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WHO releases HCV treatment guidelines
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WHO unveiled its first-ever treatment guidelines for hepatitis C virus during a press conference at the International Liver Congress, the annual meeting of the European Association for the Study of the Liver.
Stefan Witkor, MD, team leader for the WHO Global Hepatitis Program, introduced the guidelines and described HCV as “a rapidly changing therapeutic environment.”
Witkor acknowledged that there are other guidelines for HCV available, but that the WHO seal of approval provides a “normative document” for the world to follow.
“Low- and middle-income countries will look to this document to develop national treatment policies,” he said. “They can be assured that the recommendations are based on the soundest evidence.”
The team conducted a systematic review, graded the evidence and, with this new announcement, took the first step in dissemination of the guidelines. The document covers awareness, diagnosis, screening, referral, disease stage, treatment and monitoring of patients.
Isabelle Andrieux Meyer
“Most people do not know they are infected,” Witkor said. “They receive a diagnosis with cirrhosis and cancer, when it is too late. We hope to change that.”
Witkor said a risk-based approach to screening is recommended. However, he noted that different strategies may be used in different countries: “In countries like Egypt, where the prevalence is so high, the entire country should be screened.”
Alcohol interventions form the backbone of behavioral interventions for care. Assessment of fibrosis is the next key care recommendation. Witkor added that WHO has developed a tool to assess for fibrosis.
“Most low- and middle-income countries lack treatment programs,” Witkor said, adding that everyone should be assessed for antiviral treatment. He also said that individuals with advanced fibrosis and cirrhosis (stage F3 and F4) should be prioritized for treatment.
Pegylated interferon is preferred over standard interferon. “We realize that novel direct-acting antivirals are available, but those drugs are not yet available in many low- and middle-income countries,” Witkor said. “There are strong recommendations for sofosbuvir [Sovaldi, Gilead] and simeprevir [Olysio, Janssen] based on strong evidence of effect. As a footnote, when we made the recommendations, we only knew the price of sofosbuvir in the United States. We felt that we couldn’t take resource use into consideration. But clearly based on evidence we felt the recommendations were strong for these two drugs.”
Witkor said there is a need for simplified treatments.
“It might take time until that perfect regimen comes out,” he said. “In the meantime, as new drugs are approved, we will be updating the guidelines and releasing interim documents. But, there are implementation considerations because we are dealing with larger systems. Keeping up to date is very difficult. Our process is longer because it is a very thorough evidence-based process to review data.”
Summary of evidence
Joe Doyle, MD, MSc, from Burnet Institute in Melbourne, Australia, reviewed the evidence used by the panel to create the recommendations. The analysis included 16 studies investigating screening.
“The key result showed that targeted testing compared with non-targeted testing resulted in increases in testing uptake,” Doyle said. Results indicated an RR of 2.9 (95% CI, 2.0-4.2) for targeted testing vs. non-targeted testing and an RR of 1.7 (95% CI, 1.3-2.2) for cases detected with this approach.
Regarding when to confirm a diagnosis of chronic HCV and when to look at RNA testing, there were no studies that met the criteria. “People are not doing those studies,” Doyle said. “RNA testing is underutilized and there is only indirect evidence, which is why the recommendation is conditional.”
Joe Doyle
In terms of care, the main focus was on reducing alcohol intake because pharmacologic interventions were not evaluated and intensive programs also were not included due to the resources required to implement them, according to Doyle.
“The key in all of these studies was that people had high rates of alcohol use. Baseline use was still moderate to high, and we only saw a small reduction in behaviors,” he said.
Regarding assessment of fibrosis and cirrhosis, Doyle said the best performance was attained with two cutoffs: one low and one high. “If a patient was below the low cutoff, they do not have significant fibrosis, but if they are above the high cutoff, they have a high risk of fibrosis,” he said.
Analysis of treatment methods demonstrated a clear result with regard to interferon therapy. “Interferon or pegylated interferon is better than no therapy,” Doyle said. “Thirteen studies prove this.”
Doyle highlighted data that indicated sustained virologic response was improved with the use of boceprevir (Victrelis, Merck) and telaprevir (Incivek, Vertex) compared with pegylated interferon. The data for sofosbuvir and simeprevir are newer, and few studies exist comparing these drugs with pegylated interferon and ribavirin.
“It was difficult to directly compare them,” he said.
Stimulating response
Isabelle Andrieux Meyer, MD, from Doctors Without Borders, discussed access issues, particularly for resource-limited parts of the world.
“We hope these guidelines will stimulate a national response and stimulate political will,” she said. “At the country level, we are hoping to develop referral systems, decentralize efforts, create models of care and encourage non-governmental organizations to start HCV treatment programs. At the WHO level, we hope to help resource-limited countries implement these programs.”
Meyer highlighted countries like Pakistan, Egypt and China as examples of simplified models of care.
“The price of the drugs cannot stay at this sky-high level,” Meyer added. “We need to have the best possible pan-genotypic regimen combined and tested for use in resource-limited settings.”
Charles Gore, president of the World Hepatitis Alliance, was less tempered in his comments. “We are doing a terrible job of treating people,” he said. “There is a lack of government programs to deal with this disease.”
He said there is a lack of awareness about HCV, in addition to the stigma and discrimination surrounding the infection.
“There is also a lack of patient pathways,” he said. “Many patients wonder why they would bother to engage in the health care system if they don’t think they can afford care.”
To the point of affordable care, Wahid Doss, MD, from the National Hepatology and Tropical Medicine Institute in Egypt, discussed ways that country is dealing with a nearly overwhelming HCV epidemic.
“In 2008, we found that the rate of HCV was 15%,” he said. “We established a program and treated 350,000 patients.”
Witkor suggested that the economics of the approach in Egypt are compelling and instructive for WHO. Many of the patients paid nothing, and the success rate was 50%. “We need to do better,” Doss said.
The country negotiated a deal with Gilead wherein sofosbuvir would cost 1% of the price in the United States: “We told them we could compensate price for volume. All companies want to enter Egypt because of the huge market, but we are not letting them in unless they offer good prices. We hope to treat a million patients in Egypt.”
Despite ongoing epidemics in countries like Egypt — and even in the United States — the panel was hopeful that the WHO guidelines would move the fight forward.
“Today is the first step,” Witkor said.
Disclosure: The presenters report no relevant financial disclosures.