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1.
Hepatol Commun ; 6(4): 867-877, 2022 04.
Article in English | MEDLINE | ID: mdl-34811949

ABSTRACT

The aim of this study was to examine the impact of features of dysmetabolism on liver disease severity, evolution, and clinical outcomes in a real-life cohort of patients treated with direct acting antivirals for chronic hepatitis C virus (HCV) infection. To this end, we considered 7,007 patients treated between 2014 and 2018, 65.3% with advanced fibrosis, of whom 97.7% achieved viral eradication (NAVIGATORE-Lombardia registry). In a subset (n = 748), liver stiffness measurement (LSM) was available at baseline and follow-up. Higher body mass index (BMI; odds ratio [OR] 1.06 per kg/m2 , 1.03-1.09) and diabetes (OR 2.01 [1.65-2.46]) were independently associated with advanced fibrosis at baseline, whereas statin use was protective (OR 0.46 [0.35-0.60]; P < 0.0001 for all). The impact of BMI was greater in those without diabetes (P = 0.003). Diabetes was independently associated with less pronounced LSM improvement after viral eradication (P = 0.001) and in patients with advanced fibrosis was an independent predictor of the most frequent clinical events, namely de novo hepatocellular carcinoma (HCC; hazard ratio [HR] 2.09 [1.20-3.63]; P = 0.009) and cardiovascular events (HR 2.73 [1.16-6.43]; P = 0.021). Metformin showed a protective association against HCC (HR 0.32 [0.11-0.96]; P = 0.043), which was confirmed after adjustment for propensity score (P = 0.038). Diabetes diagnosis further refined HCC prediction in patients with compensated advanced chronic liver disease at high baseline risk (P = 0.024). Conclusion: Metabolic comorbidities were associated with advanced liver fibrosis at baseline, whereas statins were protective. In patients with advanced fibrosis, diabetes increased the risk of de novo HCC and of cardiovascular events. Optimization of metabolic comorbidities treatment by a multi-disciplinary management approach may improve cardiovascular and possibly liver-related outcomes.


Subject(s)
Carcinoma, Hepatocellular , Cardiovascular Diseases , Diabetes Mellitus , Hepatitis C, Chronic , Liver Neoplasms , Antiviral Agents/therapeutic use , Carcinoma, Hepatocellular/epidemiology , Cardiovascular Diseases/complications , Cohort Studies , Diabetes Mellitus/drug therapy , Hepatitis C, Chronic/complications , Humans , Liver Cirrhosis/diagnosis , Liver Neoplasms/epidemiology , Sustained Virologic Response
2.
J Hepatol ; 70(3): 379-387, 2019 03.
Article in English | MEDLINE | ID: mdl-30472321

ABSTRACT

BACKGROUND AND AIMS: The efficacy and safety of glecaprevir/pibrentasvir (G/P) for patients infected with hepatitis C virus (HCV) have only been investigated in clinical trials, with no real-world data currently available. The aim of our study was to investigate the effectiveness and safety of G/P in a real-world setting. METHODS: All patients with HCV consecutively starting G/P between October 2017 and January 2018 within the NAVIGATORE-Lombardia Network were analyzed. G/P was administered according to drug label (8, 12 or 16 weeks). Fibrosis was staged either histologically or by liver stiffness measurement. Sustained virological response (SVR) was defined as undetectable HCV-RNA 12 weeks after the end of treatment. RESULTS: A total of 723 patients (50% males) were treated with G/P, 89% for 8 weeks. The median age of our cohort was 58 years, with a median body mass index of 23.9 kg/m2, and median liver stiffness measurement of 6.1 kPa; 84% were F0-2 and 16% were interferon-experienced. Median HCV-RNA was 1,102,600 IU/ml, and 49% of patients had HCV genotype 1 (32% 1b), 28% genotype 2, 10% genotype 3 and 13% genotype 4. The median estimated glomerular filtration rate was 90.2 ml/min, platelet count 209x103/mm3 and albumin 4.3 g/dl. The SVR rates were 94% in intention-to-treat and 99.3% in per protocol analysis (8-week vs. 12 or 16-week: 99.2% vs. 100%). Five patients failed therapy because of post-treatment relapse; a post-treatment NS5A resistance-associated substitution was detected in 1 case. SVR rates were lower in males (p = 0.002) and in HCV genotype-3 (p = 0.046) patients treated for 8 weeks, but independent of treatment duration, fibrosis stage, baseline HCV-RNA, HIV co-infection, chronic kidney disease stage and viral kinetics. Mild adverse events were reported in 8.3% of the patients, and 0.7% of them prematurely withdrew treatment. Three patients died of drug-unrelated causes. CONCLUSIONS: In a large real-world cohort of Italian patients, we confirmed the excellent effectiveness and safety of G/P administered for 8, 12 or 16 weeks. LAY SUMMARY: A large number of patients with hepatitis C virus have been treated with glecaprevir/pibrentasvir (G/P) within the NAVIGATORE-Lombardia Network, in Italy. This is the first real-world study evaluating effectiveness and safety of G/P in patients with hepatitis C virus treated according to international recommendations. This study demonstrated excellent effectiveness (with sustained virological response rates of 99.3%) and safety profiles.


Subject(s)
Benzimidazoles , Hepatitis C, Chronic , Liver/pathology , Quinoxalines , Sulfonamides , Aminoisobutyric Acids , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Benzimidazoles/administration & dosage , Benzimidazoles/adverse effects , Biopsy/methods , Cohort Studies , Cyclopropanes , Drug Combinations , Elasticity Imaging Techniques/methods , Female , Hepacivirus/drug effects , Hepacivirus/genetics , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/epidemiology , Humans , Italy/epidemiology , Lactams, Macrocyclic , Leucine/analogs & derivatives , Liver Cirrhosis/diagnosis , Liver Cirrhosis/etiology , Male , Middle Aged , Proline/analogs & derivatives , Pyrrolidines , Quinoxalines/administration & dosage , Quinoxalines/adverse effects , RNA, Viral/analysis , Sulfonamides/administration & dosage , Sulfonamides/adverse effects , Sustained Virologic Response , Treatment Outcome
4.
Cytometry B Clin Cytom ; 78 Suppl 1: S61-8, 2010.
Article in English | MEDLINE | ID: mdl-20839339

ABSTRACT

BACKGROUND: Monoclonal B cell lymphocytosis (MBL) is a preclinical condition characterized by an expansion of clonal B cells in the absence of B lymphocytosis (BALC < 5 × 10(9)/L) in the peripheral blood, without clinical signs, suggestive of a lymphoproliferative disorder. B cell clonal expansions are also associated with hepatitis C virus (HCV) infection and they can evolve into lymphoproliferative disorders such as mixed cryoglobulinemia and non-Hodgkin lymphomas (NHL). The relationship between MBL and HCV infection has not been established yet. METHODS: By five-colour flow cytometry, we analyzed 123 HCV positive subjects with diagnosis of chronic hepatitis (94) or cirrhosis (29); 16 of those with cirrhosis had a diagnosis of hepatocellular carcinoma. RESULTS: MBL were identified in 35/123 (28.5%), at significantly higher frequency than in the general population. Sixteen/thirty-five were atypical-chronic lymphocytic leukemia (CLL) MBL (CD5(+), CD20(bright)), 13/35 were CLL-like MBL (CD5(bright), CD20(dim)), and 6/35 were CD5(-) MBL. Twenty-four/ninety-four (25.5%) patients affected by chronic hepatitis had MBL, whereas 11/29 (37.9%) patients with cirrhosis showed a B cell clone. A biased usage of IGHVgenes similar to HCV-associated NHL was evident. CONCLUSIONS: All three types of MBL can be identified in HCV-infected individuals at a higher frequency than in the general population, and their presence appears to correlate with a more advanced disease stage. The phenotypic heterogeneity is reminiscent of the diversity of NHL arising in the context of HCV infection. The persistence of HCV may be responsible for the dysregulation of the immune system and in particular of the B cell compartment.


Subject(s)
B-Lymphocytes/pathology , Hepatitis C, Chronic/pathology , Leukocytosis/pathology , Liver Cirrhosis/pathology , Adolescent , Adult , Aged , Aged, 80 and over , B-Lymphocytes/immunology , B-Lymphocytes/virology , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/pathology , Clone Cells , Female , Flow Cytometry , Gene Rearrangement, B-Lymphocyte, Heavy Chain/genetics , Hepacivirus/genetics , Hepacivirus/immunology , Hepacivirus/isolation & purification , Hepatitis C, Chronic/etiology , Humans , Immunoglobulin Heavy Chains/genetics , Immunophenotyping , Leukocytosis/etiology , Liver Cirrhosis/etiology , Liver Neoplasms/etiology , Liver Neoplasms/pathology , Lymphocyte Count , Male , Middle Aged , Young Adult
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