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News Review

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

October 25 , 2007
Volume 4, Issue 19


Liz Highleyman

To download pdf version click here


In This Issue:

Hepatitis C

• Variceal Bleeding

• Liver Retransplantation

• Pegylated Interferon Active Against both HCV and HIV

• HCV Treatment Reduces Antiretroviral Liver Toxicity


Variceal Bleeding

Bleeding varices (weak, dilated veins) in the esophagus are one manifestation of portal hypertension due to liver cirrhosis. Two common management strategies are “banding” (endoscopic variceal ligation, in which an elastic band is put on an enlarged vein to prevent bleeding) and beta blocker drugs, which lower blood pressure. In the September 2007 issue of Liver Transplantation, L. Norberto and colleagues reported on a study comparing these approaches. The investigators enrolled 62 patients with advanced liver disease (Child stage B-C cirrhosis) awaiting transplantation; they were randomly assigned to undergo variceal banding or to receive the beta blocker propranolol (Inderal). Among the 31 individuals who underwent banding, two experienced severe hemorrhage a few days after treatment; one recovered, the other died. Among the remaining patients, during a mean follow-up period of nearly 15 months, two died of liver failure and 14 received liver transplants. Among the 31 patients who took propranolol, five discontinued due to drug-related complications such as slow heart rate or low blood pressure. Among the remainder, three eventually experienced variceal bleeding, two died from such bleeding, and 10 underwent liver transplantation. Both treatments reduced the risk of bleeding, to about 10% with propranolol and 7% with banding (compared with 30% expected for untreated patients). While the two approaches were comparably effective, banding was associated with more severe complications and was more expensive, leading the researchers to conclude that beta blockers should be the first-line treatment for preventing variceal bleeding due to cirrhosis.

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Liver Retransplantation

Among patients with advanced liver disease who undergo liver transplantation, some require a second transplant due to various complications. Some past research suggests that transplant recipients with HCV - which usually infects the new liver - may have poorer outcomes than patients who receive liver transplants for other reasons. As reported in the September 2007 issue of Transplantation International, M. Bahra and colleagues analyzed outcomes in 18 patients who were retransplanted due to recurrent HCV, 11 HCV-infected patients retransplanted due to initial graft non-function, and 169 retransplanted for other reasons. After five years, survival rates in the three groups were 59%, 84%, and 60%, respectively, leading the researchers to conclude that, “Five-year survival after re-transplantation in patients with recurrent hepatitis C is similar to that in patients undergoing liver re-transplantation for other indications.” The factors that predicted poorer post-transplant outcomes were elevated ALT and serum bilirubin levels, increased white blood cell count, and higher MELD score.

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Pegylated Interferon Active Against both HCV and HIV

Pegylated interferon is active against both HCV and HIV in coinfected individuals, but patterns of antiviral activity differ. As reported in the September 2007 issue of AIDS, A. Neumann and colleagues measured HCV and HIV viral kinetics and their relationship to interferon pharmacokinetics in nine coinfected patients with HCV genotype 1 treated with pegylated interferon alpha-2b (PegIntron) plus weight-based ribavirin. They found that while HCV showed a biphasic (two-stage) decline, HIV showed a slow, continuous decline during the first week, with no rebound when pegylated interferon levels fell. The magnitude of the anti-HIV effect was similar to that of antiretroviral drugs: about a 1-log decline in HIV RNA after seven days. Laboratory studies showed that pre-incubating cell cultures with interferon led to greater HIV suppression than treating the cells after infection. These findings suggest that while the major antiviral effect of interferon on HCV is to inhibit production of new virus particles in infected cells, the main effect on HIV is to block infection of new cells. “The complimentary antiviral properties of interferon-alpha and antiretroviral therapy suggest a role for pharmacokinetically improved formulations of interferon as part of salvage therapy for HIV-infected individuals,” the researchers concluded.

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HCV Treatment Reduces Antiretroviral Liver Toxicity

As effective anti-HIV therapy has reduced the rate of AIDS-related opportunistic infections, liver disease has emerged as a major cause of illness and death for HIV positive individuals. Liver disease is often related to HCV coinfection, and liver toxicity due to antiretroviral drugs also plays a role. Prior studies have indicated that HIV/HCV coinfected patients have about three times the risk of liver toxicity as those with HIV alone, suggesting that successful treatment of hepatitis C might reduce the risk. In the September 1, 2007 Journal of Infectious Diseases, P. Labarga and colleagues reported results from a retrospective study looking at the incidence of severe liver enzyme (ALT and AST) elevations during antiretroviral therapy in 132 HIV/HCV coinfected patients at two HIV clinics in Spain after they completed a full course of interferon-based anti-HCV therapy.

Overall, 33% achieved sustained virological response (SVR) and 40% had advanced liver fibrosis after interferon-based therapy. The researchers identified 49 total episodes of liver toxicity, occurring an average of 35 months after competing anti-HCV therapy (a rate of 9.7% per year). However, the annual incidence of liver toxicity was greater among patients who did not achieve SVR compared with those who did (12.9% vs. 3.1% per year), and among patients with advanced compared to absent or mild fibrosis (14.4% vs. 7.6% per year). The anti-HIV drugs most commonly associated with toxicity-related hepatic events were ddI (Videx) and d4T (Zerit) (40% together) and nevirapine (Viramune) (30%). Efavirenz (Sustiva) and protease inhibitors were associated with a reduced risk of liver toxicity. “Sustained HCV clearance after interferon-based therapy reduces the risk of liver toxicity during antiretroviral therapy, which should further encourage the treatment of chronic hepatitis C in HIV coinfected patients,” the authors concluded. In an accompanying editorial, C. Cooper suggested that for patients with less advanced HIV disease and a high CD4 cell count, treating hepatitis C first may be a viable strategy¾thereby reducing the risk of antiretroviral toxicity later on¾but that anti-HIV therapy should not be delayed for patients who fall within the current treatment guidelines.

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