Treatment failure may lead to accelerated fibrosis progression in patients with chronic hepatitis C (original) (raw)
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Fibrosis Regression Post Direct-acting Antiviral Treatment in Hepatitis C Virus Patients
Medical journal of Bakirköy, 2023
Objective: We studied long-term serial changes in aspartate aminotransferase/platelet ratio index (APRI) and fibrosis-4 (FIB-4) scores in hepatitis C virus patients with a sustained virologic response after direct-acting antiviral (DAA) therapy. Methods: Seventy-five patients treated with DAA were included in this study. APRI and FIB-4 scores were calculated at the beginning of DAA treatment, at the end of treatment (EOT), one and two years after treatment. Results: Twenty-eight patients had cirrhosis. APRI and FIB-4 scores (1.38 vs. 0.49, p<0.001; 4.25 vs. 2.79, p<0.001) Improved in all patients at the EOT. There was also a trend toward decreased scores for APRI and FIB-4 at follow-up based on EOT of 2 nd-year results (APRI, 0.49 vs. 0.41, p=0.87; FIB-4, 2.79 vs. 2.50, p=0.44). There were significant improvements in cirrhotic patients' two-year APRI and FIB-4 scores (0.86 vs. 0.58, p<0.001; 4.74 vs. 3.59, p<0.001). Similarly, in the 1 st and second years, APRI and FIB-4 scores were compared after EOT in cirrhotic patients (0.84 vs. 0.58, p=0.007; 4.74 vs. 3.59, p=0.004) and showed remarkable improvement. Conclusion: Improvements in liver fibrosis markers were prominent in patients with advanced fibrosis. The regression in liver fibrosis based on non-invasive tests has persisted even two years after the treatment.
PLOS ONE, 2016
Background and Aim Liver biopsy (LB) has lost popularity to stage liver fibrosis in the era of highly effective antihepatitis C virus (HCV) therapy, yet diagnosis of persistent cirrhosis may have important implications following HCV eradication. As performance of serological non-invasive tests (NITs) to predict residual fibrosis in non-viremic HCV patients is unknown, we investigated accuracy of NITs to predict residual fibrosis in cirrhotics after a sustained virological response (SVR) to interferon (IFN). Methods Thirty-eight patients with a pre-treatment histological diagnosis of cirrhosis and a 48-104 months post-SVR LB were tested with APRI, CDS, FIB-4, FibroQ, Forns Score, GUCI Index, King Score, Lok Index, PLF, ELF. In 23 (61%) patients, cirrhosis had histologically regressed. Results All NITs values declined after SVR without any significant difference between regressors and non-regressors (AUROC 0.52-0.75). Using viremic cutoffs , PPV ranged from 34% to 100%, with lower NPV (63%-68%). NITs performance did not improve using derived cutoffs (PPV: 40%-80%; NPV: 66%-100%). PLF, which combines several NITs with transient elastography, had the best diagnostic performance (AUROC 0.75, Sn 61%, Sp 90%, PPV 80%, NPV 78%). After treatment, none of the NITs resulted significantly associated with any of the histological features (activity grade, fibrosis stage, area of fibrosis).
Endocrine, Metabolic & Immune Disorders - Drug Targets
Introduction: The goal of treatment of chronic hepatitis C (HCV) is viral eradication. However, obtaining histological regression is even more important, because it will reduce the overall morbidity and mortality related to cirrhosis. Introduction of direct-acting antivirals (DAAs) in HCV improves rates of sustained virologic response (SVR). However, fibrosis regression has not been extensively assessed. The aim of this study was to detect the factors affecting fibrosis regression in chronic HCV patients treated with interferon containing regimens versus interferon-free DAA regimens. Methods: This prospective observational cohort study was conducted at the Tropical Medicine and Infectious Diseases Department, Tanta University, Egypt, between October 2015 and December 2017. Transient elastography (FibroScan®) examination was performed before therapy, at SVR12, 6 months and 1 year after completing therapy for cured patients. Results: Reduction in fibrosis was reported in; 46.7% and 49...
Journal of Hepatology, 2011
Background & Aims: Fibrosis progression in patients with chronic hepatitis C (CHC) is highly variable. A Cirrhosis Risk Score (CRS) based on seven genetic variants has been recently developed for identifying patients at risk for cirrhosis. The objective of this study was to assess the role of the CRS for the early prediction of fibrosis progression in CHC patients with mild liver fibrosis. In addition, we evaluated the potential benefit, for prediction accuracy, of a recently described non-invasive fibrosis staging assay, the Enhanced Liver Fibrosis (ELF) test. Methods: Two separate cohorts of HCV patients (Brussels, Belgium/Hannover, Germany) were retrospectively analyzed. Only patients with a fibrosis Ishak or METAVIR score of F0-F1 at baseline were included. Patients were classified as progressors if they showed an increase P2 fibrosis stages at the second histological evaluation after a follow-up P5 years. The CRS was calculated locally. Genotyping was performed by PCR and oligonucleotide ligation with the resulting signal detected with a Luminex Ò 200TM and computer analysis. Results: In Brussels, 12/25 patients progressed (48%); similarly in Hannover, 16/31 (52%) patients progressed. In both sample sets, the CRS was significantly associated with fibrosis progression (p = 0.050 in Brussels; p = 0.018 in Hannover). The ELF test was only a significant predictor in Hannover (p = 0.015). In multivariate analysis the CRS remained the only variable associated with fibrosis progression (odds-ratio = 2.23, 95%CI 1.21-4.11 p = 0.01). Conclusions: Although conducted on a limited number of patients, this study in two independent centres confirms that the CRS predicts fibrosis progression in initially mild CHC. Ó
Factors Influencing the Rate of Fibrosis Progression in Chronic Hepatitis C
Digestive Diseases and Sciences, 2004
Alcohol consumption, age at infection, and male gender have been identified as risk factors for faster fibrosis progression in patients with chronic hepatitis C (CHC). Yet the influence of liver steatosis, light to moderate alcohol consumption, or iron overload on this progression remains controversial. To analyze the effect of individual risk factors and their interaction on fibrosis progression in a group of patients with CHC and a definite date of infection, we studied 133 consecutive untreated patients. Covariates included were age, body mass index (BMI), gender, age at infection, alcohol intake, serum lipids, glycemia, serum ALT, AST, GGT, iron, and ferritin, grade and stage (METAVIR and Scheuer), and hepatic stainable iron (Perl’s stain). The rate of fibrosis progression was inferred from the METAVIR score. By logistic regression analysis, hepatic steatosis (odds ratio [OR], 3.035; 95% confidence interval [CI], 1.16–7.93), serum ferritin levels higher than 290 ng/ml (OR, 5.5; 1.6–18.65), and light to moderate ethanol intake (1–50 g/day) (OR, 5.22; 1.5–17.67) were independently associated with faster fibrosis progression. There was no effect of interaction between these variables on the rate of fibrosis progression. Liver steatosis, serum ferritin levels, and light to moderate alcohol intake are associated with faster fibrosis progression in chronic hepatitis C. Combination of these factors did not further accelerate this progression. The impact of modification of these factors on progression should be tested in longitudinal studies.
A new scoring system for prediction of fibrosis in chronic hepatitis C
Hepatitis monthly, 2011
Background: Liver biopsy (LB) is still considered to be the gold standard for assessment of liver fibrosis. Objectives: To evaluate the effectiveness of various non-invasive methods for predicting liver fibrosis, including transient elastography (TE), APRI score, Lok score, Forns score, FIB-4 score, Fibrosis Index, King score, and Bonacini score, in comparison with the effectiveness of LB and to create a new scoring system for fibrosis prediction. Patients and Methods: This study included 212 patients with chronic HCV hepatitis. LB, TE, and various biological tests were performed during a single hospital visit. Using established formulae, data from these tests were used to create scores for assessment of liver fibrosis. Results: The results of all the tests showed significant correlation with histological fibrosis. TE results (r = 0.62), King score (r = 0.57), and APRI score (r = 0.56) showed the closest correlation with severity of fibrosis. The following formula was derived from our data by multiple regression: Predicted liver fibrosis score (PLF score) = 0.956 + 0.084 × TE-0.004 × King score + 0.124 × Forns score + 0.202 × APRI score. A direct correlation (r = 0.68) was found between the PLF score and liver fibrosis. The cutoff values of the PLF score for various stages of fibrosis were: F ≥ 1, 1.77 (Area under ROC curve (AUROC) = 0.76); F ≥ 2, 2.18 (AUROC = 0.78); F ≥ 3, 2.47 (AUROC = 0.86); and F = 4, 2.98 (AUROC = 0.97). Conclusions: We found that our newly developed PLF score, which is derived from the scores of multiple tests, is more strongly correlated with fibrosis than each component score used individually. The PLF score is more effective than TE for predicting severe fibrosis, but they have similar effectiveness in predicting liver cirrhosis.
Gut, 2010
Objectives The aim of this study was to explore the association of serum fibrosis marker levels with the risk of clinical and histological disease progression in a large cohort of patients with chronic hepatitis C (CHC). Methods 462 prior non-responders to peginterferon and ribavirin enrolled in the randomised phase of the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial had baseline and annual serum samples tested for hyaluronic acid (HA), N-terminal peptide of procollagen type 3, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and YKL-40. All patients underwent a pretreatment liver biopsy and follow-up biopsies at years 2 and 4. Histological progression was defined as a 2pointincreaseinIshakfibrosisscoreinpatientswithoutcirrhosis.Clinicaloutcomesincludeddevelopmentofdecompensation,hepatocellularcancer,deathoranincreaseintheCTP(ChildeTurcotteePugh)scoreto2 point increase in Ishak fibrosis score in patients without cirrhosis. Clinical outcomes included development of decompensation, hepatocellular cancer, death or an increase in the CTP (ChildeTurcotteePugh) score to 2pointincreaseinIshakfibrosisscoreinpatientswithoutcirrhosis.Clinicaloutcomesincludeddevelopmentofdecompensation,hepatocellularcancer,deathoranincreaseintheCTP(ChildeTurcotteePugh)scoreto7. Results Mean patient age was 49.5 years and 39% had histological cirrhosis at entry. Baseline HA, YKL-40 and TIMP-1 levels combined with other laboratory parameters were all significantly associated with clinical outcomes in the 69 (15%) patients with disease progression (p<0.0001). The best multivariate model to predict clinical outcomes included baseline bilirubin, albumin, international normalised ratio (INR) and YKL-40 levels. All of the baseline serum fibrosis marker levels were also significantly associated with histological fibrosis progression that developed in 70 (33%) of the 209 patients with cirrhosis (p <0.0001). However, baseline HA and platelet counts were best at predicting histological progression (area under the curve (AUC)¼0.663). Conclusion Pretreatment serum fibrosis marker levels are significantly increased in patients with CHC at risk of clinical and histological disease progression. If validated in additional cohorts, measurement of these markers could help identify patients with CHC who would benefit from more frequent and intensive monitoring. Trial Registration Number NCT00006164.