Longitudinal effects of hepatitis C virus treatment on hepatic mitochondrial dysfunction assessed by C-methionine breath test.
BACKGROUND
Hepatitis C virus (HCV) infection is characterized by remarkable levels of oxidative stress induced by virus interactions with hepatic mitochondria.


OBJECTIVE
To examine hepatic mitochondrial function in HCV-infected patients assessed by a non-invasive (13)C-methionine breath test (MeBT) and to explore longitudinal effects of antiviral treatment.


METHODS
Twenty-one patients with chronic hepatitis C undergoing antiviral treatment with pegIFNalpha and ribavirin and 20 healthy controls were studied. MeBT was performed at baseline, week 12, end-of-treatment and after 24 weeks of follow-up in all patients with early virological response (n = 15).


RESULTS
Twelve patients achieved sustained virological response (SVR); three patients relapsed for HCV-RNA replication. Cumulative percentage 13C-exhalation (cPDR(1.5h)) was significantly decreased in HCV-infected individuals compared to controls irrespective of genotype and fibrosis stage (P < 0.001). Antiviral treatment induced a further decay in cPDR(1.5h) (P < 0.01). After treatment cessation, 13C-exhalation returned at least to baseline values in all patients. SVR was even associated with a mean cPDR(1.5h) increase of 70% compared to baseline.


CONCLUSIONS
Hepatitis C virus infection and antiviral treatment synergistically impair hepatic mitochondrial function, which may return to normal after sustained virus elimination. MeBT may be a valuable diagnostic instrument for monitoring hepatic mitochondrial function in particular in patients with mitochondrial comorbidities.
Department of Internal Medicine, St Josef Hospital, Ruhr University of Bochum, Bochum, Germany. mbanasch@gmx.de
M
M
Banasch
R
R
Emminghaus
M
M
Ellrichmann
W E
WE
Schmidt
O
O
Goetze
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001944:Breath Tests; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008111:Liver Function Tests; D008137:Longitudinal Studies; D008297:Male; D008715:Methionine; D008875:Middle Aged; D008930:Mitochondria, Liver / Q000378:metabolism / Q000821:virology; D028361:Mitochondrial Diseases / Q000821:virology*; D018384:Oxidative Stress / Q000502:physiology; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D008715:Methionine; C100416:peginterferon alfa-2a