Increased risk of cholestatic hepatitis C in recipients of grafts from living versus cadaveric liver donors

Abstract

Histologic injury caused by recurrent hepatitis C virus (HCV) has been reported in up to 90% of HCV-infected patients who undergo liver transplantation with a cadaveric graft. However, the natural history of HCV after living donor liver transplantation (LDLT) is not well described. We performed a retrospective analysis of 68 consecutive HCV-infected adult patients: 45 recipients of cadaveric grafts (CAD) were compared with 23 LDLT patients. Elevated serum transaminases, positive HCV RNA, and liver biopsy consistent with histologic evidence of HCV defined recurrence. When comparing CAD with LDLT, both the incidence of HCV recurrence and time to recurrence were not different. The overall incidence of severe sequelae of HCV recurrence, either cholestatic hepatitis, grade III-IV inflammation, and/or HCV-induced graft failure requiring retransplantation, was also not different when comparing CAD with LDLT. However, when comparing CAD versus LDLT, no CAD patient developed cholestatic hepatitis C, compared with 17% of LDLT who developed this complication (P ‫؍‬ .001). Thus, in this patient population, the timing and incidence of HCV recurrence were not different when comparing CAD versus LDLT, but the incidence of cholestatic hepatitis was significantly greater in patients with HCV who underwent LDLT. (Liver Transpl 2003;9:1028-1035.) E nd stage liver disease caused by hepatitis C virus (HCV) is the most common indication for liver transplantation in the United States. However, complications caused by recurrent HCV infection are increasingly being recognized; in patients with active HCV replication before transplantation, reacquisition of viremia after transplantation is universal, and allograft hepatitis caused by HCV occurs in up to 90% of patients followed for 5 years. 1-9 Although histologic injury in the allograft caused by HCV is exceedingly common, disease progression after the development of hepatitis is variable, with some patients experiencing indolent disease and others rapidly progressing to cirrhosis and liver failure. In patents who develop HCV-associated cirrhosis posttransplantation, rapid decompensation is a common occurrence. It has been reported that up to 42% of patients with HCV-associated cirrhosis posttransplantation develop decompensation manifested as ascites, encephalopathy, or hepatic hydrothorax, and fewer than 50% of patients survive more than 1 year after the development of decompensation. 10-12 Thus, both prospective and retrospective data are emerging that indicate that the progression of HCV after orthotopic liver transplantation is accelerated when compared with nontransplantation patients. This has been attributed to multiple factors, including the impact of immunosuppression on viral replication and host defenses. 13 Several lines of anecdotal evidence suggest that HCV recurrence might be more severe in recipients of living donor liver transplantation (LDLT). We hypothesize that postoperative liver regeneration in the partial graft procured from living donors may facilitate HCV repli...

Accelerated hepatitis C virus kinetics but similar survival rates in recipients of liver grafts from living versus deceased donors†‡

“…In theory, at least 4 mechanisms might contribute to these higher levels: (1) Cellular proliferation is enhanced, creating a cell population in which the HCV replication rate is higher, as previously discussed 11,23,24 ; (2) The HCV-susceptible cells in LD grafts are in a superior functional state, and this leads to enhanced HCV replication; (3) The LD grafts receive a larger inoculum of virus because of more efficient uptake, coupled with less loss during surgery, and thus they have more foci of viral production; and (4) The smaller size of LD grafts compromises their ability to metabolize drugs, resulting in excessive immunosuppression and reduced antiviral defenses. In all likelihood, several mechanisms, including some not listed above, act in concert.…”

“…4,8 Studies of biopsy specimens have yielded conflicting results regarding the severity of recurrent hepatitis and the rate of progressive graft injury. 7,10,11 HCV may interact differently with LD grafts than with DD grafts, and this difference may lead to greater LD graft injury. Exceptionally high HCV RNA levels in the early postoperative period are associated with greater long-term liver damage in DDLT patients, 18,19 and a similar association may exist in LDLT patients.…”

“…1 Several studies have compared outcomes of LD liver transplantation (LDLT) and DDLT in HCV patients. [2][3][4][5][6][7][8][9][10][11] Results have been inconsistent, in part, because of differences in experimental design and small sample sizes. [12][13][14][15][16][17] Concerning survival, no short-term difference was observed in a study of 65 DD versus 35 LD patients, 6 and analysis of the United Network for Organ Sharing liver transplant database showed that the 2-year survival of 279 LD and 3,955 DD recipients was virtually identical.…”

Living donor liver transplantation in patients with hepatitis C

“…6 A greater percentage of living donor liver transplant recipients (80%) developed recurrent HCV compared with cadaveric transplant recipients (58%; P Ͻ .05). Severe recurrent HCV infection (fibrosing cholestatic hepatitis, Ն grade 3 inflammation, or retransplantation) occurred in 17% of LDLT patients compared with 12% of cadaveric transplantation patients.…”

Role of adult living donor liver transplantation in patients with hepatitis C

“…[5][6][7] Data regarding long-term patient and graft survival in HCV-infected living donor liver transplant recipients currently are lacking. The purpose of this report is to review outcomes of LDLT in HCV-infected transplant recipients, define risk factors for severe recurrence, and recommend selection criteria for LDLT in HCV-infected recipients.…”