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External Validation of aMAP Hepatocellular Carcinoma Risk Score in Patients With Chronic Hepatitis B-Related Cirrhosis Receiving ETV or TDF Therapy.

ABSTRACT: Background and Aim: A prediction model of hepatocellular carcinoma (HCC) risk in patients with chronic liver diseases, based on age, male sex, albumin-bilirubin, and platelets (aMAP), has been previously reported. We validated the aMAP score and compared its performance to those of other risk scores in an independent at-risk cohort. Methods: Treatment-naïve patients with chronic hepatitis B-related compensated cirrhosis who received entecavir or tenofovir monotherapy for at least 12 months were enrolled in this study. The performances of the aMAP and other HCC risk scores were assessed using Harrell's c-index, and predefined cut-off values were evaluated using survival analysis. Results: Of the 1,042 patients, 131 (12.6%) developed HCC during a median follow-up of 41 months. The aMAP score provided the highest Harrell's c-index (0.724), followed by CAMD (0.719), mPAGE-B (0.719), and PAGE-B (0.695). The 5-year cumulative HCC probabilities were 2.9% for patients with a low aMAP score (<50), 11.2% for patients with an intermediate aMAP score (50-60), and 27.9% for patients with a high aMAP score (>60). Using both aMAP and mPAGE-B, 11.6% of patients were identified as low risk with a negative predictive value of 98.2% for not developing HCC within 5 years. Patients with aMAP >60 and diabetes exhibited an extremely high risk of HCC, with a cumulative incidence of 49.3% at 5 years. The predictive performance of aMAP with a reassessment at 1 year after the initiation of antiviral therapy outperformed the predictive performance of aMAP at enrollment. Conclusions: The aMAP score accurately predicted the risk of HCC in at-risk patients with compensated cirrhosis undergoing antiviral therapy. A combination of the aMAP score and diabetes status could further stratify the risk of HCC.

SUBMITTER: Gui H

PROVIDER: S-EPMC8371628 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Cirrhosis poses an increased risk of postoperative mortality, yet it remains challenging to accurately risk stratify patients in clinical practice. The VOCAL-Penn cirrhosis surgical risk score was recently developed and internally validated in the national Veterans Affairs health system; however, to date this score has not been evaluated in independent cohorts. The goal of this study was to compare the predictive performance of the VOCAL-Penn to the Mayo risk, Model for End-Stage Liver Disease (MELD), and MELD-sodium (MELD-Na) scores in 2 large health systems. We performed a retrospective cohort study of patients with cirrhosis undergoing surgical procedures of interest at the Beth Israel Deaconess Medical Center or University of Pennsylvania Health System from January 1, 2008, to October 1, 2015. The outcomes of interest were 30-day and 90-day postoperative mortality. Concordance statistics (C-statistics), calibration curves, Brier scores, and the index of prediction accuracy (IPA) were compared for each predictive model. A total of 855 surgical procedures were identified. The VOCAL-Penn score had the numerically highest C-statistic for 90-day postoperative mortality (eg, 0.82 versus 0.79 Mayo versus 0.78 MELD-Na versus 0.79 MELD), although differences were not statistically significant. Calibrations were excellent for the VOCAL-Penn, MELD, and MELD-Na; however, the Mayo score consistently overestimated risk. The VOCAL-Penn had the lowest Brier score and highest IPA at both time points, suggesting superior overall predictive model performance. In subgroup analyses of patients with higher MELD scores, the VOCAL-Penn had significantly higher C-statistics compared with the MELD and MELD-Na. The VOCAL-Penn score (www.vocalpennscore.com) has excellent discrimination and calibration for postoperative mortality among diverse patients with cirrhosis. Overall performance is superior to the Mayo, MELD, and MELD-Na scores. In contrast to the MELD/MELD-Na, the VOCAL-Penn retains excellent discrimination among patients with higher MELD scores.

Project description:Background & aimsPatients chronically infected with the hepatitis B virus (HBV) and receiving long-term treatment with nucleoside or nucleotide analogues are at risk of selecting HBV strains with complex mutational patterns. We herein report two cases of HBV-infected patients with insufficient viral suppression, despite dual antiviral therapy with entecavir (ETV) and tenofovir (TDF). One patient died from aggressive hepatocellular carcinoma (HCC).MethodsSerum samples from the two patients at different time points were analyzed using ultra-deep pyrosequencing analysis. HBV mutations were identified and transiently transfected into hepatoma cells in vitro using replication-competent HBV vectors, and functionally analyzed. We assessed replication efficacy, resistance to antivirals and potential impact on HBV secretion (viral particles, exosomes).ResultsSequencing analyses revealed the selection of the rtS78T HBV polymerase mutation in both cases that simultaneously creates a premature stop codon at sC69 and thereby deletes almost the entire small HBV surface protein. One of the patients had an additional 261bp deletion in the preS1/S2 region. Functional analyses of the mutations in vitro revealed that the rtS78T/sC69∗ mutation, but not the preS1/S2 deletion, significantly enhanced viral replication and conferred reduced susceptibility to ETV and TDF. The sC69∗ mutation caused truncation of HBs protein, leading to impaired detection by commercial HBsAg assay, without causing intracellular HBsAg retention or affecting HBV secretion.ConclusionsThe rtS78T/sC69∗ HBV mutation, associated with enhanced replication and insufficient response to antiviral treatment, may favor long-term persistence of these isolates. In addition to the increased production of HBV transcripts and the sustained secretion of viral particles in the absence of antigenic domains of S protein, this HBV mutation may predispose patients to carcinogenic effects.Lay summaryLong-term treatment with antiviral drugs carries the risk of selecting mutations in the hepatitis B virus (HBV). We herein report two cases of patients with insufficient response to dual tenofovir and entecavir therapy. Molecular analyses identified a distinct mutation, rtS78T/sC69∗, that abolishes HBsAg detection, enhances replication, sustains exosome-mediated virion secretion and decreases susceptibility to antivirals, thereby representing a potentially high-risk mutation for HBV-infected individuals.

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External Validation of aMAP Hepatocellular Carcinoma Risk Score in Patients With Chronic Hepatitis B-Related Cirrhosis Receiving ETV or TDF Therapy.

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