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Increased Mortality Among Persons With Chronic Hepatitis C With Moderate or Severe Liver Disease: A Cohort Study
Javier A Cepeda1, David L Thomas2, Jacquie Astemborski3
1Division of Global Public Health, Department of Medicine, University of California, San Diego, La Jolla.
Insights
Delaying hepatitis C virus (HCV) treatment increases mortality risk, even with moderate liver fibrosis. Predicting disease progression is unreliable, suggesting earlier treatment for all HCV patients is crucial.
Area of Science:
- Hepatology
- Viral Hepatitis
- Public Health
Background:
- Hepatitis C virus (HCV) treatment is often delayed until significant liver fibrosis or cirrhosis due to cost.
- This delay is based on the assumption that moderate fibrosis has no immediate consequences and progression is predictable.
Purpose of the Study:
- To investigate the medical consequences of moderate liver fibrosis in HCV patients.
- To assess the predictability of disease progression from mild to moderate fibrosis in HCV infection.
Main Methods:
- Transient elastography was used to assess liver stiffness in 964 chronically HCV-infected individuals.
- Liver stiffness was monitored semiannually from 2006-2014, using established cutoffs for fibrosis staging.
- Statistical models were used to evaluate mortality risks and predict fibrosis progression.
Main Results:
- 62% had no/mild fibrosis, 23% moderate, and 15% severe fibrosis/cirrhosis at baseline.
- Moderate fibrosis was associated with increased all-cause and non-accidental mortality (aHR 1.42 and 1.66, respectively).
- Predictive models failed to accurately forecast the transition from mild to moderate fibrosis (C-statistic = 0.72).
Conclusions:
- Delayed HCV treatment, even with moderate fibrosis, poses a significant mortality risk.
- The inability to reliably predict fibrosis progression underscores the need for earlier treatment initiation for all HCV-infected individuals.
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.
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