Incidence of Hepatocellular Carcinoma after HBsAg Seroclearance in Chronic Hepatitis B Patients: a Need for Surveillance (original) (raw)
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Hepatoma Research, 2019
Aim: Chronic persistent hepatitis B virus carriers are generally asymptomatic until the advanced stage of the disease. The “Hepatitis B-Carrier Clinics” of Chang Gung Memorial Hospital has been using alpha-fetoprotein (AFP) and liver ultrasound for early detection of hepatocellular carcinoma (HCC) in hepatitis B surface antigen (HBsAg) carriers since 1980. Methods: We evaluated the results of surveillance between 1980 and 2012 by collecting clinic data, matched cancer registry status, and national mortality database status. Results: Of 15,235 HBsAg carriers, 238 instances of HCC (1.5% or 156.2/100,000 person-years) were detected over a mean follow-up period of 10.0 ± 7.6 years. There were more men (89.1%) and patients with liver cirrhosis (70.2%) in the HCC group (P < 0.001), and both the initial and maximal alanine aminotransferase (ALT) levels were higher in this group (P < 0.001). One hundred and thirty cases of HCC (54.6%) were identified during regular follow-up sessions, 55 (23.1%) were detected after the regular schedule had lapsed (“out-of-schedule”), and 53 (22.3%) were lost to follow-up completely. The mean tumor size was smaller in the regular group than in the out-of-schedule group (2.72 cm vs. 4.59 cm, P < 0.001), and the survival rate was higher (43.8% vs. 30.9%, P < 0.001). Conclusion: The incidence of HCC was relatively low in the HBsAg-Carrier Clinics cohort. Surveillance for early diagnosis of HCC improved the survival of high-risk HBsAg carriers. To ensure cost-effectiveness, we suggest using different screening strategies according to the individual risk of hepatocarcinogenesis.
Risk calculators for hepatocellular carcinoma in patients affected with chronic hepatitis B in Asia
World journal of gastroenterology : WJG, 2014
Risk calculators are widely used in many clinical fields, and integrate several important risk factors through the conversion of a risk function into a single measure of risk. Several studies have been carried out to create risk calculators for the prediction of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). Most of them were hospital-based, with limited sample sizes and insufficient external validation. These study groups collaborated to establish the REACH-B risk score, which incorporated five clinical variables to predict HCC risk. This risk score was then validated in international clinical cohorts. Evidence suggests that quantitative serum HBsAg level provides additional predictability of HCC, especially in patients with low levels of hepatitis B virus DNA. This novel marker was incorporated into a risk calculator and was internally validated. This tool will hopefully be externally validated in the near future. Risk calculators can be used to support...
Hepatitis B-related hepatocellular carcinoma: epidemiological characteristics and disease burden
Journal of Viral Hepatitis, 2009
Worldwide, 350 million people are chronically infected with hepatitis B virus (HBV) who are at greater risk of hepatocellular carcinoma (HCC) compared with uninfected people. The relative risks of HCC among people infected with HBV ranges from 5 to 49 in case-control studies and from 7 to 98 in cohort studies. More than 50% of HCC cases worldwide and 70-80% of HCC cases in highly HBV endemic regions are attributable to HBV. Incidence of HCC (per 100 000 person/year) among people with chronic HBV infection ranges from 400 to 800 in male and from 120 to 180 in female. Factors associated with increased risk of HCC include demographic characteristics (male sex and older age), lifestyles (heavy alcohol consumption and smoking), viral factors (genotype C, D F, high level of HBV DNA, core/precore mutation) and clinical factors (cirrhosis, elevated alpha-fetoprotein (AFP) and alanine aminotransferase (ALT)). HBV-related HCC has extremely poor prognosis with median survival less than 16 months. Survival rates of HBV-related HCC ranged from 36% to 67% after 1 year and from 15% to 26% after 5 year of diagnosis. Older age, liver function impairment, vascular invasion, tumour aggressiveness and elevated AFP are associated with HCC survival. Global burden of HBV-related liver disease is still a major challenge for public health in the 21st century. While decreases in incidence of HBV infection have been observed in birth cohorts following the introduction of universal infant HBV vaccination programme, HBV-related HCC incidence in is projected to increase for at least two decades because of the high prevalence of chronic HBV infection and prolonged latency to HCC development. To reduce HBV-related HCC continued expansion of universal infant HBV vaccination is required along with antiviral therapy targeted to those individuals at highest risk of HCC. Broad public health strategies should include routine testing to identify chronic HBV infection, improved health infrastructures including human resource to provide diagnosis and treatment assessment.
Risk stratification for hepatitis B virus related hepatocellular carcinoma
Journal of Gastroenterology and Hepatology, 2013
Hepatitis B virus (HBV) infection is the major cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC) worldwide, especially in the Asia-Pacific region. Several hepatitis B viral factors predictive of clinical outcomes in HBV carriers have been identified. The Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-HBV (REVEAL-HBV) study from Taiwan illustrated the strong association between HBV-DNA level at study entry and risk of HCC over time. In this community-based cohort study, male gender, older age, high serum alanine aminotransferase level, positive hepatitis B e antigen, higher HBV-DNA level, HBV genotype C infection, and core promoter mutation are independently associated with a higher risk of HCC. Another large hospitalbased Elucidation of Risk Factors for Disease Control or Advancement in Taiwanese Hepatitis B Carriers cohort of Taiwanese patients further validated the findings of REVEAL-HBV. The risk of HCC started to increase when HBV-DNA level was higher than 2000 IU/mL. Both HBV-DNA and HBsAg levels were shown to be associated with HCC development. While HBV-DNA level had better predictive accuracy than HBsAg level, when investigating the overall cohort in patients with HBV-DNA level < 2000 IU/ mL, HBsAg level Ն 1000 IU/mL was identified as a new independent risk factor for HCC. With the results from REVEAL-HBV, a risk calculation for predicting HCC in noncirrhotic patients has been developed and validated by independent cohorts (Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B).Taken together, ample evidence indicates that HBsAg level can complement HBV-DNA level in predicting HCC development, especially in HBV carriers with low viral load. In conclusion, HBV treatment guidelines should include the risk stratification of HCC to individualize the management of HBV carriers with different levels of HCC risk.
Journal of Hepatocellular Carcinoma
We aimed to determine incidence of hepatocellular carcinoma (HCC) and decompensated liver cirrhosis in persons with chronic hepatitis B virus (HBV) infection in Denmark stratified by disease phase, liver cirrhosis, and treatment status at baseline. Additionally, we aimed to assess the prognostic value of the PAGE-B HCC risk score in a mainly non-cirrhotic population. Patients and Methods: In this register-based cohort study, we included all individuals over the age of 18, with chronic HBV infection first registered between 2002 and 2016 in at least one of three nationwide registers. The study population was followed until HCC, decompensated liver cirrhosis, death, emigration, or December 31, 2017, which ever came first. Results: Among 6016 individuals included in the study, 10 individuals with and 23 without baseline liver cirrhosis developed HCC during a median follow up of 7.3 years (range 0.0-15.5). This corresponded to five-year cumulative incidences of 7.1% (95% confidence interval (CI) 2.0-12.3) and 0.2% (95% CI 0.1-0.4) in persons with and without baseline liver cirrhosis. The five-year cumulative incidence of decompensated liver cirrhosis was 0.7% (95% CI 0.5-1.0). Among 2038 evaluated for liver events stratified by disease phase, incidence of HCC was low in all who were non-cirrhotic and untreated for HBV at baseline. PAGE-B score was evaluated in 1529 persons. The 5-year cumulative incidence of HCC was 0, 0.8 (95% CI 0.5-1.8), and 8.7 (95% CI 1.0-16.4) in persons scoring <10, 10-17 and >17, respectively (c-statistic 0.91 (95% CI 0.84-0.98)). Conclusion: We found low incidence of HCC and decompensated liver cirrhosis in persons with chronic HBV infection in Denmark. Moreover, the PAGE-B score showed good accuracy for five-year risk of developing HCC in the population with chronic HBV infection in Denmark.
World journal of gastroenterology, 2016
To determine the role of screening and surveillance of hepatocellular carcinoma (HCC) in treatment-naïve chronic hepatitis B (CHB) patients. We recruited 2293 CHB patients (both males and females; aged 20-65 years). All patients were screened and underwent surveillance using abdominal ultrasonography (AUS) and serum alpha-fetoprotein (AFP) assay every 6 mo. The diagnosis, staging and treatment of HCC followed the American Association for the Study of Liver Diseases practice guidelines and the Barcelona Clinic Liver Cancer guidelines. The exclusion criteria included: decompensated cirrhosis; a history of any cancer in the last 5 years; previous antiviral treatment for CHB; concurrent infection with hepatitis C virus or human immunodeficiency virus; a Karnofsky Performance Status score < 60%; or any medical condition preventing eligibility to complete the protocol. The prevalence and incidence rates of HCC were determined; survival rates were calculated at 3-year post HCC diagnosis...
Clinical microbiology, 2012
The ultimate goal of antiviral treatment is prevention of hepatocellular carcinoma (HCC). Currently the end point of successful antiviral treatment for patients with chronic hepatitis B is to achieve HBsAg loss or HBsAg seroconversion. We report two patients who successfully developed anti-HBs with or without antiviral therapy and yet developed HCC. Initial commercial assay showed negative HBV DNA for both patients. However, they were found to have detectable HBV DNA by a new laboratory-developed HBV DNA assay. These cases show that patients with HBsAg seroclearance continue to be at risk for HCC and surveillance for HCC should be continued. The diagnosis of occult hepatitis B with an improved HBV DNA assays is also necessary as it is important for treatment for chronic HBV and prevention of HCC.
Update on the Risk of Hepatocellular Carcinoma in Chronic Hepatitis B Virus Infection
Current Hepatitis Reports, 2011
Chronic hepatitis B virus infection is an important cause of liver-related morbidity and mortality, with hepatocellular carcinoma being the most life-threatening complication. Because of the highly variable clinical course of the disease, enormous research efforts have been made with the aim of revealing the factors in the natural history that are relevant to hepatocarcinogenesis. These include epidemiological studies of predisposing risk groups, viral studies of mutations within the hepatitis B viral genome, and clinical correlation of these risk factors in predicting the likelihood of development of hepatocellular cancer in susceptible hosts. This update addresses these risks, with emphasis on the latest research relevant to hepatocarcinogenesis.