Increased Mortality Among Persons With Chronic Hepatitis C With Moderate or Severe Liver Disease: A Cohort Study.
BACKGROUND
Despite the availability of curative treatment for hepatitis C virus (HCV) infection, because of cost, treatment is often denied until liver fibrosis has progressed to at least moderate fibrosis and, in some cases, cirrhosis. That practice is justified on assumptions that there are no medical consequences to having moderate disease and that disease stage transitions can be anticipated.


METHODS
We performed transient elastography on 964 people chronically infected with HCV with a history of injection drug use living in Baltimore, Maryland. Liver stiffness was evaluated semiannually from 2006 to 2014 using validated cutoffs for moderate fibrosis (8.0-12.3 kPa) and severe fibrosis/cirrhosis (>12.3 kPa).


RESULTS
Among 964 persons, 62%, 23% and 15% had baseline measurements suggestive of no/mild fibrosis, moderate fibrosis, and severe fibrosis/cirrhosis, respectively. All-cause and nonaccidental mortality were elevated in persons with moderate fibrosis (adjusted hazard ratio [aHR], 1.42 [95% confidence interval {CI}, .96-2.11]; aHR, 1.66 [95% CI, 1.06-2.59], respectively) after adjustment for sociodemographics, substance use, and human immunodeficiency virus status. Despite the increased risk of mortality among those with moderate fibrosis, no combination of demographic, behavioral, and clinical factors, nor changes in stiffness measurements themselves could predict the transition from mild to moderate fibrosis with sufficiently high diagnostic accuracy (C-statistic = 0.72 for best-performing model).


CONCLUSIONS
Delaying treatment for anyone chronically infected with HCV regardless of fibrosis stage may be detrimental given the increased risk of mortality even for those with moderate disease and the inability to predict the transition from mild to moderate disease.
Division of Global Public Health, Department of Medicine, University of California, San Diego, La Jolla.
Javier A
JA
Cepeda
Division of Infectious Diseases, Johns Hopkins School of Medicine.
David L
DL
Thomas
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Jacquie
J
Astemborski
Division of Infectious Diseases, Johns Hopkins School of Medicine.
Mark S
MS
Sulkowski
Division of Infectious Diseases, Johns Hopkins School of Medicine.|Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Gregory D
GD
Kirk
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Shruti H
SH
Mehta
D000328:Adult; D015331:Cohort Studies; D018450:Disease Progression; D054459:Elasticity Imaging Techniques; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000401:mortality* / Q000473:pathology / Q000821:virology; D006801:Humans; D008099:Liver / Q000000981:diagnostic imaging / Q000473:pathology / Q000821:virology; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015819:Substance Abuse, Intravenous / Q000150:complications
hepatitis C virus; injection drug use; mortality; transient elastography