By Annette M. Boyle
LOS ANGELES — While achieving undetectable viral loads reduces the risk of death associated with hepatitis C by 45% and other adverse liver-related complications by 27%, only 4% of eligible patients in a large VA study undertook treatment and obtained even a single laboratory test result showing 25 IU/mL or less, according to a study recently published in the Journal of the American Medical Association and presented at the American Association for the Study of Liver Diseases (AASLD). 1
“Most patients don’t accept treatment. If they do, very few achieve viral suppression,” said lead author Jeffrey McCombs, PhD, department of clinical pharmacy and pharmaceutical economics and policy at the School of Pharmacy and Leonard Schaeffer Center for Health Policy and Economics at the University of Southern California in Los Angeles. “Just 4% actually achieve suppression.”
The authors attributed the low rate of successful viral suppression in “real-world clinical conditions” to both reluctance to initiate treatment and a high rate of adverse effects. Only 24.3% of patients with a detectable hepatitis C viral (HCV) load opted to begin treatment. Only 16.4% of those who started an HCV therapy achieved the minimum treatment response of a single undetectable viral load test, which the authors defined as less than 25 IU/mL. In this study, only 39 of 97,485 untreated patients achieved undetectable viral loads.
The researchers analyzed data from the VA clinical case registry system for HCV-infected patients for the period 1999 to 2010. Of 360,857 unique patients in the case registry system, 128,769 met the study requirements for detectable baseline HCV viral loads and recorded genotypes. The mean follow-up period was 6.1 years.
Patients who achieved viral load suppression had unadjusted death rates of 6.8 per 1,000 person-years compared to 21.8 deaths per 1000 person-years for those who did not achieve suppression. During the study period, patients experienced 35,253 composite events, and 15,458 died. Patients with genotype 2 had the lowest risk, and those with genotype 3 had the highest risk for both mortality and morbidity.
“The study showed there is clearly an essential need for new products. Interferon and ribavirin are simply not cutting the mustard for HCV treatment,” McCombs told U.S. Medicine. The researchers will be looking at an additional two years of data, which will include more patients who received the current triple therapy of pegylated interferon alpha, ribavirin and a protease inhibitor, either telaprevir or boceprevir. Most of the patients in the study who initiated treatment received the standard dual therapy of pegylated interferon alpha and ribavirin.
The authors noted that “the use of HCV protease inhibitors is associated with a significant increase in SVR [sustained virological response] rates relative to standard therapy but also with increases in frequency and severity of adverse effects such as anemia, neutropenia, thrombocytopenia, rash, and gastrointestinal events.”
In an editorial that accompanied the JAMA article, Mitchell Katz, MD, director of the Los Angeles County Department of Health Services, wrote that he and other clinicians “have been reluctant to treat patients who are healthy despite their hepatitis C infection because I have felt that they had time to wait until better treatments were available. Conversely, I have been reluctant to treat patients who have already experienced severe liver damage from hepatitis C because I have feared that they could not tolerate the adverse effects of treatment and because it is unclear whether even if the virus is suppressed their clinical function would improve.”2
To find the point between “too healthy to subject to treatment” and “too ill to tolerate treatment,” McCombs and his colleagues conducted another study to determine what laboratory tests and values could be used to define a “trip wire” or a point at which a clinician should “step in and say it’s time to start treatment now,” according to McCombs.
They found that abnormal results on any of five laboratory tests — aspartate aminotransferases/alanine aminotransferase (AST/ALT ratio), gamma glutayltransferase, platelets, albumin and alpha fetoprotein — correlated with increased risk of liver-related events. However, “treatment effectiveness is diminished if treatment is initiated after these laboratory tests become abnormal,” according to the presentation poster. 3
“If you start to destabilize, standard treatment is not effective. That may also be true for triple therapy,” McCombs said. “Clearly we need to convince patients to start therapy earlier or make the therapy less burdensome.”
1 McCombs J, Matsuda T, Tonnu-Mihara I, Saab S, Hines P, L’Italien G, Juday T, Yuan Y. The risk of long-term morbidity and mortality in patients with chronic hepatitis C: Results from an analysis of data from a Department of Veterans Affairs Clinical Registry. JAMA Intern Med. Published online November 05, 2013.
2 Katz MH. Hepatitis C treatment: Stuck between a rock and a hard place but hoping to be rescued soon. JAMA Intern Med. Published online November 05, 2013.
3 McCombs J, Matsuda T, Tonnu-Mihara I, Saab S, Hines P, L’Italien G, Juday T, Yuan Y. Using laboratory data to predict long-term morbidity and mortality in chronic hepatitis C patients in the U.S. Veterans Health Administration. AASLD poster presentation. October 1, 2013.