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Liz Highleyman
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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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