Multimarker Panels for Detection of Early Stage Hepatocellular Carcinoma: A Prospective, Multicenter, Case-Control Study

Early Stage; Hepatocellular CarcinomaEtapa temprana; Carcinoma hepatocelularEtapa primera; Carcinoma hepatocel·lularHepatocellular carcinoma (HCC), the sixth most common cancer worldwide, has an incidence rate equal to mortality. Over 80% of HCC cases occur within a high-risk population, mainly patients with both cirrhosis and chronic hepatitis B or C. With a 5-year survival rate ranging from 90% for early stage HCC, there is a high medical need for the early detection of HCC. In this study, we systematically evaluated biomarkers mentioned in international guidelines and peer-reviewed literature for HCC surveillance and diagnosis with the aim of identifying combinations that display high sensitivity and specificity for early stage HCC. Fifty biomarkers were measured in the first sample panel, panel A (n = 110), and subjected to univariate analysis. Of these, 35 biomarkers (38 assays) from panel A and an additional 13 biomarkers from the literature were prioritized for subsequent multivariate evaluation with lasso regression and exhaustive search of two- to four-biomarker combinations (panel B). Panel B included 1,081 samples from patients with HCC (n = 308) or with chronic liver diseases (n = 740). Among all patients, 61.0% had hepatitis B, 32.9% had hepatitis C, and 60.5% had cirrhosis; 40.6% of patients with HCC had early stage cancer. Protein induced by vitamin K absence-II (PIVKA-II; also known as des-gamma-carboxy prothrombin [DCP]) and alpha-fetoprotein (AFP) demonstrated the best clinical performance, both individually and in combination, and the addition of a third biomarker (Lens culinaris agglutinin-reactive fraction of AFP [AFP-L3], cartilage oligomeric matrix protein [COMP], insulin-like growth factor-binding protein 3 [IGFBP3], or matrix metalloproteinase 3 [MMP3]) further increased sensitivity for the detection of both early stage and all-stage HCC. The addition of age and sex to the three-biomarker panel resulted in an improved diagnostic performance. Conclusion: The combination of AFP and PIVKA-II, with either IGFBP3, COMP or MMP3, plus age and sex, demonstrated the best performance for the detection of early- and all-stage HCC. These novel panels performed similar to that of the GALAD score (sex [gender], age, plus serum levels of AFP, AFP-L3 and DCP [PIVKA-II]), a promising screening tool developed for HCC detection.Supported by Roche Diagnostics GmbH

52-week efficacy and safety of telbivudine with conditional tenofovir intensification at week 24 in HBeAg-positive chronic Hepatitis B

Background and Aims: The Roadmap concept is a therapeutic framework in chronic hepatitis B for the intensification of nucleoside analogue monotherapy based on early virologic response. The efficacy and safety of this approach applied to telbivudine treatment has not been investigated. Methods: A multinational, phase IV, single-arm open-label study (ClinicalTrials.gov ID NCT00651209) was undertaken in HBeAg-positive, nucleoside-naive adult patients with chronic hepatitis B. Patients received telbivudine (600 mg once-daily) for 24 weeks, after which those with undetectable serum HBV DNA (<300 copies/mL) continued to receive telbivudine alone while those with detectable DNA received telbivudine plus tenofovir (300 mg once-daily). Outcomes were assessed at Week 52. Results: 105 patients commenced telbivudine monotherapy, of whom 100 were included in the efficacy analysis. Fifty-five (55%) had undetectable HBV DNA at Week 24 and continued telbivudine monotherapy; 45 (45%) received tenofovir intensification. At Week 52, the overall proportion of undetectable HBV DNA was 93% (93/100) by last-observation-carried-forward analysis (100% monotherapy group, 84% intensification group) and no virologic breakthroughs had occurred. ALT normalization occurred in 77% (87% monotherapy, 64% intensification), HBeAg clearance in 43% (65% monotherapy, 16% intensification), and HBeAg seroconversion in 39% (62% monotherapy, 11% intensification). Six patients had HBsAg clearance. Myalgia was more common in the monotherapy group (19% versus 7%). No decrease in the mean glomerular filtration rate occurred in either treatment group at Week 52. Conclusions: Telbivudine therapy with tenofovir intensification at Week 24, where indicated by the Roadmap strategy, appears effective and well tolerated for the treatment of chronic hepatitis B. Trial Registration: ClinicalTrials.gov NCT0065120

Regional differences in clinical presentation and prognosis of patients with post-sustained virologic response (SVR) hepatocellular carcinoma.

Background& Amis: Widespread use of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection has resulted in increased numbers of patients with hepatocellular carcinoma (HCC) after achieving sustained virologic response ('post-SVR HCC') worldwide. Few data compare regional differences in presentation and prognosis of patients with post-SVR HCC.MethodsWe identified patients with advanced fibrosis (F3/F4) who developed incident post-SVR HCC between March, 2015 and October, 2021 from 30 sites in Europe, North America, South America, Middle East, South Asia, East Asia, and Southeast Asia. We compared patient demographics, liver dysfunction, and tumor burden by region. We compared overall survival by region using Kaplan-Meier analysis and identified factors associated with survival using multivariable Cox regression analysis.ResultsAmong 8,796 patients with advanced fibrosis or cirrhosis who achieved SVR, 583 (6.6%) developed incident HCC. There was marked regional variation in the proportion of detection by surveillance (range: 59.5-100%), median maximum tumor diameter (range: 1.8-5.0 cm), and proportion with multinodular HCC (range: 15.4-60.8%). Prognosis of patients highly varied by region (HR range: 1.82-9.92), with the highest survival in East Asia, North America, and South America, and lowest in the Middle East and South Asia. After adjusting for geographic region, HCC surveillance was associated with early-stage detection (BCLC stage 0/A: 71.0% vs. 21.3%, pConclusionsClinical characteristics, including early-stage detection, and prognosis of post-SVR HCC significantly differed across geographic regions. Surveillance utilization appears to be a high-yield intervention target to improve prognosis among patients with post-SVR HCC globally

A surveillance for hepatitis C virus infection in northeastern, Thailand: a 10-year cohort: HCV surveillance

Introduction. &nbsp;Hepatitis C virus (HCV) infection is an infection that may lead to cirrhosis and hepatocellular carcinoma. Most patients with HCV infection are asymptomatic. The previous study conducted in age group of 30-64 years and in two provinces. Additionally, most surveillance studies conducted in a point period; not longitudinally. This study aimed to evaluate HCV infection rate in all age groups in the northeastern, Thailand in a longitudinal fashion. Methods. This was a surveillance study conducted in 20 provinces of northeastern, Thailand. The study period was between July 2010 and November 2019. During the surveillance, demographic data of participants were collected. HCV screening test was performed in each participant by using a rapid point-of-care assay. Rates of HCV infection in each province and in overall were calculated. Results. During the surveillance period, there were 31,855 subjects who participated the project. Of those, 1,285 subjects (4.037%) were tested positive for HCV infection (Table 1). The HBV infection rate was highest in 2011 (8.98%): ranges 1.28 to 9.59%. The age group of over 50 years had 690 subjects with HCV infection (5.45%) out of 12,660 subjected tested in this age group. There was significant different among age groups (p &lt; 0.001) and difference of age over 30 years and sex (p 0.043). Conclusions: This longitudinal surveillance showed that HCV infection rates in northeastern, Thailand were varied across the provinces with the highest rate of 9.59%. The HCV infection should be aware in male with age over 30 years

Vitamin D-related gene polymorphism predict treatment response to pegylated interferon-based therapy in Thai chronic hepatitis C patients

Abstract Background Patients with chronic hepatitis C (HCV) infection have high prevalence of vitamin D deficiency. Genome-wide association study data has showed that several genetic variants within vitamin D cascade affect vitamin D function. This study aimed to determine whether genetic polymorphisms of genes in the vitamin D pathway are associated with treatment responses to pegylated interferon (PEG-IFN)-based therapy in patients with chronic HCV infection. Methods The study included 623 Thai patients from 2 university hospitals diagnosed with chronic HCV infection who were treated with a PEG-IFN and ribavirin. Patients were genotyped for functional variants on vitamin D synthetic pathway including GC (rs4588, rs7041, rs22020, rs2282679), CYP2R1 (rs2060793, rs12794714), CYP27B1 (rs10877012), and DHCR7 (rs12785878). Pre-treatment predictors of sustained virologic response (SVR) at 24 weeks following discontinuation of therapy were identified using a logistic regression analysis. Results SVR was achieved by 60.5% of patients (52.9% with HCV genotype 1; 66.7% with HCV non-genotype 1). In 44.6% of HCV genotype 1-infected patients, only the variant rs12785878 in the DHCR7 locus was significantly associated with an SVR. HCV genotype 1 patients who had DHCR7 rs12785878 GT/TT had a higher rate of SVR than those with the GG allele (59.7% vs. 43.4%, P = 0.03), but in HCV non-genotype 1-infected patients, the SVR rate did not differ between the two groups (63.3% and 59.1% for GT/TT and GG allele, P = 0.54). By multivariate analysis, liver fibrosis stage 0–1 (OR = 5.00; 95% CI, 2.02–12.37; P < 0.001), and DHCR7 rs12785878 GT/TT allele (OR = 2.69; 95% CI, 1.03–7.05; P = 0.04) were independent pre-treatment predictors of SVR following PEG-IFN-based therapy in HCV genotype 1 patients. Baseline HCV RNA < 400,000 IU/ml (OR = 1.96; 95% CI, 1.13–3.39; P = 0.02) was the only independent predictor of SVR in HCV non-genotype 1 patients. The polymorphisms of GC, CYP2R1 and CYP27B1 were not associated with treatment outcome even in genotype 1 or non-genotype 1 HCV infection. Conclusion The DHCR7 polymorphism may be a pre-treatment predictive marker for response to PEG-IFN-based therapy in chronic HCV genotype 1 infection