Patient Selection for Living Donor Liver Transplantation in Acute-on-chronic Liver Failure.

Background and objectives: Acute-on-chronic liver failure (ACLF) is associated with high short-term mortality without liver transplantation (LT). The selection criteria for LT in these patients are not well defined. The objective of this study was to determine factors associated with post-transplant survival in ACLF. Methods: This was a single-center retrospective study of patients who underwent living donor liver transplantation (LDLT) for ACLF between 2012 and 2022. Out of 1093 transplants, 110 patients had underlying ACLF, based on the European Association for the Study of the Liver-Chronic Liver Failure Consortium (EASL-CLIF) criteria. We looked at factors associated with 1-year posttransplant survival. Results: The median model for end-stage liver disease (MELD) score was 33.5 (31-38), and the 1-year posttransplant survival was 72%. Six risk factors were associated with posttransplant survival, namely, body mass index > 30 kg/m2 [HR, 4.4; 95% CI, 1.8-10.7], platelet count < 66,000/µl [HR, 2.91; CI,1.2-6.6], poor response to medical treatment [HR, 2.6; CI, 1.1-5.7], drug-resistant bacterial or fungal cultures [HR, 4.2; CI, 1.4-12.4], serum creatinine > 2.5 mg/dl [HR, 3.4; CI, 1.5-7.7], and graft-to-recipient weight ratio < 0.7 [HR, 4.8; CI, 1.4-16.3]. The 1-year post-transplant survival was 84% in patients with 0-2 risk factors (n = 89) and was 6% with 3 risk factors (n = 15) (P < 0.001). For 1-year posttransplant survival, the area under curve (AUC) for the current model was 0.8 (0.69-0.9). The AUC for CLIF-ACLF, Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA), and EASL-CLIF ACLF grades was < 0.5. Conclusion: In LT for ACLF, acceptable survival can be achieved when less than three high-risk factors are present.

Liver transplantation with interposition saphenous vein conduits for arterial reconstruction: Impact of morbidity and arterial ischemia time.

BACKGROUND: The outcomes of liver transplantation with hepatic arterial reconstruction using interposition saphenous vein conduits are not widely reported. Here, we share our experience using great saphenous vein conduits for hepatic arterial reconstruction in living donor liver transplantation. METHODS: This was a single-center retrospective review of patients who underwent living donor liver transplantation (n = 950). The saphenous vein conduits were used in 39 patients. We compared hepatic artery thrombosis, graft dysfunction, and 30-day and 1-year survival in the early (2012-2017) and late (2017-2020) transplant periods. RESULTS: Among 39 patients (of whom 30 [76.9%] were males, median Model for End-Stage Liver Disease was 24 [interquartile range, 17-27], median age was 50 [interquartile range, 43-54]), saphenous vein conduits were placed on supra celiac aorta in 7 (17.9%), infrarenal aorta in 25 (64.1%), and other arteries in 7 (17.9%) patients. The number of biliary and hepatic vein anastomoses, total arterial ischemia time, portal vein-hepatic artery reperfusion time, and duration of surgery was different in the 2 groups (P < .05). The 30-day mortality was 5/21 (23.8%) and 0 in the early and late periods (P = .05). The 30-day survival was >90% in patients with portal vein-hepatic artery reperfusion time <240 minutes, ≤2 grade 3 complications, no graft dysfunction, and later period of transplantation (P < .05). The 1-year survival with standard transplantation, transplantation with saphenous vein conduits in the early and late period was 87%, 62%, and 89% (P = .022). CONCLUSION: Liver transplantation with saphenous vein conduits is associated with acceptable outcomes. Major complications and arterial ischemia times are major determinants of outcomes.

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.

Clinical Utility of Protein Induced by Vitamin K Absence-II in Patients with Hepatocellular Carcinoma.

OBJECTIVE: Despite moderate sensitivity, alpha fetoprotein (AFP) is widely used in screening and prognostication for hepatocellular carcinoma (HCC). The objective of the current study was to assess clinical utility of Prothrombin induced by Vitamin K absence-II (PIVKAII) in addition to AFP in patients with HCC. METHODS: We retrospectively reviewed 244 patients with documented AFP, PIVKA II and dynamic imaging of the liver. Using ROC curves, cutoff values for AFP and PIVKAII for HCC detection, tumor grade and microvascular invasion (MVI) were assessed. In patients who underwent liver transplantation (LT) for HCC, survival was determined using Kaplan Meier curves. RESULTS: The median PIVKAII in healthy living donors was 28.6mAU/ml (15.9-55). In cirrhotics, the sensitivity of an AFP cutoff of 7.6 ng/ml or PIVKAII  cutoff of 250 mAU/ml for HCC detection was 91.7% (176/192) and specificity was 62.9%(68/108) (p <0.0001). In patients with HCC, PIVKAII values were significantly elevated with tumor size > 5 cm (P < 0.0001), tumor nodules > 3(P=0.01), and macrovascular invasion(p <0.0001).  The high risk group (patients with AFP ≥ 40 ng/ml + PIVKAII ≥ 350 mAU/ml), had a sensitivity of (23/33) 69.6% and specificity of (22/22)100% for MVI (P <0.001). The estimated 3 year RFS after LT in the low risk group (AFP.

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.