Revisiting chronic rejection following living donor liver transplantation in the tacrolimus era: A single center experience.

BACKGROUND AND AIMS: Chronic rejection (CR) is an uncommon but important cause of graft dysfunction, leading to graft loss and often requires retransplantation. This study evaluates the incidence and outcome of the patients with CR at a large living donor liver transplant (LDLT) center. METHODS: Data of patients with CR were retrospectively analyzed in 1232 adult (age >18 years) LDLT on tacrolimus (mainly)-based immunosuppression. Sirolimus/everolimus (mammalian target of rapamycin [mTOR] inhibitors) was added to baseline immunosuppression as rescue therapy in patients with CR. Data are shown as median (interquartile range [IQR]). RESULTS: Twenty-three patients (22 males), aged 42 (IQR 45-56) years, had biopsy-proven chronic rejection at 21 (8-44) months after liver transplantation. The incidence of chronic rejection was 1.9% in this cohort. The patients with CR (n = 23) had a significantly higher incidence of cytomegalovirus (CMV) viremia, acute cellular rejection, and history of anastomotic biliary strictures as compared to patients without CR. Five patients were noncompliant with immunosuppression before the diagnosis of CR. Twelve patients (52%) responded to addition of mTOR inhibitors, whereas 11 did not respond and had poor outcome. CONCLUSION: The incidence of chronic rejection is low in LDLT. Treatment with mTOR inhibitors can reverse graft dysfunction in approximately half of the patients.

Poor Outcomes after Recidivism in Living Donor Liver Transplantation for Alcohol-Related Liver Disease.

BACKGROUND: Recidivism in patients who underwent liver transplantation for alcohol-related liver disease (ALD) is shown to be associated with poor survival in some studies. METHODS: Living donor liver transplantation (LDLT) recipients for ALD with at least 2 years of follow-up and history of significant alcohol relapse were included. The recipients underwent LDLT from June 2010 to December 2016, and data were analyzed until June 2019. The cohort had a median follow-up of 54 (33-78 IQR) months. Recidivism (significant alcohol intake) was defined as >21 units per week. RESULTS: A total of 27 of 463 (5.8%) LDLT recipients (all men), aged 43.5 ± 9.6 years, had significant alcohol intake. A liver biopsy was performed on demand in 14 patients (in the presence of raised levels of liver enzymes or jaundice). The histological diagnoses in these patients were as follows: alcoholic hepatitis in 7 (50%), alcoholic hepatitis and acute cellular rejection or chronic rejection in 4 (28.5%), cirrhosis in 2 (14.2%), and acute cellular rejection and cirrhosis in 1 (7.1%) patient. Four of 5 patients with a biopsy diagnosis of acute or chronic rejection were noncompliant with immunosuppression. Six of these patients died. The mortality after 1 year of transplant was significantly more in patients with recidivism. CONCLUSION: Recidivism was associated with significant morbidity and mortality after liver transplantation.

Good Long-Term Outcomes in Patients With Primary Sclerosing Cholangitis Undergoing Living Donor Liver Transplantation.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a progressive cholestatic disorder with liver transplantation (LT) being the only definitive treatment in end-stage disease. Recurrence of PSC after LT is a significant concern which can lead to graft loss. The aim of this study is to find out the disease recurrence and long-term outcome after living donor liver transplantation (LDLT) in PSC. METHODS: We conducted a retrospective review of all patients undergoing LDLT for PSC at our centre. Of 2268 adult LTs from August 2004 to July 2018, 32 (1.4%) patients underwent LDLT for PSC including 6 with PSC and autoimmune hepatitis overlap. The data were reviewed to look for PSC recurrence, complications, and overall survival. All patients received tacrolimus-based immunosuppression. Data are shown as number, percentage, median, and interquartile range (IQR). RESULT: The mean age of 32 LDLT recipients was 44 ± 12 years (males 22, females 10). At the time of transplantation, the mean child's score was 9 ± 1.6 and model for end-stage liver disease score was 18.9 ± 6.4. Ulcerative colitis was seen in 7 patients and none had cholangiocarcinoma. Majority of patients (n = 29) received right lobe graft and all but 3 underwent hepaticojejunostomy for biliary reconstruction. PSC recurrence was seen in 6 (20%) patients during a median follow-up of 59 (29-101) months, after exclusion of 2 patients with early mortality. A total of five patients died during follow-up, and one of these deaths was due to PSC recurrence. There were 2 perioperative deaths due to sepsis and 3 deaths on follow-up (sepsis in 2 and PSC recurrence in 1). CONCLUSION: LDLT can be performed in PSC with good overall long-term outcomes.

De Novo Malignancy After Living Donor Liver Transplantation: A Large Volume Experience.

BACKGROUND AND AIMS: Liver transplantation (LT) recipients such as all organ transplant recipients, have a risk of developing de novo malignancies owing to prolonged immunosuppression. However, there is limited data on this after living donor liver transplantation (LDLT), wherein immunosuppression levels are less than in deceased donor transplantation. We aim to describe experience of de novo malignancies from a predominantly LDLT center. MATERIALS AND METHODS: A total of 2100 adults (age >18 years) who underwent LT between January 2006 and December 2017 were retrospectively analyzed from a prospectively collected database. The data were analyzed up to June 2019. Data are shown as number, percentage, mean ± standard deviation, and median (interquartile range). RESULTS: Of 2100 patients who underwent LDLT, 21 (1%) patients developed de novo malignancy after transplantation. The de novo malignancy cohort comprised 20 males and 1 female, aged 50 ± 8.8 years. The distribution of de novo malignancies was as follows: 7 oropharyngeal (carcinoma of buccal and oral mucosa), 4 lung, 2 squamous cell carcinoma of skin, 2 lymphoma, 1 each of brain, colonic, gastric; ovary, pancreatic, and prostate. These malignancies were diagnosed at a median follow-up of 42 months (32-73) after LT. Over a median follow-up of 38 months (10-56) after the diagnosis of de novo malignancy, 6 patients (28.5%) died. Patients with de novo malignancy had a higher follow-up after LDLT, 94.3 ± 32.9 versus 62.5 ± 41.8 months, P = 0.000. Patients with alcohol as etiology for LT had higher trend of de novo malignancies (33.3% versus 26.4%), P = 0.46. CONCLUSION: The incidence of de novo malignancy was 1% at a median follow-up of 42 (32-73) months. De novo malignancies following LDLT, although uncommon, are associated with significant mortality. A careful screening protocol should be followed after transplantation for early detection of de novo malignancies.

Safe Use of Right Lobe Live Donor Livers With up to 20% Macrovesicular Steatosis Without Compromising Donor Safety and Recipient Outcome.

BACKGROUND: The principle in right lobe living donor liver transplantation is to use "near-perfect" grafts to maximize recipient benefit with minimal donor risk. Whether and what degree of graft macrovesicular steatosis is safe for both recipient and donor is debatable. METHODS: We compared donor and recipient outcomes in 623 primary right lobe living donor liver transplantations, using grafts with (Group A; 10%-20% steatosis, n = 92) and without (Group B; <10%, n = 531) significant macrovesicular steatosis, on pre- or intraoperative biopsy. RESULTS: Group A donors had higher body mass index, transaminases, fasting blood sugar, triglyceride, low density lipoprotein level, and lower high density lipoprotein, and liver attenuation index on CT scan, and similar future liver remnant. Mean postoperative day (POD) 7, aspartate aminotransferase (61.13 + 24.77 vs 73.17 + 53.71 IU/L; P = 0.04), and prothrombin time-international normalized ratio (1.16 + 0.36 vs 1.28 + 0.24; P = 0.0001) were lower in Group A donors. POD3 of 7 total bilirubin and alanine aminotransferase; POD3 aspartate aminotransferase and prothrombin time-international normalized ratio; postoperative morbidity (Dindo-Clavien >3b), hospital stay were similar in both groups. Recipients in both groups had similar age, model for end-stage liver disease score. Right lobe graft weight (764.8 + 145.46 vs 703.24 + 125.53 grams; P < 0.0001) and GRWR (1.09 + 0.29 vs 1.00 + 0.21; P = 0.0004) were higher in Group A. All biochemical parameters at POD 3 of 7, as well as hospital stay, 30-day mortality were similar in recipients of both groups, even after matching both groups for age, model for end-stage liver disease, and GRWR. CONCLUSIONS: Use of well-selected right lobe grafts (adequate future liver remnant in donor, GRWR in recipient), with up to 20% macrovesicular steatosis, does not compromise graft function and outcomes and is safe for the donor.