title: Lactic acidosis in patients with hepatitis C virus cirrhosis and combined ribavirin/sofosbuvir treatment.
abstract: OBJECTIVE
  Sofosbuvir (SOF) based interferon-alfa free antiviral therapy has become the treatment of choice for patients with chronic hepatitis C virus (HCV) infection. Little is known about safety of drug combinations using two nucleos(t)ide polymerase inhibitors in patients with HCV associated advanced cirrhosis. Here, we report frequent occurrence of lactic acidosis associated with acute-on-chronic hepatic decompensation during ribavirin (RBV) plus SOF based antiviral therapy.
  
  
  METHODS
  Thirty-five patients with chronic hepatitis C and advanced fibrosis, compensated cirrhosis, and decompensated cirrhosis without and after liver transplantation were treated with SOF based antiviral therapy with and without RBV. Adverse events including lactic acidosis (pH <7.35, lactate >20 mg/dl) were recorded 24 weeks before and during (mean ±SD, 18±11 weeks) antiviral therapy. Efficacy was determined by assessment of serum HCV RNA.
  
  
  RESULTS
  We observed severe adverse events in 15/35 (43%) patients before (24 weeks) and in 12/35 (34%) patients during antiviral therapy, the majority in association with acute-on-chronic hepatic decompensation. Lactic acidosis occurred in 5/35 (14%) patients during therapy, while no event of lactic acidosis was observed prior to therapy. Lactic acidosis was associated with hepatic decompensation including renal failure and infection, and was severe (pH <7.3) in two patients.
  
  
  CONCLUSIONS
  RBV in combination with SOF based antiviral therapy in patients with HCV associated advanced cirrhosis may be associated with the development of lactic acidosis. Impaired renal function, and higher MELD/Child-Pugh scores were identified as potential risk factors.
authors.affiliation: Medizinische Klinik 1, Universitätsklinikum Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. Electronic address: Welker@med.uni-frankfurt.de.
authors.forename: Martin-Walter
authors.initials: MW
authors.lastname: Welker
authors.affiliation: Medizinische Klinik 1, Universitätsklinikum Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Luhne
authors.affiliation: Medizinische Klinik 1, Universitätsklinikum Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Lange
authors.affiliation: Medizinische Klinik 1, Universitätsklinikum Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Vermehren
authors.affiliation: Medizinische Klinik 1, Universitätsklinikum Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Farnik
authors.affiliation: Institut für Biostatistik und Mathematische Modellierung, Goethe Universität Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Herrmann
authors.affiliation: Medizinische Klinik 1, Universitätsklinikum Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
authors.forename: Tania
authors.initials: T
authors.lastname: Welzel
authors.affiliation: Medizinische Klinik 1, Universitätsklinikum Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.affiliation: Medizinische Klinik 1, Universitätsklinikum Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Sarrazin
mesh_terms: D000140:Acidosis, Lactic / Q000139:chemically induced*; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects*; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects*; D000069474:Sofosbuvir / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral; D012254:Ribavirin; D000069474:Sofosbuvir
keywords: HCV; Lactic acidosis; OLT; Ribavirin; Sofosbuvir