April 26, 2015
Delaying HCV Tx Reduces Likelihood of Eradication
Dr. David Bernstein, Chief, Hepatology, North Shore-LIJ
VIENNA -- Delaying treatment of hepatitis C virus infection markedly increased the risk of not being able to clear the virus in these patients, according to a new retrospective analysis that looked at patients treated before the introduction of targeted hepatitis drugs.
When patients with fibrosis-4 (FIB4 greater than 3.25) liver scarring were treated early in the course of their disease, the number to treat to reach an undetectable viral load was 180, but when treatment was delayed in these patients, the number to treat to get an undetectable viral load soared to 325 individuals, said Jeff McCombs, PhD, associate professor of pharmaceutical economics and policy at the University of Southern California.
In his oral presentation at the International Liver Conference, sponsored by the European Association for the Study of the Liver, McCombs noted that his report involved patients in the era before targeted therapies became common. He illustrated that patients with less advanced fibrosis scores (FIB4>1 or FIB4>1.45) are not affected by the time when their disease is treated as far as numbers to treat were concerned.
"Delaying treatment until after a patient's FIB4 level exceeds 3.25 has a clear detrimental effect on treatment effectiveness," McCombs reported.
The number to treat for early disease stage for those patients diagnosed with FIB4>1 was 142; the number to treat among those patients with delayed therapy was 128. For patients diagnosed with FIB4>1.45, the number to treat was 137 for early therapy and 144 for later treatment, McCombs said.
During the time period of his study, McCombs said, treatment was mainly based on interferon, pegylated interferon, and other drugs in an era that seems like ancient history
-- except that his Veterans Affairs health system population included patients treated from 1999 to 2010 "before the newer agents were available."
He said the idea behind his retrospective work was to determine if there is a way to "allocate the scarce resources we all have to eradicate this disease -- an opportunity that does not come along often in medicine -- without breaking the bank. Can we delay therapy in some sort of reasonable way?"
The researchers accessed data from the VA electronic medical records system, identifying patients through hospital code or positive laboratory tests and tracking patient admissions, laboratory test results, outpatient encounters, outpatient medications, demographics, and vital signs. McCombs said that hepatitis C virus infection was diagnosed in about 5.4% of the VA population.
The researchers considered treatment success as the time to the first viral load at zero.
Sustained virologic response (SVR) was not referred to in that time frame, he said. The researchers were looking for what came first: a viral load of zero or a composite event that included cirrhosis, decompensated cirrhosis, hospitalization related to hepatitis C infection, development of hepatocellular carcinoma, or death.
McCombs and his colleagues used multiple variables in their analysis including sex, age, race, ethnicity, and hepatitis C virus genotype. They also factored in the patients' medical histories and diabetes status at baseline, as well as the time to achieving undetectable viral load, time to abnormal laboratory values, FIB4 levels, and time to treatment.
During the study period, he said that 25% of the patients actually started therapy -- 75% of patients diagnosed with hepatitis C viral infection refused treatment in the population studies. Of the 25% who accepted therapy, just 16% achieved a viral load of 0 -- "which is a whopping 4% of the entire population." His study included 187,860 patients.
Today's landscape differs significantly from the interferon-treatment era, said David Bernstein, MD, director of the Center for Liver Disease at North Shore-LIJ Medical Group, Manhasset, N.Y., and professor of medicine at Hofstra North Shore-LIJ School of Medicine.
"People refused treatment when offered interferon because those were awful treatments compared with today's drugs. The Veterans Affairs population is not representative, because many of those patients have a lot of comorbidities and the patients' doctors may have not even offered those treatments," he told MedPage Today.
"I don't have anyone refusing treatment these days," he said. "The problem is not the direct-acting antiviral treatments, it is access to treatment."
McCombs, in his talk, said that previous studies indicated that viral load suppression reduced the risk of future liver events by 27% and reduced the risk of mortality by 45%.
Initiating treatment before FIB4>1.00 reduced morbidity by 41% and death by 36%.
Initiating treatment after FIB4>1.00 remained effective but diminished the morbidity risk reduction achieved to 30%, McCombs reported. "This is not the case if treatment initiation is delayed until after FIB4>3.25. The risk reductions associated with treatment initiation before FIB4>3.25 were 34% for the composite event and 45% for death but if initiated after FIB4>3.25 were only 11% and 25%, respectively."
He added, "These detrimental effects of delaying treatment until FIB4>3.25 were due to a reduction in the likelihood that treated patients would achieve viral load suppression and a reduced impact of viral load suppression on morbidity."
Bernstein, in commenting on the study, said he is not sure if delaying treatment with direct-acting antivirals would be detrimental. "The truth of the matter is that I don't
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direct-acting antivirals would be detrimental. "The truth of the matter is that I don't think we know the answer because we have not done any real prospective study to answer that question," he said.
"We do believe that from data that we have, and his data would substantiate that, that delaying treatment in patients with significant liver fibrosis certainly can be detrimental to people's health," Bernstein said. "When someone has minimal disease, we don't know it will cause harm. We do know that the 5-year all-cause mortality is reduced in people who are treated."
McCombs disclosed no relevant relationships with industry. Bernstein disclosed no relevant relationships with industry. Bernstein disclosed relationships with Gilead, BMS, Merck, AbbVie, Janssen and Genentech.