L. Donnarumma

Incidence of DAA failure and the clinical impact of retreatment in real-life patients treated in the advanced stage of liver disease: Interim evaluations from the PITER network

Background Few data are available on the virological and clinical outcomes of advanced liver disease patients retreated after first-line DAA failure. Aim To evaluate DAA failure incidence and the retreatment clinical impact in patients treated in the advanced liver disease stage. Methods Data on HCV genotype, liver disease severity, and first and second line DAA regimens were prospectively collected in consecutive patients who reached the 12-week post-treatment and retreatment evaluations from January 2015 to December 2016 in 23 of the PITER network centers. Results Among 3,830 patients with advanced fibrosis (F3) or cirrhosis, 139 (3.6%) failed to achieve SVR. Genotype 3, bilirubin levels >1.5mg/dl, platelet count <120,000/mm3 and the sofosbuvir+ribavirin regimen were independent predictors of failure by logistic regression analysis. The failure rate was 7.6% for patients treated with regimens that are no longer recommended or considered suboptimal (sofosbuvir+ribavirin or simeprevir+sofosbuvir±ribavirin), whereas 1.4% for regimens containing sofosbuvir combined with daclatasvir or ledipasvir or other DAAs. Of the patients who failed to achieve SVR, 72 (51.8%) were retreated with a second DAA regimen, specifically 38 (52.7%) with sofosbuvir+daclatasvir, 27 (37.5%) with sofosbuvir+ledipasvir, and 7 (9.7%) with other DAAs ±ribavirin. Among these, 69 (96%) patients achieved SVR12 and 3 (4%) failed. During a median time of 6 months (range: 5–14 months) between failure and the second DAA therapy, the Child-Pugh class worsened in 12 (16.7%) patients: from A to B in 10 patients (19.6%) and from B to C in 2 patients (10.5%), whereas it did not change in the remaining 60 patients. Following the retreatment SVR12 (median time of 6 months; range: 3–12 months), the Child-Pugh class improved in 17 (23.6%) patients: from B to A in 14 (19.4%) patients, from C to A in 1 patient (1.4%) and from C to B in 2 (2.9%) patients; it remained unchanged in 53 patients (73.6%) and worsened in 2 (2.8%) patients. Of patients who were retreated, 3 (4%) had undergone OLT before retreatment (all reached SVR12 following retreatment) and 2 (2.8%) underwent OLT after having achieved retreatment SVR12. Two (70%) of the 3 patients who failed to achieve SVR12 after retreatment, and 2 (2.8%) of the 69 patients who achieved retreatment SVR12 died from liver failure (Child-Pugh class deteriorated from B to C) or HCC complications. Conclusions Failure rate following the first DAA regimen in patients with advanced disease is similar to or lower than that reported in clinical trials, although the majority of patients were treated with suboptimal regimens. Interim findings showed that worsening of liver function after failure, in terms of Child Pugh class deterioration, was improved by successful retreatment in about one third of retreated patients within a short follow-up period; however, in some advanced liver disease patients, clinical outcomes (Child Pugh class, HCC development, liver failure and death) were independent of viral eradication.

Prevalence of and risk factors for HBV infection in a metropolitan Southern Italian area: Evidence for the effectiveness of universal Hepatitis B vaccination

BACKGROUND Available data on HBV prevalence in Italy are outdated and assessed with studies conducted in small towns. We aimed to evaluate prevalence of and risk factors for HBV infection in the metropolitan area of Naples, 24 years after the introduction of mass vaccination campaign against Hepatitis B in Italy. METHODS A random systematic sample of the adult general population of Naples was selected from the register of 3 general practitioners in 3 different socio-economic districts. Independent predictors of the likelihood of HBV infection were identified by logistic regression analysis. RESULTS Among 900 selected subjects, 772 (85.8%) participated in the study. The overall HBsAg and anti-HBc prevalences were 1.7% and 14.4%, respectively. Both markers were more likely detected in the district at low socioeconomic status than in those at medium-high status (p<0.01). Anti-HBc prevalence linearly increased from 0% in subjects 30 years old or younger to 28.0% in those older than 60 years of age (p<0.01). At multivariate analysis, age >60 years (OR3.38; 95%CI:1.98-5.74), low socioeconomic district of residence (OR3.26; 95%CI:1.72-6.18), and low educational qualification (OR2.73; 95%CI:1.45-5.16) were independent predictors of anti-HBc positivity. CONCLUSION Differences in socioeconomic conditions have played a major role in the past spread of HBV infection in Naples. Hepatitis B vaccination has resulted very effectively in preventing HBV infection, regardless of the district of residence, as none of the subjects in the vaccinated cohorts was exposed to the infection.

Eradication of HCV in Renal Transplant Recipients and Its Effects on Quality of Life

Background The use of direct antiviral agents (DAA) has radically modified the course of HCV hepatitis in renal patients. Aim of this study was to assess the effects of HCV eradication on quality of life (QOL) in renal transplant recipients (RTR), measured by CLDQ and SF-36. Methods Sixteen RTR with well preserved GFR (mean: 60.3±19.3 ml/min) and chronic HCV infection with moderate liver stiffness (9.3±1.7 kPa) were given a sofosbuvir-based regimen for 12 weeks and had a 1 year follow-up. Results At end of treatment (EOT) a complete viral clearance was observed in all the patients, with normalization of most laboratory data and a consistent reduction in liver stiffness. All these parameters remained stable after 1 year, as well as renal function and proteinuria. Questionnaire data showed consistent amelioration in different “emotional” domains at EOT, which persisted after 1 year and were associated with a globally improved QOL, although there was no change in most of the “physical” domains in both questionnaires. One patient under ribavirin developed an acute anemia and withdrew from the study, but no further adverse episode was observed throughout the study. Conclusions Our data, while confirming the efficacy of oral DAA, show that HCV infection represents a heavy psychological burden in renal transplant recipients, greatly alleviated by viral eradication, which determines a significant improvement in QOL that represents an important outcome in management of all transplant recipients. This trial is registered with ISRCTN97560076.

P.1.18: LONG-TERM HCV-ERADICATION. A 20 YEARS CLINICAL, VIROLOGICAL AND BIOCHEMICAL PROSPECTIVE STUDY

Background and aim: In patients with chronic hepatitis C, therapy is considered effective when the sustained virological response (SVR) is achieved. SVR is defined as HCV-RNA negativity in serum 6 months after the end of therapy. Although the persistence of HCV eradication in short or medium-term period (3-5 years) is wellestablished, data about the long-term follow-up are still uncertain. The aim of the study was to evaluate the long-term persistence of HCV eradication in patients with chronic hepatitis C (CHC) who obtained SVR. In particular, we wanted to assess the risk of long-term virological relapse and liver related-complications. Material and methods: From January 1989 to Aprill 2008, 150 consecutive subjects (M/F 100/50, median age 47.69 years, range 22-67) with CHC and SVR after interferon-based therapy, were enrolled in a long-term follow-up study. 137 patients had pre-treatment diagnosis of CHC and 13 patients had cirrhosis. All of the patients received interferon-based therapy, with or without Ribavirin (66 with conventional IFN-monotherapy, 25 with conventional IFN and ribavirin, and 59 with pegylated IFN and ribavirin).The patients were followed with clinical, biochemical, virological and ultrasonographic assessments every 6 months until the 3th year of follow-up and than every 12 months. HCV-RNA assessment in serum was determined by quantitative RT-PCR. Results: The median follow-up was 8.6 years (range: 2-19.8 years). Serum HCV-RNA remained undetectable in all patients, indicating no risk of HCV recurrence, independently from the schedule of therapy used.During the observation period 3 liver-related complications (2 HCC, 1 variceal bleeding) were observed. The incidence rate of complications was 0.23%/person/year. All 3 of the events occurred in patients with pre-treatment cirrhosis. Only 1 out of 150 patients deceased for liver-related causes (HCC) with a mortality rate of 0.077%/person/year Conclusions: In this cohort of CHC patients with SVR, the eradication of the virus lasted up to 20 years after treatment. Thus, patients with CHC and SVR show an excellent prognosis with no risk of viral recurrence and a very low rate of mortality, meaning that they can be considered healed. Patients with pre-treatment evidence of cirrhosis show a rate of liver complications that cannot be neglected.