title: Detection of Occult Hepatitis C Virus Infection in Patients Who Achieved a Sustained Virologic Response to Direct-Acting Antiviral Agents for Recurrent Infection After Liver Transplantation.
abstract: Occult infection with hepatitis C virus (HCV) is defined as the presence of the HCV genome in either liver tissue or peripheral blood monocytes, despite constant negative results from tests for HCV RNA in serum. We investigated whether patients who maintained a sustained virologic response 12 weeks after therapy (SVR12) with direct-acting antiviral (DAA) agents for recurrent HCV infection after liver transplantation had occult HCV infections. We performed a prospective study of 134 patients with recurrent HCV infection after liver transplantation who were treated with DAAs, with or without ribavirin, from 2014 through 2016 (129 patients achieved an SVR12). In >10% of the patients who achieved SVR12 (n = 14), serum levels of aminotransferases did not normalize during or after DAA therapy, or they normalized transiently but then increased sharply after DAA therapy. Of these 14 patients, 9 were assessed for occult HCV infection by reverse transcription quantitative polymerase chain reaction. This analysis revealed that 55% of these patients (n = 5) had an occult infection, with the detection of negative strand viral genome, indicating viral replication. These findings indicate the presence of occult HCV infection in some patients with abnormal levels of serum aminotransferases, despite SVR12 to DAAs for HCV infection after liver transplantation.
authors.affiliation: Department of Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Sandra
authors.initials: S
authors.lastname: Elmasry
authors.affiliation: Department of Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Sanya
authors.initials: S
authors.lastname: Wadhwa
authors.affiliation: Department of Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Bo-Ram
authors.initials: BR
authors.lastname: Bang
authors.affiliation: Department of Laboratory Medicine, School of Medicine, University of Washington, Seattle, Washington; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Linda
authors.initials: L
authors.lastname: Cook
authors.affiliation: Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Shefali
authors.initials: S
authors.lastname: Chopra
authors.affiliation: Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Gary
authors.initials: G
authors.lastname: Kanel
authors.affiliation: Department of Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Brian
authors.initials: B
authors.lastname: Kim
authors.affiliation: Department of Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Tammy
authors.initials: T
authors.lastname: Harper
authors.affiliation: Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio.
authors.forename: Zongdi
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Department of Laboratory Medicine, School of Medicine, University of Washington, Seattle, Washington; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Keith R
authors.initials: KR
authors.lastname: Jerome
authors.affiliation: Department of Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California. Electronic address: jkahn@usc.edu.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Kahn
authors.affiliation: Department of Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California; Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California; Molecular Microbiology and Immunology, University of Southern California, Research Center for Liver Diseases, Los Angeles, California. Electronic address: saitotak@usc.edu.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Saito
mesh_terms: D000410:Alanine Transaminase / Q000097:blood*; D000998:Antiviral Agents / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood*; D001562:Benzimidazoles / Q000627:therapeutic use; D002219:Carbamates; D004359:Drug Therapy, Combination; D005260:Female; D005449:Fluorenes / Q000627:therapeutic use; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D057230:Limit of Detection; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011759:Pyrrolidines; D012367:RNA, Viral / Q000097:blood*; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012254:Ribavirin / Q000627:therapeutic use; D000069616:Simeprevir / Q000627:therapeutic use; D000069474:Sofosbuvir / Q000627:therapeutic use; D000072230:Sustained Virologic Response; D014633:Valine / Q000031:analogs & derivatives; D019562:Viral Load; D014779:Virus Replication / Q000235:genetics*
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D002219:Carbamates; D005449:Fluorenes; D007093:Imidazoles; D011759:Pyrrolidines; D012367:RNA, Viral; C586541:ledipasvir; D012254:Ribavirin; D000069616:Simeprevir; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D014633:Valine; C549273:daclatasvir; D000069474:Sofosbuvir
keywords: Limit of Detection; Persistence; Treatment Outcome; Viral Hibernation