HCV -4 Spreads From Egypt and Africa Into Europe

By C. Vidya Shankar MD

NEW YORK (Reuters Health) Dec 31 - Hepatitis C virus (HCV) genotype 4, previously limited to Egypt and other parts of Africa, has now spread to southern Europe and other parts of world, an international panel says in a review published online December 9th in the Journal of Hepatology.

Genotype 4, or the Egyptian genotype, now accounts for roughly 20% of HCV infections in Europe and worldwide.

This strain is more difficult to treat than genotypes 2 and 3, which have traditionally been relatively more common in Europe, said Dr. Stephen Harrison, a panelist from the Brooke Army Medical Center, Houston, Texas, in email to Reuters Health.

Still, he said, "We approach the treatment of (HCV 4) the same way we do (HCV 1). Current standard of care is 48 weeks of pegylated interferon and weight based ribavirin."

HCV is classified into six genotypes based on nucleotide sequences. While type 4 is uncommon in the U.S., with a prevalence of 1%, it accounts for 90% of HCV infections in Egypt, according to the review.

Along with lead author Dr. Mahmoud A. Khattab, from the University of Minia, Egypt, Dr. Harrison and colleagues point out in the article that the HCV-4 epidemic in Egypt probably traces its origins to an anti-schistosomiasis campaign that involved parenteral injections on a large scale. Whereas sexual transmission and traditional medical practices like scarification were responsible for its spread through Africa and Middle East, immigration and intravenous drug use may have spread the virus worldwide, they say.

Though the clinical features and microscopy findings are similar to that of other genotypes, co-existent schistosomiasis hastens hepatic fibrosis and reduces the odds of spontaneous resolution. Severe steatosis without sinusoidal fibrosis is a typical finding on liver biopsy, the panelists said.

HCV-4, like the other types, is a major cause of chronic liver disease. "A possible association had been suggested between HCV-4 and hepatocellular carcinoma (HCC) based on the similarity of distribution of HCC and HCV-4 in Egypt," the authors wrote.

Dr. Sam Lee, a panelist from the University of Calgary, Canada, told Reuters Health that of all the HCV genotypes, 1, 4 and 6 "appear to be the most resistant to treatment, with success rates of about 50% in viral clearance with a longer course of treatment." This compares to "much more favorable" success rates of about 70-85%, with shorter treatment, in patients with genotypes 2 and 3, he said.

"About 5-35% of patients stop treatment prematurely due to side effects," Dr. Lee added.

HIV co-infection, cirrhosis and high initial viral load are the main predictors of a delayed treatment response, according to the panelists. Response-guided therapy is the accepted standard, they say; while patients who have virological clearance within four weeks can benefit from a 24 week regimen, delayed responders may need a longer course.

Newer drugs like nitazoxanide (NTZ) and the cyclophillin inhibitor Debio 025 show promise and need further trials, the panelists concluded.

J Hepatol. Posted December 8, 2010. Abstract