Optimal liver transplant procedure in progressive familial intrahepatic cholestasis type 1 treated with biliary diversion or intestinal transplantation: Lessons learned from three cases treated with different approaches.

BACKGROUND: Progressive familial intrahepatic cholestasis type 1 (PFIC1) is an autosomal recessive cholestatic liver disorder caused by ATP8B1 gene mutations. Although liver transplantation (LT) is indicated for progressive liver disease, postoperative complications, including severe diarrhea and graft steatohepatitis leading to graft loss, have been reported. CASES: The first patient had jaundice, pruritus, diarrhea, and growth retardation (weight z-score: -2.5; height z-score: -3.7). She underwent LT with total internal biliary diversion (TIBD) to the colon at 2 years of age. Graft biopsy at the 7-year follow-up examination revealed microvesicular steatosis (60%). Her diarrhea improved, and her growth failure was recovering (weight z-score: -1.0; height z-score: -1.7). The second patient underwent sequential intestine-liver transplantation at 8 years of age due to end-stage liver disease (ESLD) and short bowel syndrome caused by massive bowel resection for internal hernia after partial external biliary diversion (PEBD) at 21 months of age. She developed severe pancreatitis induced by steroid-bolus therapy for rejection after transplantation. She died 1.7 years after intestinal transplantation due to an uncontrollable pancreatic abscess and acute respiratory distress syndrome. The third patient underwent PEBD at 15 months of age and received LT with TEBD at 15 years of age due to ESLD with hepatic encephalopathy. Throughout the perioperative period, she showed no abdominal symptoms, including diarrhea and pancreatitis. Graft biopsy at the 2-year follow-up examination revealed macrovesicular steatosis (60%) with inflammation. CONCLUSIONS: The patients showed different outcomes. Effective therapeutic options to mitigate post-LT complications in patients with PFIC1 must be considered individually.

Is a Preservation Solution for Living Donor Liver Transplantation Needed? Adding a New Chapter in LDLT!

Preservation solutions are required for organ viability in deceased donor liver transplantation (LT). However, their role in live donor LT (LDLT) has not been standardized. Methods: Eighty adult recipients who underwent right lobe LDLT at the Department of Liver Transplantation Surgery, Gambat, Pakistan, were studied. Based on shorter cold ischemia time and no back table reconstruction work, recipients were assigned to receive "no preservation solution" (cases/non-histidine-tryptophan-ketoglutarate group; n = 40) or "HTK group" (controls; n = 40). Early allograft dysfunction (bilirubin, transaminases, and international normalized ratio), postoperative complications (biliary and vascular), hospital stay, and 1-y survival were reported. The direct cost was also reported. Results: Demographics and clinical characteristics were comparable in the 2 groups. Comparing cases versus controls, mean bilirubin, alanine aminotransferase, aspartate aminotransferase, and international normalized ratio on postoperative day 7 were similar in the 2 groups. Five (12.5%) cases and 4 (10%) controls developed early allograft dysfunction (P = 0.72). Post-LT complications (biliary leak 2.5% in cases versus 0 in control), strictures (15% in cases versus 17.5% in controls), hepatic artery thrombosis (2.5% versus 00%)' and portal vein thrombosis (0 versus 2.5%) were comparable. Mean hospital stay (10.80 + 2.36 and 11.78 + 2.91 d) and 30 d mortality (2.5% versus 5%) were also comparable. Finally, 1-y survival based on Kaplan-Meier analysis was comparable in both groups (ie, 92.5%; non-HTK group versus 90%; HTK group) (P = 0.71). The direct cost of using a non-HTK-based approach was less than the HTK solution. Conclusion: In a selected cohort of right lobe LDLT recipients, preservation solutions can be avoided safely with comparable outcomes.

ABO incompatible living donor liver transplant with antibody titer of 1:4: First case report from Pakistan.

Introduction and importance: The most common reason for live liver donor rejection is ABO incompatibility. With breaching this incompatibility barrier, probably an additional 25%-35% of liver transplantation (LT) procedures would become possible. Also, ABOi-LT can be lifesaving in acute settings. Initially, ABOi-LT reported a poor prognosis secondary to antibody-mediated rejection (AMR) which is more common in ABOi allograft recipients. AMR may be avoided by desensitization. Various desensitization protocols are practiced globally, however, there is no consensus available on the optimal desensitization protocol for the ABOi-LT. The ABO-incompatible (ABOi) can expand the liver donor pool tremendously. We report the first case of ABO incompatible-liver transplantation (ABOi-LT) from Pakistan. Case presentation: A 48 years old male, presented with decompensated liver diseaseand hepatocellular carcinoma secondary to HCV infection. LT was advised as the optimal modality of treatment. Due to the non-availability of a compatible donor, ABOi-LT was planned.His daughter agreed to donate.Pre-LT desensitization was started on the 23rd-day pre-LT with intravenous (I/V) rituximab 700 mg/body (375 mg/m2) along with I/V Bortezomib 2mg (1.3 mg/m2). Bortezomib was repeated subcutaneously (S/C) on the 20th, 16th, and 13th days pre-LT. One week before LT oral Mycophenolate mofetil 500 mg and Tacrolimus 1 mg were started twice daily. Therapeutic plasmapheresis was done on the 5th, 3rd, and 1st-day pre-LT. Per-operatively, Basiliximab was administeredI/V with a dose of 0.8 gm/kg during the anhepatic phase. Anti-A & Anti-B titer level was determined on the 5th day before plasmapheresis and repeated on the 2nd and 1st-day pre-LT. Then post-LT plasmapheresis was done onthe 15th day and at 3 months. The CD 19 activity was determined one day before LT and on the 15th-day post-LT. His LT was performed uneventfully and was discharged on the 15th postoperative day (POD). However, on the 26th POD, he was diagnosed with left subclavian vein thrombosis which was treated successfully with anticoagulation therapy for 6 months. Till the last follow up patient is doing well. Clinical discussion: Desensitization is the removal of preformed anti-ABO antibodies and depleting serum B cells production. Antibody-mediated rejection irreversibly damages the graft and predisposes it to graft failure. The prognosis of ABOi-LT has dramatically improved since the introduction of desensitization protocols. Conclusion: Antibody-mediated rejection may be avoided by desensitization. The intravascular infusion therapies and splenectomy can be omitted from the desensitization protocol. ABO-i LT can tremendously increase the liver donor pool.

Expanding the living liver donor pool in countries having limited deceased donor activity: Pakistani perspective.

Over the last decades, liver transplantation (LT) has evolved into a life-saving procedure. Due to limited deceased donor activities in the eastern world, living donor liver transplantation (LDLT) had flourished tremendously in most Asian countries. Yet, these LDLT activities fall short of meeting the expected demands. Pakistan, a developing country, bears a major burden of liver diseases. Currently, only few centers offer LDLT services in the country. On the other hand, deceased donor liver transplantation (DDLT) activities have not started due to social, cultural, and religious beliefs. Various strategies can be adopted successfully to overcome the scarcity of live liver donors (LLDs) and to expand the donor pool, keeping in view donor safety and recipient outcome. These include consideration of LLDs with underlying clinical conditions like G6PD deficiency and Hepatitis B core positivity. Extended donor criteria can also be utilized and relaxation can be made in various donors' parameters including upper age and body mass index after approval from the multidisciplinary board. Also, left lobe grafts, grafts with various anatomical variations, and a low graft-to-recipient ratio can be considered in appropriate situations. ABO-incompatible LT and donor swapping at times may help in expanding the LLDs pool. Similarly, legislation is needed to allow live non-blood-related donors for organ donations. Finally, community education and awareness through various social media flat forms are needed to promote deceased organ donation.

An Innovation in the Technique of Recipient Hepatectomy in Living Donor Liver Transplantation.

Recipient hepatectomy is a challenging surgical procedure. Coagulopathy, multiple collaterals, and dense adhesions secondary to previous spontaneous bacterial peritonitis in cirrhotics are the major contributing factors. However, the appropriate recipient hepatectomy technique can limit the massive blood loss and minimize the operative time. The hepatoduodenal dissection has a key role in recipient hepatectomy. The hilar structures of partial graft in live donor liver transplantation (LDLT) usually have a short length and a small caliber. The concerning task in LDLT recipient hepatectomy is to preserve the integrity, quality, and adequacy of hilar structures for successful implantation. The high hilar dissection technique is usually practiced for getting the adequate length of hilar structures. However, the problems with high hilar dissection inducted the authors to tailor the technique over time. In this report, a modified technique of recipient hepatectomy characterised by the artery-first approach is described. This technique is good in terms of preventing arterial dissection and minimising the anhepatic phase. Key Words: Recipient hepatectomy, Hepatoduodenal dissection, Liver transplantation, Technique.

Safety of glucose-6 phosphate dehydrogenase deficient donors in living right lobe liver donation.

BACKGROUND: The literature lacks data on World Health Organization (WHO) class II and III deficient liver donors who underwent right hepatectomy during living donor liver transplantation (LDLT). METHODS: In this prospective cohort study, we compared the perioperative outcomes of 15 glucose-6 phosphate dehydrogenase (G6PD) deficient living liver donors with a matched cohort of 39 nondeficient living liver donors undergoing right lobe donation. RESULTS: Out of 15 G6PD deficient donors, four (26.67%) donors had class II, and 11 (73.34%) had class III G6PD deficiency. The mean postoperative trough hemoglobin level was significantly lower in the deficient group than the nondeficient group (9.38 ± 1.59 g/dL vs. 10.27 ± .91 g/dL, p = .046). The mean peak indirect bilirubin level was significantly higher in the deficient group than the nondeficient group (2.22 ± 1.38 mg/dL vs. 1.40 ± .89 mg/dL, p = .047), and a similar trend was observed in total serum bilirubin (3.99 ± 2.57 mg/dL vs. 2.99 ± 1.46 mg/dL, p = .038). Biochemical evidence of hemolysis was found only in three (20%) deficient donors, but none of them needed a blood transfusion. No mortality was observed in either group. All other parameters, including demographics, operative parameters, graft characteristics, and hospital stay were comparable between both groups (p > .05). CONCLUSION: G6PD deficiency with WHO class II and above should not be considered a contraindication for right lobe donation.

Small-for-Size versus Standard-Size Graft in Living Donor Liver Transplantation.

OBJECTIVE: To compare the outcome of small-for-size grafts versus standard-size grafts regarding the frequency of postoperative complications, early graft dysfunction, and 1-year survival. STUDY DESIGN: Retrospective cohort study. PLACE AND DURATION OF STUDY: Pir Abdul Qadir Shah Jeelani Institute of Medical Sciences (PAQSJIMS) Hospital, Gambat, Sindh, Pakistan from March 2019 to April 2020. METHODOLOGY: A total of 147 living donor liver transplant recipients' data were retrospectively evaluated. Study participants were divided into two groups; small-for-size graft (GRWR <0.8%) and standard-size graft (GRWR >0.8%). Recipients' demographics, graft characteristics, operative parameters, postoperative complications, and graft survival were compared in both groups. RESULTS: Out of 147 recipients, 21 were found to have small-for-size graft, while 126 patients had the standard-size graft. Mean GRWR in small-for-size graft group was 0.73 + 0.4 (0.63-0.79), while 0.93 + 0.82 (0.81-3.0) in standard-size graft group. A statistically significant difference was found while comparing body mass index (p <0.001), hepatic venous reconstruction (p = 0.013), and liver attenuation index (p <0.001) between both study groups. While all other recipient and donor characteristics, demographical data, operative variables, postoperative lab, and complications were comparable in both groups (p >0.05). Kaplan-Meier analysis showed that 1-year survival rate for small-for-size graft recipients was 90.5%, while the survival rate for the standard-size graft was 96.0% (p = 0.272). CONCLUSION: Frequency of post-op complications was comparable in both groups. The graft survival in small-for-size grafts was as good as for standard-size grafts. Key Words: Living donor liver transplantation, GRWR, Small-for-size graft, Standard-size graft.

Challenges of continuation of live liver donor programme during COVID-19 pandemic in Pakistan: outcomes and lessons learned.

BACKGROUND: COVID-19 pandemic has globally affected healthcare including the transplantation programmes. MATERIALS AND METHODS: We retrospectively studied the impact of COVID-19 on live liver donor (LLD) programme at liver transplant centre in Gambat, Pakistan. Standard operative procedures (SOPs) including COVID-19 nasopharyngeal swab PCR, CT scans, personal protective equipment use, 6-feet distancing were developed for LLD and transplant team to mitigate COVID-19 exposure. We compared the complications, healthcare utilisation (hospital stay, readmission) and mortality between two LLD cohorts-before and during COVID-19 pandemic from March 2019 to December 2020. RESULTS: During study period 300 LLD surgeries were performed. There was an increase in rate of LLDs from 132 (44%) in pre-COVID to 168 (56%) during COVID-19 era. Average numbers of transplants per month performed during pre-COVID and during COVID-19 era were 10.1 and 14, respectively. No donor has developed COVID-19 infection during hospitalisation. Rate of all LLD complications (32 (21.47%) and 49 (29.16%), p=0.43), uneventful discharges (120/168 (71.4%) and 88/132 (66.6%), p<0.05), mean hospital stay (6±2 days and 5±2 days, p=0.17) and readmission (5 (4%) and 3 (1.8%), p=0.43) were similar during the pre-COVID and COVID-19 era. No donor mortality was observed during study period. CONCLUSION: With the implementation of mindful SOPs, rate of LLD increased without any case of COVID-19 infection. Our SOPs were helpful in continuation of LLD programme in a developing country during COVID-19 pandemic.

Hepatic hemangioendothelioma - A rare case report.

INTRODUCTION AND IMPORTANCE: Hepatic hemangioendothelioma (HHE) is a very rare mild-moderate malignant tumor of the hepatic vascular endothelium. The etiology is yet not fully understood. Patients can be asymptomatic or may present with non-specific symptoms or hepatic insufficiency. CT and MRI scans show various radiographic features but a definitive diagnosis can be made with histological analysis and immunohistochemistry. Here we report a case of a patient who presented with a non-resectable disease for which living donor liver transplantation was done. CASE PRESENTATION: A 19-year-old female patient presented with intermittent moderate dull pain in the right hypochondrium for 9 months. Examination revealed mild tender hepatomegaly. On abdominal ultrasound, two hypoechoic lesions were noted in both lobes of the liver that were confirmed on CT scan. Histologic examination of the ultrasound-guided fine-needle aspiration cytology of the voluminous right lobe lesion clinched the diagnosis of HHE. The patient underwent successful living donor liver transplantation due to the multifocal bi-lobar nature of the lesions. At 8 months follow up, she is fine and doing well. CONCLUSION: HHE is a very rare mild-moderate malignant tumor of hepatic vascular origin. Resection is the preferable treatment option in patients with resectable disease. However, liver transplantation has become the treatment of choice for patients with non-resectable multifocal and bi-lobar lesions. The long-term outcome of this malignancy is not fully known and there is a need for long-term follow-up studies to determine the actual recurrence rate of this disease.

Primary biliary cirrhosis in early childhood - A rare case report.

INTRODUCTION AND IMPORTANCE: Primary biliary cirrhosis (PBC) is a chronic and progressive autoimmune liver disease with no known etiology. This disease is mainly characterized by granulomatous destruction of intrahepatic biliary ducts, severe peri-portal inflammation, and ultimate progress to liver fibrosis and cirrhosis. Here, we report a five-year-old girl diagnosed with PBC, presented to us with end-stage liver disease for liver transplantation. Our patient successfully underwent liver transplantation with an uneventful recovery. This case highlights the need for awareness to report further PBC cases in the pediatric age group. CASE PRESENTATION: A five-year old female child presented with a 6 months history of progressive jaundice. She had multiple admissions for hepatic encephalopathy and this time she was admitted for hepatic transplantation. On examination, she was icteric and had hepatomegaly. After thorough workup, she underwent successful hepatic transplantation and was alright post-operatively. At 6 months follow up, she is doing well. CONCLUSION: PBC is rare in childhood. The natural history and exact incidence of PBC in childhood are not known. Hence, there is a need for awareness to report further PBC cases in the pediatric age group.