Issues Clinical Practice Guidelines for Management of HCV

From Medscape Medical News

EASL Issues Clinical Practice Guidelines for Management of HCV

Daniel M. Keller, PhD

April 4, 2011 (Berlin, Germany) — Here at the opening session of the European Association for the Study of the Liver (EASL) 46th Annual Meeting, new guidelines were announced to help healthcare providers, patients, and interested individuals make decisions about the management of patients with acute and chronic hepatitis C virus (HCV) infections.
The guidelines encompass all aspects of the diagnosis and treatment of chronic HCV infection and address the use of diagnostic, therapeutic, and preventive techniques. They are the fifth in a series that the EASL has issued for liver diseases.
As evidenced by a wealth of clinical trial presentations that are being made here at the conference on new drugs in development to treat HCV, it is expected that many more treatments will be licensed in the next few years.

However, the guidelines issued here are restricted to therapies that have been approved at the time of publication. EASL has committed to update the guidelines on a regular basis upon approval of additional therapies.

Antonio Craxi, MD, professor of gastroenterology and internal medicine at the University of Palermo in Italy, and director of gastroenterology and hepatology at the university's Academic Department of Internal Medicine, coordinated the development of the guidelines. He discussed them in a news conference and said that part of the rationale for them is to set standards of diagnosis and treatment for specific patient profiles. They were developed by an expert panel that reviewed the scientific literature on the subject through December 2010. If clinical data were unavailable, expert experience and opinion were included.
The guidelines comprise sections on diagnosis, therapy, follow-up to therapy, measures to improve treatment success rates, and factors to consider when deciding on retreatment if therapy has failed.

Dr. Craxi emphasized that history and physical examination of the patient must be part of diagnosis, and that diagnosis cannot rely solely on serology that identifies anti-HCV antibodies or the level of HCV RNA in the blood.
"We had to . .  decide on a very crucial point — whether a biopsy was still necessary to assess the severity of liver disease," Dr. Craxi said.

Although biopsy remains the reference method for assessing the degree of fibrosis, most patients dislike it, and it carries risk for complications. "It won't be acceptable to have a liver biopsy as a prerequisite for all treatment," he said, noting that it can usually be dispensed with for HCV genotypes 2 and 3, which are easier forms of the virus to eradicate with current therapy. And a biopsy is not always necessary for the more difficult-to-treat genotypes 1 and 4, since other methods such as transient elastography (FibroScan) and serum biomarkers are available to determine the degree of liver fibrosis.

Eradication of HCV Infection Is Therapeutic Goal
Eliminating virus from the body can prevent complications such as fibrosis, cirrhosis, liver cancer, and death. The desired end point of therapy is a sustained virological response, determined by undetectable HCV RNA in the blood 24 weeks after the end of therapy, Dr. Craxi noted.
The current standard approach is treatment with a combination of pegylated interferon alfa plus ribavirin. The University of Palermo investigator said large studies have shown that the 2 commercially available pegylated interferons are equivalent, and neither is recommended over the other.
He pointed out that the new guidelines consider the virological response to pegylated interferon/ribavirin to guide therapy, taking into account the speed of response and the degree of viral suppression. "For the first time, there is a clear statement that patients with a rapid response and with genotype 1 can be treated for 24 weeks [and that treatment can be extended] beyond 24 weeks for patients who have a delayed viral response."

Separate decision maps in the published guidelines, which will appear in the Journal of Hepatology, delineate response-guided therapy for genotypes 1 and 4 and for genotypes 2 and 3.
Previous American guidelines were issued more than 5 years ago, Dr. Craxi noted, and they did not involve response-guided therapy. Additionally, ribavirin dosage adjustment according to patient weight is now recommended, since heavier weight adversely affects the response to therapy.
The expert panel made recommendations for the follow-up of untreated patients with or without cirrhosis and for the retreatment of patients for whom previous therapy failed. Dr. Craxi said that patients with resistant disease might respond to some of the new small-molecule drugs currently in development, and it might be worthwhile to delay treatment for some of them until the new drugs are available, depending on their current state of health.

Mark Thursz, MD, EASL vice secretary and professor of hepatology at Imperial College, London, United Kingdom, noted that not recommending a liver biopsy for every patient is an important development for patients. "It's no longer necessary for every patient. In fact, it's probably only appropriate when there's a doubt about the contribution of different diseases," such as heavy alcohol consumption and HCV, or obesity and HCV. Response-guided therapy can also be positive for patients, sparing some of them unnecessary adverse effects if they can be treated for a shorter time. It should have a positive economic impact, as well, he noted.

Dr. Thursz said he reviewed the guidelines before publication but was not involved in their development.

Dr. Craxi reports receiving research support and lecture fees from, and taking part in clinical trials for, Roche, MSD, Siemens, and Abbott. Dr. Thursz has disclosed no relevant financial relationships.
European Association for the Study of the Liver (EASL) 46th Annual Meeting: Opening session. Presented March 31, 2011.