Clinical Scoring System to Predict Hepatocellular Carcinoma in Chronic Hepatitis B Carriers
ABSTRACT Hepatitis B virus (HBV) infection is an important etiology for hepatocellular carcinoma (HCC). We aim to develop a simple clinical score in predicting the risk of HCC among HBV carriers.
We first evaluated 1,005 patients and found that the following five factors independently predicted HCC development: age, albumin, bilirubin, HBV DNA, and cirrhosis. These variables were used to construct a prediction score ranging from 0 to 44.5. The score was validated in another prospective cohort of 424 patients.
During a median follow-up of 10 years, 105 patients (10.%) in the training cohort and 45 patients (10.6%) in the validation cohort developed HCC. Cutoff values of 5 and 20 best discriminated HCC risk. By applying the cutoff value of 5, the score excluded future HCC development with high accuracy (negative predictive value = 97.8% and 97.3% in the training and validation cohorts, respectively). In the validation cohort, the 5-year HCC-free survival rates were 98.3%, 90.5%, and 78.9% in the low-, medium-, and high-risk groups, respectively. The hazard ratios for HCC in the medium- and high-risk groups were 12.8 and 14.6, respectively.
A simple prediction score constructed from routine clinical and laboratory parameters is accurate in predicting HCC development in HBV carriers. Future prospective validation is warranted.
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ABSTRACT: OBJECTIVES:This study aimed to evaluate the risk of development of hepatocellular carcinoma (HCC) according to underlying liver status and virological response (VR) to entecavir (ETV) in chronic hepatitis B patients with cirrhosis. Procollagen III N-terminal peptide (PIIINP) concentration during ETV treatment and its association with HCC development were also evaluated.METHODS:A total of 306 patients with clinically diagnosed liver cirrhosis were treated with ETV for ≥12 months and were subsequently followed up for the occurrence of HCC (median follow-up duration: 37.0 months). Patients who developed HCC within 12 months were excluded. VR was defined as a hepatitis B virus DNA level <20 IU/ml at 12 months after ETV treatment.RESULTS:A total of 209 patients (68.3%) had compensated cirrhosis, and the remaining patients (31.7%) had decompensated cirrhosis. The 5-year cumulative incidence of HCC was 26.8%. A multivariate Cox regression analysis identified the following independent risk factors for developing HCC in all the patients: age >50 years (hazard ratio (HR)=8.41; 95% confidence interval (CI)=3.86-18.28; P=0.000), male sex (HR=4.24; 95% CI=1.83-9.81; P=0.001), high serum PIIINP level at 12 months (HR=1.07; 95% CI=1.02-1.13; P=0.007), and no VR at 12 months (HR=2.10; 95% CI=1.02-4.33; P=0.043). The subgroup analyses showed that no VR at 12 months is a significant risk factor for developing HCC in the patients with decompensated cirrhosis (HR=7.74; 95% CI=1.34-44.78; P=0.022) but not in those with compensated cirrhosis (P=0.749).CONCLUSIONS:The antiviral treatment with ETV did not completely eliminate the risk of developing HCC in our patients with cirrhosis. However, VR to ETV was associated with a low probability that the patients with decompensated cirrhosis would develop HCC.Am J Gastroenterol advance online publication, 3 June 2014; doi:10.1038/ajg.2014.145.The American Journal of Gastroenterology 06/2014; 109(8). DOI:10.1038/ajg.2014.145 · 9.21 Impact Factor
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ABSTRACT: Chemoprevention of hepatocellular carcinoma (HCC) is listed as a yet highly debated long-term benefit of a successful treatment of patients with chronic viral hepatitis. In the hepatitis B virus (HBV) arena, the retrospective scrutiny of both interferon and nucleos(t)ide analogs (NUC) studies failed to provide robust evidence for HCC chemoprevention, due to a number of confoundings in the studies that were originally designed to assess the antiviral activity of interferon therapy. However, the reanalysis of outcomes following patients stratification for risk factors of HCC, provided a clue to find an association between NUC therapy and a reduced risk of liver cancer in non cirrhotic patients, only. In the hepatitis C scenario, a meta analysis of 30 observational studies of patients treated with interferon demonstrated a more than 70% reduction of HCC risk occurring independently of severity of underlying liver fibrosis which was less pronounced in aged patients and those with more advanced liver fibrosis. While the reasons for the residual risk of HCC in virological responders remain largely unexplained, international societies recommend surveillance for HCC of both HBV and HCV responders to antiviral therapy.Baillière' s Best Practice and Research in Clinical Gastroenterology 10/2014; 28(5). DOI:10.1016/j.bpg.2014.07.017 · 3.28 Impact Factor
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ABSTRACT: The hepatitis B virus (HBV) carrier rate has decreased in Japan; however, the incidence of HBV infection among hepatocellular carcinoma (HCC) patients has not decreased accordingly. In this study, we aimed to assess the time trends of the clinical characteristics in HCC patients with chronic HBV infection. Between 2000 and 2012, we enrolled a total of 156 HCC patients with chronic HBV infection in our field survey. The HCC risk was evaluated using the HCC prediction score, which is constructed from the characteristics of age, presence of liver cirrhosis and serum levels of albumin, bilirubin and HBV DNA. Lifestyle factors and the presence of diabetes mellitus were also evaluated. The time trends of patient characteristics were analyzed using the Jonckheere-Terpstra proportion trend test. Among HCC patients with chronic HBV infection, the proportion of patients at high risk according to the HCC prediction score significantly decreased during the study period (P=0.0005). Similarly, the proportion of patients with liver cirrhosis, ≤3.5 g/dl serum albumin level, >4 log copies/ml serum HBV DNA level and ≥60 g/day alcohol intake were also significantly decreased. The proportion of male and obese patients was not significantly altered, whereas the proportion of elderly (≥65 years) and diabetic patients tended to increase during the study period (P=0.0654 and P=0.0528, respectively). In this study, we analyzed the time trends of the clinical characteristics in HCC patients with chronic HBV infection and demonstrated that aging and diabetes mellitus may be involved in the hepatocarcinogenesis in patients with chronic HBV infection.Molecular and Clinical Oncology 11/2014; 2(6):927-934. DOI:10.3892/mco.2014.398