AT THE INTERNATIONAL LIVER CONGRESS 2015
VIENNA (FRONTLINE MEDICAL NEWS) – Delaying hepatitis C virus (HVC) treatment can have a detrimental effect on the outcomes of some patients, according to the results of a large 10-year retrospective analysis involving more than 187,000 U.S. veterans.
Indeed, waiting until a patient with HCV infection develops advanced cirrhosis, as measured by the Fibrosis-4 (FIB4) index, can reduce the chances that treatments will be effective and significantly increases morbidity and mortality. Health economist Jeffrey McCombs, Ph.D., of the University of Southern California, Los Angeles, presented data from a 10-year retrospective analysis of the Department of Veteran’s Affairs Veterans Health Administration HCV clinical registry involving more than 187,000 U.S. veterans with detectable HCV levels.
The caveat is that older treatments rather than newer all-oral direct-acting agents were used in the study population at the time of data analyses.
The analysis built on three previous analyses of data from the VA System, the first of which found that viral load suppression reduced the risk of liver events by around 27% and death by 45% ( JAMA Intern. Med. 2014;174: 204-12 ). This analysis also found that relative to patients with genotype 1 (GT1), patients with GT2 were at lower risk and patients with GT3 were at higher risk of liver events and death.
The second analysis looked at treatment timing and found that treatment effectiveness was significantly reduced if treatment was started after common laboratory tests to detect liver changes became abnormal.
The third analysis looked at using the FIB4 index to monitor the risk of long-term morbidity and mortality and found that a FIB4 in excess of 3.4 was associated with a significantly increased risk for liver events and death, whereas a FIB4 of 1.45 was associated with moderate risk.
“This brought us to the last research question, looking at the relationship between treatment efficacy and exceeding certain FIB4 levels,” Dr. McCombs said at the meeting sponsored by the European Association for the Study of the Liver. The analysis compared treating early versus treating late, based on FIB4 levels – FIB4 of 1.0, FIB4 of 1.45, and FIB4 of 3.25.
Initiating treatment early before patients’ FIB4 exceeded 1.0 was associated with a 41% reduction in morbidity and a 36% reduction in mortality. Waiting until the FIB4 exceeded 1.0 resulted in a 30% reduction in liver events and 40% in mortality.
Treating patients early before exceeding a FIB4 of 1.45 was associated with morbidity and mortality reductions of 39% and 40% and waiting until the FIB4 exceeded this threshold was associated with reductions of 27% and 39%, respectively.
Using the FIB4 threshold of 3.25 showed even smaller reductions in morbidity and mortality. When treating early, the reductions were 36% and 45%; when treating late, the reductions were 11% and 25%.
“This is the kind of information you need when you talk with your payers,” Dr. McCombs said. “If you restrict access to treatment, you are not going to be as effective.”
Treating early or late appeared to have a similar effect on viral load and the number needed to treat (NNT) increased using the FIB4 3.5 threshold. Indeed, if treatment is initiated before the FIB4 rises above 3.25, the NNT is 180 patients to prevent one death, Dr. McCombs said, but if treatment is delayed, then the NNT jumps to 325 patients.
In patients with low FIB4 a ‘watch and wait strategy’ could potentially be feasible, he acknowledged in an interview. “The bottom line is that we can’t afford to treat everybody now,” he said.
“The FIB4 is a parameter we can probably watch, but it is unknown exactly how long we can wait,” Dr. McCombs said.
The data were derived from a study that was supported by a grant from Bristol-Myers Squibb. Dr. McCombs had no disclosures.