In the era of effective antiviral therapies, liver cancer risk scores that were previously developed in cohorts of untreated chronic hepatitis B (CHB) patients may be of inadequate predictability.1 In light of this, the research team led by Prof. Grace LH Wong from the Chinese University of Hong Kong (CUHK), and Dr. Chun-Ying Wu from the China Medical University (CMU) in Taiwan, developed and validated a simple scoring tool for CHB patients continuously receiving entecavir (ETV) or tenofovir (TDF).1 With the use of simple information (i.e. cirrhosis, age, male sex, and diabetes mellitus), the easily calculable CAMD score discriminates the risk of liver cancer with a concordance rate of around 75-80% during the first 3 years on therapy. The study was published in the Journal of Hepatology.1
High viral load, advanced age, male sex, and cirrhosis are some of the core components of the three well-established hepatocellular carcinoma (HCC) risk scores: CU-HCC, GAGHCC, and REACH-B scores, which were derived and validated prior to the era of potent antivirals.2 Given that nucleos(t)ide analogues (NAs) modify the natural history of CHB (by offering virological remission in almost all compliant patients) and alters other laboratory parameters (e.g. alanine aminotransferase [ALT] reduction),2 some components of the pre-existing risk scores may not provide sufficient discriminatory power in treated patients.3 Indeed, a recent cohort of 1,531 ETV-treated patients indicated that the negative predictive values of the three scores to exclude HCC were high (98-100%), but the positive predictive values of the scores were only 0.2-10.3%.4 This signifies the need of developing a new risk score to accurately predict HCC development in patients receiving antiviral therapy.
The CAMD score is composed of 4 parameters: cirrhosis status (with age interaction), age, gender, and diabetes mellitus, with a total score ranging from 0 to 19 points (Table 1).1 Patients with a score <8 and >13 points were exposed to distinctly lower and higher risks, respectively.1 In general, the predictability was around 75-80% during the first 3 years on therapy (c index=0.83, 0.82, 0.82 at the first, second, and third year of development cohort; c index=0.74, 0.75, 0.75 at the first, second, and third year of validation cohort), and could be extrapolated to 5 years on treatment with similar accuracy.1
Unlike the previous scores, the CAMD score is uniquely free of any specific laboratory test.1 Cirrhosis was clinically defined without tissue proof in most patients.1
“In the everyday practice, not all patients were routinely tested for platelet count, serum alfa-fetoprotein, ALT levels, HBeAg status, HBsAg quantity, viral genotype, and HBV DNA at exact time points along the course of treatment. Despite lacking laboratory components, our CAMD score appeared to be similarly accurate with the well-established PAGE-B score that has been validated in Caucasian and Asian populations,“ researchers wrote.1
The score was developed from a cohort of 23,851 CHB patients from the National Health Insurance Research Database (NHIRD) in Taiwan, and then validated in a cohort of 19,321 patients from the Hospital Authority (HA) database in Hong Kong.1 Patients with decompensated cirrhosis were excluded in the analysis.1
The two cohorts were dissimilar in the baseline demographics, comorbidities, and drug exposure.1 In particular, the rate of cirrhosis in the Hong Kong cohort was remarkably lower than that in Taiwan (7.1 % vs. 26.5%).1 Nonetheless, the concordance indices of 0.74-0.76 in the validation cohort confirmed the generalizability of the CAMD score in different populations.1
To sum up, the CAMD score has demonstrated high predictability and applicability in real-life practice.1 This easily calculable risk score may serve as a useful mean to inform clinical practice and healthcare policy in the era of effective antiviral treatment for CHB.
1. Hsu YC, Yip T, Ho HJ, et al. Development of a scoring system to Predict Hepatocellular Carcinoma in Asians on Antivirals for Chronic Hepatitis B. J Hepatol. 2018 [Epub ahead of print].
2. Wong GL, Wong VW. Risk prediction of hepatitis B virus-related hepatocellular carcinoma in the era of antiviral therapy. World J Gastroenterol. 2013;19(39):6515-22.
3. Wong VW, Janssen HL. Can we use HCC risk scores to individualize surveillance in chronic hepatitis B infection? J Hepatol. 2015;63(3):722-32.
4. Wong GL, Chan HL, Chan HY, et al. Accuracy of risk scores for patients with chronic hepatitis B receiving entecavir treatment. Gastroenterology. 2013;144(5):933-44.