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News Review

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

December 25 , 2006
Volume 3, Issue 22


Liz Highleyman

To download pdf version click here


In This Issue:

Hepatitis C

• HCV Replication in Sustained Responders

• New Risk Factors for HCV

• HCV Reinfection in Injection Drug Users

• Insulin Resistance and Steatosis

• Coinfection and Lipid Abnormalities


HCV Replication in Sustained Responders

Chronic hepatitis C patients who achieve sustained virological response (SVR) with interferon-based therapy are generally considered “cured.” In the November 15, 2006 issue of Clinical Infectious Diseases, however, I. Castillo and colleagues reported that HCV may continue to replicate in the livers of sustained responders. The researchers assessed the presence of positive- and negative-strand HCV RNA in liver biopsy and peripheral blood mononuclear cell (PBMC) samples from 20 sustained responders whose response had persisted for a mean 47 months after the end of therapy. They found positive-strand HCV RNA in 19 of 20 biopsy samples (95%), 15 (79%) of which also had negative-strand RNA. Further, 13 of 20 PBMC samples (65%) had detectable positive-strand HCV RNA, 12 (92%) of which also had negative-strand RNA. Post-treatment biopsy samples from 15 subjects showed evidence of necroinflammation and seven had fibrosis, although liver damage improved in all but two patients after treatment. “HCV persisted and replicated in the livers and peripheral blood mononuclear cells of most sustained responders,” the investigators concluded. “Thus, these patients did not experience HCV infection clearance, despite apparent clinical disease resolution.”

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New Risk Factors for HCV

Although certain risk factors, such as accidental needle-sticks or sharing drug injection equipment, are clearly linked to HCV infection, an estimated 20%-40% of people with hepatitis C have no identified transmission route. In the November 2006 Journal of Viral Hepatitis, M. Karmochkine and colleagues reported on a case-control study of 450 HCV positive French patients with no history of blood transfusion or injection drug use and 757 HCV negative control subjects matched for characteristics such as sex, age, and place of residence. Interviews revealed 15 independent risk factors for HCV infection: nosocomial, or inpatient medical procedures (admission to a medical facility or surgical ward, digestive endoscopy, surgical abortion); outpatient medical procedures (skin ulcer or wound care, diathermy, gamma globulin administration, varicose vein sclerotherapy, acupuncture, intravenous or intramuscular injections); and lifestyle factors (intranasal cocaine use, contact sports, beauty treatments, professional manicures/pedicures). Together, these risk factors explained 73% of community-acquired HCV infections. The researchers concluded that in addition to known risk factors such intranasal cocaine use, previously unidentified factors such as abortions and contact sports also carry a risk of HCV infection.

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HCV Reinfection in Injection Drug Users

In the November 2006 issue of Hepatology, J. Grebely and colleagues from British Columbia reported that spontaneous HCV clearance may provide some protection against reinfection with the virus. The researchers studied a community-based cohort of 3,553 inner-city residents, most of whom were injection drug users. A total of 658 subjects had detectable HCV at baseline, but 152 (23%) spontaneously cleared the virus over a median follow-up period of about 5 years. The occurrence of new HCV infections was lower among individuals with previous infection and spontaneous clearance, compared with a group of 926 initially HCV negative subjects (9.2% vs 18.6%). Reinfection vs first infection rates were 1.8 vs 8.1 cases per 100 person-years, respectively. After controlling for other potential confounding factors, individuals with previous HCV infection and spontaneous clearance were four times less likely to be reinfected than previously uninfected subjects were to be infected for the first time. The researchers concluded that, “Individuals with clearance of HCV infection may have a lower risk of acquiring HCV than individuals who have never been infected, despite ongoing exposure to HCV.”

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Insulin Resistance and Steatosis

Chronic HCV infection influences glucose and fat metabolism in ways that are not fully understood, but appear to differ based on genotype. Blood glucose abnormalities are associated with more severe liver fibrosis and steatosis (fat accumulation), and management of metabolic complications is an increasingly important aspect of the care of patients with hepatitis C. As reported in the December 2006 issue of Hepatology, E. Bugianesi and colleagues analyzed the relationship between insulin resistance (a condition in which higher levels of insulin are needed to process glucose) and clinical and histological characteristics in 132 patients with “viral” steatosis (associated with genotype 3 HCV infection) and 132 subjects with “metabolic” steatosis (associated with non-alcoholic fatty liver disease, or NAFLD). Overall, insulin resistance was more common in NAFLD patients. Univariate analysis revealed that advanced fibrosis was associated with steatosis in NAFLD patients, but not in genotype 3 HCV patients. In a multivariate analysis, low platelet count and greater insulin resistance predicted advanced fibrosis in genotype 3 HCV patients, while insulin resistance, degree of liver fat accumulation, and ferritin level (a protein that stores iron) were linked with severe fibrosis in NAFLD patients. The researchers concluded that insulin resistance is an independent predictor of advanced fibrosis in both genotype 3 HCV and NAFLD patients. But, they added, while steatosis contributes to advanced liver disease in patients with NAFLD, virus-induced steatosis in genotype 3 HCV patients “does not contribute significantly to liver fibrosis.”

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Coinfection and Lipid Abnormalities

Because HIV and the drugs used to treat it also affect metabolism, metabolic complications are even more complex in HIV/HCV coinfected individuals. In the November 2006 issue of HIV Medicine, R. Bedimo and colleagues reported on an evaluation of blood lipid (fat) profiles of 359 HIV positive patients (25% of whom were HIV/HCV coinfected) and 112 HCV monoinfected patients at the Veterans Administration Medical Center in Dallas. Among the HIV positive patients, coinfection was associated with a reduced risk of elevated cholesterol (10% vs 25%) and triglycerides (48% vs 60). After controlling for factors including race, ALT level, platelet count, and duration of protease inhibitor use, HCV coinfection remained an independent predictor of abnormal blood fat levels (dyslipidemia). “HCV coinfection independently predicted lower rates of dyslipidemia among HIV-infected patients,” the investigators concluded. However, the rate of blood lipid abnormalities was lower among HCV monoinfected individuals compared with HIV/HCV coinfected subjects, confirming past research suggesting that HCV is somehow protective against blood fat elevation, though the mechanism is not well-understood.

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