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In This Issue:
• Diabetes Raises Risk of Fibrosis and HCC
• Glucose Abnormalities and Treatment Response
• Longer Treatment Recommended for Genotype 6
• Acute Hepatitis C
• Liver Steatosis in HIV/HCV Coinfected Patients
• Higher LDL Predicts Better Treatment Response
Diabetes Raises Risk of Fibrosis and HCC
Research continues to clarify the association between metabolic factors and liver disease progression in people with chronic hepatitis C. In the May 2008 American Journal of Gastroenterology, S. Petta and colleagues assessed whether increasing degrees of insulin resistance – up to frank type 2 diabetes mellitus – were linked to liver steatosis (fat accumulation) and fibrosis in 201 Italian patients with HCV genotype 1. About half had normal insulin response, 38% had insulin resistance short of diabetes (HOMA-IR score > 2.7), and 14% were diabetic. In a multivariate analysis, insulin resistance was among the factors that predicted advanced fibrosis (stage F3 or higher), independent of steatosis. Diabetic patients were twice as likely to have severe fibrosis as those with lesser degrees of insulin resistance (60 vs. 30%).
In a related study reported in the June 2008 issue of Hepatology, B.J. Veldt and colleagues found that diabetes was also associated with a higher risk of hepatocellular carcinoma (HCC). The international research team analyzed 541 chronic hepatitis C patients with advanced fibrosis, 85 of whom (16%) had diabetes. The prevalence of diabetes rose along with Ishak fibrosis scores, from 11% for patients with F4 fibrosis, to 13% for F5, to 19% for F6. During a median follow-up period of four years, 13% of diabetic patients developed HCC, compared with 6% of those without diabetes. At five years, the HCC incidence rates were 11% and 5%, respectively. “For patients with chronic hepatitis C and advanced cirrhosis,” the investigators concluded, “diabetes mellitus increases the risk of developing HCC.”
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Glucose Abnormalities and Treatment Response
While abnormal glucose metabolism ups the risk of liver disease progression, sustained response to hepatitis C treatment can normalize blood sugar, according to a study in the May 2008 Journal of Hepatology. M. Romero-Gomez and colleagues analyzed 1,059 chronic hepatitis C patients in Spain who were treated with interferon plus ribavirin. About 20% had impaired fasting glucose (100 to 125 mg/dL), while 10% had frank type 2 diabetes (glucose > 126 mg/dL). Individuals with impaired fasting glucose or diabetes were significantly less likely to achieve sustained virological response (SVR) than those with normal blood glucose (44% vs. 59%). Furthermore, 24% of non-responders had abnormal glucose levels, compared with 11% of sustained responders. Conversely, sustained responders were less likely to develop impaired fasting glucose or diabetes during follow-up. “SVR reduces the risk of impaired fasting glucose and/or type 2 diabetes mellitus development in patients with chronic hepatitis C while altered glucose metabolism impairs sustained response to viral treatment,” the researchers concluded.
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Longer Treatment Recommended for Genotype 6
Most studies of chronic hepatitis C treatment have focused on individuals with HCV genotypes 1 or 4 (for whom standard therapy lasts 48 weeks), or genotypes 2 or 3 (usually treated for 24 weeks). Much less is known about treatment of HCV genotype 6, which is mainly seen in Southeast Asia and China. As reported in the May 2008 American Journal of Gastroenterology, M.H. Nguyen and colleagues conducted a retrospective analysis of 190 Asian-Americans in Northern California diagnosed with HCV genotype 6 between 2001 and 2004. A subgroup of 66 previously untreated individuals completed 24 or 48 weeks of treatment with conventional or pegylated interferon plus ribavirin. Among participants treated for 24 weeks, conventional and pegylated interferon produced statistically similar SVR rates (52% vs. 39%). However, among participants who received pegylated interferon plus ribavirin, those treated for 48 weeks were significantly more likely to achieve SVR than those treated for 24 weeks (75% vs. 39%). Based on these findings, the researchers concluded that, “Treatment-eligible patients with HCV genotype 6 should be treated with a full course of 48 weeks as tolerated.”
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Acute Hepatitis C
Also in the May 2008 American Journal of Gastroenterology, S.M. Kamal presented a systematic review of acute hepatitis C, or the first six months after infection. About 25% of people with acute HCV infection spontaneously clear the virus without treatment, while the rest go on to develop chronic infection. A MEDLINE medical literature search of prior studies revealed no consistent, reliable predictors of spontaneous HCV clearance. Several clinical trials found that treatment of acute hepatitis C with interferon-based therapy produced high SVR rates ranging from 75% to 100%. But because acute HCV infection is often asymptomatic, many people are never diagnosed during this early stage; in addition, decisions about therapy are complicated by the fact that some patients will clear the virus even if left untreated. “Optimization of therapy for acute hepatitis C infection and identification of predictors of SVR represent a real challenge,” the researchers concluded. “[A]n improvement in our ability to diagnose and treat patients with acute hepatitis C would have a significant impact on the prevalence of chronic hepatitis and its associated complications particularly in countries with a high endemic background of the infection.”
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Liver Steatosis in HIV/HCV Coinfected Patients
Liver steatosis, or accumulation of fat in hepatocytes, is common among people with chronic hepatitis C, and has been shown to have a negative effect on treatment response in individuals with HCV alone; less is known about steatosis in HIV/HCV coinfected patients. As reported in the May 2008 Journal of Hepatology, M. Rodriguez-Torres and an international team of colleagues analyzed data from 283 participants (out of a total of 868) from the APRICOT trial (which compared conventional vs. pegylated interferon with or without ribavirin in coinfected patients) who had pre- and post-treatment liver biopsies. Among this subgroup, 23% had evidence of steatosis. Individuals with steatosis were significantly more likely to have HCV genotype 3, bridging fibrosis or cirrhosis, higher HCV RNA levels, larger hip circumference, and increased triglyceride levels, but had lower cholesterol levels. The presence of steatosis did not appear to influence the effectiveness of hepatitis C treatment among patients of any genotype; however, sustained response to therapy did reduce steatosis among individuals with genotype 3.
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Higher LDL Predicts Better Treatment Response
Another study looking at factors associated with treatment response in HIV/HCV coinfected patients was published in the May 11, 2008 issue of AIDS. J. del Valle and colleagues conducted a retrospective analysis of 260 HIV/HCV coinfected individuals with available serum lipid (cholesterol and triglyceride) data; about half had genotype 1, 39% had genotype 3, and 8% had genotype 4. All were treated with pegylated interferon plus 800-1400 mg/day weight-based ribavirin for 24 or 48 weeks; none were taking lipid-lowering medications. Overall, 24% of genotype 1 or 4 patients and 63% of genotype 2 or 3 patients achieved SVR. But sustained response was significantly more likely in individuals with higher low-density lipoprotein (LDL) cholesterol levels. Across all genotypes, 44% of patients with LDL of 100 mg/dL or greater achieved SVR vs. 36% with lower LDL values – an effect that was independent of other predictive factors including baseline HCV viral load. Looking at genotype 1 patients, the corresponding SVR rates were 31% vs. 17%; for patients with genotypes 2 or 3, the SVR rates were 73% and 58%. Other blood lipids, including high-density lipoprotein (HDL) cholesterol and triglycerides, were not associated with treatment response. Elevated LDL – which is a risk factor for cardiovascular disease – has also been linked to improved treatment response in HIV negative individuals with hepatitis C, possibly because the LDL receptor plays a role in HCV entry into host cells.
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