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A Bi-Monthly Publication of the Hepatitis Support Project

February 24, 2005 Volume 2, Issue 3

Liz Highleyman

To download pdf version click here

In This Issue: Hepatitis C

New Laboratory Model of HCV Replication

Noninvasive Measures of Fibrosis

Hepatotoxicity of HIV Therapy

New Laboratory Model of HCV Replication

Nine out of ten genotype 1 chronic hepatitis C patients treated with standard doses of pegylated interferon (Pegasys) plus high doses of ribavirin achieved sustained virological response (SVR), according to a prospective pilot study reported in the February issue of Hepatology. Karin Lindahl from the Karolinska Institute in Stockholm, Sweden, and colleagues examined 10 patients (7 men, 3 women; mean age 51 years) with genotype 1 HCV and high baseline viral loads. None of the subjects had cirrhosis, were coinfected with HIV, or were of African descent—populations known to respond less well to interferon-based therapy. All were treated with standard-dose (180 mcg/week) Pegasys plus high-dose (mean 2,540 mg/day; range 1,600-3,600 mg/day) ribavirin for 48 weeks. Ribavirin doses were individually tailored to reach a target blood concentration. The average ribavirin dose in this study was about twice the usual recommended dose of 1,000-1,200 mg/day. After 48 weeks of therapy plus 24 weeks of follow-up, 90% of the patients had undetectable HCV RNA. Unsurprisingly, however, given the high doses of ribavirin used, subjects experienced serious side effects, primarily hemolytic anemia. All subjects required erythropoietin to boost red blood production; nevertheless, two patients still required blood transfusions. Although this study was small, it suggests that higher ribavirin doses may help prevent HCV relapse and lead to higher SVR rates if side effects can be adequately managed.

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Study Sheds More Light on Anemia

In the February issue of the American Journal of Gastroenterology, Vijayan Balan and colleagues provided further information on the association of hepatitis C therapy and anemia. In an eight-week study of 97 subjects, the researchers found that mean hemoglobin levels during treatment with pegylated interferon plus ribavirin decreased from 14.4 to 11.9 g/dL. (Normal hemoglobin levels in healthy adults are about 14-18 g/dL for men and about 12-16 g/dL for women.) Overall, patients’ ribavirin doses were reduced by an average of 73 mg/day (from 986 to 913); still, about three-quarters were able to remain on their initial ribavirin dose. In addition, subjects in this study had lower than expected blood levels of natural erythropoietin given their degree of anemia (compared, for example, to individuals with iron-deficiency anemia). These results suggest that, in addition to ribavirin’s direct destructive effect on red blood cells, people with hepatitis C may have decreased endogenous (internal) erythropoietin production and reduced stimulation of new red blood cell production— a phenomenon also seen in patients with HIV or cancer.

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Reasons for Not Receiving Hepatitis C Treatment

A considerable proportion of individuals with hepatitis C do not receive treatment because they are unaware they are infected. But in some populations, treatment rates are low even among those who know they have the disease. In the January 2005 Journal of Viral Hepatitis, A.A. Butt and colleagues looked at reasons for nontreatment in a cohort of 354 veterans referred to a hepatology specialty clinic (99% male, 71% white, median age 48 years). In this group, 70% were not treated. The most common reasons were failing to attend a follow-up visit (24%), concurrent medical conditions (11%), substance use (9%), and co-existing psychiatric problems (7%). Some individuals were judged not to need treatment due to normal liver enzyme levels (14%) or undetectable HCV RNA (5%). In addition, 7% had advanced liver disease, 6.4% were referred for evaluation for liver transplants, 5% refused care, and 5% were transferred to another facility. The researchers determined that untreated patients were more likely to have 12 or fewer years of education and/or a history of incarceration. Subjects who either refused treatment or were lost to follow-up were again more likely to have a history of incarceration, as well as current alcohol or illegal drug use.

In a related study in the same issue, A. Restrepo and colleagues studied the rate of hepatitis C treatment among 104 HCV/HIV coinfected patients at a New York City gastroenterology clinic between July 2001 and June 2002 (72% male, mean age 47 years, 90% with a history of injection drug use). Out of the total group, 15% were treated, but among the one-fifth who received liver biopsies, 67% received treatment. Overall, 75 individuals were deemed ineligible for therapy for various reasons, including nonadherence (40%), co-existing medical conditions (24%), active substance use (15%), decompensated cirrhosis (13%), and psychiatric problems (8%). In addition, 13 people refused HCV therapy. The authors concluded that a majority of those who were not candidates for therapy had “potentially modifiable psychosocial factors leading to nontreatment.”

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Concerns of People with Hepatitis C

In order to determine the major concerns and issues of people with hepatitis C, Gerald Minuk from the University of Manitoba in Canada and colleagues conducted a survey of 70 individuals newly diagnosed with hepatitis C and 115 HCV positive patients returning for follow-up care. Results were published in the January issue of the Journal of Viral Hepatitis. When asked to state their primary concerns, the most often mentioned were disease progression (27%), premature death (19%), infecting family members (13%), and side effects of treatment (11%). When asked to prioritize a prepared list of possible concerns, respondents ranked infecting family members first, followed by development of liver cancer, infecting others [non-family], development of cirrhosis, social stigma, need for liver transplant, and loss of employment. Concerns expressed by newly diagnosed and follow-up patients were similar, and responses did not differ significantly on the basis of sex, age, racial/ethnic group, education level, method of HCV acquisition, or duration of follow-up. The results of this study can be used to help guide counselors and support group leaders in addressing the most pressing concerns of people with hepatitis C.

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Coffee and Caffeine Reduce Risk of ALT Elevation

Consumption of caffeine may help reduce the chances of elevated blood levels of the liver enzyme alanine aminotransferase (ALT), according to a report in the January issue of Gastroenterology. Constance Ruhl and colleagues from the National Institute of Diabetes and Digestive and Kidney Diseases examined data from a subset of 5,944 adults taking part in the Third U.S. National Health and Nutrition Examination Survey (1988-1994) who were at risk for liver damage due to viral hepatitis, heavy alcohol consumption, iron overload disease, impaired glucose metabolism, or being overweight. In this high-risk population, 8.7% had elevated ALT levels, an indicator of liver inflammation. In a multivariate analysis, the researchers found that the risk of ALT elevation decreased as consumption of coffee or caffeine increased. Individuals who drank more than two cups of coffee per day were about half as likely to develop elevated ALT levels as those who did not drink coffee (odds ratio .56). These results were consistent across the different liver disease risk groups. While the results of this study do not imply that hepatitis C patients should consume large amounts of caffeine, they do suggest that moderate coffee consumption is not harmful and may, in fact, offer some benefit. 

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