Background & Aims: This study investigated whether obesity, diabetes, and other metabolic factors are independently associated with hepatocellular carcinoma (HCC), stratified by hepatitis B virus ...(HBV) and hepatitis C virus (HCV) serostatus, and explored the possible joint influence of obesity/diabetes and HBV/HCV infections on the risk of HCC. Methods: A total of 23,820 residents in Taiwan were recruited and followed up for 14 years. All analyses were stratified by hepatitis B surface antigen (HBsAg) and antibody to HCV (anti-HCV) at enrollment, and 218 subjects positive for both seromarkers were excluded. Incident HCC cases were identified via linkage to the national cancer registry. Multivariate-adjusted relative risk (RRa ) and 95% confidence interval (95% CI) were estimated using Cox proportional hazards models. Results: Extreme obesity (body mass index ≥30 kg/m2 ) was independently associated with a 4-fold risk of HCC (RRa , 4.13; 95% CI, 1.38–12.4) among anti-HCV–seropositive subjects and a 2-fold risk (RRa , 2.36; 95% CI, 0.91–6.17) in persons without HBV and HCV infections, after controlling for other metabolic components, but not in HBsAg-seropositive subjects (RRa , 1.36; 95% CI, 0.64–2.89). Diabetes was associated with HCC in all 3 groups, with the highest risk in those with HCV infection (RRa , 3.52; 95% CI, 1.29–9.24) and lowest in HBV carriers (RRa , 2.27; 95% CI, 1.10–4.66). We found more than 100-fold increased risk in HBV or HCV carriers with both obesity and diabetes, indicating synergistic effects of metabolic factors and hepatitis. Conclusions: The finding that both obesity and diabetes are predictors of HCC risk, possibly differently depending on HBV and HCV infection status, may shed some light in preventing HCC.
Chronic hepatitis B is a worldwide public health challenge. Knowledge of natural history of chronic hepatitis B is important for the management of the disease. A community‐based prospective cohort ...study was carried out to evaluate the risk predictors of progression of chronic hepatitis B in Taiwan. A total of 23 820 participants were enrolled in 1991–1992 from seven townships in Taiwan. Their serum samples were collected at study entry and tested for hepatitis B surface antigen (HBsAg) and e antigen (HBeAg), antibodies against hepatitis C virus (anti‐HCV), alanine aminotransferase (ALT), and α‐fetoprotein (AFP). A subcohort of 3653 male and female participants who were seropositive for HBsAg and seronegative for anti‐HCV was included in the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer‐Hepatitis B Virus (REVEAL‐HBV) study. Newly developed cases of cirrhosis and hepatocellular carcinoma (HCC) were ascertained through follow‐up examination and data linkage with profiles of the National Cancer Registry, National Health Insurance Database and Death Certification System. The incidence of both HCC and cirrhosis were significantly associated with serum HBV DNA levels in a dose‐response relationship from < 300 (undetectable) to ≥ 1 000 000 copies/mL. The biological gradients remained significant (P < 0.001) after adjustment for age, sex, habits of cigarette smoking and alcohol drinking, HBeAg serostatus, and serum ALT level at cohort entry. A significant association with risk of cirrhosis and HCC was also observed for HBV genotype, precore G1896A mutant and basal core promoter A1762T/G1764A double mutant. Nomograms have been developed for the long‐term risk prediction of cirrhosis and HCC for patients with chronic hepatitis B. Inactive carriers of HBV have an increased HCC incidence and liver‐related mortality than HBsAg‐seronegative controls. Serum HBV DNA level at study entry is a major predictor of spontaneous seroclearance of HBeAg, HBV DNA and HBsAg. These findings may inform the effective and efficient management of chronic hepatitis B.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Integrating host and HBV characteristics, this study aimed to develop models for predicting long‐term cirrhosis and hepatocellular carcinoma (HCC) risk in chronic hepatitis B virus (HBV) patients. ...This analysis included hepatitis B surface antigen (HBsAg)‐seropositive and anti‐HCV‐seronegative participants from the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer in HBV (R.E.V.E.A.L.‐HBV) cohort. Newly developed cirrhosis and HCC were ascertained through regular follow‐up ultrasonography, computerized linkage with national health databases, and medical chart reviews. Two‐thirds of the participants were allocated for risk model derivation and another one‐third for model validation. The risk prediction model included age, gender, HBV e antigen (HBeAg) serostatus, serum levels of HBV DNA, and alanine aminotransferase (ALT), quantitative serum HBsAg levels, and HBV genotypes. Additionally, the family history was included in the prediction model for HCC. Cox's proportional hazards regression coefficients for cirrhosis and HCC predictors were converted into risk scores. The areas under receiver operating curve (AUROCs) were used to evaluate the performance of risk models. 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 HCC. The risk scores estimated from the derivation set could accurately categorize participants with low, medium, and high cirrhosis and HCC risk in the validation set (P < 0.001). The AUROCs for predicting 3‐year, 5‐year, and 10‐year cirrhosis risk ranged 0.83‐0.86 and 0.79‐0.82 for the derivation and validation sets, respectively. The AUROC for predicting 5‐year, 10‐year, 15‐year risk of HCC ranged 0.86‐0.89 and 0.84‐0.87 in the derivation and validation sets, respectively. Conclusion: The risk prediction models of cirrhosis and HCC 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;58:546‐554)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Two years on from the World Health Organization's official declaration of the pandemic, I've been thinking about lessons I've learnt toggling between science and public service. The government must ...do its part to encourage compliance, such as paying for low-income people to get to vaccination centres and sending them free face masks and hand sanitizer. Each time I return to academia, my government experience leads me to pay more attention to the earlier parts of the disease process: more prevention, swifter detection and less time to treatment.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Serum levels of hepatitis B virus (HBV) DNA (≤2000 IU/mL) and hepatitis B surface antigen (HBsAg) (<1000 IU/mL) have been shown to distinguish inactive carriers with high accuracy. The goal of this ...study was to validate the predictability of one‐time measurement of quantitative HBsAg and HBV DNA levels for inactive carrier status and chronic hepatitis B (CHB) progression in a community‐based cohort. This study included 1529 participants chronically infected with HBV genotype B or C from the REVEAL‐HBV cohort. They were ascertained as inactive or active CHB after 18 months of follow‐up. Validity of the one‐time measurement was assessed by sensitivity, specificity, and receiver operating characteristic curves, while associations with clinical outcomes were calculated with Cox proportional hazards regressions. The one‐time baseline measurement of HBsAg <1000 IU/mL and HBV DNA <2000 IU/mL distinguished inactive carriers from active CHB with a sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of 71%, 85%, 83%, 74%, and 78%, respectively. Those identified as inactive carriers using the one‐time baseline measurement had multivariate adjusted hazard ratios of 0.36 (95% confidence interval CI, 0.20‐0.63) and 0.36 (0.23‐0.56) for hepatocellular carcinoma and liver cirrhosis, respectively, and an adjusted rate ratio of 6.97 (95% CI, 5.21‐9.33) for HBsAg seroclearance. Areas under the receiver operating characteristic curve of predicting these outcomes using the one‐time definition were similar to those obtained when using long‐term follow‐up defined carrier status for prediction. Conclusion: This study confirms the predictability of a one‐time combined HBsAg and HBV DNA measurement for future inactive carriers. This single‐point strategy provides new and complementary information useful for management of patients with chronic hepatitis B infection. (Hepatology 2016;64:381‐389)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background & Aims: Cirrhosis develops as a result of hepatic inflammation and subsequent fibrosis in chronic hepatitis B infection. We report on the relationship between hepatitis B viremia and ...progression to cirrhosis in chronic hepatitis B infection. Methods: This was a population-based prospective cohort study of 3582 untreated hepatitis B–infected patients established in Taiwan from 1991 to 1992. Serum samples were tested for HBV DNA on cohort entry serum samples and the diagnosis of cirrhosis was by ultrasound. Results: During a mean follow-up time of 11 years, the 3582 patients contributed 40,038 person-years of follow-up evaluation and 365 patients were newly diagnosed with cirrhosis. The cumulative incidence of cirrhosis increased with the HBV-DNA level and ranged from 4.5% to 36.2% for patients with a hepatitis B viral load of less than 300 copies/mL and 106 copies/mL or more, respectively (P < .001). In a Cox proportional hazards model adjusting for hepatitis B e-antigen status and serum alanine transaminase level among other variables, hepatitis B viral load was the strongest predictor of progression to cirrhosis relative risk 95% confidence interval was 2.5 1.6–3.8; 5.6 3.7–8.5; and 6.5 4.1–10.2 for HBV-DNA levels ≥104 − <105; ≥105 − <106; ≥106 copies/mL, respectively. Conclusions: These data show that progression to cirrhosis in hepatitis B–infected persons is correlated strongly with the level of circulating virus. The risk for cirrhosis increases significantly with increasing HBV-DNA levels and is independent of hepatitis B e-antigen status and serum alanine transaminase level.
Background & Aims The risk and the predictors of liver disease progression in carriers of inactive hepatitis B virus (HBV) are unclear. Methods Participants in the Risk Evaluation of Viral Load ...Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus (REVEAL-HBV) study who were seronegative for hepatitis B e antigen; had serum levels of HBV DNA <10,000 copies/mL; and did not have cirrhosis, hepatocellular carcinoma, or increased serum levels of alanine aminotransferase were classified as carriers of inactive HBV (n = 1932). Study participants who were seronegative for HB surface antigen and antibodies against hepatitis C virus, yet had similar clinical liver features, were the controls (n = 18,137). Liver-related death and new cases of hepatocellular carcinoma were ascertained through computerized data linkage with National Cancer Registry and Death Certification profiles. The disease progression rates were estimated. The multivariate-adjusted hazard ratios for risk predictors were derived from Cox regression models. Results There were 20,069 participants, contributing a total of 262,122 person-years, with a mean follow-up of 13.1 years. Annual incidence rates of hepatocellular carcinoma and liver-related death were 0.06% and 0.04%, respectively, for inactive HBV carriers; rates were 0.02%, and 0.02% for controls, respectively. The multivariate-adjusted hazard ratios for carriers of inactive HBV, compared to controls, were 4.6 (95% confidence interval: 2.5–8.3) for hepatocellular carcinoma and 2.1 (95% confidence interval: 1.1–4.1) for liver-related death. Older age and alcohol drinking habits were independent predictors of risk for carriers of inactive HBV to develop hepatocellular carcinoma. Conclusions Carriers of inactive HBV have a substantial risk of hepatocellular carcinoma and liver-related death compared with individuals not infected with HBV.
CONTEXT Serum hepatitis B virus (HBV) DNA level is a marker of viral replication and efficacy of antiviral treatment in individuals with chronic hepatitis B. OBJECTIVE To evaluate the relationship ...between serum HBV DNA level and risk of hepatocellular carcinoma. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study of 3653 participants (aged 30-65 years), who were seropositive for the hepatitis B surface antigen and seronegative for antibodies against the hepatitis C virus, recruited to a community-based cancer screening program in Taiwan between 1991 and 1992. MAIN OUTCOME MEASURE Incidence of hepatocellular carcinoma during follow-up examination and by data linkage with the national cancer registry and the death certification systems. RESULTS There were 164 incident cases of hepatocellular carcinoma and 346 deaths during a mean follow-up of 11.4 years and 41 779 person-years of follow-up. The incidence of hepatocellular carcinoma increased with serum HBV DNA level at study entry in a dose-response relationship ranging from 108 per 100 000 person-years for an HBV DNA level of less than 300 copies/mL to 1152 per 100 000 person-years for an HBV DNA level of 1 million copies/mL or greater. The corresponding cumulative incidence rates of hepatocellular carcinoma were 1.3% and 14.9%, respectively. The biological gradient of hepatocellular carcinoma by serum HBV DNA levels remained significant (P<.001) after adjustment for sex, age, cigarette smoking, alcohol consumption, serostatus for the hepatitis B e antigen (HBeAg), serum alanine aminotransferase level, and liver cirrhosis at study entry. The dose-response relationship was most prominent for participants who were seronegative for HBeAg with normal serum alanine aminotransferase levels and no liver cirrhosis at study entry. Participants with persistent elevation of serum HBV DNA level during follow-up had the highest hepatocellular carcinoma risk. CONCLUSION Elevated serum HBV DNA level (≥10 000 copies/mL) is a strong risk predictor of hepatocellular carcinoma independent of HBeAg, serum alanine aminotransferase level, and liver cirrhosis.
Summary Background Therapy for chronic hepatitis B reduces the risk of progressing to hepatocellular carcinoma (HCC); however, there is no suitable and accurate means to assess risk. This study aimed ...to develop and validate a simple scoring system to predict HCC risk in patients with chronic hepatitis B. Methods The development cohort consisted of 3584 patients without cirrhosis from the community-based Taiwanese REVEAL-HBV study (of whom 131 developed HCC during follow-up), and a validation cohort of 1505 patients from three hospitals in Hong Kong and South Korea (of whom 111 developed HCC during follow-up). We used Cox multivariate proportional hazards model to predict risk of HCC at 3, 5, and 10 years. Variables included in the risk score were sex, age, serum alanine aminotransferase concentration, HBeAg status, and serum HBV DNA level. We calculated the area under receiver operating curve (AUROC) and calibration of predicted and observed HCC risk. Findings A 17-point risk score was developed, with HCC risk ranging from 0·0% to 23·6% at 3 years, 0·0% to 47·4% at 5 years, and 0·0% to 81·6% at 10 years for patients with the lowest and highest HCC risk, respectively. AUROCs to predict risk were 0·811 (95% CI 0·790–0·831) at 3 years, 0·796 (0·775–0·816) at 5 years, and 0·769 (0·747–0·790) at 10 years in the validation cohort, and 0·902 (0·884–0·918), 0·783 (0·759–0·806), and 0·806 (0·783–0·828), respectively, after exclusion of 277 patients in the validation cohort with cirrhosis. Predicted risk was well calibrated with Kaplan-Meier observed HCC risk. Interpretation A simple-to-use risk score that uses baseline clinical variables was developed and validated. The score accurately estimates the risk of developing HCC at 3, 5, and 10 years in patients with chronic hepatitis B. Clinicians can use this score to assess risk of HCC in patients with chronic hepatitis B and subsequently make evidence-based decisions about their clinical management. Funding The Academia Sinica; the National Health Research Institute, Taiwan; and Bristol-Myers Squibb.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background
The smoking prevalence among men in China is high, but the head and neck cancer incidence rates are low. This study's purpose was to investigate the impact of tobacco, betel quid, and ...alcohol on head and neck cancer risk in East Asia.
Methods
A multicenter case‐control study (921 patients with head and neck cancer and 806 controls) in East Asia was conducted. The odds ratio (OR) and 95% confidence interval (CI) were estimated using logistic regression.
Results
Head and neck cancer risks were elevated for tobacco (OR = 1.58), betel quid (OR = 8.23), and alcohol (OR = 2.29). The total attributable risk of tobacco and/or alcohol was 47.2%. Tobacco/alcohol appeared to account for a small proportion of head and neck cancer among women (attributable risk of 2.2%). Betel quid chewing alone accounted for 28.7% of head and neck cancer.
Conclusions
Betel quid chewing is the strongest risk factor for oral cavity cancer in this Chinese population. Alcohol may play a larger role for head and neck cancer in this population than in European or U.S. populations.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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