Living Donor Liver Transplant in High-Risk Patients Is Effective
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Living-donor liver transplantation is more effective for overcoming the consequences of organ shortage when performed in patients at high risk of death on the waiting list, reports the latest Liver Transplantation issue.

Living donors represent a recognized alternative for facilitating the access to transplantation in a period of organ shortage. However, which candidates should be preferentially considered for living-donor liver transplantation is debated. Dr François Durand and colleagues from France determined which strategies of selection for living-donor liver transplantation provide the most efficient contribution. The investigative team created statistical models assess the strategies. The team included 331 patients listed for deceased-donor transplantation and 128 transplanted with living donors.

3-year survival was 70% in those at highest risk of death vs 64% with the lowest risk – Liver Transplantation

Statistical models predicting the events following listing were created and combined in a multistate model to compare the results. This allowed the testing of different strategies of selection for living-donor liver transplantation. The investigators took 3-year survival after listing as the principal end-point. The team found that selecting the 20% patients at highest risk of death on the waiting list gave 3-year survival results in 70%. Selecting the 20% patients at lowest risk of death after living-donor liver transplantation lead to 3-year survival rates in 64%. These strategies resulted in waiting list mortality rates of 17% and 8%, respectively. The team noted that 1-year survival after living-donor liver transplantation was lower in high-risk patients at 85% than in low-risk patients at 91%. However, the 1-year survival benefit derived from living-donor liver transplantation was 75% in high-risk patients.The investigators observed that the 1-year survival was nil in low-risk patients. Dr Durand's team concludes, “Living-donor liver transplantation is more effective for overcoming the consequences of organ shortage when performed in patients at high risk of death on the waiting list.” “On an individual basis, the sickest patients are those who derive the most important benefit from living-donor liver transplantation.” “This study provides incentives for considering living-donor liver transplantation in high-risk patients.”

Liv Transplant 2006: 12(2): 231-9

Hepatitis C Recurs Rapidly after Liver Transplant

When a diseased liver is removed from a patient with hepatitis C, serum HCV levels (HCV RNA) decline quickly and significantly. However, after receiving a healthy liver transplant, HCV levels rebound and can surpass pre-transplant levels within a few days, according to a new study published in the February 2006 issue of Liver Transplantation. The journal is available online via Wiley InterScience.

Hepatitis C is the number one reason for liver transplantation in the . Unfortunately, the virus always recurs in the new liver. Since mathematical models have been useful in the study of the viral dynamics of HIV and hepatitis B, researchers, led by Kimberly A. Powers and Ruy M. Ribeiro of the Los Alamos National Laboratory in , sought to use a mathematical model to quantify the liver reinfection dynamics of HCV.

The researchers, in collaboration with a surgical team lead by John McHutchison now at , followed six HCV-infected patients who received cadaveric liver transplants. They collected blood samples before, during and after transplantation to assess changing levels of HCV RNA that was measured using reverse transcription polymerase chain reaction assay. They then plugged the data into a mathematical model, correcting for fluid balance, and analyzed the results using linear regression.

“In most patients,” the authors report, “HCV RNA levels decreased rapidly during and after transplantation and subsequently began to increase – reaching above pre-transplant levels in all but one patient – within a few days of the procedure.” They found that when the diseased liver was removed, virus levels dropped with an average half-life of 48 minutes. After the new liver was implanted, they found that virus levels continued to drop for up to 23 hours, then began to rise, doubling every 2 days.

Notably, in three patients, the virus levels plateaued before rising, suggesting, say the authors “that a non-hepatic source supplied virions and balanced their intrinsic clearance.” The authors estimate, however, that non-hepatic sources can only account for 4 percent of total viral production. Ninety-six percent of it occurs in the liver.

The patterns of viremia decline and increase seen in this study are consistent with previous studies, although this study indicates a much faster virion half-life than previously suggested. The findings also support the notion that HCV can replicate rapidly in the post-transplant immunosuppressed patient, leading the authors to suggest that early anti-HCV therapy may delay or prevent reinfection.  

The study was limited by the small number of patients and the single compartment model, which did not separately account for liver and extrahepatic sites of viral replication. “Nevertheless,” report the authors, “the rapid HCV RNA decline in the anhepatic phase, followed by the postoperative increase observed in several patients…suggest that the liver is the primary site of viral replication, with at most small contributions from extrahepatic sites.”

In conclusion, the authors write, “Continued work towards elucidating extrahepatic replication, the time-course of reinfection, the effects of immunosuppressive therapy, and the relationships among viremia, infection and liver damage will be beneficial in optimizing treatment for HCV patients undergoing liver transplantation.”

02/03/06

Reference
K A Powers and others. Kinetics of Hepatitis C Virus Reinfection after Liver Transplantation. Liver Transplantation 12(2): 207-216. February 2006.

 http://www.hivandhepatitis.com/hep_c/news/2006/020306_b.html

Abstract:
Background. Whether hepatitis C virus recurrence occurs earlier and with greater severity for living donor liver transplantation (LDLT) than for deceased donor liver transplantation (DDLT) has recently become a subject of debate.

Methods. We retrospectively evaluated clinical outcomes for a cohort of 91 HCV-positive patients who underwent LDLT at Kyoto University with a median follow-up period of 25 months.

Results. Overall 5-year patient survival for HCV patients was similar to that for non-HCV patients (n=209) who underwent right-lobe LDLT at our institute (69% vs. 71%). Survival rate of patients without HCC (n=34) tended to be better than that of patients with HCC (n=57) (82% vs. 60%, P=0.069). According to annual liver biopsy, rate of fibrosis progression to stage 2 or more (representing significant fibrosis) was 39% at 2 years after LDLT. Univariate analysis showed that female recipient and male donor represented significant risk factors for significant fibrosis. Progression to severe recurrence (defined as the presence of liver cirrhosis (F4) in a liver biopsy and/or the development of clinical decompensation) was observed in five patients.

Conclusions. Postoperative patient survival was similar for HCV-positive and -negative recipients in our adult LDLT series. Rates of progression to severe disease due to HCV recurrence seemed comparable between our LDLT recipients and DDLT recipients described in the literature. Although longer-term follow-up is required, our results suggest that LDLT can produce acceptable outcomes also for patients suffering from HCV-related cirrhosis.

(C) 2006 Lippincott Williams & Wilkins, Inc.

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