Safety and efficacy of ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in patients over 65 years with HCV genotype 1 cirrhosis
Purpose: To analyse safety and efficacy of treatment based on ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in the sub-group of GT1 patients older than 65 years. Methods: We collected data extracted from the ABACUS compassionate-use nationwide Italian programme, in patients with cirrhosis due to hepatitis C virus (HCV) Genotype-1 (GT1) or 4 and at high risk of decompensation. GT1-HCV-infected patients received once-daily ombitasvir/paritaprevir, with the pharmacokinetic enhancer ritonavir (25/150/100 mg) and twice-daily dasabuvir (250 mg) plus Ribavirin (RBV) (OBV/PTV/r + DSV + RBV) for 12 (GT1b) or 24 (GT1a) weeks. Endpoints were to evaluate safety and efficacy, the latter def…
The obesity paradox: Analysis from the SMAtteo COvid-19 REgistry (SMACORE) cohort
Summary Background and aims Obesity has been suggested as a possible risk factor for a more severe course of COVID-19; however, conclusive evidence is lacking and few studies have investigated the role of BMI as a risk factor for admission to intensive care unit (ICU) and mortality. We retrospectively analysed a COVID-19 cohort recruited during the first 40 days of the epidemic in Italy. We examined the association between obesity and 30-day mortality, admission to ICU, mortality and length of hospital stay in patients with COVID-19. Methods and results Demographic, clinical and outcome data were retrospectively analyzed in 331 patients with COVID-19 admitted to hospital between 21 February…
Critical reappraisal of risk factors for occurrence of hepatocellular carcinoma in patients with hepatitis C virus.
More than one and half of current cases of hepatocellular carcinoma in the US, Europe, and Japan are attributable to hepatitis C virus (HCV) infection. HCV is also the primary cause of death in patients with HCV-related cirrhosis, with annual incidences of 0.5%-5% in Europe and 4%-10% in Asia. Screening is based on serum alpha-fetoprotein determination and liver ultrasound scan, but the sensitivity of the former is far less than optimal, and screening intervals are still poorly defined for the latter. Risk factors related to the host or environment, or both, appear to be more relevant than viral factors, such as HCV genotype, in determining disease progression to cirrhosis and cancer, and i…
Occult hepatitis B virus infection
Many studies have shown that hepatitis B virus infection may also occur in hepatitis B surface antigen-negative patients. This occult infection has been identified both in patients with cryptogenic liver disease and in patients with hepatitis C virus-related chronic hepatitis, and much evidence suggests that it may be a risk factor of hepatocellular carcinoma development. However several aspects of this occult infection remain unclear such as its prevalence and the factor(s) involved in the lack of circulating hepatitis B surface antigen. Moreover, it is uncertain whether the occult hepatitis B virus infection may contribute to chronic liver damage, considering that it is usually associated…
Assessment of hepatitis C virus-RNA clearance under combination therapy for hepatitis C virus genotype 1: performance of transcription-mediated amplification assay
Monitoring of HCV-RNA in blood during antiviral therapy is performed mostly by commercially available reverse transcription polymerase chain reaction-based (RT-PCR) assays, with a lower detection limit of 30-50 IU/mL of HCV-RNA. Use of different tests in the pivotal trials of combination therapy has generated some discordance, in terms of predictive value of the early virological response (EVR). To evaluate whether the use of a more sensitive test, as a qualitative assay based on transcription mediated amplification (TMA) with a lower detection limit of 5-10 IU/mL of HCV-RNA, may obtain a better prediction of EVR and of the ultimate virological outcome, we retrospectively evaluated serial s…
Insulin resistance is associated with steatosis in nondiabetic patients with genotype 1 chronic hepatitis C.
Conflicting data exist regarding the relationship between hepatitis C virus genotype 1 and hepatic steatosis as well as the latter's role in the progression of fibrosis and treatment response. We assessed factors associated with hepatic steatosis in genotype 1 chronic hepatitis C and the impact of hepatic fat on fibrosis development and interferon responsiveness. Two hundred ninety-one non-diabetic patients with genotype 1 chronic hepatitis C were examined for the presence of steatosis and its correlation with clinical, virological, and biochemical data, including insulin resistance (IR), evaluated by the homeostasis model assessment (HOMA) score. Steatosis was graded as mild (1%-20% of hep…
Management of infections in cirrhotic patients: Report of a Consensus Conference
a b s t r a c t The statements produced by the consensus conference on infection in end-stage liver disease promoted by the Italian Association for the Study of the Liver, are here reported. The topics of epidemiology, risk factors, diagnosis, prophylaxis, and treatment of infections in patient with compensated and decompensated liver cirrhosis were reviewed by a scientific board of experts who proposed 26 statements that were graded according to level of evidence and strength of recommen- dation, and approved by an independent jury. Each topic was explored focusing on the more relevant clinical questions. By systematic literature search of available evidence, comparison and discussion of e…
Statements from the Taormina expert meeting on occult hepatitis B virus infection
Giovanni Raimondo*, Jean-Pierre Allain, Maurizia R. Brunetto, Marie-Annick Buendia, Ding-Shinn Chen, Massimo Colombo, Antonio Craxi, Francesco Donato, Carlo Ferrari, Giovanni B. Gaeta, Wolfram H. Gerlich, Massimo Levrero, Stephen Locarnini, Thomas Michalak, Mario U. Mondelli, Jean-Michel Pawlotsky, Teresa Pollicino, Daniele Prati, Massimo Puoti, Didier Samuel, Daniel Shouval, Antonina Smedile, Giovanni Squadrito, Christian Trepo, Erica Villa, Hans Will, Alessandro R. Zanetti, Fabien Zoulim
Peginterferon alfa-2b plus ribavirin for naïve patients with genotype 1 chronic hepatitis C: a randomized controlled trial
We assessed the effectiveness and safety of an induction dose of peginterferon alfa-2b (PEG-IFN) plus ribavirin for initial treatment of patients with genotype 1 chronic HCV infection in a randomized, controlled, multicenter trial.Three hundred and eleven naïve patients infected with genotype 1 and chronic hepatitis were randomly assigned to 48-week treatment with PEG-IFN once weekly (80-100 micrograms depending on body weight for 8 weeks, followed by 50 micrograms for the next 40 weeks), or standard interferon alfa-2b (IFN) 6 million units on alternate days, both in combination with ribavirin (1000-1200 mg/day).PEG-IFN plus ribavirin significantly increased sustained virological response (…
Clinical features and comorbidity pattern of HCV infected migrants compared to native patients in care in Italy: A real-life evaluation of the PITER cohort
Background: Direct-acting antivirals are highly effective for the treatment of hepatitis C virus (HCV) infection, regardless race/ethnicity. We aimed to evaluate demographic, virological and clinical data of HCV-infected migrants vs. natives consecutively enrolled in the PITER cohort. Methods: Migrants were defined by country of birth and nationality that was different from Italy. Mann-Whitney U test, Chi-squared test and multiple logistic regression were used. Results: Of 10,669 enrolled patients, 301 (2.8%) were migrants: median age 47 vs. 62 years, (p < 0.001), females 56.5% vs. 45.3%, (p < 0.001), HBsAg positivity 3.8% vs. 1.4%, (p < 0.05). Genotype 1b was prevalent in both gro…
HCV E1E 2‐ MF 59 vaccine in chronic hepatitis C patients treated with PEG ‐ IFN α2a and R ibavirin: a randomized controlled trial
Hepatitis C virus (HCV) vaccines may be able to increase viral clearance in combination with antiviral therapy. We analysed viral dynamics and HCV-specific immune response during retreatment for experienced patients in a phase Ib study with E1E2MF59 vaccine. Seventy-eight genotype 1a/1b patients [relapsers (30), partial responders (16) and nonresponders (32) to interferon-(IFN)/ribavirin-(RBV)] were randomly assigned to vaccine (V:23), Peg-IFNα2a-180-ug/qw and ribavirin 1000-1200-mg/qd for 48 weeks (P/R:25), or their combination (P/R + V:30). Vaccine (100 μg/0.5 mL) was administered intramuscularly at week 0-4-8-12-24-28-32-36. Neutralizing of binding (NOB) antibodies and lymphocyte prolife…
Ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin for patients with hepatitis C virus genotype 1 or 4 infection with cirrhosis (ABACUS): a prospective observational study
Summary Background We ran a compassionate use nationwide programme (ABACUS) to provide access to ombitasvir, paritaprevir, and ritonavir, with dasabuvir, plus ribavirin for hepatitis C virus (HCV) genotype 1 infection and ombitasvir, paritaprevir, and ritonavir, plus ribavirin for HCV genotype 4 infection in patients with cirrhosis at high risk of decompensation while approval of these regimens was pending in Italy. Methods In this prospective observational study, we collected data from a compassionate use nationwide programme from March 17, 2014, to May 28, 2015. Patients with HCV genotype 1 infection and cirrhosis at high risk of decompensation were given coformulated ombitasvir (25 mg), …