohort study of 22,472 participants from 7 townships in Taiwan who underwent evaluation for liver disease from 1991 through 1992. Those who received a first diagnosis of HCC from January 1, 1991 to December 31, 2008 were identified from the Taiwanese cancer registry. RESULTS: There were 374 cases of incident HCC over 362,268 person-years of follow-up. The cumulative risk of HCC in HB surface antigen (HBsAg) sero-negative patients without a family history of HCC was 0.62%, in those with a family history was 0.65%, in HBsAg sero-positive patients without a family history of HCC was 7.5%, and in HBsAg sero-positive patients with a family history was 15.8% (P<.001). The multivariate-adjusted hazard ratio for HBsAg seropositive individuals with family history, compared with HBsAg sero-negative individuals without family history of HCC, was 32.33 (95% confidence interval, 20.8-50.3; P<.001). The relative excess risk due to interaction was 19, the attributable proportion was 0.59, and the synergy index value was 2.54. These findings indicate synergy between family HCC history and HBsAg serostatus. The synergy between these factors remained significant in stratification analyses by HBeAg serostatus and serum level of HBV DNA. CONCLUSIONS: Family history of HCC multiplies the risk of HCC at each stage of HBV infection. Patients with a family history of HCC require more intensive management of HBV infection and surveillance for liver cancer.Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 05/2013; · 5.64 Impact Factor -
Article: Prediction models of long-term cirrhosis and HCC risk in chronic hepatitis B patients: Risk scores integrating host and virus profiles.
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ABSTRACT: BACKGROUND & AIMS: Integrating host and HBV characteristics, this study aimed to develop models for predicting long-term cirrhosis and hepatocellular carcinoma risk in chronic hepatitis B patients. METHODS: This analysis included HBsAg-seropositive and anti-HCV-seronegative participants from R.E.V.E.A.L.-HBV cohort. The newly-developed cirrhosis and hepatocellular carcinoma was ascertained through regular follow-up ultrasonography, computerized linkage with national health databases, and medical chart reviews. Two-thirds participants were allocated for risk model derivation and another one-third for model validation. The risk prediction model included age, gender, HBeAg serostatus, serum levels of HBV DNA, and alanine aminotransferase (ALT), quantitative serum HBsAg levels and HBV genotypes. The family history was included in prediction model for hepatocellular carcinoma additionally. Cox's proportional hazards regression coefficients for cirrhosis and hepatocellular carcinoma predictors were converted into risk scores. The areas under receiver operating curve (AUROCs) were used to evaluate the performance of risk models. Results: Elder age, male, HBeAg, genotype C, and increasing levels of ALT, HBV DNA and HBsAg were all significantly associated with an increased risk of cirrhosis and hepatocellular carcinoma. The risk scores estimated from the derivation set could accurately categorize participants with low, medium and high cirrhosis and hepatocellular carcinoma risk in validation set (p<0.001). The AUROCs for predicting 3-, 5- and 10-year cirrhosis risk ranged 0.83-0.86 and 0.79-0.82 for the derivation and validation set, respectively. The AUROC for predicting 5-, 10-, 15-year risk of hepatocellular carcinoma ranged 0.86-0.89 and 0.84-0.87 in the derivation and validation set, respectively. CONCLUSIONS: The risk prediction models of cirrhosis and hepatocellular carcinoma by integrating host and HBV profiles have excellent prediction accuracy and discriminatory ability. They may be used for clinical management of chronic hepatitis B patients. (HEPATOLOGY 2013.).Hepatology 03/2013; · 11.66 Impact Factor -
Article: Predictability of liver-related seromarkers for the risk of hepatocellular carcinoma in chronic hepatitis B patients.
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ABSTRACT: Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is a major global health problem. A few risk calculators have been developed using mainly HBV seromarkers as predictors. However, serum HBV DNA level, HBV genotype, and mutants are not routinely checked in regular health examinations. This study aimed to assess the predictability of HCC risk in chronic hepatitis B patients, using a combination of liver-related seromarkers combined with or without HBV seromarkers. A prospective cohort of 1,822 anti-HCV-seronegative chronic HBV carriers was included in this study. Liver-related seromarkers including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alpha-fetoprotein (AFP), gamma-glutamyltransferase (GGT), total bilirubin, total protein, albumin, serum globulins, apolipoprotein A1, and apolipoprotein B were examined. Hazard ratios of HCC with 95% confidence intervals were estimated using Cox proportional hazards regression models. Regression coefficients of seromarkers significantly associated with HCC risk in multivariate analyses were used to create integer risk scores. The predictability of various risk models were assessed by area under receiver operating characteristic curves (AUROCs). During a median follow-up of 5.9 years, 48 newly-developed HCC cases were ascertained. Elevated serum levels of ALT (≥28 U/L), AFP (≥5 ng/mL), and GGT (≥41 U/L), an increased AST/ALT ratio (AAR, ≥1), and lowered serum levels of albumin (≤4.1 g/dL) and alpha-1 globulin (≤0.2 g/dL) were significantly associated with an increased HCC risk (P<0.05) in multivariate analysis. The risk model incorporating age, gender, AAR, and serum levels of ALT, AFP, GGT, albumin, and alpha-1 globulin had an AUROC of 0.89 for predicting 6-year HCC incidence. The AUROC was 0.91 after the addition of HBV seromarkers into the model, and 0.83 for the model without liver-related seromarkers, with the exception of ALT. Liver-related seromarkers may be combined into useful risk models for predicting HBV-related HCC risk.PLoS ONE 01/2013; 8(4):e61448. · 4.09 Impact Factor -
Article: A Predictive Scoring System for the Seroclearance of HBsAg in HBeAg-seronegative Chronic Hepatitis B Patients with Genotype B or C Infection.
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ABSTRACT: BACKGROUND: Seroclearance of hepatitis B surface antigen (HBsAg) is the most ideal endpoint in the treatment of chronic hepatitis B. This study develops a predictive scoring system to assess whether the addition of serum levels HBsAg may improve the predictability of HBsAg loss. METHODS: This study included 2491 untreated participants with genotype B or C HBV infection, who were HBsAg-seropositive, HBeAg-seronegative, anti-HCV-seronegative, and cirrhosis free at study entry. Regression coefficients of predictors in Cox Regression models were converted into integer scores for predicting HBsAg seroclearance. Predictive accuracy was assessed with area under the receiver operating characteristic curves (AUROC), and predictive accuracies of models with and without serum HBsAg levels were compared. [Results] Low serum levels of both HBsAg and HBV DNA were the strongest predictors of spontaneous HBsAg seroclearance. Compared to baseline serum HBsAg levels ⩾1000 IU/mL, the multivariate adjusted rate ratio of spontaneous HBsAg seroclearance was 10.96 (7.92-15.16) for those with baseline serum HBsAg levels <100 IU/mL. The predictive ability of HBsAg levels was modified by HBV viral load, showing a weaker effect in those with higher viral loads, and the strongest effect among those with undetectable viral loads. The inclusion of serum HBsAg levels greatly improved the AUROC for predicting HBsAg seroclearance at the fifth (from 0.79 [0.787-0.792] to 0.89 [0.889-0.891]) and tenth year (from 0.73 [0.728-0.732] to 0.84 [0.839-0.841]) after study entry. CONCLUSION: Incorporated into an easy-to-use scoring system, HBV viral load and quantitative serum HBsAg levels can accurately predict HBsAg seroclearance.Journal of Hepatology 12/2012; · 9.26 Impact Factor -
Article: Association of body mass index and risk of death from pancreas cancer in Asians: findings from the Asia Cohort Consortium.
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ABSTRACT: We aimed to examine the association between BMI and the risk of death from pancreas cancer in a pooled analysis of data from the Asia Cohort Consortium. The data for this pooled analysis included 883 529 men and women from 16 cohort studies in Asian countries. Cox proportional-hazards models were used to estimate the hazard ratios and 95% confidence intervals for pancreas cancer mortality in relation to BMI. Seven predefined BMI categories (<18.5, 18.5-19.9, 20.0-22.4, 22.5-24.9, 25.0-27.4, 27.5-29.9, ≥30) were used in the analysis, with BMI of 22.5-24.9 serving as the reference group. The multivariable analyses were adjusted for known risk factors, including age, smoking, and a history of diabetes. We found no statistically significant overall association between each BMI category and the risk of death from pancreas cancer in all Asians, and obesity was unrelated to the risk of mortality in both East Asians and South Asians. Age, smoking, and a history of diabetes did not modify the association between BMI and the risk of death from pancreas cancer. In planned subgroup analyses among East Asians, an increased risk of death from pancreas cancer among those with a BMI less than 18.5 was observed for individuals with a history of diabetes; hazard ratio=2.01 (95% confidence interval: 1.01-4.00) (P for interaction=0.07). The data do not support an association between BMI and the risk of death from pancreas cancer in these Asian populations.European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 10/2012; · 2.21 Impact Factor
