by Michael Smith
North American Correspondent, MedPage Today
Meeting Coverage 03.01.2015
-- Even successful treatment carries risk if it is delayed, model suggests.
SEATTLE -- Delaying hepatitis C (HCV) treatment in patients who also have HIV increases the risk of liver complications and death even if the therapy is successful, a researcher said.
In a computer modeling study, treating a patient in METAVIR stage F3 disease instead of stage F2 increased the risk of liver-related death from 5% to 10%, according to Cindy Zahnd, a research assistant at the University of Bern in Switzerland.
And if successful HCV treatment was delayed until stage F4, the risk of liver-related death rose to 25%, compared with therapy at stage F2, Zahnd said here at the 2015 Conference on Retroviruses and Opportunistic Infections.
That's because "people who are living with HIV have many other risk factors that maintain them at a certain risk even after HCV clearance," Zahnd said.
It might seem obvious that delayed treatment increases the risk of complications or death, Zahnd told MedPage Today, but there is little long-term follow-up of actual patients that quantifies that danger.
"The point of this exercise was to project the long-term risk," she said.
The issue is important, especially in the U.S. where there is "push-back" against paying for some of the new and expensive anti-HCV agents early in the disease course, commented David Thomas, MD, of Johns Hopkins University School of Medicine, who moderated a media conference at which the data was discussed.
"Sometimes drugs aren't paid for in patients in a lower stage of disease," he said, because of a "mental model that someone would have to go to F4 before they get into trouble."
So insurers and other payers are often content to wait, he said, especially since some newer agents have been controversial because of their costs.
What the study shows, he added, is that "this approach has consequences."
The researchers used data from the Swiss Hepatitis C Study for the period before the newer agents were available to obtain estimates of the risk of progression in coinfected patients, Zahnd said.
In those days, treatment was with pegylated interferon and ribavirin, only about 60% of patients attempted the treatment, and only about 40% were able to clear HCV, she noted.
Those data suggested, however, that successful treatment would reduce the risk of liver fibrosis progression by a factor of 10, the risk of decompensated cirrhosis by the same factor, and the risk of hepatocellular carcinoma by a factor of 2.6.
Their model assumed that uptake of treatment with newer agents would be 100% and that cure rates would be about 90%, Zahnd said.
In that scenario, if treatment is provided soon after diagnosis -- between a month and a year later -- less than 3% of patients would die of liver complications, the model showed.
On the other hand, if treatment was delayed until METAVIR stage F2 or higher, the risks gradually increased, reaching 25% in those treated at stage F4, Zahnd said.
The investigators were "a bit surprised" to find that the proportion of liver-related deaths was so high despite successful treatment in most patients, Zahnd said, and concluded that some of the events would have taken place after the HCV was cleared.
Indeed, at the higher stages, most liver-related deaths would occur after the patient had cleared HCV, she said. In some patients, she reported, fibrosis progression would be maintained through persistent risk factors, such as drug toxicity, coinfections, or metabolic liver disease.
One implication of the analysis, Zahnd said, is that delaying treatment -- aside from the individual risks -- also increases the risk of transmitting HCV to others.
Indeed, she said, delaying treatment until METAVIR stage F4 would quadruple the infectious period.
She cautioned that the study had heterogeneous data sources, and also explained that it modeled a closed cohort with no transmission so the analysis probably under-estimates the positive impact of early HCV treatment.
And the model did not include the possibility of re-treatment, Zahnd said, which might have led to an over-estimate of the number of people experiencing liver-related complications.
The analysis was part of the Swiss HIV and the Swiss Hepatitis C Cohort studies. Zahnd did not disclose any relevant relationships.
Thomas disclosed no relevant relationships.
Reviewed by F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner
last updated 03.02.2015
Conference on Retroviruses and Opportunistic Infections