title: Sofosbuvir and ribavirin for genotype 2 HCV infected patients with cirrhosis: A real life experience.
abstract: Sofosbuvir (SOF) and weight-based ribarivin (RBV) represented until recently the standard of care in hepatitis C virus (HCV) genotype (GT)2 patients. In registration studies 12-16weeks duration were associated with a 90% sustained virological response at 12weeks (SVR12). Real life cohorts showed lower SVR12 rates.
  
  
  
  SVR12 rates attained in an Italian real life cohort and possible benefits of a duration extended up to 20weeks was investigated in HCV GT2 patients with cirrhosis. The role of 2k/1b chimeras as potential predictor of treatment failure was also analysed.
  
  
  
  Overall, 291 HCV GT2 infected patients with bridging fibrosis or cirrhosis were evaluated. Median age was 68years (18-87); 163 were treatment naïve. Of 168 cirrhotic patients, 149 had Child-Pugh score A and 19 B, 50 platelets count <100,000/mm3and 62 albumin <3.5g/dl. SVR12 were 95.53% overall, with 99.15% in non-cirrhotic patients and 93.06% in cirrhotic patients. In patients who completed treatment, SVR rates for cirrhotic patients resulted in 94.51%, and 94.94% after 16 or 20weeks respectively. Predictors of SVR were low platelet count and esophageal varices (OR 7.2; 95% CI 1.67-31.25; p=0.0022 and OR 0.1; 95% CI 0.01-0.72; p=0.0079, respectively). Anemia was mild in 12.4%, moderate in 3.4%, and severe in 2.4% of cases. Anemia was slightly more frequent among longer duration but not associated with treatment discontinuations. No 2k/1b strains or genotypes different from those at baseline were identified at relapse.
  
  
  
  In GT2 cirrhotic patients, SOF/RBV for 16 or 20weeks is associated with real life SVR12 rates of 95%.
  
  
  
  A duration of treatment of 16-20weeks was recommended for treatment of HCV GT2 patients using the combination of sofosbuvir and ribavirin. Real life experiences, where patients received 12weeks of treatment regardless of the severity of liver disease, suggested that response rates are lower than expected, in particular in patients with liver cirrhosis. A misleading genotyping of a 2k/1b strain as GT2 was also hypothesized as a further explanation for less effectiveness. We demonstrated that using the recommended extended duration in patients with more severe disease 95% of patients with severe liver disease including cirrhosis can be cured and that 2k/1b strain plays only a secondary role in specific countries like Germany. Although this combination has been recently replaced by sofosbuvir and velpatasvir fixed dose combination as the standard of care for treating HCV GT2 patients, our findings may inform physicians from countries where the new regimen is not yet available.
authors.affiliation: Liver Unit, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy. Electronic address: a.mangia@tin.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mangia
authors.affiliation: Johann Wolfgang Goethe University Medical Center, Frankfurt am Main, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Susser
authors.affiliation: Liver Unit, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Piazzolla
authors.affiliation: Internal Medicine Clinica "Mater Dei", Bari, Italy.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Agostinacchio
authors.affiliation: Infectious Diseases Unit, Presidio ospedaliero Madonna delle Grazie, Matera, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: De Stefano
authors.affiliation: Medical Clinic "A. Murri", Policlinico di Bari, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Palmieri
authors.affiliation: Gastroenterology Unit, Ospedale Valduce, Como, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Spinzi
authors.affiliation: Infectious Diseases Unit, Ospedale "Vito Fazzi", Lecce, Italy.
authors.forename: Immacolata
authors.initials: I
authors.lastname: Carraturo
authors.affiliation: Interventional ultrasound Unit, Ospedale "Perrino", Brindisi, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Potenza
authors.affiliation: Infectious Diseases Unit, Presidio Opedaliero Bisceglie, Italy.
authors.forename: Ruggero
authors.initials: R
authors.lastname: Losappio
authors.affiliation: Liver Unit, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Arleo
authors.affiliation: Liver Unit, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Miscio
authors.affiliation: Liver Unit, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Santoro
authors.affiliation: Medizinische Klinik 1, Goethe University Hospital, Frankfurt, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Sarrazin
authors.affiliation: Biostatic Unit, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Copetti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000008:administration & dosage*; D015331:Cohort Studies; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007558:Italy; D008103:Liver Cirrhosis / Q000150:complications; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D011995:Recombination, Genetic; D012254:Ribavirin / Q000008:administration & dosage*; D000069474:Sofosbuvir / Q000008:administration & dosage*; D000072230:Sustained Virologic Response; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral; D012254:Ribavirin; D000069474:Sofosbuvir
keywords: Cirrhosis; Genotype 2; HCV; Ribavirin; Sofosbuvir