Dual Graft Living Donor Liver Transplantation for High Acuity Patients: A Single-Center Experience.

Background: The outcomes of dual graft living donor liver transplantation (DGLDLT) in high acuity patients remain underreported. The objective of this study was to report long-term outcomes from a single center in this select group of patients. Methods: This was a retrospective review of patients who underwent DGLDLT between 2012 and 2017 (n = 10). High acuity patients were defined as patients with model for end stage liver disease (MELD) ≥30 or Child Pugh score ≥11. We looked at 90-day morbidity and mortality and 5-year overall survival (OS). Results: The median MELD score and Child Pugh score were 30 (26.7-35) and 11 (11-11.2). The median recipient weight was 105 (95.2-113.7) and ranged from 82 to 132 kg. Out of 10 patients, 4 (40%) required perioperative renal replacement therapy, and 8 (80%) required hospital admission for optimization. The estimated graft to recipient weight ratio (GRWR) with right lobe graft alone was <0.8 in all patients, between 0.75 and 0.65 in 5 (50%) patients, and <0.65 in 5 (50%) patients. The 90-day mortality was 3/10 (30%), and there were 3/10 (30%) deaths during long-term follow-up. Among 155 high acuity patients, the 1-year OS with standard LDLT, standard LDLT with GRWR <0.8, and DGLDLT was 82%, 76%, and 58%, respectively (P = 0.123). With a median follow-up of 40.6 (1.9-74.4) months, the 5-year OS for DGLDLT was 50%. Conclusion: The use of DGLDLT in high acuity patients should be prudent and low GRWR grafts should be considered a viable alternative in selected patients.

Clinical Profile and Treatment of Hepatocellular Carcinoma: A Single-Center Experience.

Background Very few centers in Pakistan have all established treatments for hepatocellular carcinoma (HCC) available under one roof. With a dedicated hepato-pancreato-biliary surgery and liver transplant unit, we have gathered one of the largest data on HCC in our population. Aims The objective of the current study was to assess the clinical spectrum of HCC in Pakistani patients. Settings and Design This retrospective review of patients diagnosed with HCC was conducted between 2011 and 2016. Materials and Methods Patients were allocated to treatment groups based on the Barcelona clinic liver cancer (BCLC) staging algorithm and our local guidelines. The treatment options were grouped as curative (radiofrequency ablation [RFA], percutaneous ethanol injection [PEI], liver resection, and liver transplantation), palliative (transarterial chemoembolization [TACE]/sorafenib), and the best supportive care (BSC). Statistical Analysis Kaplan-Meier curves were used for the statistical analysis. Results The mean age was 57.9 ± 10.1 years (range: 18-90 years). The male-to-female ratio was (1,099/391) 2.8:1. Hepatitis B and hepatitis C were the most common underlying etiological factor in 1,350 of 1,490 (90.6%) patients. Macrovascular invasion (MVI) was seen in 492 of 1,490 (33%) patients. Out of the total, 191 (12.8%) additional patients were offered potentially curative treatments when compared with BCLC recommendations. The actuarial 5-year overall survival for patients who underwent liver transplant, RFA/PEI, TACE, sorafenib, and BSC was 87, 64, 18, 5, and 0%, respectively. Alpha fetoprotein cut-off of 400 ng/mL had a significant impact on survival irrespective of treatment received (41 vs. 11%, p < 0.0001). Conclusion MVI is the most frequent poor prognostic marker in our patients with HCC. Local treatment guidelines are effective in yielding comparable outcomes to BCLC.

Recipient Outcomes with Younger Donors Undergoing Living Donor Liver Transplantation.

Introduction The impact of donor age on liver transplantation is well known. Data on an appropriate donor age cut-off for living donor liver transplantation (LDLT) with a background of hepatitis C (HCV) is generally limited. The objective of this study was to determine whether limiting donor age to less than 35 years improved outcomes in patients with HCV-related end-stage liver disease (ESLD). Methods This was a retrospective review of 169 patients who underwent LDLT for HCV-related ESLD. The patients were divided into two groups based on whether they received grafts from donors ≤ 35 (Group 1) or > 35 (Group 2) years of age. Kaplan Meier curves were used to determine survival. Uni and multivariate analysis were performed to determine independent predictors of mortality. Results Mean donor age was 25.1 ± 5.2 and 40.1 ± 3.4 years (P < 0.0001). Early allograft dysfunction (EAD) was seen in 11.7% patients in Group 1 versus 29.6% in Group 2 (P = 0.02). A significant difference in mortality was present between the two groups, i.e., 33.3% versus 15.8% (P = 0.04). The estimated four-year overall survival (OS) was 78% and 64% (P = 0.03). Upon doing univariate analysis, the donor age (P = 0.04) and EAD (P = 0.006) were found to be significant variables for mortality. On multivariate analysis, EAD was the only independent predictor of mortality (Hazard ratio: 2.6; confidence interval: 1.1 - 5.8; P = 0.01). Conclusion Opting for younger donors (≤ 35 years) for HCV-related ESLD patients lowers the risk of EAD and improves overall survival.

Living Donor Liver Transplantation for Hepatocellular Carcinoma: A Single-Center Experience from Pakistan.

BACKGROUND: Living donor liver transplantation (LDLT) is an established treatment for patients with cirrhosis and hepatocellular carcinoma (HCC) within Milan criteria. Acceptable outcomes have been demonstrated in patients fulfilling extended criteria. Here, we share our experience with LDLT for patients with HCC within and beyond Milan criteria, with emphasis on poor prognostic factors. METHODS: We retrospectively reviewed patients who underwent LDLT between 2012 and 2017 and had HCC proven on explant liver histopathology. A total of 117 patients were included. Patients who died early after transplant (in <30 days) were excluded. For outcomes, patients were divided into prognostic groups. These groups were based on (1) alpha fetoprotein >600, (2) poor differentiation, and (3) the presence of lymphovascular invasion. Recurrence-free survival (RFS) was determined using Kaplan-Meier curves. RESULTS: Median age was 53 (30-73) years. Median follow-up was 20.3 (1-63.2) months. Median model for end stage liver disease (MELD) score was 19 (9-34). Of a total of 117 patients, 74 (63.2%) patients met Milan criteria. Recurrence rate was 12/117 (10.3%). Actuarial 5-year RFS was 88% and 82% (P = 0.3) in patients within and outside Milan criteria. There was no difference in 3-year RFS in patients with 0, 1, or 2 poor prognostic factors within Milan criteria (92%, 87%, and 75%, respectively; P = 0.3). However, a significant difference in RFS was seen in patients outside Milan criteria (92%, 93%, and 53%; P = 0.03). CONCLUSIONS: Patients within Milan criteria have acceptable RFS even in the presence of poor prognostic factors. However, the presence of two or more poor prognostic variables significantly impacts RFS of patients outside Milan criteria.

Living Donor Liver Transplantation for Acute on Chronic Liver Failure Based on EASL-CLIF Diagnostic Criteria.

BACKGROUND: The European association for the study of the liver and chronic liver failure consortium (EASL-CLIF) recently proposed diagnostic criteria for acute on chronic liver failure (ACLF). There is lack of data regarding liver transplant outcomes in ACLF patients based on these criteria. The objective of this study was to determine outcome following living donor liver transplantation (LDLT) in ACLF patients. METHODS: We retrospectively reviewed patients who underwent LDLT for ACLF based on European association for the study of the liver and chronic liver failure consortium (EASL-CLIF) diagnostic criteria (group 1) (N = 60) and compared them with ACLF patients who did not undergo transplantation (group 2) (N = 59). The primary outcome of interest was 30 day mortality. We also looked at one year survival in these patients. Survival was calculated using Kaplan-Meier curves and Log rank test was used to determine significance between variables. RESULTS: Median MELD scores for group 1 and 2 patients in ACLF grade 1 was 28 (20-38) and 31 (24-36), in ACLF grade 2 was 35 (24-42) and 36 (24-42) and in ACLF grade 3 was 36 (29-42) and 38 (32-52). For group 1 and 2, 30 day mortality in ACLF grade 1, 2 and 3 was 2/43(4.6%) versus 9/15(60%) (P < 0.001), 1/15 (6.6%) versus 13/19 (68.4%), 0/2 (0%) versus 20/25 (80%) (P < 0.001). Actuarial 1 year overall survival was 92% versus 11% (P < 0.001) in patients who underwent transplantation versus those who did not. One year survival in patients with grade 1 and 2 ACLF who received transplant versus medical treatment was 91% versus 13% and 93% versus 15% (P < 0.001) respectively. CONCLUSION: LDLT has excellent outcomes in patients with EASL-CLIF grade 1 and 2 ACLF. Without transplantation, ACLF patients have a very poor prognosis.

Living Donor Liver Transplantation in South Asia: Single Center Experience on Intermediate-Term Outcomes.

BACKGROUND: There is paucity of data on intermediate-term post liver transplant outcomes from South Asia. The objective of this study was to determine survival outcomes in patients who underwent living donor liver transplantation (LDLT) in a busy liver transplant center in Pakistan. METHODS: This study was a review of patients who underwent LDLT between 2012 and 2016. A total of 321 patients were included in this study. Early (within 90 days) and late (>90 days) morbidity and mortality was assessed. Estimated 1- and 4-year survival was determined. RESULTS: Median age was 48 (18-73) years. Male to female ratio was 4.5:1. Out of total 346 complications, 184 (57.3%) patients developed 276 (79.7%) complications in early post-transplant period, whereas there were 70 (21.3%) late complications. Most common early complication was pleural effusion in 46 (16.6%) patients. Biliary complications were the most common late complication and were seen in 31/70 (44.2%) patients. Overall 21.4% patients had a biliary complication. The 3-month mortality was 14%. The estimated 1- and 4-year OS for a MELD cutoff of 30 was 84.5 versus 72 and 80 versus 57% (P = 0.01). There was no donor mortality. CONCLUSION: Acceptable intermediate-term post-transplant outcomes were achieved with LDLT. There is a need to improve outcomes in high-MELD patients.

Outcome of liver transplantation for haemophilia.

BACKGROUND: Prior to routine screening of blood products many patients with haemophilia were infected with hepatitis C virus (HCV) and have subsequently gone on to develop end-stage liver disease (ESLD). PATIENTS AND METHODS: We report our experience of liver transplantation (LT) in patients with haemophilia that developed ESLD secondary to HCV. Patients transplanted from 1994 to 2008 were identified retrospectively. Patient demographics pre-, intra- and post-operative details and outcome were documented. RESULTS: A total of 3800 LT were performed of which 13 had haemophilia A, 4 haemophilia B and one factor (F)X deficiency. All patients were male with a median age of 52 years (range 26-59), all were HCV antibody positive, 5 (28%) were human immunodeficiency virus (HIV) positive and 4 (22%) had hepatocellular carcinoma. Median intra-operative blood loss was 4.2 l (range 0.8-12) and all received coagulation factor support peri-operatively. Coagulation was unsupported by 72 h post-operatively in all recipients. Two patients developed complications as a result of post-operative bleeding. At a median follow-up of 90 months, 8 patients have died, including 4 of the 5 patients that were HIV positive. The median survival of patients with and without HIV co-infection was 26 and 118 months, respectively. CONCLUSION: LT in patients with haemophilia cures the coagulation disorder and in the absence of HIV/HCV co-infection is associated with long-term patient survival.

Liver transplantation for acute intermittent porphyria: a viable treatment?

BACKGROUND: Acute intermittent porphyria (AIP) is the most common hepatic porphyria. Its clinical presentation includes severe disabling and life-threatening neurovisceral symptoms and acute psychiatric symptoms. These symptoms result from the overproduction and accumulation of porphyrin precursors, 5-aminoleuvulinic acid (ALA) and porphobilinogen (PBG). The effect of medical treatment is transient and is not effective once irreversible neurological damage has occurred. Liver transplantation (LT) replaces hepatic enzymes and can restore normal excretion of ALA and PBG and prevent acute attacks. METHOD: Two cases of LT for AIP were identified retrospectively from a prospectively maintained LT database. RESULT: LT was successful with resolution of AIP in two patients who suffered from repeated acute attacks. CONCLUSION: LT can correct the underlying metabolic abnormality in AIP and improves quality of life significantly.

Outcome of liver transplantation in hereditary hemochromatosis.

Hereditary hemochromatosis (HH) is a genetic disorder of iron metabolism. It is an uncommon indication for liver transplantation (LT). It has been suggested that patients who undergo LT for cirrhosis related to HH have higher morbidity and mortality from cardiac, infectious and malignant complications. The purpose of this retrospective review was to determine whether these observations hold true in the current era. We analysed the data of 22 patients who had LT for HH from 1996 to 2007 at our center. Thirteen patients had LT for complications of end-stage liver disease, seven for hepatocellular carcinoma (HCC) and two for subacute liver failure. Cofactors promoting liver disease were identified in 15 patients. Ten patients had iron reduction with venesection before transplantation. Patient and graft survival at 1 and 5 years were 80.7%, and 74% respectively. There were seven deaths after a median follow up of 46 months either because of multiorgan failure, or caused by HCC recurrence. Bacterial infections were the commonest cause of morbidity. Patients with HH remain at a higher risk of developing HCC. Infectious complications are common. Iron reduction with preoperative venesection reduces the risk of cardiac and infection complications postoperatively. Improved survival post-LT reflects changes in selection, disease modification through venesection, and improvement in immunosuppression.

Surgery for secondary tumors of the pancreas.

BACKGROUND: The majority of pancreatic tumors are primary. The pancreas can however be the site of metastasis from renal cell cancer, lung, colon and breast cancers. The value of surgical treatment is unclear in such situations. The aim of this study was to evaluate the outcome of surgical therapy in patients with isolated metastases to the pancreas. METHODS: All patients who underwent pancreatic surgery for malignant disease from 1999 to 2005 (n=338) at the department of hepatobiliary and pancreatic surgery, the Royal London Hospital, London, were evaluated from a retrospective pancreatic database. Five patients had metastatic pancreatic cancer. Surgical outcome and survival were examined in this subset of patients. RESULTS: The primary cancer was renal cell carcinoma (n=2), breast (n=1), colon (n=1) and ovarian (n=1). The two patients with renal cell carcinoma developed pancreatic metastases years from the primary diagnosis. Both patients are alive 56 and 36 months post surgery. Two patients with breast and ovarian primary presented years after diagnosis of the primary but had advanced unresectable disease. There was one patient with colonic primary and synchronous pancreatic metastasis, and had a colectomy and Whipple's operation, and is alive 64 months postoperatively. CONCLUSION: The pancreas is an uncommon site for metastasis. Patients can present years after the treatment of primary. Long-term survival can be achieved with pancreatic resection in a highly selected subset of patients, and patients with primary renal cell carcinoma seem to have a favorable prognosis.