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News Review

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HEPATITIS JOURNAL REVIEW:
A Bi-Monthly Publication of the Hepatitis Support Project

June 12 , 2006
Volume 3, Issue 9


Liz Highleyman

To download pdf version click here


In This Issue: Hepatitis C

Higher Estimated U.S. Hepatitis C Rate

Impact of HCV on HIV Disease Progression — and Vice Versa

Response to HAART in Coinfected Patients

Treatment of Acute Hepatitis C


Higher Estimated U.S. Hepatitis C Rate

The most common estimate of the number of hepatitis C cases in the U.S. is 3.9 million, based on data from the 1988-1994 National Health and Nutrition Examination Survey (NHANES). But according to a report by G. Armstrong and colleagues in the May 16, 2006 Annals of Internal Medicine, 4.1 million may be a more accurate estimate. The earlier NHANES found that 1.8% of U.S. residents, or 3.9 million, had been infected with, 2.7 million of whom had chronic infection. The more recent 1999-2002 NHANES found that the HCV prevalence rate had declined slightly, to 1.6%; however, since the total population size had increased, the new estimate was 4.1 million infected, 3.2 million of whom have chronic infection. A majority of hepatitis C cases are now seen in the 40-49 age group, reflecting the aging of a cohort that was infected in the past. Within this age group, the estimated prevalence was 4.3%; among blacks, the prevalence was 9.4%, compared with 3.8% among whites. Nearly half of HCV-positive adults reported a history of injection drug use; other risk factors included lower income and education levels, non-injection drug use, and more than 20 lifetime sexual partners. The latest NHANESs estimate may still be too low since it excludes certain groups at higher risk for HCV, including the homeless, incarcerated individuals, and hospital and nursing home patients. A recent analysis by Brian Edlin taking these groups into account suggested that a more accurate estimate may be 5 million, including 3.4 million with chronic infection.

Impact of HCV on HIV Disease Progression – and Vice Versa.

In the May 12, 2006 issue of AIDS, P. Sullivan and colleagues reported results of a review of medical records from nearly 10,500 HIV positive patients at 100 U.S. medical centers followed for a median of 1.9 years between 1998 and 2004; 19% were coinfected with HCV. Coinfection was not associated with progression to AIDS-defining opportunistic illnesses (OIs) or death. These results add to the evidence that while concurrent infection with HIV clearly seems to accelerate liver disease progression due to hepatitis C, HCV does not appear to worsen HIV disease progression.

In addition to being associated with worse liver disease progression, HIV/HCV coinfection also appears to impair response to hepatitis C treatment. The reasons for this are unclear, but in the May 2006 issue of AIDS Research and Human Retroviruses, R. Solar and colleagues reported on a study showing that this phenomenon is not due to poorer adherence. In a prospective study of 79 HIV/HCV coinfected and 78 HCV monoinfected patients treated with conventional interferon plus ribavirin for 48 weeks, the degree of adherence (defined as taking at least 80% of doses of both drugs for at least 80% of the expected duration of therapy) did not differ significantly in the coinfected and HCV monoinfected groups (72% vs 81%, respectively). Nevertheless, among those who were adherent, the SVR rate was 30% for the coinfected patients compared with 52% for the monoinfected patients; among non-adherent patients, the SVR rate was low for both groups, 9% vs 7%, respectively.

Response to HAART in Coinfected Patients

Studies have produced mixed data about whether immune recovery is slower after starting antiretroviral therapy in HIV/HCV coinfected patients than in individuals with HIV alone. In Sullivan’s study, CD4 cell counts increased by similar amounts during the year after starting highly active antiretroviral therapy (HAART) in coinfected patients HIV monoinfected individuals; short-term HIV viral load reductions were also comparable. This was also observed in a study by L. Al-Harthi and colleagues reported in the May 1, 2006Journal of Infectious Diseases. The study included 294 HIV positive women initiating antiretroviral therapy in the Women’s Interagency HIV Study; 12% were HCV antibody positive but HCV RNA negative and 45% were both HCV antibody and HCV RNA positive. Here, too, coinfection did not impair CD4 or CD8 response after starting HAART.

A recent Danish study, however, found that HIV/HCV coinfection was associated with poorer outcomes after starting HAART. As reported in the May 15, 2006 issue of Clinical Infectious Diseases, N. Weis and colleagues conducted a prospective nationwide study of more than 2700 HIV positive patients enrolled between January 1995 and January 2004; 16% also had HCV. Compared with HIV monoinfected individuals, coinfected patients were 34% less likely to start antiretroviral therapy. Among those who did, coinfected individuals experienced less suppression of HIV RNA, were less likely to achieve undetectable HIV viral load, and had smaller increases in CD4 count compared with HIV monoinfected patients; this difference was most apparent among patients with a history of injection drug use. Coinfected patients were also more likely to discontinue HAART (30% vs 14%). Suboptimal treatment response and more treatment interruptions contributed to significantly decreased survival times in the coinfected group. The coinfected patients had an increased rate of mortality relative to those with HIV alone (63 vs 28 deaths per 1000 person years), due to both liver-related and AIDS-related causes. These two studies add to the conflicting data on response to HAART and survival among HIV/HCV coinfected patients, and further research on this issue is needed.

Treatment of Acute Hepatitis C

Studies have shown that treatment of acute HCV infection is highly successful; for example, a 44-person German study published in 2001 found an SVR rate of 98% with conventional interferon monotherapy (although some of these people no doubt would have achieved spontaneous HCV clearance without treatment.) More recently, S. Kamal and colleagues conducted a study of 161 individuals with acute HCV infection; results were published in the May 2006 issue of Hepatology. Among this group, 30 refused treatment, 29 experienced spontaneous viral clearance, and 102 with persistent HCV were randomly assigned to receive pegylated interferon alpha-2b (Peg-Intron) monotherapy for 8, 12, or 24 weeks. In an intent-to-treat analysis, 68%, 82%, and 91%, respectively, achieved SVR (continued undetectable HCV viral load 24 weeks after the end of treatment), and all had undetectable HCV RNA 48 weeks after the end of therapy. Treatment for 8 or 12 weeks was effective for patients with genotypes 2, 3, and 4, while those with genotype 1 required 24 weeks.

In another recent study by S. Dominguez and colleagues reported in the May 12, 2006 issue of AIDS, 25 HIV positive patients with well-controlled HIV were observed for 12 weeks following acute HCV infection. Here, only one individual experienced spontaneous HCV clearance. Of the remainder, 19 started treatment with pegylated interferon alfa-2a (Pegasys) plus ribavirin. After 24 weeks, 10 of the 14 patients who completed therapy (71%) experienced SVR.

However, many people with acute HCV infection do not experience symptoms and most cases of hepatitis C are not identified during this phase. But according to a study in the June 15 issue of Clinical Infectious Diseases, certain settings lend themselves to early detection of HCV among injection drug users, a group at high risk for infection. In this study by B. McGovern and colleagues, on-site medical providers at prisons and detoxification treatment facilities were educated about risk factors for and symptoms of hepatitis, and asked to refer all potential cases to a specialty clinic. Over 30 months, 21 patients were diagnosed with acute hepatitis C, three were diagnosis with hepatitis B, and one was diagnosed with hepatitis A. Of the 21 acute HCV patients, 19 were identified in prison shortly after incarceration. Among 17 patients who received follow-up, eight experienced spontaneous HCV clearance; five with persistent HCV were treated with pegylated interferon, and two achieved SVR. All patients agreed to receive HIV testing and vaccination against hepatitis A and B. The authors concluded that, “Incarceration presents a unique opportunity to identify injection drug users with acute HCV infection, to initiate counseling regarding other blood-borne pathogens, and to facilitate immunizations and HCV treatment.”



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