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.

Outcome of pediatric living donor liver transplant: Experience from Pakistan; a resource limited setting.

INTRODUCTION: Liver transplantation (LT) has emerged as a lifesaving modality for many liver diseases in children. Pediatric LT is an established treatment in the Western world but is relatively a new procedure in resource-limited countries like Pakistan. The study aims to highlight the outcomes and survival of pediatric recipients from the first pediatric liver transplant center in Pakistan. METHOD: A retrospective analysis of pediatric LT was done from 2012 to 2019. The study was conducted in the Hepatobiliary and liver transplant department of Shifa International Hospital (SIH), Islamabad. A detailed analysis for indications for pediatric LT, survival, and complications was done. RESULTS: Forty-five patients under 18 years of age underwent Living donor liver transplant (LDLT) in SIH. Median age was 9 years and M:F of 2:1. Cryptogenic liver disease followed by Wilson disease were the two most common indications of LT. The majority of patients had chronic liver disease 34 (75%) while 11 (24%) had acute liver failure. The right lobe graft was the most common type of graft 19 (42.2%). Thirty days, 1-year, 3-year, and 5-year survival was 77.8%, 75.6%, 73.3%, and 60.6% respectively. Mortality was highest in patients with biliary atresia 4 (33%). Causes of death included pulmonary embolism, sepsis, surgical complications, and acute kidney injury. Mean survival was 88.850 months (±7.899) (CI 73.369-104.331). CONCLUSION: Pediatric LDLT has offered disease-free survival for patients. Survival can improve further with nutritional rehabilitation and anticipation and management of post-operative complications.

Calcifying Nested Stromal-Epithelial Tumor: An Extremely Rare Hepatic Tumor.

Calcifying nested stromal-epithelial tumor is a rare hepatic malignancy with approximately 50 cases reported in the literature. Its clinical presentation is nonspecific, and the diagnosis is mainly based on histology which shows nests of spindle and epithelioid cells along with a desmoplastic myofibroblastic stroma containing variable calcification and ossification. In this report, we present a case of a 24-year-old woman with a history of abdominal pain, distension, and dyspepsia. She had a palpable liver with normal liver function test results. Serum alpha-fetoprotein levels were within normal range, and serologies for hepatitis B and C virus remained negative. Radiological investigations (magnetic resonance imaging and computed tomography) showed a large, right hepatic lobe mass with tumor invasion into the right posterior portal vein, but the 2 modalities could not characterize the lesion. Finally, an ultrasound-guided biopsy of the liver lesion provided the diagnosis of calcifying nested stromal-epithelial tumor. The tumor was resected successfully.

Donor Safety First: Postoperative Hepatectomy Outcomes in Living Liver Donors.

BACKGROUND: Living donor liver transplantation (LDLT) has become a popular treatment option because some countries lack a deceased organ program and the growing demand for liver transplants. Although postoperative outcomes are similar to deceased donor liver transplants, there is still an element of risk to the donor. The Clavien-Dindo classification system has been used to standardize reporting across different institutions and surgeons to categorize surgical outcomes. METHODS: Between January 1, 2022, and December 31, 2022, 207 living donors underwent hepatectomies at our center. All donors underwent a 3-step process of mandatory screening. Postsurgical complications were classified using the Clavien-Dindo classification. RESULTS: A total of 207 donor hepatectomies for LDLT were performed during our study period. Most donors (92.8%) were aged between 18 and 39 years. The most common type of graft used was a right lobe without the middle hepatic vein (82.6%). Most donors (91.7%) experienced an intraoperative blood loss of ≤500 mL. A total of 140 patients had an ordinary postoperative course. Grade 1 complications were observed in 16.9%, grade 2 in 12.1%, and grade 3 in 3.4% of the remaining patients. No grade 4 or grade 5 (patient death) complications were observed in this cohort. CONCLUSIONS: Living donor liver transplantation remains the most practiced liver transplant surgery in Pakistan. Our findings highlight the safety of the LDLT program with minimal risk of significant complications. The study also underscores the importance of careful screening and monitoring of living donors and the need for standardized reporting of surgical outcomes using the Clavien-Dindo classification system.

Anatomical variations in living donors for liver transplantation-prevalence and relationship.

PURPOSE: Living donor liver transplantation (LDLT) is a widely accepted option to address the lack of a deceased liver program for transplantation. Understanding vascular and biliary anatomy and their variants is crucial for successful and safe graft harvesting. Anatomic variations are common, particularly in the right hepatic lobe. To provide evidence for screening potential liver transplant donors, the presence of vascular and biliary anatomic variations in Pakistan's preoperative assessment of transplantation donor candidates was explored. METHODS: This retrospective cross-sectional study evaluated the hepatic artery, portal vein, hepatic vein, and biliary variations in living liver donors. The study included 400 living liver donors; data were collected from March 2019 to March 2023. We used a CT scan and MRCP to assess the anatomical variations. RESULTS: The study examined 400 liver donors aged 18 to 53 years. Conventional arterial anatomy was the most common (65.8%), followed by replaced right hepatic artery (16%) and replaced left hepatic artery (10.8%). Conventional type 1 biliary anatomy was seen in 65.8% of cases. The dominant right hepatic vein was found in 13.3% of donors. There was a significant association between the prevalence of variant portal venous anatomy with variant biliary anatomy. CONCLUSION: Variations of the hepatic arterial, portal venous, and biliary systems are frequent and should be carefully evaluated while selecting a suitable living donor. A strong relationship between variant portal venous and biliary anatomy was found. These findings can aid in selecting suitable candidates and improving surgical planning for liver transplantation.

Exploring safety and efficacy of rivaroxaban after living donor liver transplantation: a retrospective study.

PURPOSE: Thromboembolic complications remain a significant concern in postoperative patients, particularly those who have undergone liver transplantation. Warfarin has been the standard oral anticoagulant. Direct oral anticoagulants (DOACs) have several advantages over warfarin, including rapid onset of action and standardized dose guidelines. We aimed to assess the safety of rivaroxaban in living donor liver transplantation (LDLT) recipients. METHODS: This study was a single-center, retrospective descriptive analysis of LDLT recipients who received rivaroxaban between December 2020 and April 2022. A total of 27 recipients received rivaroxaban postoperatively. Liver function tests, immunosuppression levels, serum creatinine, and INR were recorded before the initiation of rivaroxaban and then on post-therapy days 1, 7, 14, 28, 90, and 180. RESULTS: Among the 27 recipients receiving rivaroxaban postoperatively, portal venous thrombosis was the most prevalent indication for anticoagulation (44.4%), followed by Budd-Chiari syndrome (29.6%). Nine patients had a twofold increase in either ALT or AST values, two of whom were treated for biliary strictures and the others for rejection. Eighteen patients were given tacrolimus, and eight were on cyclosporine, with one patient switched from tacrolimus to cyclosporine due to insufficient therapeutic levels. There were no incidents of bleeding or re-thrombosis during the 180-day follow-up period. CONCLUSION: Rivaroxaban may be a safe and effective alternative in LDLT recipients with no significant adverse incidents. Further studies with larger sample sizes are needed to confirm these findings and determine this population's optimal dose and duration of rivaroxaban therapy.

Liver Transplantation: A Right or a Privilege? Sustainable Liver Transplant Financing With an Innovative Model for the Developing World.

Living donor liver transplant in addition to its lifesaving therapy is a cost-effective alternate to long-term disease management in patients with chronic liver disease. Financial constraint is the biggest hurdle faced by patients in developing countries in availing the liver transplantation. So, we conducted this study to report a government-funded financial support system for liver transplant services. A total of 198 patients who underwent living donor liver transplant with at least 90 days follow-up were included in the study. According to proxy means test score, 52.2% patients were from low and middle socioeconomic groups and 64.6% of patients underwent liver transplantation through government support. Out of 198 patients who underwent liver transplantation 29.6% had monthly income below 25,000 Pakistani rupees ($114). In recipients, 90-day mortality was 7.1% and morbidity was 67.1%. Donor morbidity was 23.2% without any mortality. This financial model can serve as a valuable source for middle and low income group countries to overcome the financial challenge and make liver transplant an accessible, affordable, and economically viable option.

Launching Liver Exchange and the First 3-Way Liver Paired Donation.

This article discusses the successful implementation of a liver exchange mechanism that led to 3 liver allotransplants and 3 hepatectomies between 3 incompatible patient-donor pairs.

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.

Biliary atresia-An experience from the first pediatric liver transplant center in Pakistan.

BACKGROUND: Biliary atresia (BA) is the most common cause of neonatal cholestatic syndrome. The true incidence of BA in Pakistan is largely unknown. AIM: This study aimed to report the clinical features, age at diagnosis and outcomes of biliary atresia from the first pediatric liver transplant center in Pakistan. METHODS: The study was done in Shifa International hospital from 2013 to 2020. All babies who had biliary atresia confirmed by laboratory investigation were included. Demographic data, age of presentation, clinical presentation, supporting investigations like liver function tests, ultrasound abdomen, HIDA scan and liver biopsy were noted. Outcome related to Kasai portoenterostomy, liver transplant, complications and immunosuppressant agents were noted. RESULT: A total of 42 children were included, 23 (54.7%) males and 19 (45.2%) were females. Jaundice was seen in all patients (100%) followed by acholic stools (81%). Associated malformations were noted in 6 (14.2%) patients. Liver function tests confirmed obstructive cholestasis (p 0.04). Kasai was done in 19 (45%) patients only, living donor liver transplant was performed in 6 (14%) patients. Age range of transplant patients was from 3 months to 1 year. Indication for liver transplant was failed Kasai in 1(16.7%) patient and chronic liver disease in 5 (83.3%) patients. LDLT survivors were 10 months to 1 year of age at the time of transplant, mean age was 10.6 months. Maximum survival noted so far is 7 years. Acute complications seen post-transplant were sepsis (three patients), surgical site infections (two patients), biliary leaks and acute cellular rejection in one patient each. Chronic graft rejection, portal vein stricture needing stenting was done in one patient. DISCUSSION: All patients underwent LDLT from related donors wih no donor related mortality. All are deceased patients were yonger and had advanced disease. BA remains third most commo indication of transplant in our center. CONCLUSION: Liver transplant is the only lifesaving procedure after failed Kasai or as primary liver transplant due to advance liver disease. The advent of liver transplantation services offers survival and improving outlook of the disease.

Primary squamous cell carcinoma of liver. First case report from Pakistan and South Asia.

INTRODUCTION AND IMPORTANCE: Primary squamous cell carcinoma (PSCC) of liver is quite rare and very few cases reported in literature. It has high metastatic rate with poor prognosis. The pathogenesis is unclear, but is generally considered to be correlated with the long-term inflammation or metaplasia of biliary epithelial cells or congenital cyst of the liver. We report here a case of PSCC of liver which mimicked a complex hydatid cyst. CASE PRESENTATION: A 25 years male admitted with right hypochondrium pain associated with fever and yellowish discoloration of eyes for 20 days. He was jaundiced with epigastric tenderness and deranged liver function tests. When thoroughly investigated with ultrasound, CT abdomen and MRI liver, he was found to have a large cystic lesion in right lobe of the liver. He underwent right hepatectomy, peri-cystectomy of the cyst and T-tube placement in common bile duct. Histopathology of the resected sample showed primary squamous cell carcinoma of liver. Patient was discharged after 7 days and died after 6 months due to acute liver failure. CLINICAL DISCUSSION: Because of a very low incidence of hepatic SCC, there is not a single definite therapeutic regime and various different methods of management include surgical resection, generalized chemotherapy, radiotherapy, Hepatic Arterial ChemoEmbolization (HACE) and the combinations of these therapies. CONCLUSION: PSCC is a rare condition of the liver and is associated with other benign liver conditions such as non-parasitic and epidermoid cysts. Histopathology with radiological investigations are needed to diagnose and treat this aggressive tumor before it metastasizes.

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.

Wilson Disease in Children; Chelation Therapy or Liver Transplantation? A 10-Year Experience from Pakistan.

BACKGROUND Wilson disease (WD) is a rare genetic disorder with vast clinical presentations and a higher incidence in areas where consanguinity is common. Most patients can be treated with oral chelation, but some require advanced surgical intervention, like liver transplantation (LT). This study aims to review outcomes of WD patients presenting to a tertiary care center over a period of 10 years. MATERIAL AND METHODS This retrospective analysis was conducted at Shifa International Hospital, Islamabad, Pakistan. Patients <18 years who were diagnosed with WD per ESPAGHAN guidelines from 2010 to 2020 were included. Presentation, diagnosis, treatment, and LT and its complications were recorded. Follow-ups were recorded, and patients were contacted by phone in cases of interrupted follow-up. Frequencies and percentages of variables were calculated. RESULTS A total of 48 patients with WD were identified. Symptomatic disease was seen in 45 patients, with 3 diagnosed on screening. The hepatic form was common (62.2%). Mean age at diagnosis was 9.74 (range 5-17) years, 28 (58.3%) were male, while 17 (35.4%) were female. Urinary copper was increased in all patients (645.82±528.40). Oral treatment with penicillamine was given to 34 (75.5%) patients; 4 (8.9%) died while on oral treatment. Living donor LT was performed in 11 (22.9%) patients, who had a mean King's Wilson index of 11 (range, 6-14). Currently, all LT patients are alive, with maximum graft survival of 7 years. CONCLUSIONS LT offers a promising treatment with good outcomes in pediatric WD. However, timely diagnosis and management with oral chelation therapy can prolong survival without LT.

Long term outcomes after pancreaticoduodenectomy: A single center experience from Pakistan.

OBJECTIVE: To report long-term outcomes after pancreaticoduodenectomy from a single centre. METHODS: The retrospective study was conducted at Shifa International Hospital, Islamabad and comprised pancreaticoduodenectomy procedures performed by four surgeons at a single centre from January 2011 to June 2019. Outcome was assessed on the basis of morbidity, in-hospital mortality and survival. Data was analysed using SPSS 20. RESULTS: Of the 155 patients, 103(66.5%) were males. The overall mean age was 56.8±13.5 years (range: 8-85 years). Overall morbidity was 84 (54.2%). Multivisceral and venous resections were performed in 22(14.2%) and 20(12.9%) patients respectively. Grade B pancreatic fistula was seen in 5(3.2%) patients and grade C in 6(3.8%). In-hospital mortality was 5(3.2%). The difference between the estimated 5-year overall survival for pancreatic and non-pancreatic cancers was non-significant (p=0.2), while the difference in the estimated 3-year overall survival rate was significant (p<0.05). CONCLUSIONS: With standardisation of operative technique and peri-operative management, low in-hospital mortality and acceptable long-term outcomes were achieved with standard and extended pancreaticoduodenectomy.

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.

Genetic Susceptibility to Chronic Liver Disease in Individuals from Pakistan.

Chronic liver disease, with viral or non-viral etiology, is endemic in many countries and is a growing burden in Asia. Among the Asian countries, Pakistan has the highest prevalence of chronic liver disease. Despite this, the genetic susceptibility to chronic liver disease in this country has not been investigated. We performed a comprehensive analysis of the most robustly associated common genetic variants influencing chronic liver disease in a cohort of individuals from Pakistan. A total of 587 subjects with chronic liver disease and 68 healthy control individuals were genotyped for the HSD17B13 rs7261356, MBOAT7 rs641738, GCKR rs1260326, PNPLA3 rs738409, TM6SF2 rs58542926 and PPP1R3B rs4841132 variants. The variants distribution between case and control group and their association with chronic liver disease were tested by chi-square and binary logistic analysis, respectively. We report for the first time that HSD17B13 variant results in a 50% reduced risk for chronic liver disease; while MBOAT7; GCKR and PNPLA3 variants increase this risk by more than 35% in Pakistani individuals. Our genetic analysis extends the protective role of the HSD17B13 variant against chronic liver disease and disease risk conferred by the MBOAT7; GCKR and PNPLA3 variants in the Pakistani population.

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.