HCV-related Advanced Fibrosis Research Articles

Decreased Incidence of Hepatocellular Carcinoma after Directly Acting Antiviral Therapy in Patients with Hepatitis C-Related Advanced Fibrosis and Cirrhosis.

Background and AimExisting data are controversial regarding the incidence of hepatitis C (HCV)–related hepatocellular carcinoma (HCC) following directly acting antiviral (DAA) therapy. This prospective study aimed to assess incidence, and risk factorss of HCC following DAA therapy in patients with HCV-related advanced fibrosis (F3) and cirrhosis (F4).MethodsIncidence of HCC was calculated in 1,630 patients with HCV-related F3 and F4 treated with DAA prospectively followed for up to 43 months in a single tertiary referral center and compared to historical controls. Risk factors of incident HCC were also determined.ResultsThe crude outcome rate was 2.15/100 person-years, significantly lower than a similar historical cohort (5.57/100 person-years). Risk of developing HCC was higher with the presence of cirrhosis (F4 vs F3, AHR 3.59) and treatment failure (vs achieving SVR, AHR 3.37). Presence of decompensated cirrhosis, platelet count <100×103/mL, and high AFP were independent risk factors of developing HCC.ConclusionIncidence of HCC was significantly lower in patients with HCV-related advanced fibrosis and cirrhosis treated with DAAs than in a historical cohort of untreated patients. Decompensated cirrhosis, baseline AFP ≥10 ng/mL, diabetes, and nonresponse to DAA were independent risk factors of incident HCC.

Improvement of platelet in thrombocytopenic HCV patients after treatment with direct-acting antiviral agents and its relation to outcome

Little is known about evolution of platelet count after treatment with direct-acting antiviral agents (DAAs). The study aimed to evaluate the changes in platelet count after treatment with DAAs among thrombocytopenic patients with HCV-related advanced fibrosis and cirrhosis. A total of 915 chronic HCV patients with advanced fibrosis and cirrhosis who were treated with different DAAs-based regimens were retrospectively enrolled in final analysis. Included patients were those with thrombocytopenia (TCP). Platelet count was recorded at baseline, end of treatment (EOT) and 24-weeks after EOT (SVR24). Changes in platelet count and its relation to SVR were analyzed. The overall SVR24 rate was 98.8%. The platelet count showed statistically significant improvement from baseline to EOT (107 (84–127) × 103/mm3 vs. 120 (87–153) × 103/mm3(P = <0.0001) but remained unchanged thereafter to SVR24. Among responders, the platelet count significantly increased at SVR24 compared to baseline (P = <0.0001) but in relapsers, there was improvement in platelet count that didn’t reach statistical significance (P = 0.9). Logistic regression analysis showed that higher Child-Pugh score and more advanced fibrosis at baseline were significant predictors of decreasing of platelet count and development of severe TCP at SVR24. Among thrombocytopenic patients with HCV-related advanced fibrosis and cirrhosis, the platelet count improved after treatment with DAAs regardless to treatment response.

IL-28B genotypes as predictors of long-term outcome in patients with hepatitis C-related severe liver injury.

Patients with severe fibrosis or cirrhosis are at high risk for liver-related complications, even after successful antiviral treatment and/or regression of fibrosis. These are the first published results concerning the role of IL-28B genotypes as predictors of the durability of sustained virological response (SVR) and long-term outcome, in patients with baseline severe fibrosis and cirrhosis caused by hepatitis C (HCV) infection. Genetic testing for three different single nucleotide polymorphisms (SNP) near the IL28B gene, rs12979860, rs12980275 and rs8099917, was performed in 42 patients with HCV-related advanced fibrosis and cirrhosis, who achieved SVR after successful interferon-based treatment. Baseline clinical and laboratory parameters were analysed, as well as IL28B genotype association with late virological relapse, fibrosis progression and clinical outcomes. The most prevalent genotypes in all three tested SNP positions were: CCrs12979860 genotype in 69% of patients, GTrs8099917 in 78.6% and GGrs12980275 in 47.6% of patients. The presence of IL28B CCrs12979860 genotype was identified as a negative predictor of late virological relapse. Further analysis did not confirm the association of other IL28B genotypes with the progression of fibrosis and clinical outcomes. Varying long-term prognosis in patients with HCV-related severe fibrosis and cirrhosis is due to multiple interactions between host genetic factors, virus and environment. These are first published results demonstrating the significance of IL28B CCrs12979860 genotype as a negative predictor of late virological relapse. A further investigation concerning genetic factors is necessary to identify patients under risk for late relapse, complications and unfavorable outcomes, so that they can be reevaluated and offered new treatment options.

THU-303 - Risk and outcome of hepatitis B virus reactivation during chronic hepatitis C treatment with direct-acting antivirals in patients with HCV-related advanced fibrosis: a single-center experience

THU-303 - Risk and outcome of hepatitis B virus reactivation during chronic hepatitis C treatment with direct-acting antivirals in patients with HCV-related advanced fibrosis: a single-center experience

Risk and outcome of hepatitis B virus (HBV) reactivation during chronic hepatitis C treatment with direct-acting antivirals (DAAs) in patients with HCV-related advanced fibrosis: A single-center experience

Risk and outcome of hepatitis B virus (HBV) reactivation during chronic hepatitis C treatment with direct-acting antivirals (DAAs) in patients with HCV-related advanced fibrosis: A single-center experience

Data Mining and Machine Learning Algorithms Using IL28B Genotype and Biochemical Markers Best Predicted Advanced Liver Fibrosis in Chronic Hepatitis C.

IL28B single nucleotide polymorphism (rs12979860) is an etiology-independent predictor of hepatitis C virus (HCV)-related hepatic fibrosis. Data mining is a method of predictive analysis which can explore tremendous volumes of information from health records to discover hidden patterns and relationships. The current study aims to evaluate and compare the prediction accuracy of scoring system like aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4) index versus data mining for the prediction of HCV-related advanced fibrosis. This retrospective study included 427 patients with chronic hepatitis C. We used data mining analysis to construct a decision tree by reduced error (REP) technique, followed by Auto-WEKA tool to select the best classifier out of 39 algorithms to predict advanced fibrosis. APRI and FIB-4 had sensitivity-specificity parameters of 0.523-0.831 and 0.415-0.917, respectively. REPTree algorithm was able to predict advanced fibrosis with sensitivity of 0.749, specificity of 0.729, and receiver operating characteristic (ROC) area of 0.796. Out of the 16 attributes, IL28B genotype was selected by the REPTree as the best predictor for advanced fibrosis. Using Auto-WEKA, the multilayer perceptron (MLP) neural model was selected as the best predictive algorithm with sensitivity of 0.825, specificity of 0.811, and ROC area of 0.880. Thus, MLP is better than APRI, FIB-4, and REPTree for predicting advanced fibrosis for patients with chronic hepatitis C.

Hepatitis C Virus Clearance in Older Adults.

To determine whether older adults with the hepatitis C virus (HCV) achieve a sustained viral response (SVR) after treatment with direct-acting antiviral therapy. Individuals aged 80 and older with chronic HCV infection (N=253; n=213 with cirrhosis, n=40 with advanced fibrosis). We investigated the efficacy, safety, and global clinical effect of treatment with different combinations of direct antiviral agents (DAAs). Participants with cirrhosis were staged according to Child-Pugh-Turcotte class, Model for End-Stage Liver Disease score, and the D'Amico staging system. The type and number of comorbidities at baseline and hepatic and nonhepatic events during follow-up were registered. Ninety-five percent of participants with cirrhosis and 95% of those with advanced fibrosis attained SVR. The rate was independent of sex, HCV genotype, and treatment schedule. During a mean follow-up of 14±4months (range 5-23months), 34 events occurred in 27 participants: 10 hepatocellular carcinomas, 12 hepatic decompensations, 9 nonhepatic events, 3 deaths. Multivariate analysis of risk factors for experiencing adverse events during follow up showed that participants in D'Amico Stages 4 and 5, with a baseline serum albumin level of 3.5mg/dL or less, and 3 or more comorbidities were the most at risk. In a real-world setting, DAAs are safe and effective in older adults with HCV-related advanced fibrosis or cirrhosis. Individuals with preserved albumin synthesis and fewer than 3 comorbidities at baseline have the most to gain from long-term DAA therapy.

PTU-075 Liver and Spleen Stiffness Measurements Based on Acoustic Radiation Force Impulse Elastography for Noninvasive Assessment of Esophageal Varices in HCV-Related Advanced Fibrosis

Introduction Acoustic radiation force impulse elastography (ARFI) and Transient elastography (TE) are noninvasive methods of measuring liver stiffness (LS) and spleen stiffness (SS). They were proposed as non-invasive predictors of portal hypertension in patients with HCV-related cirrhosis, a highly prevalent disease in Egypt. This is the first egyptian study aimed to validate the reliability of liver and spleen stiffness measured by ARFI and other non-invasive methods as non-invasive predictors for presence of esophageal varices (EV). Methods This cross-sectional study included 200 patients (mean age was 54.9±8 years) with HCV-related advanced fibrosis (METAVIR score ≥F3) diagnosed by FibroScan® (≥ 9.5 kilopascal) including Child Turcotte Pugh class A/B liver cirrhosis; 82/18%. Demographic, clinical, biochemical, endoscopic and ultrasonographic data were collected. LOK index and FIB-4 score were calculated. Liver and spleen stiffness were assessed by 10 ARFI measurements, both in the liver and in the spleen; median values were calculated, expressed in m/sec. The accuracy of these diagnostic methods in diagnosing EV was evaluated on the basis of area under receiver operating characteristic (AUROC) curves. Results Liver stiffness measurement by FibroScan® revealed F4 in 95.5% and esophageal varices were present in 90 patients (39 Grade I, 30 Grade II, 18 Grade III, 3 Grade IV). Spleen longitudinal diameter (cutoff value 14.85 cm), splenic vein diameter(cutoff value 7.9 mm); platelets to spleen diameter ratio (cutoff value 960), LOK index (cutoff value 0.62)and FIB-4 score (cutoff value 2.81) were the best parameters among all the ultrasonographic and biochemical parameters for prediction of esophageal varices; AUROC 0.79, 0.76, 0.76, 0.74 and 0.71, respectively. Using ARFI, SS had better diagnostic performance than LS with cutoff value of 3.25 m/sec and 2.61 m/sec; AUROC =0.76 and 0.70, respectively. Moreover, the calculation of simple prediction models including LS and/or SS improved the reliability of ARFI for the prediction of esophageal varices; (Spleen longitudinal diameter × Splenic vein diameter × SS) and (LS× SS / Platelets/Spleen diameter ratio) with AUROC = 0.85 and 0.83 respectively. Conclusion Liver stiffness and spleen stiffness represent a non-invasive reliable tool for the prediction of clinically significant portal hypertension as evident by the presence of esophageal varices in chronic liver disease patients. Disclosure of Interest M. Abdelbary: None Declared, S. Kamal, None Declared, A. Albuhairi: None Declared, A. Khairy Grant/research support from: ABBVIE, Speaker bureau with: Astra Zeneca, N. Zayed Grant/research support from: ABBVIE, A. Yosry Consultant for: Roche, Janssen, Gilead, MSD, Speaker bureau with: Roche, Janssen, Gilead, MSD

Branched-chain amino acids reduce hepatic iron accumulation and oxidative stress in hepatitis C virus polyprotein-expressing mice.

Background & AimsBranched-chain amino acids (BCAA) reduce the incidence of hepatocellular carcinoma (HCC) in patients with cirrhosis. However, the mechanisms that underlie these effects remain unknown. Previously, we reported that oxidative stress in male transgenic mice that expressed hepatitis C virus polyprotein (HCVTgM) caused hepatic iron accumulation by reducing hepcidin transcription, thereby leading to HCC development. This study investigated whether long-term treatment with BCAA reduced hepatic iron accumulation and oxidative stress in iron-overloaded HCVTgM and in patients with HCV-related advanced fibrosis.MethodsMale HCVTgM were fed an excess-iron diet that comprised either casein or 3.0% BCAA, or a control diet, for 6 months.ResultsFor HCVTgM, BCAA supplementation increased the serum hepcidin-25 levels and antioxidant status [ratio of biological antioxidant potential (BAP) relative to derivatives of reactive oxygen metabolites (dROM)], decreased the hepatic iron contents, attenuated reactive oxygen species generation, and restored mitochondrial superoxide dismutase expression and mitochondrial complex I activity in the liver compared with mice fed the control diet. After 48 weeks of BCAA supplementation in patients with HCV-related advanced fibrosis, BAP/dROM and serum hepcidin-25 increased and serum ferritin decreased compared with the pretreatment levels.ConclusionsBCAA supplementation reduced oxidative stress by restoring mitochondrial function and improved iron metabolism by increasing hepcidin-25 in both iron-overloaded HCVTgM and patients with HCV-related advanced fibrosis. These activities of BCAA may partially account for their inhibitory effects on HCC development in cirrhosis patients.

Peginterferon plus ribavirin and sustained virological response rate in HCV-related advanced fibrosis: a real life study

BackgroundTolerance and response to antiviral HCV treatment is poor in advanced fibrosis. The aim of this study was to assess SVR rate and its predictive factors in HCV advanced fibrosis patients treated in real life with full dose PEG-IFN plus RBV and to evaluate the adverse events related to treatment. MethodsA multicentric, retrospective study was conducted at six university hospitals. METAVIR F3 and F4 HCV monoinfected patients who were treated with PEG-IFN and RBV had their data analyzed. A stepwise logistic regression analysis was performed to identify the variables independently related to SVR. Adverse events were recorded during treatment. Results308 patients were included, 75% genotype 1 and 23% genotype 3. METAVIR F3 was present in 39% and F4 in 61% of patients. The median Child Pugh score for F4 patients was 5 (5–9). The global SVR rate was 34%, 11% were relapsers and 55% were nonresponders. SVR rates were similar between patients treated with PEG-IFN alfa 2a or alfa 2b (p=0.24). SVR rates according to Child–Pugh score were 26% (Child A) and 18% (Child B). The independent factors related to SVR in F4 patients were genotype 3, RVR and fewer Child Pugh score points. Treatment interruption occurred in 31% patients and death occurred in 1.9%, all with liver cirrhosis. ConclusionTreatment of HCV in patients with advanced fibrosis should not be postponed. However, a very careful evaluation of cirrhotic patients must be performed before treatment is indicated and careful monitoring is required during treatment.