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A Bi-Monthly Publication of the Hepatitis Support Project

October 25 , 2006
Volume 3, Issue 18

Liz Highleyman

To download pdf version click here

In This Issue:

Hepatitis C

• Fibrosis in Women with Hepatitis C

• Glycyrrhizin for Hepatitis C

• Colchicine May Delay Hepatocellular Carcinoma

• HCV Recurrence after Liver Transplantation

• Predictors of Hepatitis C Treatment

Fibrosis in Women with Hepatitis C
Rates of liver fibrosis progression differ between men and women with hepatitis C, which may be due to the anti-fibrogenic effect of estrogen. In the September 26, 2006 online edition of Gut, L. Codes and colleagues from Brazil reported on a study of 251 women, 52% of whom were past menopause. They found that women with moderate to severe (stage F2-F4) fibrosis were more often post-menopausal (67% vs 47%), and within this group, those taking hormone replacement therapy were less likely to have stage F2-F4 fibrosis. Steatosis (fatty liver) was also more frequent and more severe in post-menopausal women. The researchers concluded that, “These results reinforce the hypothesis of a protective role of estrogens in the progression of fibrosis.”

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Glycyrrhizin for Hepatitis C
Glycyrrhizin, an active component of licorice root (Glychyrrhiza glabra) used in Chinese medicine to treat liver disease, is among the more promising alternative therapies for chronic hepatitis C. Previous studies showed that four weeks treatment with glycyrrhizin lowered ALT levels. As reported in the October 2006 Journal of Hepatology, H. Orlent and colleagues from the Netherlands conducted a study in which 121 patients with elevated ALT and marked fibrosis or necro-inflammation received six weekly infusions of glycyrrhizin for four weeks. The 72 patients with reduced ALT at Week 4 continued treatment for 22 weeks, receiving glycyrrhizin either once, three times, or six times weekly. At the end of treatment, the rates of continued ALT response were 9%, 24%, and 60%, respectively, in the three dose-frequency groups. Patients receiving glycyrrhizin also reported improved quality of life. “ALT responses induced by four weeks glycyrrhizin therapy can be maintained in a subset of chronic hepatitis C patients receiving at least three injections weekly,” the researchers concluded, but added that “the observed ALT response was not reflected in a significant histological improvement after six months treatment.”

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Colchicine May Delay Hepatocellular Carcinoma
Colchicine is an anti-inflammatory agent that inhibits mitosis (cell division) and fibrogenesis (production of fibrous tissue). As reported in the October 15, 2006 issue of Cancer, O. Arrieta and colleagues conducted a retrospective study of 186 patients with liver cirrhosis due to viral hepatitis, of whom 116 were treated with colchicine. After a median follow-up of 84 months, significantly fewer patients in the colchicine group developed hepatocellular carcinoma (HCC) compared with the untreated group (9% vs 29%). Further, the average time to develop HCC was 222 months in the colchicine group versus 150 months in the untreated patients. While past research has failed to show that colchicine slows fibrosis progression in cirrhotic patients, the authors concluded that the results of this study “suggest that treatment with colchicine prevents and delays the development of HCC in patients with hepatitis virus-related cirrhosis.”

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HCV Recurrence after Liver Transplantation
Several recent journal articles have looked at HCV recurrence after liver transplantation. As reported in the October 2006 Annals of Surgery, A.M. Cameron and colleagues conducted a retrospective analysis of factors associated with HCV recurrence and liver disease progression in 307 patients who underwent liver transplantation over a 10-year period. The recurrence-free survival rate was 69% at one year and 34% at five years after transplantation. Variables that predicted recurrence were advanced donor or recipient age, prolonged donor hospitalization, and higher recipient MELD score; genetic mismatch between donors and recipients did not affect survival.

In the October 2006 American Journal of Transplantation, E. Oton and colleagues reported on a study of 55 patients who received standard full doses of pegylated interferon plus ribavirin for 48 weeks, starting 12 or more months after receiving liver transplants. The end-of-treatment response rate was 66.7% and the sustained virological response (SVR) rate was 43.6%. Low baseline HCV viral load and a period of 2-4 years between transplantation and treatment were predictors of SVR. The most frequent side effects were neutropenia, anemia, and infections, and 29% discontinued therapy due to toxicity. In 15 patients with post-treatment biopsies, histological activity index scores improved significantly, but fibrosis scores did not change. “HCV therapy after liver transplantation was very effective,” the authors concluded, “although it led to a significant rate of toxicity.”

In a study reported in the August 2006 Journal of Viral Hepatology, A. Feliu and colleagues assessed whether response to interferon-based therapy differed before and after transplantation. They evaluated 22 patients with HCV who received antiviral therapy while awaiting transplants and experienced HCV recurrence after the procedure; 11 received a renewed course of anti-HCV treatment. Of the retreated patients, 73% showed identical early virological response (EVR) or non-response to both pre- and post-transplant therapy. However, response changed in 27% of patients: two previous non-responders achieved EVR after transplantation, and one with previous EVR became a non-responder. The authors concluded that, “in HCV-infected patients undergoing liver transplantation, the pattern of response to antiviral treatment may change after transplantation, and this possibility needs to be incorporated in clinical practice.”

Finally, in the September 28, 2006 online edition of Gut, K. Barber and colleagues reported on a study of long-term survival, life expectancy, and life-years lost using data from the U.K. National Transplant Database, which includes information on more than 3,600 adult liver recipients. After reaching the six-month milestone, the estimated median survival time was 22 years, compared with about 29 years for the general population of the same age. Women had a longer post-transplant life expectancy than men (26 vs 18 years), while those transplanted due to cancer, hepatitis C, or alcoholic liver disease had the greatest loss of life-years. The authors noted that while 1-year survival rates have increased over the years, “death rates beyond this period have remained more or less the same” – perhaps because, while surgical techniques have improved, patients undergoing transplantation today include older and sicker individuals.

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Predictors of Hepatitis C Treatment
Many people with chronic hepatitis C never receive treatment for reasons ranging from minimal liver disease to physicians’ expectation of poor adherence. In the September 26, 2006 electronic edition of Gut, A.A. Butt reported on a study of the rate and predictors of hepatitis C treatment using the Department of Veterans Affairs (VA) National Patient Care Database. Nearly 114,000 veterans under VA care with a diagnosis of HCV were identified, of whom 11.8% were prescribed treatment. Patients not prescribed treatment were older, more likely to be black or Hispanic, more likely to use alcohol or illegal drugs, and more likely to have co-existing medical and psychiatric conditions including anemia, coronary artery disease, depression, bipolar disorder, or schizophrenia. These results suggest that many patients are needlessly missing out on treatment, since the National Institutes of Health consensus statement no longer recommends that active substance users be excluded from hepatitis C therapy, and conditions such as anemia and depression can be successfully managed in many patients.

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