Long-term medical and quality of life outcomes among voluntary liver donors.

BACKGROUND: Long-term medical and quality of life (QOL) outcomes in voluntary liver donors remain under investigated. The objective of the current study was to report long-term medical outcomes and re-evaluate QOL in living liver donors. METHODS: This was a single-center retrospective cohort study of donors who underwent donor hepatectomy between 2012 and 2018. We investigated long-term outcomes in 7 domains. These include medical problems, surgical procedures, work-related issues, pregnancy outcomes, psychiatric interventions, willingness to donate again, and long-term mortality. QOL was evaluated using short-form 36. RESULTS: The median follow-up time was 61.4 months (53.3-83.7). Among 698 donors, 80 (11.5%) experienced medical problems, 4 (0.6%) had work-related issues, and 20 (2.9%) needed psychiatric assistance. Surgery was performed in 49 donors (7%), and females were more likely to have undergone incisional hernia repair (5.8% vs 1.9%, P = .006). There were 79 postdonation pregnancies including 41 normal vaginal deliveries (51.9%), 35 cesarean sections (44.3%), and 3 miscarriages (3.8%). Willingness to donate again was reported by 658 donors (94.3%). Donors whose recipients were alive were more likely to donate again (95.5% vs 90.5%, P = .01). There were 3 deaths (0.4%) in the long-term. The mean physical composite score at initial and follow-up evaluation was 86.7 ± 13.9 and 76.5 ± 20.9 (P = .001), and the mean mental composite score at initial and follow-up evaluation was 92.1 ± 13.5 and 80.7 ± 16 (P = .001). CONCLUSION: The overall long-term outlook in living liver donors is promising. QOL parameters might deteriorate over time and frequent re-evaluation might be considered.

Pancreaticoduodenectomy with Para-aortic Lymph Node Dissection for Periampullary Cancer.

There is no consensus on the utility of para-aortic lymph node dissection (PALND) in patients undergoing pancreaticoduodenectomy (PD) for periampullary cancer. The objective of this study was to assess survival in patients who underwent PD with PALND for pancreatic (PAC) and non-pancreatic (non-PAC) adenocarcinoma. All patients who underwent PD and PALND between 2011 and 2019 were reviewed (n = 114). We looked at the impact of tumor type (PAC versus non-PAC) and pathologically confirmed PALN metastasis (PALNM) on overall survival (OS). Out of 114 patients, PALNM were pathologically confirmed in 17(14.9%) patients. Without PALND, pathological staging would be pN0 in1(0.8%), pN1 in 3(2.5%), and pN2 in 13(11.2%) patients. The 30-day mortality was 3(2.6%) and 65(57%) patients received adjuvant treatment. The 4-year OS for PAC and non-PAC was 9% and 39% (P = 0.001). Advanced nodal involvement (pN2) was seen in 14/17(82.4%) and 21/97(21.6%) patients with and without PALNM, respectively (P < 0.001). For PAC, 4-year OS for patients with pN0-N1, pN2, and PALNM was 12%, 8%, and not reached (P = 0.067). For non-PAC, 4-year OS was 45%, 19%, and 12% (P = 0.006). In patients with non-PAC, despite metastatic involvement of PALN, acceptable long-term survival can be achieved with curative resection. For PAC, survival benefit with curative resection remains questionable.

National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma.

A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26, 2023, at the Pakistan Kidney and Liver Institute & Research Centre (PKLI & RC) after initial consultations with the experts. The Pakistan Society for the Study of Liver Diseases (PSSLD) and PKLI & RC jointly organised this meeting. This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma (hCCA). The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients. This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation. The diagnostic and staging workup includes high-quality computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography. Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis. However, histopathologic confirmation is not always required before resection. Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging. The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification. Selected patients with unresectable hCCA can be considered for liver transplantation. Adjuvant chemotherapy should be offered to patients with a high risk of recurrence. The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions. Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage. Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.

Outcomes of hepaticojejunostomy for post-cholecystectomy bile duct injury.

OBJECTIVES: Long-term results of hepaticojejunostomy (HJ) for complex bile duct injury (BDI) remain under-reported. The objective of this study was to assess short-term and long-term outcomes of HJ for post-cholecystectomy BDI. METHODS: This was a retrospective cohort study and included patients who underwent Roux-en-Y HJ for BDI (n = 87). Short-term (90-day) and long-term morbidity and mortality were assessed. RESULTS: At presentation, 42 (48.2%) patients had E3 or E4 BDI, 27 (31%) patients had vascular injury, and liver resection was performed in 12 (13.7%) patients. The 90-day morbidity was 51.7% (n = 45), and the 90-day mortality was 2.3% (n = 2). The long-term mortality was 3.4% (n = 3). The 10-year estimated stricture-free survival was 95%. The 10-year estimated overall survival rate was 100% in patients who underwent major hepatectomy and 91% in patients who did not. The 10-year estimated overall survival rate was 100% in patients with vasculobiliary injury and was not reached in patients without vascular injury. CONCLUSIONS: Vascular injury with proximal BDI is not uncommon. Excellent long-term outcomes might be achieved with Roux-en-Y HJ for BDI with vascular injury and in patients requiring liver resection.

Survival after extended resections for gallbladder cancer.

Backgrounds/Aims: Locally advanced gallbladder cancer (GBC) is associated with survival limited to a few months. Extended resections (ER) are occasionally performed in this group and outcomes remain inconclusive. This study assessed outcomes after ER for locally advanced GBC. Methods: Patients who underwent ER for GBC between 2011 and 2020 were reviewed. ER was defined as a major hepatectomy alone (n = 9), a pancreaticoduodenectomy (PD) with or without minor hepatectomy (n = 3), a major hepatectomy with PD (HPD) (n = 3) or vascular resection and reconstruction (n = 4). We assessed 30-day morbidity, mortality, and 2-year overall survival (OS). Results: Among 19 patients, negative margins were achieved in 14 (73.6%). The 30-day mortality was 1/9 (11.1%) for a major hepatectomy, 0/3 (0%) for a minor HPD, 2/3 (66.7%) for a major HPD, and 1/4 (25.0%) for vascular resection. All short term survivors (< 6 months) (n=8) had preoperative jaundice and 6/8 (75.0%) underwent a major HPD or vascular resection. There were five (26.3%) long term survivors. The median OS in patients with and without preoperative jaundice was 4.1 months (0.7-11.1 months) and 13.7 months (12-30.4 months), respectively (p = 0.009) (2-year OS = 7% vs. 75%; p = 0.008). The median OS in patients who underwent a major hepatectomy alone or a minor HPD was 11.3 months (6.8-17.3 months) versus 1.4 months (0.3-4.1 months) (p = 0.02) in patients who underwent major HPD or vascular resection (2 year OS = 33% vs. not reached) (p = 0.010) respectively. Conclusions: In selected patients with GBC, when ER is limited to a major hepatectomy alone, or a minor HPD, acceptable survival can be achieved.

Textbook outcome among voluntary donors undergoing major living donor hepatectomy.

PURPOSE: Textbook outcome (TO) is a composite measure of outcome and provides superior assessment of quality of care after surgery. TO after major living donor hepatectomy (MLDH) has not been assessed. The objective of this study was to determine the rate of TO and its associated factors, after MLDH. METHODS: This was a single center retrospective review of living liver donors who underwent MLDH between 2012 and 2021 (n = 1022). The rate of TO and its associated factors was determined. RESULTS: Among 1022 living donors (of whom 693 [67.8%] were males, median age 26 [range, 18-54] years), TO was achieved in 714 (69.9%) with no donor mortality. Majority of donors met the cutoffs for individual outcome measures: 908 (88.8%) for no major complications, 904 (88.5%) for ICU stay ≤ 2 days, 900 (88.1%) for hospital stay ≤ 10 days, 990 (96.9%) for no perioperative blood transfusion, 1004 (98.2%) for no 30-day re-admission, and 1014 (99.2%) for no post-hepatectomy liver failure. Early donation era (before streamlining of donor operative pathways) was associated with failure to achieve TO [OR 1.4, CI 1.1-1.9, P = 0.006]. TO was achieved in 506/755 (67%) donors in the early donation era versus 208/267 (77.9%) in the later period (P = 0.001). CONCLUSION: Despite zero mortality and low complication rate, TO was achieved in approximately 70% donors. TO was modifiable and improved with changes in donor operative pathway.

Living donor liver transplantation for advanced hepatocellular carcinoma including macrovascular invasion.

BACKGROUND: The indications for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) continue to evolve. The aim of this study was to report outcomes in patients who underwent living donor liver transplantation (LDLT) for HCC outside traditional criteria including macrovascular invasion (MVI). METHODS: We reviewed outcomes in patients who met the University of California San Francisco (UCSF) criteria (n = 159) and our center-specific criteria (UCSF+) (largest tumor diameter ≤ 10 cm, any tumor number, AFP ≤ 1000 ng/ml) (n = 58). We also assessed outcomes in patients with MVI (n = 27). RESULTS: The median follow was 28 (10.6-42.7) months. The 5 year overall survival and risk of recurrence (RR) in the UCSF and UCSF + group was 71% vs 69% (P = 0.7) and 13% vs 36% (P = 0.1) respectively. When patients with AFP > 600 ng/ml were excluded from the UCSF + group, RR was 27% (P = 0.3). Among patients with MVI who had downstaging (DS), 4/5(80%) in low-risk group (good response and AFP ≤ 100 ng/ml) and 2/10 (20%) in the high-risk group (poor response or AFP > 100 ng/ml) were alive at the last follow-up. When DS was not feasible, 3/3 (100%) in the low-risk group (AFP ≤ 100 ng/ml + Vp1-2 MVI) and 1/9 (9.1%) in the high-risk group (AFP > 100 or Vp3 MVI) were alive. The 5 year OS in the low-risk MVI group was 85% (P = 0.003). CONCLUSION: With inclusion of AFP, response to downstaging and degree of MVI, acceptable survival can be achieved with LDLT for HCC outside traditional criteria.

Risk Score Model for Liver Transplant Outcomes after Preoperative Locoregional Therapy for Hepatocellular Carcinoma.

PURPOSE: The role of preoperative locoregional therapy (LRT) for hepatocellular carcinoma (HCC) before liver transplantation (LT) remains unclear. Moreover, LRT in the setting of living donor liver transplantation (LDLT) merits further exploration. The objective of the current study was to determine risk factors for poor outcomes after LDLT in patients who received locoregional therapy (LRT). METHODS: We reviewed patients (n = 46) who underwent LDLT after LRT. Multivariate analysis was performed to determine independent predictors of recurrence-free survival (RFS). Risk scores were developed to define prognostic groups. RESULTS: Median tumor size was 3.7 (1.2-12) cm and tumor number was 1 (1-6). Macrovascular invasion was seen in 10/46 (21.7%) patients. There was a significant difference in 5-year RFS with > 3 tumor nodules (P = 0.005), tumors outside University of California San Francisco criteria (P = 0.03), bilobar disease (P = 0.002), AFP > 600 ng/ml (P = 0.006), and poor response to LRT (P = 0.007). On multivariate analysis, bilobar disease (HR = 2.9, P = 0.01), AFP > 600 ng/ml (HR = 2.3 P = 0.008), and poor response to LRT (HR = 2, P = 0.02) were predictors of 5-year RFS. The 5-year RFS in low risk (score = 0), intermediate risk (score = 1-3), and high risk (score = 4-7) groups was 86%, 76%, and 9% (P < 0.0001). There was no recurrence seen in 4/4 (100%) patients with macrovascular invasion in the low-intermediate risk group. The 5-year RFS in the low-intermediate risk group within and outside Milan criteria was 100% and 74% (P = 0.1). CONCLUSIONS: LDLT can provide excellent long-term RFS in patients after preoperative LRT in the low and intermediate risk groups.

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.

Living Donor Liver Transplantation During the COVID-19 Pandemic: an Evolving Challenge.

BACKGROUND: Maintaining standards of living donor liver transplantation (LDLT) can be a challenge during the corona virus disease 2019 (COVID-19) pandemic. Center-specific protocols have been developed and transplant societies propose limiting elective LDLT. We have looked at outcomes of LDLT during the pandemic in an exclusively LDLT center. METHODS: Patients were grouped into pre-COVID (January 2019-February 2020) (n = 162) and COVID (March 2020-January 2021) (n = 53) cohorts. We looked at patient characteristics, 30-day morbidity, and mortality. Outcomes were also assessed in donors and recipients who underwent surgery after recovery from COVID-19. RESULTS: The average number of transplants reduced from 11.5/month to 4.8/month. Fewer patients with MELD > 20 underwent LDLT in the COVID cohort (41.3% versus 24.5%, P = 0.03). Out of nine patients with a positive pretransplant COVID-19 PCR, there were 2 (22.3%) deaths on the waiting list. Seven patients underwent LT after recovery from COVID-19 with one 30-day mortality due to biliary sepsis. Three donors with positive COVID-19 PCR underwent uneventful donation after testing negative for COVID-19. No significant difference in 30-day survival was observed in the pre-COVID and COVID cohorts (93.2% versus 90.6%) (P = 0.3). Out of two recipients who developed COVID-19 pneumonia within 30 days after LT, there was one mortality. The 1-year survival for the entire cohort with a MELD cutoff of 20 was 90% and 84% (P = 0.2). CONCLUSION: Despite comparable outcomes, fewer sick patients might undergo LDLT during the pandemic. Individuals recovered from COVID-19 might be safely considered for donation or transplantation.

Influence of ABCB1 gene polymorphism on concentration to dose ratio and adverse effects of tacrolimus in Pakistani liver transplant recipients.

OBJECTIVE: To evaluate the possible association of ABCB1 single nucleotide polymorphism (SNPs) of the ABCB1 gene with tacrolimus dosages, concentration-to-dose ratios (CDR) and adverse effects in Pakistani liver transplant recipients. METHODS: This observational study was conducted at Shifa International Hospital, Shifa Tameer-e-Millat University, Islamabad and Basic Medical Sciences Institute, Karachi from September 2016 to July 2020. Eighty-one liver transplant recipients were included. Demographics, clinical data, tacrolimus trough levels and doses were monitored. Electrochemiluminescence immunoassay (ECLIA) was used to measure tacrolimus trough levels. Transplant recipients were genotyped for three ABCB1 SNPs (rs1045642, rs2032582 and rs1128503). Acute cellular rejection (ACR), sepsis and other adverse events were monitored. RESULTS: ABCB1 rs1045642 CC genotype showed lower tacrolimus CDR as compared to CT and TT genotype in the first week of the post-transplantation period (p=0.02). There was a significant association of polymorphisms in rs1045642, rs2032582 and rs1128503 with psychosis, sepsis and ACR respectively. CONCLUSION: Identification of ABCB1 rs1045642 polymorphism may shorten the time to achieve optimum levels of tacrolimus during dose titration. ABCB1 polymorphism rs1045642, rs2032582 and rs1128503 may predict adverse effects in liver transplant recipients receiving tacrolimus.

Multivisceral central pancreatectomy for pancreatic neuroendocrine tumor: A case report on a novel surgical technique.

INTRODUCTION: Central pancreatectomy (CP) is considered a viable alternative to subtotal distal pancreatectomy, for lesions involving the neck or proximal pancreatic body. Multivisceral central pancreatectomy (MVCP) for locally advanced tumors of the pancreatic body remains unreported. PRESENTATION OF CASE: We hereby report a case of locally advanced pancreatic neuroendocrine tumor (NET) with gastric involvement. The patient underwent successful central pancreatectomy with subtotal gastrectomy for locally advanced NET of the pancreas. In the follow up period, relevant complications like pancreatic insufficiency or pancreatic fistula were not encountered. The patient is doing well more than ten months after resection. DISCUSSION: A MVCP can be considered in patients with limited pancreatic involvement, as long as sufficient pancreatic parenchyma can be preserved. Additional organ involvement mandating resection should not be considered a contra indication to this procedure. With careful surgical planning and meticulous technique, risk of post operative complications after MVCP can be minimized with added benefit of long term endocrine and exocrine integrity. CONCLUSIONS: CP is a viable alternative and can be performed with adjacent organ resection, with acceptable post operative outcomes.

Preoperative Endoscopic Biliary Stenting Before Pancreaticoduodenectomy: Does Timing Matter?

Background. The role of preoperative biliary stenting (PBS) before pancreaticoduodenectomy (PD) in patients with obstructive jaundice is debatable. The objective of the current study was to assess PD outcomes after upfront surgery or PBS and determine the impact of stent to surgery duration on PD outcomes. Methods. We reviewed patients who underwent PD between 2011 and 2019. Patients were grouped based on whether they underwent upfront surgery (n = 67) or PBS (n = 66). We further assessed outcomes based on stent to surgery duration. Results. There was no significant difference in 30-day mortality (3% vs. 2.9%, P = 1), 90-day mortality (7.5% vs. 4.4%, P = .4), and Grade B-C pancreatic fistula rates (7.5% vs. 4.4%, P = .4) in the PBS and upfront surgery groups, respectively. A significant increase in wound infections (22.7% vs. 7.4%, P = .01) and readmissions (10.6% vs. 0, P = .006) was seen in the PBS group. The highest rate of wound infection was seen when stent to surgery duration was 4-6 weeks (41.6%). The wound infection rates in the upfront surgery group, high-risk PBS group (4-6 weeks), and low-risk PBS group were 5/67(7.4%), 5/12(41.6%), and 7/36(19.4%), respectively (P = .008). Conclusions. PBS increases postoperative wound infections when compared with upfront surgery. Patients operated between 4 and 6 weeks after stenting have the highest rate of wound infection.

When to call it off: defining transplant candidacy limits in liver donor liver transplantation for hepatocellular carcinoma.

BACKGROUND: Living donor liver transplantation (LDLT) is an acceptable treatment option for hepatocellular carcinoma (HCC). Traditional transplant criteria aim at best utilization of donor organs with low risk of post transplant recurrence. In LDLT, long term recurrence free survival (RFS) of 50% is considered acceptable. The objective of the current study was to determine preoperative factors associated with high recurrence rates in LDLT. METHODS: Between April 2012 and December 2019, 898 LDLTs were performed at our center. Out of these, 242 were confirmed to have HCC on explant histopathology. We looked at preoperative factors associated with ≤ 50%RFS at 4 years. For survival analysis, Kaplan Meier curves were used and Cox regression analysis was used to identify independent predictors of recurrence. RESULTS: Median AFP was 14.4(0.7-11,326.7) ng/ml. Median tumor size was 2.8(range = 0.1-11) cm and tumor number was 2(range = 1-15). On multivariate analysis, AFP > 600 ng/ml [HR:6, CI: 1.9-18.4, P = 0.002] and microvascular invasion (MVI) [HR:5.8, CI: 2.5-13.4, P <  0.001] were independent predictors of 4 year RFS ≤ 50%. When AFP was > 600 ng/ml, MVI was seen in 88.9% tumors with poor grade and 75% of tumors outside University of California San Francisco criteria. Estimated 4 year RFS was 78% for the entire cohort. When AFP was < 600 ng/ml, 4 year RFS for well-moderate and poor grade tumors was 88 and 73%. With AFP > 600 ng/ml, RFS was 53% and 0 with well-moderate and poor grade tumors respectively (P <  0.001). CONCLUSION: Patients with AFP < 600 ng/ml have acceptable outcomes after LDLT. In patients with AFP > 600 ng/ml, a preoperative biopsy to rule out poor differentiation should be considered for patient selection.

Living Donor Liver Transplantation for Hepatocellular Carcinoma: Appraisal of the United Network for Organ Sharing Modified TNM Staging.

Background: In deceased donor liver transplantation (DDLT), transplant eligibility for T3-T4 HCC requires successful downstaging (DS). Living donor liver transplantation (LDLT) can be considered selectively in these patients without DS, but its role is not defined. The objective of the current study was to assess outcomes of LDLT for HCC based on UNOS staging with no prior DS. Materials and Methods: Patients who underwent LDLT for HCC (n = 262) were staged based on modified UNOS TNM staging. High-risk factors were identified and 5-year recurrence free survival was compared in patients with T2-T4 HCC. Results: Median follow-up was 30.2 (16.4-46.3) months. Recurrence rate in T1, T2, T3, T4a, and T4b HCC was 0, 10.1, 16.1, 5.9, and 37.5% (P = 0.02), respectively. On multivariate analysis, AFP > 600 ng/mL [HR:11.7, P < 0.001] and T4b HCC (macrovascular invasion) [HR = 5.6, P = 0.03] were predictors of recurrence. After exclusion of AFP > 600 ng/mL, 5-year RFS for T2, T3, and T4a HCC was 94, 86, and 92% (P = 0.3). Rate of microvascular invasion between T2 and T3 HCC was 24.3 vs. 53.6% (P = 0.005), and between T2 and T4a HCC was 24.3 vs. 36.7% (P = 0.2). Overall, 26 (19.4%) patients were overstaged and 23 (17.1%) were understaged on preoperative imaging. The 5-year RFS in patients with identical preoperative and histopathological staging was 94, 87, and 94% (P = 0.6). Conclusion: LDLT without prior DS leads to comparable survival for UNOS T2, T3, and T4a HCC as long as AFP is < 600 ng/mL.

Clinical Efficacy and Safety of Tacrolimus in Pakistani Living Donor Liver Transplant Recipients.

OBJECTIVE: To evaluate the association between tacrolimus trough levels and dosage in Pakistani patients undergoing live donor liver transplantation (LDLT), and the efficacy and adverse effects at different tacrolimus trough levels and dosages. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: Shifa International Hospital, Shifa Tameer-e-Millat University, Islamabad and Basic Medical Sciences Institute, Karachi, from September 2016 to October 2018. METHODOLOGY: Sixty liver transplant recipients were included. Demographics, clinical data, tacrolimus trough levels and doses were monitored as per routine protocol. Electrochemiluminescence immunoassay (ECLIA) was used to measure tacrolimus trough levels. Acute cellular rejection (ACR), sepsis and other adverse events were monitored at different tacrolimus trough levels in early post-transplantation period. RESULTS: Mean age of transplant recipients was 49.1 ± 10.6 years. Mean tacrolimus trough levels were 6.1 ± 2.2 ng/ml and mean dose was 0.94 ± 0.3 mg. Sepsis (27%) psychosis (20%), seizures (10%), and renal insufficiency (13%) were the most common adverse effects. Acute cellular rejection (ACR) was observed in 15% patients. Patients with sepsis had significantly high mean tacrolimus levels of 7.7 ± 2.5 ng/ml versus 5.5 ± 1.9 ng/ml (p=0.001). Mean tacrolimus trough levels in patients with ACR were significantly lower (4.05 ± 1.6 ng/ml vs. 6.43 ± 2.2ng/ml, p=0.003). None of the patients with a single tacrolimus trough level >10 ng/ml experienced ACR. CONCLUSION: A tacrolimus trough level between 5 to 7.5 ng/ml appears to be safe in Pakistani liver transplant recipients significantly minimising the risk of ACR and other adverse events.