Liver transplantation prognosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]

Liver trasnsplantation Microchapters
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Acute rejection
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Prognosis

Liver transplantation prognosis

Living-donor recipients have been noted to have a higher incidence of surgical complications post-transplant compared with whole-liver recipients.

Early data suggested that outcomes (graft survival) might be inferior to those in whole-liver transplants, especially if the patients were matched for severity of liver disease [39].

Partial grafts have smaller vessels, more complicated biliary reconstructions, and a cut surface, all of which make for a technically more challenging procedure and a higher incidence of surgical complications.

Maluf et al. and Fan et al. reported that despite smaller graft size and higher technical complexity, the graft and patient survival rates of patients with right-liverLDLTare not different from those of patients receiving whole-graft DDLT [40,41].

The only difference is a higher incidence of biliary complications in the LDLT patients (25.8 versus 7.1%) [40].

Most centers have reported a 15–46% incidence of biliary complications, including early bile leaks, after transplant, and a 15–20% incidence of late biliary strictures.

These figures are significantly higher than are generally reported for whole-liver recipients (9–15%) [40]. The possible factors associated with an increased risk of postoperative biliary complications include having multiple bile ducts to reconstruct and an inadequate arterial perfusion in patients with a high preoperative MELD score [42,43].

With advances in microsurgical techniques, the incidence of vascular complications such as hepatic artery thrombosis has decreased and is now not significantly different from that in deceased-liver transplants [44–47]. Certain subgroups of recipients may do worse after living-donor transplants. Critically ill adult recipients with advanced liver failure, high MELD scores, and numerous secondary complications have generally been reported to have worse outcomes with this procedure. Such recipients have minimal functional reserve and are probably ill equipped to manage the lower hepatocyte mass and the higher complication rate associated with partial transplants. However, in parts of the world where DDLTs are uncommon, living donors have been used for critically ill patients, with good results [40].

Recurrence

The disorders most commonly associated with recurrence include hepatitis B virus (HBV) and hepatitis C virus (HCV).

Recurrence of HBV after liver transplantation can be prevented by administering hepatitis B immune globulin at the time of transplantation and at regular intervals thereafter in combination with antivirals such as tenofovir or entecavir.

Hepatitis C virus

• Early treatment post-transplantation with interferon-based regimens has not been shown to improve patient and graft outcomes, and currently there is no established role for prophylactic or preemptive therapy following transplantation [2].
• No effective immunoglobulin prophylaxis exists for HCV.
• Combination therapy (peginterferon or standard interferon and ribavirin), monotherapy (peginterferon, standard interferon, or ribavirin), and anti-HCV immune globulin.
• Treatment was initiated within six weeks of the transplantation.
• Interferon-based treatment is no longer recommended in liver transplant recipients.
• Direct-acting antiviral agents 
• Studies are now emerging showing efficacy of direct-acting antiviral agents for the treatment of HCV recurrence following liver transplantation.
• Sofosbuvir
• Sofosbuvir is an NS5B nucleotide analog used for the treatment of HCV. [83].
• Treatment resulted in persistently undetectable HCV ribonucleic acid (RNA) 12 weeks after stopping treatment in 28 of 40 patients (70 percent). All of the cases of virologic failure were due to relapse. As a result, sofosbuvir is usually now given in combination with one of several additional direct-acting antivirals (ledipasvir, simeprevir, and daclatasvir), with or without ribavirin [83-90].

Non-alcoholic fatty liver

• Recurrence of NAFLD has been reported following liver transplantation [42-44]. In a series of 622 liver transplants, eight patients, all female, had features consistent with NASH pre-transplantation [44]. At a median follow-up of 15 months, six developed persistent fatty infiltration, three of whom had hepatic degeneration consistent with NASH. In two of the patients, the histologic progression from mild steatosis to steatohepatitis occurred within two years.

Carcinoma

• No large randomized trials have directly compared OLT with other forms of therapy for early HCC. Retrospective studies that included adjustment for disease severity suggest that survival following OLT is as good or better than after alternative treatments in carefully selected patients. For patients with anatomically resectable HCC and adequate hepatic reserve, resection remains the standard with which alternative treatment methods must be compared.
• Observational series suggest that long-term results after transplantation are at least as good and may be superior to those of resection in some groups [4,14-16]:
• An important caveat is that the results of transplantation cited above include only patients who actually received a transplant. Not included are patients with HCC who were listed for transplant but ultimately did not receive a liver transplant because their tumor progressed and exceeded transplant eligibility criteria before the transplant could be performed. Accordingly, intent-to-treat analyses of liver transplantation for HCC consistently demonstrate lower survival rates.
• Ultimately, despite the demonstrated benefit of transplantation, particularly in cirrhotic patients with small tumors, the group of patients with HCC who are candidates for OLT and who actually receive a graft is very small. Worldwide, the majority of patients with early stage HCC (often detected in the setting of formal surveillance programs) are treated in the Far East and Asian countries, where OLT is not a wide-spread option because of religious beliefs, lack of living-donor transplant programs, and its prohibitive cost. Without screening (ie, in most of the West), few patients who have cirrhosis and early stage HCC are identified as candidates for OLT.

Alcoholic liver disease

• Patient survival rates following liver transplantation for alcoholic liver disease are similar to rates following transplantation for non-alcohol related diagnoses [51-53]. In a study of 123 patients with alcoholic liver disease, one-, five-, and seven-year patient and graft survival rates were 84 and 81 percent (one year), 72 and 66 percent (five years), and 63 and 59 percent (seven years), respectively [51]. In comparison, five-year survival without liver transplantation is as low as 23 percent.

Primary biliary cirrhosis

• A precise estimate of the recurrence rate is uncertain since not all studies have used uniform criteria for defining recurrent PBC, and studies have had variable follow-up. [9,13-19].
• Two of the largest series with the longest follow-up (in which the diagnosis of recurrent PBC was based upon histologic features) probably represent the best available estimates [9,13].
• Methods to prevent recurrence may include immunosuppression using cyclosporine rather than tacrolimus and giving ursodeoxycholic acid (UDCA) following liver transplantation.

Primary sclerosing cholangitis

• Recurrent PSC following liver transplantation in 14 to 20 percent of patients [83,86-96].
• Only approximately one-third of patients with recurrence develop progressive disease leading to retransplantation or death.
• Risk factors for recurrence include age, sex mismatch, male sex, coexistent IBD, presence of an intact colon after transplantation, cytomegalovirus (CMV) infection, recurrent acute cellular rejection, steroid-resistant cellular rejection, use of OKT3.