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A Bi-Monthly Publication of the Hepatitis Support Project

April 25, 2006
Volume 3, Issue 7

Liz Highleyman

To download pdf version click here

In This Issue: Hepatitis C

“A la Carte” Hepatitis C Therapy

HCV/HBV Coinfection

Treatment of Acute Hepatitis C

“A la Carte” Hepatitis C Therapy
Given the variable response to hepatitis C treatment, researchers have taken an interest in individualized therapy tailored to specific patients. In the March 2006 Journal of Viral Hepatitis, C. D’Arondel and colleagues reported on an assessment of “a la carte” therapy with pegylated interferon (Peg-Intron) plus ribavirin in patients with chronic hepatitis C. A total of 96 patients began taking the combination regimen. After 24 weeks, those who still had detectable HCV RNA stopped treatment (based on the fact that few patients who do not respond by 12¾or even 4¾weeks will go on to become sustained responders). For the remaining patients, the researchers looked at five risk factors for relapse to determine whether to continue treatment: patient sex, age, HCV genotype, baseline HCV viral load, and fibrosis stage. Those with two or more risk factors (88%) continued therapy for an additional 24 weeks. The researchers used the noninvasive FibroTest and ActiTest to assess whether treatment improved liver histology. At the conclusion of the study period, 73% of patients overall achieved sustained virological response (SVR; 85% for genotypes 2/3, 64% for other genotypes); 20% were nonresponders and 7% were relapsers. The noninvasive assays showed significantly decreased fibrosis and inflammatory activity at the 12-week follow-up visit; improved inflammatory activity was seen even in virological nonresponders. The authors concluded that assessment of several risk factors is an efficient way to tailor HCV treatment for individual patients.

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HCV/HBV Coinfection
Much research in recent years has been devoted to hepatitis C/HIV coinfection. However, people may also be coinfected with chronic hepatitis B and C, though this has received considerably less attention. In the February 2006 Journal of Clinical Virology, Chee-Kin Hui and colleagues reported on a retrospective study of liver fibrosis progression and prevalence of severe fibrosis (stage 3 or 4) in chronic hepatitis C patients coinfected with occult (hidden) hepatitis B virus (HBV). Out of 74 patients tested, 31 (41.9%) had detectable serum HBV DNA. Looking at consecutive liver biopsies, the researchers determined that 11 out of 31 patients with occult HBV had fibrosis progression (at least a one-stage increase), compared with 12 out of 43 patients without occult HBV (35.5% vs 27.9%, respectively, a non-significant difference). A similar proportion of subjects with and without occult HBV developed severe fibrosis (19.4% vs 18.6%, respectively). The authors concluded that “chronic HCV patients with occult HBV coinfection [do] not seem to progress more than patients without occult HBV infection.”

In contrast, M.C. Kew reported in the March 2006 Journal of Viral Hepatitis that HCV/HBV coinfection does appear to increase the risk of hepatocellular carcinoma (HCC). Various studies looking at HCV/HBV coinfection have produced conflicting results, which Kew attributed to “the rarity of concurrent infection with HBV and HCV in individuals without clinically evident liver disease.” To get a clearer picture, Kew conducted two meta-analyses, one based on studies of Chinese patients and a second using studies from several different countries. Both showed that HCV/HBV coinfection led to a synergistic increase in HCC risk (that is, higher than the risk due to HCV and HBV added together). The mechanisms underlying this increased risk require further study, as does the interaction between the two viruses in the liver.

Underscoring this uncertainty, Evangelista Sagnelli and colleagues reported a case series of four HCV/HBV coinfected patients in the March 2006 Journal of Clinical Virology. The researchers found that HBV and HCV appeared to interfere with the replication of the other virus. In all four patients, previously detectable HBV DNA became undetectable after superinfection with HCV (although it later reappeared in one patient). Conversely, HCV RNA decreased in all four coinfected patients, becoming undetectable in two of them. For reasons that remain unclear, three of the patients with acute hepatitis C had a normal clinical course, but the fourth developed severe liver disease with ascites and decreased prothrombin activity.

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Treatment of Acute Hepatitis C
Several recent journal articles have looked at treatment of acute HCV infection. In the March 2006 issue of Gastroenterology, S.M. Kamal and colleagues reported high sustained response rates in patients treated soon after infection. The researchers screened 175 patients with acute (recent) HCV infection. Those who did not experience spontaneous viral clearance within eight weeks (129 patients) were randomly assigned to receive once weekly Peg-Intron (1.5 mcg/kg) starting at week 8, 12, or 20. After 12 weeks of therapy plus follow-up, the overall SVR rate was 87%, but differed based on when treatment was initiated: 95% if started at week 8; 92% at week 12; and 76% at week 20. As expected, patients with genotype 2, 3, or 4 had higher response rates than those with genotype 1. Peg-Intron monotherapy in patients with acute hepatitis C “induces high sustained virologic response rates, prevents chronic evolution, and is well tolerated,” the authors concluded, adding that initiation of therapy at week 8 or 12 leads to higher SVR rates than starting at week 20.

In related news, Judith Aberle and colleagues reported in the May 2006 Journal of Hepatology that acute hepatitis C patients who cleared the virus had a distinct pattern of immune response. In a study of 20 acutely infected or reinfected patients, the researchers found that CD4 T-cells producing Th1 cytokines (chemical messengers) were most frequently seen in the reinfected patients, producing rapid viral clearance within three weeks. All acutely infected patients (whether reinfected or infected for the first time) who subsequently cleared HCV showed Th1 CD4 cell activity. In contrast, those who went on to develop chronic hepatitis C showed either an absence of antiviral Th1 cytokine-producing cells from the first weeks after infection, or else gradually waning Th1 activity. These data “highlight the variability of immune response pattern in acute hepatitis C,” the authors concluded, suggesting that assessment of T-cell activity might “be used as criteria in selecting candidates for early antiviral treatment.”

Finally, two research teams shed additional light on the variability in spontaneous clearance. In the January 24 online edition of Gut, I. Bakr and colleagues reported that females are more likely to spontaneously clear HCV compared to males. The researchers examined data from a 4720-person study of hepatitis C in Egypt. They defined clearance as the presence of antibodies against HCV in the absence of serum HCV RNA. The overall prevalence of HCV antibodies was 19.3%. Of these, 38.5% had evidence of HCV clearance and 61.5% had chronic infection. However, the clearance rate among females was 44.6%, compared with 33.7% among males.

J.D. Scott and colleagues looked at spontaneous HCV clearance after establishment of chronic infection, which has been assumed to be rare. As reported in the April 2006 issue of Clinical Infectious Diseases, the researchers enrolled 815 Alaskan natives in a prospective study started in 1994; 139 had established chronic hepatitis C (positive HCV RNA tests on three separate occasions at least one year apart). During a mean seven years of follow-up, 11 of the 139 subjects (8%) with established chronic infection had at least one undetectable HCV RNA test; seven were classified as having “possible or probable clearance of the virus,” for a clearance rate of 0.74% per person-year. A low initial HCV viral load was significantly associated with later undetectability. The authors concluded that, “Spontaneous HCV RNA negativity during chronic HCV infection is a surprisingly frequent event,” and suggested that better understanding of the immunological mechanisms underlying such clearance “may open up avenues of novel therapy.

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