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In This Issue:
Extended Treatment for Genotype 1b
In an attempt to improve treatment response for hard-to-treat chronic hepatitis C patients, T. Ide and colleagues conducted a study in which 113 participants with HCV genotype 1b and high pre-treatment HCV viral load were randomly assigned to receive pegylated interferon plus ribavirin for the standard 48-week duration or extended therapy lasting 44 weeks after they achieved undetectable HCV RNA (total duration of 48 to 68 weeks). As reported in the January 2009 American Journal of Gastroenterology, the SVR rate was somewhat higher in the extended duration group (53% vs. 36%), but the difference did not reach statistical significance. Among 20 participants who first became HCV RNA negative between weeks 16 and 24, however, individuals in the extended duration group were significantly more likely to achieve SVR (78%) than those in the standard duration group (9%), although the numbers were small. "The extended treatment significantly increased the SVR rate in patients who were HCV RNA negative at 16-24 weeks," the researchers concluded.
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Hepatocellular Carcinoma Risk
Two recent studies looked at risk factors for hepatocellular carcinoma (HCC) in people with hepatitis C. As reported in the January 2009 Gastroenterology, A. Lok and colleagues evaluated the incidence rate and risk factors for HCC in the HALT-C study, a trial comparing low-dose (90 mcg once-weekly) Pegasys maintenance therapy for 3.5 years versus no further treatment in 1,005 chronic hepatitis C patients with bridging fibrosis or cirrhosis who did not respond to standard therapy. During a median 4.6 years of follow-up (maximum 6.7 years), 48% developed HCC. The cumulative five-year HCC incidence rate was similar for participants in the maintenance therapy arm (5.4%) and those who received no further treatment (5.0%). People with cirrhosis were almost twice as likely to develop HCC as those with bridging fibrosis (7.0% vs. 4.1%). Eight patients (17%) whose serial biopsy specimens showed only fibrosis developed HCC.
In a second study, reported in the February 2009 Journal of Hepatology, M. Hassan and colleagues analyzed the influence of family history of liver cancer on development of HCC. The study included 347 patients at the University of Texas with confirmed HCC and 1,075 healthy control subjects. Individuals who had a first-degree relative (parent, sibling, or child) with liver cancer were about four times more likely to develop HCC, independent of hepatitis B or C status (adjusted odds ratio 4.1). Having siblings with liver cancer in particular was associated with an even greater risk, with or without hepatitis B or C (adjusted odds ratio 5.7). All cases in which a person had multiple relatives with liver cancer were HCC patients with chronic HBV or HCV. Considering only individuals with hepatitis B or C, those with a family history of liver cancer were about 60 times more likely to develop HCC (adjusted odds ratio 61.9).
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Biliary and Pancreatic Cancer
As reported in the January 2009 Hepatology, H. El-Serag and colleagues sought to determine whether—in addition to their established risk for HCC—people with chronic hepatitis also have a higher rate of "hepatopancreaticobiliary" malignancies, or cancers of the liver, pancreas, and biliary system (gall bladder and bile ducts). This retrospective cohort study included more than 718,000 patients who received care at U.S. Veterans Affairs health facilities. A total of 146,394 hepatitis C patients were matched with up to four uninfected control subjects. During 1.37 million person-years of follow-up (average 2.3 years per patient), the researchers identified 37 cases of intrahepatic cholangiocarcinoma (ICC; cancer of bile ducts within the liver), 75 cases of extrahepatic cholangiocarcinoma (ECC; cancer of bile ducts outside the liver), 617 cases of pancreas cancer, and 1679 cases of HCC. Individuals with hepatitis C, as expected, had a 15-fold higher risk of developing HCC, and also a 2.55-fold higher risk of ICC; excess risk of ICC remained even after controlling for factors such as cirrhosis, HBV infection, and heavy alcohol use. Hepatitis C patients had a slightly elevated risk of pancreas cancer (1.23-fold), but this was erased after adjusting for alcohol use and other factors. People with hepatitis C had a small increase in ECC risk (1.5-fold), but this was not statistically significant.
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HCV Diagnosis in Coinfected People
The increasing recognition of likely sexual transmission of HCV among HIV positive individuals has led to calls for regular HCV screening, but people with compromised immunity may not produce enough antibodies to show up on a standard test. As described in the January 2, 2009 issue of AIDS, E. Thomson and colleagues compared the sensitivity of standard HCV antibody testing versus RT-PCR HCV RNA testing for diagnosing acute HCV infection in people with HIV. The researchers looked at stored plasma samples from 43 HIV positive individuals in the St. Mary's Acute Hepatitis C Cohort in London; they generally did not have advanced immune suppression (median CD4 cell count of 570) and about half were taking combination antiretroviral therapy.
At the time of their first positive HCV RNA test, the median ALT level was 65 IU/mL and 75% tested negative for HCV antibodies. After three months, 37% still had a negative antibody test, which remained the case for 10% after nine months and 5% after one year; one person did not experience HCV seroconversion until year 3. The estimated median time between HCV RNA detection and development of HCV antibodies was about three months (range 0 to 1206 days). Elevated ALT was found to be a significantly more sensitive measure than HCV antibody testing for detecting acute HCV in people with HIV. Time to HCV antibody seroconversion did not differ significantly between people with spontaneous HCV clearance and those with persistent infection, but individuals with low HCV viral load or low ALT at the time of the first positive HCV RNA test took longer to develop HCV antibodies. "Delayed seroconversion in HIV positive individuals with acute HCV may result in delayed diagnosis and treatment," the researchers concluded. "Where there is a clinical suspicion of recent HCV infection…HIV-infected patients should be screened for HCV RNA by RT-PCR."
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Pegasys vs. PegIntron for Coinfected Patients
In a study reported in the January 2009 Hepatology, M. Laguno and colleagues compared the efficacy and safety of the two marketed brands of pegylated interferon. In this prospective open-label trial, 182 interferon-naive coinfected participants (63% genotype 1 or 4; 29% fibrosis stage 3 or higher) were randomly assigned to receive 180 mcg/week pegylated interferon alfa-2a (Pegasys) or 80-150 mcg/week pegylated interferon alfa-2b (PegIntron) plus 800-1200 mg/day weight-adjusted ribavirin, for 48 weeks. Overall early virological response (EVR) rates at week 12 were 80% in the Pegasys arm and 70% in the PegIntron arm—not a statistically significant difference. Individuals receiving Pegasys and PegIntron also had similar SVR rates 24 weeks after finishing treatment (46% vs. 42%, again not statistically significant). For genotype 1 or 4 patients, SVR rates were 32% with Pegasys vs. 28% with PegIntron, while for genotypes 2 or 3 the corresponding rates were 71% vs. 62%. Likelihood of early treatment discontinuation due to side effects was also similar in the Pegasys (13%) and PegIntron (8%) arms. Based on these findings, the researchers concluded that the two types of pegylated interferon "had no significant differences in efficacy and safety."
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