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In This Issue: Hepatitis C
• Hepatitis C in Patients Older Than 65
• Low Doses of Peg-Intron
• Neutropenia and Infections in People with Hepatitis C
• Beliefs about Hepatitis C and Lifestyle Changes
Hepatitis C in Patients Older Than 65
Many people who contracted HCV years ago are now reaching an age at which long-term liver damage is becoming apparent. As reported in the June 2006 American Journal of Gastroenterology, T. Thabut and colleagues assessed the severity of chronic hepatitis C and the efficacy of antiviral therapy in relation to age. Among 4,182 patients seen at a Paris hospital, those aged 65 or more years were older at the time of HCV infection, had a longer duration of infection, and were more likely to have genotype 1. Among those who underwent liver biopsy, bridging fibrosis (stages F2-F4) was more common among patients aged 65 or older, regardless of duration of infection. Among patients who received treatment with pegylated interferon plus ribavirin, 45% achieved sustained virological response (SVR). In a second group of more than 33,000 patients who received the FibroTest, FibroSure, or Actitest noninvasive biomarker panels, cirrhosis was observed in 58% of patients over 80 years of age, 37% of those between 65 and 80, and 14% of those younger than 65. Cirrhotic individuals older than 80 were more likely to have normal ALT levels compared with patients younger than 65 (43% vs 31%). The researchers concluded that among patients aged 65 or older, chronic hepatitis C is more severe and presents with lower ALT; however, treatment can be effective, and biochemical markers may be “particularly useful as a noninvasive alternative” for assessing fibrosis in this population.
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Low Doses of Peg-Intron
The recommended dose of pegylated interferon alfa-2b (Peg-Intron) is 1.5 mcg per kilogram of body weight once weekly when used in combination with ribavirin (or 1.0 mcg/kg/week when used as monotherapy). Two recently published studies looked at the efficacy of lower doses. As reported in the June 2005 American Journal of Gastroenterology, E.L. Krawitt and colleagues conducted a prospective randomized trial of low versus standard doses of Peg-Intron plus ribavirin. Patients weighing less than 75 kg received 50 or 100 mcg/week, while those weighing 75 kg or more received 150 mcg/week, all with 1000 mg daily ribavirin, for 24 weeks or 48 weeks (depending on response at week 24). The overall SVR rates were 45% with standard-dose and 33% with low-dose Peg-Intron (P = 0.02). For genotypes 2 or 3, the rates were 65% with standard-dose and 56% with low-dose Peg-Intron (P = 0.51), and for genotype 1, the corresponding rates were 38% and 24% (P = 0.03). For genotype 1 patients whose body weight was such that they received at least 1.25 mcg/kg Peg-Intron and at least 12.5 mg/kg ribavirin, the SVR rate was 51%. The authors concluded that the results of their study “underscore the importance of adequate dosing of ribavirin as well as pegylated interferons.”
According to a related report in the July 2006 Journal of Viral Hepatitis, B. Meyer-Wyss and colleagues conducted a randomized, open-label study of 227 patients, comparing 1.0 mcg/kg vs 1.5 mcg/kg Peg-Intron, both in combination with 400 mg twice daily ribavirin, for 24 or 48 weeks (depending on genotype). The researchers found that virological response rates did not differ significantly between the two doses of Peg-Intron. For patients with genotype 1 or 4, SVR rates were 38% with 1.0 mcg/kg vs 39% with 1.5 mcg/kg (P = ns); the corresponding rates for those with genotype 2 or 3 were 71% and 81% (P = ns). Unsurprisingly, there were fewer temporary or permanent dose reductions due to adverse events in the lower-dose arm (42% vs 59%; P = 0.015). The authors concluded that in combination with ribavirin, 1.0 mcg/kg Peg-Intron was as effective as 1.5 mcg/kg, but the lower dose was better tolerated.
These apparently conflicting studies are not strictly comparable, since Krawitt’s team used fixed doses of Peg-Intron for patients above and below the threshold of 75 kg (about 165 pounds, a typical weight for a large woman or a small man). Also, the Meyer-Wyss study used a lower dose of ribavirin, which plays a role in preventing anemia. Further study is needed to clarify optimal pegylated interferon dosing, but research to date points to the benefits of tailoring therapy to individual patient characteristics such as body weight.
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Neutropenia and Infections in People with Hepatitis C
Neutropenia - a low level of neutrophils, a type of immune system white blood cell - is a possible side effect of interferon-based therapy. Experts often discontinue or reduce doses of interferon as patients’ neutrophil counts fall, for fear that neutropenia will lead to infections. However, a study in the June 15, 2006 issue of Clinical Infectious Diseases suggested that low neutrophil counts in individuals receiving hepatitis C treatment are not associated with an increased risk of infection. C.L. Cooper and colleagues followed 192 patients who received 211 courses of therapy for hepatitis C; none used granulocyte colony-stimulating factor (G-CSF, Neupogen) to promote white blood cell production. After a median 17 weeks of therapy, 57 patients (30%) experienced 67 infectious complications, for a rate of 1.17 infections per 100 person-weeks of therapy. The rates of bacterial, viral, and fungal infections did not correlate with nadir (lowest ever) neutrophil counts, or with the magnitude of decline from baseline levels. Infection rates also did not differ based on age, sex, race, body weight, HIV coinfection status, or severity of liver disease. The authors concluded that neutrophil count “is not correlated with infection rate in recipients of interferon-based therapy for hepatitis C,” and suggested that patients who develop neutropenia during hepatitis C treatment may not require interferon dose reduction or adjunct therapy with G-CSF.
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Beliefs about Hepatitis C and Lifestyle Changes
Being diagnosed with hepatitis C can have a major impact on one’s life, and it is important that patients have accurate information about HCV, its transmission, and its potential outcomes. As reported in the July 2006 Journal of Viral Hepatitis, L. Castera and colleagues had 185 patients complete questionnaires asking about their beliefs regarding hepatitis C severity and lifestyle changes after diagnosis. Most patients (93%) identified cirrhosis and liver cancer as the two main complications of chronic hepatitis C. However, 59% incorrectly believed that chronic hepatitis C is always associated with a fatal outcome, and only 3% thought that they would remain healthy (in fact, some 75% of people with chronic hepatitis C will not develop severe liver damage, and effective antiviral treatment can further reduce the risk). Furthermore, HCV viral load was the most commonly reported factor associated with disease severity by the patients; however, unlike the case with HIV, most studies do not show a link between HCV viral load level and disease severity. More than half the respondents (58%) reported they had made changes in their sex lives, while 48% had made dietary changes. “Our results show the considerable impact of [chronic hepatitis C] diagnosis on patients’ lifestyle,” the researchers concluded. They emphasized the need for improved patient counseling in order to avoid unnecessary sex life and dietary changes. Sexual transmission of HCV among monogamous heterosexual couples is rare, and using condoms can help reduce the risk if individuals are concerned. Also, while people with hepatitis C should eat a healthy diet, experts no longer recommend changes such as restricted protein intake, except in certain cases of advanced cirrhosis. Better education could also reduce anxiety about the likelihood of severe illness or death.
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