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News Review

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

January 21, 2004 Volume 1, Issue 2


Liz Highleyman

To download pdf version click here


In This Issue:

HCV Genotype 4

Long-Term Outcome in Individuals Infected with HCV at Birth

MELD Scores and Liver Transplants

HCV Genotype 4

HCV genotype is an important consideration because it affects how well individuals respond to therapy. Genotype 1 is most common in the U.S.—accounting for about two-thirds of cases—and is most difficult to treat. The next two most common genotypes, 2 and 3, respond more rapidly to treatment. Relatively little research has been done on genotype 4, which accounts for the majority of cases in the Middle East and parts of Africa, but is rare in North America.

In the January 2004 issue of the Journal of Clinical Gastroenterology, André Lyra, MD, and colleagues reported on the epidemiology of genotype 4 HCV in the U.S. The researchers asked hepatologists for information about genotype 4 patients they had treated and searched the St. Louis University Hospital database for cases seen between 1999 and 2002. Medical charts were reviewed for patient demographics, HCV risk factors, and response to therapy. In this sample, 20 individuals with genotype 4 were identified; most had a history of injection drug use. Of the 17 patients treated with interferon plus ribavirin (14 of whom completed therapy), 10 (59%) achieved a sustained virological response (SVR).

This study confirms that HCV genotype 4 is uncommon in the U.S., but—in contrast to some previous research—indicates that this genotype causes mild to moderate liver disease and responds well to therapy. At the American Association for the Study of Liver Diseases (AASLD) conference this past October, two research teams reported genotype 4 SVRs of 61% (using Peg-Intron plus ribavirin) and 50% (using Pegasys plus ribavirin). Together, these results suggest that genotype 4 HCV may be easier to treat than previously believed.

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Long-Term Outcome in Individuals Infected with HCV at Birth

Most studies of HCV have not followed patients for more than about 25 years. In the January 2004 issue of Hepatology, Maria Antonietta Casiraghi and colleagues from Milan, Italy, reported on a study of a group of 35-year-old adults who were exposed to HCV through blood transfusions at birth. Among the 31 subjects, 18 (58%) had HCV antibodies and 16 (89%) had detectable HCV RNA; tests showed that all viremic subjects had the same strain of HCV as the infected blood donor. Among the 11 who underwent liver biopsy, nine had little or no fibrosis and two had advanced (stage 3 or 4) fibrosis. Five subjects received a second biopsy five years after the first; of these, four showed no fibrosis progression and one progressed from no fibrosis to mild fibrosis. Only two subjects received treatment, one of whom achieved a sustained virological response. The authors concluded, “[T]hese results suggest that HCV infection acquired early in life shows a slow progression and mild outcome during the first 35 years of infection.”

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MELD Scores and Liver Transplants

Three articles in the January 2004 issue of Liver Transplantation discuss changes in liver transplant outcomes since the United Network for Organ Sharing (UNOS) implemented a new system of donor liver allocation in early 2002. Under the new system, each liver transplant candidate receives a MELD (Model for End Stage Liver Disease) score based on three laboratory values: bilirubin, prothrombin time/INR (a blood clotting test), and creatinine (an indicator of kidney function). Patients with the highest scores are given priority to receive cadaver livers as they become available. The MELD system replaces an older method that took into account time spent on a waiting list; now, waiting time is only considered when patients have the same MELD score. Subjective factors (such as a doctor’s assessment of symptoms) are no longer considered, and the new system reduces the incentive for doctors to place patients on the list before they have severe liver disease.

Richard Freeman, MD, and colleagues — members of the UNOS/OPTN Liver and Intestine Transplantation Committee — reported results from the first year of the new allocation method. Since the MELD system was implemented on February 27, 2002, new liver transplant list registrations have fallen by 12%. The rate of death while on the list decreased by 3.5%, and the transplantation rate increased by 10.2%. The decrease in mortality and increase in transplantation were evenly distributed across all demographic groups. Although sicker individuals received more transplants, early patient and graft survival remained unchanged. “[T]he new system has been associated with reduced registrations and improved transplantation rates without increased mortality rates for individual groups of waiting candidates or changes in early transplant survival rates,” the authors concluded.

In the same issue, Pratima Sharma, MD, from the Mayo Clinic and colleagues reported on the impact of the MELD system on liver transplants due to hepatocellular carcinoma (HCC). A review of the UNOS database revealed that the transplantation rate for patients with HCC tripled after the implementation of the new system. Waiting time decreased from 2.28 years to about 0.69 years, with 87% of HCC patients receiving a new liver within three months. The 5-month survival rate of patients on the waiting list increased from about 90% to more than 95%. Since MELD was implemented, “[s]ignificantly higher proportions of candidates listed with the diagnosis of HCC are receiving a deceased donor liver transplant,” said Dr. Sharma. Paul H. Hayashi, MD, and colleagues from the University of Colorado Health Sciences Center reported that the proportion of patients at their center receiving a liver transplant due to HCC increased from 12% to 35%. But they concluded that “a small but significant portion” of cadaver livers went to patients misdiagnosed with HCC (that is, after transplantation, no cancer was found in the old liver)—organs that otherwise could have gone to patients with more serious liver disease related to other causes. Due to concerns that the new system might be giving people with HCC an unfair advantage at the expense of individuals with liver damage from other causes, UNOS slightly modified the MELD policy in January 2003; the effects of these changes are not yet known.

Finally, because the MELD system allocates available livers to the sickest patients first, there has been some concern that donated livers might be given to patients who are too ill to survive a transplant. In the January 15, 2004 issue of Transplantation, Niraj Desai, MD, of Washington University School of Medicine and colleagues reported that while the MELD score accurately predicts pre-transplant mortality, it is a poor predictor of post-transplant survival. The authors determined a set of four variables — age, use of mechanical ventilation, kidney dialysis, and need for re-transplantation — that they suggest might be used “to identify futile cases in which expected outcome is too poor to justify transplantation.”

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