Hepatitis C Patients Can Have Good Outcomes after Transplants Using HBV+/HCV+ Liver Grafts, but Donor Status May Affect HCV Recurrence

		SUMMARY: Hepatitis C patients who receive donor liver grafts infected with both hepatitis B virus (HBV) and hepatitis C virus (HCV) had similar survival rates as patients who received uninfected livers, although they were slightly more likely to require a second transplant, researchers reported at the 60th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2009) this month in Boston. Another transplant study found that patients who received livers from donors after cardiac death experienced more rapid and severe HCV recurrence than those who received grafts from brain-dead donors, though survival rates were similar.

By Liz Highleyman

Due to a severe shortage of donor livers, researchers have investigated transplants using suboptimal or marginal -- known as "extended criteria donor" -- organs, including giving patients who already have hepatitis B or C livers that are infected with these viruses.

P. Sreenivasan and colleagues from the University of Tennessee/Methodist University Transplant Institute compared patients and graft (donor liver) survival among 158 hepatitis C patients who received combined hepatitis B core antibody (HBc) positive and HCV antibody positive liver grafts.

Data were obtained from the Scientific Registry of Transplant Recipients database of all patients who received liver transplants in the U.S. between 2000 and 2006.

Control groups were 473 hepatitis C patients who received only HCV antibody positive (i.e., HBc negative) grafts and 11,838 who received grafts not infected with either virus. Recipient and donor ages were similar across all 3 groups; 20%-25% were women.

Results

	Recipient mortality due to graft failure was similar in the 3 groups.
	The mortality rate due to graft failure was 4.4% for recipients of dually infected livers, compared with 3.6% for recipients of only HCV-infected livers and 5.2% for recipients of uninfected grafts (a non-significant difference).
	Mortality rates due to all causes were 28.0%, 28.8%, and 28.5%, respectively.
	Average survival in the 3 groups was 1001, 1033, and 1143 days, respectively (also non-significant).
	The number of re-transplantations was not statistically different, but there was a non-significant trend towards a higher number of re-transplantations among patients who received dually infected livers.
	Re-transplantation rates were 10.8% for recipients of dually infected livers, 5.3% for recipients of only HCV-infected livers, and 6.8% for recipients of uninfected grafts.

Based on these findings, the investigators concluded, "Our study shows that the use of combined HB core antibody positive/HCV antibody positive liver allograft does not adversely affect the graft or patient survival."

Cardiac vs Brain Death

In another transplant study, Canadian researchers analyzed outcomes among hepatitis C patients who received liver allografts via donation after brain death (DBD) versus donation after cardiac death (DCD).

In prior studies, inferior long-term results have been reported among HCV positive patients when using marginal donor or DCD livers. In DCD cases, the donor liver may be deprived of blood, whereas in DBD cases the heart is kept beating artificially.

The investigators performed a retrospective cohort review of all 42 HCV positive liver transplant recipients of DBD (33 patients) and DCD (9 patients) allografts at the London Health Sciences Centre in Ontario between 2006 and 2009.

Recipient age and MELD scores, and donor age (about 49 years) and body mass index were similar in the DBD and DCD groups. All patients received similar triple combination immunosuppressive regimens of tacrolimus, mycophenolate mofetil, and tapering doses of prednisone to prevent organ rejection.

Recurrent HCV was defined as biochemical graft dysfunction (e.g., ALT elevation) with histological findings indicating HCV infection and at least stage 1 fibrosis and grade 1 inflammation. Severe HCV recurrence was defined as at least stage 2 fibrosis within the first year after transplantation.

Results

	Mean cold ischemia time (time without oxygen) was significantly longer in the DBD group than in the DCD group (385 vs 272 minutes; P = 0.07).
	67% of patients in the DCD group and 64% in the DBD group experienced histologically documented recurrent HCV.
	33% in the DCD group experienced severe HCV recurrence, compared with 6% in the DBD group.
	All cases of HCV recurrence in the DCD group occurred within 3 month of transplantation, compared with 6% in the DBD group.
	No DCD liver recipients, but 21% of DBD recipients, experienced cellular graft rejection.
	In the DCD group (mean follow-up duration of 14 months), 1 liver graft was lost due to recipient death from fibrosing cholestatic hepatitis C, occurring 3 months after transplantation.
	In the DBD group (mean follow-up duration of 22 months), 3 grafts were lost, but only 1 loss was due to HCV recurrence.

"HCV recurrence is documented earlier and is more aggressive in DCD recipients," the researchers concluded. "However, patient and graft survival was not adversely affected by the severity of HCV recurrence."

11/20/09

References

P Sreenivasan, JM Vanatta, JD Eason, and S Nair. Use of Combined HCV and Hepatitis B core Antibody positive Liver Grafts in HCV recipients. Impact on Graft and Patient Survival. 60th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2009). Boston. October 30-November 1, 2009. Abstract 615.

FA Abaalkhail, M Mawardi, K Katada, and others. Severity of HCV Recurrence in Transplant Recipients of donation after brain death (DBD) vs donation after cardiac death (DCD) allografts. 60th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2009). Boston. October 30-November 1, 2009. Abstract 508.