Delaying HCV treatment regardless of fibrosis stage may be detrimental given increased risk of mortality

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Reuters Health Information
Increased Mortality With Moderate, Severe Hep C-related Liver Disease

By Will Boggs MD

March 24, 2017

“Although increased mortality was evident among individuals with severe fibrosis/cirrhosis, we observed some increased risk of mortality even among those with moderate fibrosis,” the researchers note. “These findings, and our inability to identify with sufficiently high prognostic accuracy individuals who would transition from a lower mortality risk state (minimal liver disease) to a higher mortality risk state (moderate or severe liver disease), may not support withholding HCV treatment until that transition occurs.” 

“Fight to treat your patients as early as possible,” Dr. Cepeda urged.

NEW YORK (Reuters Health) - Mortality is increased in patients with moderate or severe liver disease related to chronic hepatitis C, and progression from mild/moderate to severe disease cannot be predicted reliably, according to the ALIVE study.

"We were surprised by the amount of morbidity and mortality in the group with moderate fibrosis, many of whom would have difficulties receiving highly curative treatment,” Dr. Javier A. Cepeda from the University of California, San Diego, in La Jolla, told Reuters Health by email.

Despite expert-group recommendations to treat nearly everyone chronically infected with hepatitis C virus (HCV), most U.S. states restrict the use of oral direct-acting antivirals (DAAs) to patients with advanced fibrosis or cirrhosis, Dr. Cepeda and colleagues note in Clinical Infectious Diseases, online March 10. This is based on an assumption of no medical consequence to low-stage HCV infection and that liver fibrosis progression can be safely monitored until advanced fibrosis/cirrhosis is detected, they add.

The team used data from 964 individuals chronically infected with HCV with a history of injection drug use to characterize mortality rates by liver disease severity before widespread availability of DAAs.

At baseline, 63% of participants had no or mild liver fibrosis, 23% had moderate fibrosis, and 15% had severe fibrosis/cirrhosis.

During a median 5.9 years of follow-up, all-cause mortality was highest among participants with severe fibrosis/cirrhosis at baseline (6.21 deaths/100 person-years), intermediate among those with moderate fibrosis at baseline (3.59 deaths/100 py) and not elevated among those with no/mild fibrosis at baseline (2.21 deaths/100 py).

After adjusting for all other prognostic variables, severe fibrosis/cirrhosis remained associated with significantly elevated mortality risk, whereas the association with moderate fibrosis was attenuated and lost statistical significance.

Among individuals with no/mild fibrosis at baseline, 19% experienced significant progression during follow-up. Factors associated with an increased risk of progression had low predictive accuracy (C statistic=0.66), and a risk score in the top quintile was only 32% sensitive for predicting transition from no/mild to moderate fibrosis at five years.

“Although increased mortality was evident among individuals with severe fibrosis/cirrhosis, we observed some increased risk of mortality even among those with moderate fibrosis,” the researchers note. “These findings, and our inability to identify with sufficiently high prognostic accuracy individuals who would transition from a lower mortality risk state (minimal liver disease) to a higher mortality risk state (moderate or severe liver disease), may not support withholding HCV treatment until that transition occurs.”

“Fight to treat your patients as early as possible,” Dr. Cepeda urged.

SOURCE: http://bit.ly/2nMIEey
Clin Infect Dis 2017.

Mortality in Persons with HCV & Liver Disease
Clin Infect Dis; ePub 2017 Mar 10; Cepeda, et al

Publish date: March 22, 2017

Delaying treatment for persons chronically infected with hepatitis C virus (HCV) regardless of fibrosis stage may be detrimental, a recent study suggests, given the increased risk of mortality even for those with moderate disease and the inability to predict the transition from mild to moderate disease. In this cohort study, transient elastography was performed on 964 persons chronically infected with HCV and with a history of injection drug use. Liver stiffness was evaluated semiannually from 2006 to 2014 using validated cutoffs from moderate fibrosis and severe fibrosis/cirrhosis. Researchers found:

• Among the study population, 62%, 23%, and 15% had baseline measurements suggestive of no/mild fibrosis, moderate fibrosis, and severe fibrosis/cirrhosis, respectively.
• All-cause and non-accidental mortality were elevated in persons with moderate fibrosis (aHRs, 1.42, 1.66, respectively) after adjustments.
• The transition from mild to moderate fibrosis could not be sufficiently predicted.

Citation: Cepeda JA, Thomas DL, Astemborski J, Sulkowski MS, Kirk GD, Mehta. Increased mortality among persons with chronic hepatitis C with moderate or severe liver disease: A cohort study. [Published online ahead of print March 10, 2017]. Clin Infect Dis. doi:10.1093/cid/cix207.
Article source - http://www.mdedge.com/idpractitioner/clinical-edge/summary/hepatitis/mortality-persons-hcv-liver-disease

Abstract

Increased mortality among persons with chronic hepatitis C with moderate or severe liver disease: a cohort study
Javier A. Cepeda, PhD, MPH David L. Thomas, MD, MPH Jacquie Astemborski, MS Mark S. Sulkowski, MD Gregory D. Kirk, MD, PhD Shruti H. Mehta, PhD, MPH

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 non-accidental mortality were elevated in persons with moderate fibrosis (adjusted hazard ratio [aHR]: 1.42, 95% CI: 0.96 – 2.11; aHR: 1.66, 95%CI: 1.06 – 2.59, respectively) after adjustment for sociodemographics, substance use, and HIV status. Despite the increased risk of mortality among those with moderate fibrosis, no combination of demographic, behavioral, 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.

https://academic.oup.com/cid/article-abstract/doi/10.1093/cid/cix207/3065487/Increased-mortality-among-persons-with-chronic?redirectedFrom=fulltext