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In This Issue:
• Hepatitis C in Asian-Americans and African-Americans
• Gene Expression Linked to Poor Treatment Response
• Aging of the U.S. IDU Population
• Mother-to-Child HCV Transmission in Twin Pregnancies
Hepatitis C in Asian-Americans and African-Americans
The epidemiology and natural history of chronic hepatitis C differs among racial/ethnic groups, as described in two recent journal articles. Hepatitis B is common among Asians and Asian-Americans, but hepatitis C in this population is less well characterized. In the December 2006 American Journal of Gastroenterology, J.T. Cheng and colleagues reported results from a retrospective survey of 260 Asian-Americans with chronic hepatitis C, most of whom (92%) were born in Asia. Half (51%) reported unsafe therapeutic injections, but unsafe injections were a risk factor only for individuals exposed to HCV outside the United States. Another large proportion (41%) reported a history of blood transfusion, which was more frequent among those exposed to HCV in the Unites States. Only 3.8% reported a history of injection drug use. A majority (64%) had genotype 1 HCV, followed by genotype 2 (18%) and genotype 6 (11%), which is common in Asia. As expected, genotype 1 patients had a lower sustained virological response (SVR) rate to interferon-based therapy (33%), while the genotype 6 response (69%) was slightly lower than that for genotype 2 (78%). Over an average follow-up period of six years, 26 patients (10%) developed hepatocellular carcinoma (HCC). The researchers concluded that Asian-Americans with a history of unsafe medical injections should be screened for HCV, antiviral therapy should be started before the development of HCC, and monitoring for HCC should be routine.
In the February 2007 Journal of Clinical Gastroenterology, N. Pyrsopoulos and L. Jeffers gave an overview of chronic hepatitis C in African-Americans. They noted that compared with the population as a whole, African-Americans have a higher prevalence of HCV infection, are more likely to have hard-to-treat genotype 1, more often have detectable HCV RNA, and tend to have higher HCV viral loads. Although African-Americans tend to experience slower liver disease progression, they are at least as likely to develop HCC. In addition, they appear to be underrepresented on liver transplant wait lists and may have shorter survival times after transplantation. As has been widely reported, African-Americans have a lower response rate than Caucasians to treatment with conventional or pegylated interferon, with or without ribavirin. Both genotype 1 and high HCV viral load are associated with poorer treatment response, but these factors do not seem to fully account for the racial differences in response, and studies are underway to determine what other mechanisms might be involved.
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Gene Expression Linked to Poor Treatment Response
Genetic differences may be among the factors that play a role in variable response to therapy. As reported in the January 31, 2007 advance online edition of the Journal of Virology, M.W. Taylor and colleagues measured gene expression in 33 African-Americans and 36 Caucasians with genotype 1 HCV during the first 28 days of treatment with pegylated interferon plus ribavirin. Overall, gene expression in response to interferon was blunted in patients with poor virological response (less than 1.5 log decrease in HCV RNA) compared to those with intermediate (1.5-3.5 log) or good (more than 3.5 log) response. In addition, the number of genes that were up- or down-regulated during treatment was smaller in patients with poor response, and induced levels of known interferon-stimulated genes (such as OAS, MX1, IRF-7, and TLR-7) were lower. Nonetheless, African-Americans had stronger interferon responses overall compared with Caucasians. While the authors concluded that, “the relative lack of viral response to interferon therapy [for] hepatitis C is associated with blunted interferon cell signaling,” they added that no specific regulatory genes could be identified that would explain the racial differences in treatment response.
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Aging of the U.S. IDU Population
Because chronic hepatitis C is highly prevalent among injection drug users (IDUs), a good understanding of the IDU population is important for predicting the future burden of liver disease. In the January 27, 2007 Archives of Internal Medicine, G.L. Armstrong of the Centers for Disease Control and Prevention presented results from an analysis of IDUs in the U.S. between 1979 and 2002. Data were obtained from the National Household Survey on Drug Abuse, an ongoing survey of drug use among adults age 12 and over; the survey does not include members of the military or institutionalized persons such as prisoners or patients in long-term care facilities.
In the 2000-2002 surveys, 1.5% of study respondents reported ever injecting drugs, for an estimated total of 3.4 million persons. A smaller proportion, 0.19%, reported injecting drugs within the past year, for an estimated total of 440,000. A history of drug injection was most common (3.1%) among persons aged 35-49 years, who accounted for more than half (59.4%) of all participants who gave this response. In addition, injection history was more common among men than among women (2.0% vs 1.0%), and more common among whites than among blacks or Hispanics (1.7%, 0.8%, and 1.1%, respectively). From 1979 through 2002, the average age of participants who reported ever injecting drugs increased from 26 to 42 years, while the age of those reporting injection within the past year increased from 21 to 36 years. Armstrong noted that the marked increase in the average age of IDUs is consistent with an epidemic of injection drug use that started in the 1960s and peaked in the 1970s and 1980s. “The increasing mean age and the fact that middle-aged adults are more likely than young adults to have ever used injection drugs would be consistent with a large decline in the initiation of [injection drug use] in the early 1990s, which could at least partly account for the large decrease in the incidence of acute hepatitis C observed in the United States at that time,” he wrote.
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Mother-to-Child HCV Transmission in Twin Pregnancies
HCV may be transmitted perinatally from mother to child during pregnancy or delivery, which is more likely to occur if the woman has a high HCV viral load or is coinfected with HIV. In the February 2007 Journal of Clinical Virology, E. Boxall and colleagues reported on four twin pregnancies investigated at Childrens Hospital in Birmingham, England. In all four cases, only one twin was infected with HCV; in three cases, it was the second-born twin that became infected. Additionally, all of the infected children were girls, and all were the larger twin in their pair. Invasive fetal monitoring and episiotomies were not performed in any of the deliveries. The authors concluded that, “Transmission of HCV is more likely to affect the second twin, perhaps because placental separation during the delivery of the second twin exposes the infant to infection.” In the one case in which the first-born twin was infected, the mother experienced premature rupture of membranes. The authors suggested that HCV positive mothers with twin pregnancies might opt for elective caesarean section to reduce the risk of infecting the second-born twin.
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