Minimizing Incision in Living Donor Liver Transplantation: Initial Experience and Comparative Analysis of Upper Midline Incision in 115 Recipients.

Living donor liver transplantation (LDLT) needs "Mercedes Benz" or "J-shaped" incision, causing short and long-term complications. An upper midline incision (UMI) is less invasive alternative but technically challenging. Reporting UMI for recipients in LDLT vs. conventional J-shaped incision. Retrospective analysis, July 2021 to December 2022. Peri-operative details and post-transplant outcomes of 115 consecutive adult LDLT recipients transplanted with UMI compared with 140 recipients with J-shaped incision. Cohorts had similar preoperative and intraoperative variables. The UMI group had significant shorter time to ambulation (3 ± 1.6 vs. 3.6 ± 1.3 days, p = 0.001), ICU stay (3.8 ± 1.3 vs. 4.4 ± 1.5 days, p = 0.001), but a similar hospital stay (15.6±7.6 vs. 16.1±10.9 days, p = 0.677), lower incidence of pleural effusion (11.3% vs. 27.1% p = 0.002), and post-operative ileus (1.7% vs. 9.3% p = 0.011). The rates of graft dysfunction (4.3% vs. 8.5% p = 0.412), biliary complications (6.1% vs. 12.1% p = 0.099), 90-day mortality (7.8% vs. 12.1% p = 0.598) were similar. UMI-LDLT afforded benefits such as reduced pleuropulmonary complications, better early post-operative recovery and reduction in scar-related complaints in the medium-term. This is a safe, non-inferior and reproducible technique for LDLT.

Effect of dulaglutide on liver fat in patients with type 2 diabetes and NAFLD: randomised controlled trial (D-LIFT trial).

AIMS/HYPOTHESIS: Liraglutide, a daily injectable glucagon-like peptide-1 receptor (GLP-1r) agonist, has been shown to reduce liver fat content (LFC) in humans. Data regarding the effect of dulaglutide, a once-weekly GLP-1r agonist, on human LFC are scarce. This study examined the effect of dulaglutide on LFC in individuals with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). METHODS: Effect of dulaglutide on liver fat (D-LIFT) was a 24 week, open-label, parallel-group, randomised controlled trial to determine the effect of dulaglutide on liver fat at a tertiary care centre in India. Adults (n = 64), who had type 2 diabetes and MRI-derived proton density fat fraction-assessed LFC of ≥6.0% at baseline, were randomly assigned to receive dulaglutide weekly for 24 weeks (add-on to usual care) or usual care, based on a predefined computer-generated number with a 1:1 allocation that was concealed using serially numbered, opaque, sealed envelopes. The primary endpoint was the difference of the change in LFC from 0 (baseline) to 24 weeks between groups. The secondary outcome measures included the difference of the change in pancreatic fat content (PFC), change in liver stiffness measurement (LSM in kPa) measured by vibration-controlled transient elastography, and change in liver enzymes. RESULTS: Eighty-eight patients were screened; 32 were randomly assigned to the dulaglutide group and 32 to the control group. Overall, 52 participants were included for per-protocol analysis: those who had MRI-PDFF data at baseline and week 24. Dulaglutide treatment resulted in a control-corrected absolute change in LFC of -3.5% (95% CI -6.6, -0.4; p = 0.025) and relative change of -26.4% (-44.2, -8.6; p = 0.004), corresponding to a 2.6-fold greater reduction. Dulaglutide-treated participants also showed a significant reduction in γ-glutamyl transpeptidase (GGT) levels (mean between-group difference -13.1 U/l [95% CI -24.4, -1.8]; p = 0.025) and non-significant reductions in aspartate aminotransferase (AST) (-9.3 U/l [-19.5, 1.0]; p = 0.075) and alanine aminotransferase (ALT) levels (-13.1 U/l [-24.4, 2.5]; p = 0.10). Absolute changes in PFC (-1.4% [-3.2, 0.3]; p = 0.106) and LSM (-1.31 kPa [-2.99, 0.37]; p = 0.123) were not significant when comparing the two groups. There were no serious drug-related adverse events. CONCLUSIONS/INTERPRETATION: When included in the standard treatment for type 2 diabetes, dulaglutide significantly reduces LFC and improves GGT levels in participants with NAFLD. There were non-significant reductions in PFC, liver stiffness, serum AST and serum ALT levels. Dulaglutide could be considered for the early treatment of NAFLD in patients with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03590626 FUNDING: The current study was supported by an investigator-initiated study grant from Medanta-The Medicity's departmental research fund and a grant from the Endocrine and Diabetes Foundation (EDF), India. Graphical abstract.

Is Portal Inflow Modulation Always Necessary for Successful Utilization of Small Volume Living Donor Liver Grafts?

Although the well-accepted lower limit of the graft-to-recipient weight ratio (GRWR) for successful living donor liver transplantation (LDLT) remains 0.80%, many believe grafts with lower GRWR may suffice with portal inflow modulation (PIM), resulting in equally good recipient outcomes. This study was done to evaluate the outcomes of LDLT with small-for-size grafts (GRWR <0.80%). Of 1321 consecutive adult LDLTs from January 2012 to December 2017, 287 (21.7%) had GRWR <0.80%. PIM was performed (hemiportocaval shunt [HPCS], n = 109; splenic artery ligation [SAL], n = 14) in 42.9% patients. No PIM was done if portal pressure (PP) in the dissection phase was <16 mm Hg. Mean age of the cohort was 49.3 ± 9.1 years. Median Model for End-Stage Liver Disease score was 14, and the lowest GRWR was 0.54%. A total of 72 recipients had a GRWR <0.70%, of whom 58 underwent HPCS (1 of whom underwent HPCS + SAL) and 14 underwent no PIM, whereas 215 had GRWR between 0.70% and 0.79%, of whom 51 and 14 underwent HPCS and SAL, respectively. During the same period, 1034 had GRWR ≥0.80% and did not undergo PIM. Small-for-size syndrome developed in 2.8% patients. Three patients needed shunt closure at 1 and 4 weeks and 60 months. The 1-year patient survival rates were comparable. In conclusion, with PIM protocol that optimizes postperfusion PP, low-GRWR grafts can be used for appropriately selected LDLT recipients with acceptable outcomes.

Living Donor Liver Transplantation for Acute-on-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute decompensation of previously diagnosed or undiagnosed liver disease with organ failure(s) with high short-term mortality. This study was conducted to report the outcomes of living donor liver transplantation (LDLT) in ACLF and assess the survival benefit of liver transplantation (LT) in these patients. It was a retrospective study of 218 ACLF patients on the basis of European Association for the Study of the Liver (EASL)-chronic liver failure criteria from January 2014 through November 2017. Patients were considered for LDLT if there was no improvement on standard medical therapy for 5-10 days. Prior to LDLT, active sepsis was excluded/treated, and renal, circulatory, and respiratory failures were improved to the greatest extent possible. The mean age was 42.9 years, and 181 patients were male. Sepsis was the most common acute precipitating event followed by alcohol. Of the patients, 35 (16.1%), 66 (30.3%), and 117 (53.7%) were classified into ACLF grades 1, 2, and 3, respectively. Although 80% of the ACLF 1 group and 72.7% of the ACLF 2 group underwent LDLT, only 35% of the ACLF 3 group could undergo LDLT. The circulatory and respiratory failures at admission were significantly higher in the nontransplant group with poor subsequent response to standard medical therapy, exclusion from LDLT, and poor outcomes. None of the patients on high support for circulatory and respiratory failure underwent LDLT. Posttransplant survival at 1 year was comparable among different grades of ACLF (92.9%, 85.4%, and 75.6%; P = 0.15). Among patients in the ACLF 3 group, survival at 90 days was extremely poor in those who could not undergo LDLT (5.9% versus 78%; P < 0.001). In conclusion, LDLT results in good survival with acceptable post-LT morbidity in patients with ACLF.

High MELD score does not adversely affect outcome of living donor liver transplantation: Experience in 1000 recipients.

In countries where deceased organ donation is scarce, there is a big gap between demand and supply of organs and living donor liver transplantation (LDLT) plays an important role in meeting this unmet need. This study was conducted to analyze the effect of pretransplant Model for End-stage Liver Disease (MELD) score on outcomes following LDLT. The outcome of 1000 patients who underwent LDLT from July 2010 to March 2015 was analyzed retrospectively. Patients were grouped into low MELD<25 and high MELD ≥25 score to compare short-term outcomes. Cumulative overall survival rates were calculated using Kaplan-Meier methods. A total of 849 recipients were in low MELD group (Mean MELD=16.90±9.2) and 151 were in high MELD group (Mean MELD=28.77±7.2). No significant difference in etiology of CLD was observed between groups except for a higher prevalence of hepatitis C virus (29.6% vs 19.9%, P=.01) in low MELD patients. No significant difference was observed in 1-year survival (88.5% vs 84.1%, P=.12) between the groups. The multivariate analysis showed that pretransplant MELD score does not predict survival of recipients. Pretransplant high MELD score does not adversely affect outcomes after LDLT. In view of shortage of deceased organs, LDLT can be a good option in high MELD recipients.

Prediction of nonalcoholic fatty liver in prospective liver donors.

BACKGROUND: Metabolic risk factors should be important in addition to imaging for prediction of steatosis in prospective liver donors. MATERIALS AND METHODS: The study group included all prospective liver donors who had a liver biopsy during workup. Risk factors of metabolic syndrome were analyzed, and body mass index (BMI) ≥25 kg/m2 was used in place of waist circumference. Three BMI cutoffs (25, 28, and 30 kg/m2 ) and two CT-measured liver attenuation index (LAI) cutoffs (<5 and ≤10) were used for steatosis assessment of ≥5%, ≥10%, and ≥20%. RESULTS: Of the 573 prospective donors (307 females), 282 (49.2%) donors had nonalcoholic fatty liver (NAFL). When donors with NAFL were compared with donors having normal histology, multivariate analysis showed BMI, ALT, triglycerides, and LAI as significant predictors of NAFL. BMI ≥25 kg/m2 and LAI <10 were better cutoffs. The presence of ≥2 metabolic risk factors had better sensitivity than CT-LAI for the presence of NAFL and ≥20% steatosis (58% and 54% vs 47% and 22%, respectively, for CT-LAI ≤10). The presence of LAI >10 and <2 metabolic risk factors predicted <10% steatosis with 96% specificity and 92% positive predictive value. CONCLUSION: The presence of ≥2 metabolic risk factors improves sensitivity of CT-LAI for prediction of donor steatosis.

Sarcopenic obesity with metabolic syndrome: a newly recognized entity following living donor liver transplantation.

OBJECTIVE: There are limited data about sarcopenic obesity in liver transplant recipients. METHODS: Living donor liver transplant recipients with at least 12 months of follow-up were included. Metabolic syndrome (MS) was defined as ≥ 3 ATP III criteria. Body composition was assessed by bioelectrical impedance. Immunosuppression protocol included short-term steroids, mycophenolate and calcineurin inhibitors (mainly tacrolimus). Data are shown as percentage, mean ± SD, or median (25-75 IQR). RESULTS: The study comprised 82 patients (males 69), aged 50.5 ± 10.65 yr, and follow-up 24 (12-38.5) months. Etiology for cirrhosis was alcohol 29%, hepatitis C 22%, hepatitis B 17%, cryptogenic 24%, and others 7%. Post-transplant sarcopenic obesity was present in 72 (88%), and MS was present in 43 (52%) of recipients with no significant difference among etiologies. There were significant differences between pre- and post-transplant body mass index, triglycerides, high-density lipoprotein, low-density lipoprotein (p = 0.000 for all), prevalence of hypertension (18% vs. 39%), and diabetes (20% vs. 56%). Patients with sarcopenic obesity had significantly higher body mass index, waist circumference, and MS (57% vs. 20%, p = 0.041) when compared to patients without sarcopenic obesity. CONCLUSION: Despite resuming routine activities, the majority of liver transplant recipients develop sarcopenic obesity and MS. The importance and role of appropriate nutrition and exercise after transplantation merits further investigation.

Estimation of normal values of serum transaminases based on liver histology in healthy Asian Indians.

BACKGROUND AND AIM: Liver biopsy-based studies have shown that serum levels of aminotransferases are lower than conventional cut-off of 40 IU/mL in persons with normal histology. There is no such study in Indian population based on liver histology. This study aims to estimate normal values of serum aminotransferases in healthy Indian population with normal liver histology. METHODS: This retrospective study includes all liver donors who underwent liver donation at our centre and had a preoperative liver biopsy done for various reasons. All the donors had negative viral markers. Nonalcoholic fatty liver (NAFL) was defined as > 5% hepatocytes having steatosis and no changes of steatohepatitis. RESULTS: The study included 331 donors (147 males) with the ages of 35.7 ± 10.2 years. NAFL was present in 167 donors (50.4%). In comparison with male donors with normal histology (n = 67), donors with NAFL (n = 80) had significantly higher age, body mass index, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, gamma-glutamyl transpeptidase, total cholesterol, low-density lipoprotein, and fasting blood sugar. In comparison with female donors with normal histology, donors with NAFL had significantly higher body mass index, ALT, and triglycerides; however, there was no significant difference regarding other parameters. Of the AST and ALT in normal histology donors, 95th percentile were 33.8 IU/L and 38.6 IU/L for males and 31 IU/L and 35.2 IU/L for females. Twenty-five donors had lean NAFL (body mass index < 23 kg/m2). CONCLUSION: Serum aminotransferase values in healthy Asian Indian population with normal histology are provided. Histological NAFL is present in half of apparently normal donors, and it has different clinical and biochemical associations in males and females.

Managing HBV and HCV Infection Pre- and Post-liver Transplant.

Hepatitis B and C are common causes of end-stage liver disease and etiologies of liver transplantation. It is important to prevent recurrence in cases of hepatitis B. Nucleos(t)ide analogs are the mainstay of HBV treatment before (in patients with decompensated cirrhosis) and after liver transplantation. After the introduction of direct-acting antivirals, the treatment of HCV has become considerably easy. In patients with advanced HCV-related cirrhosis, it is better to do transplantation first and treat them after liver transplantation. The sustained virological response rates have improved from 8 to 50% in the interferon era to 90% in the direct-acting antivirals era. In the current review, we discuss the treatment of HBV and HCV before and after liver transplantation.

Endoscopic Ultrasound-guided Liver Biopsy: Missing the Limitations in the Hype.

Endoscopic ultrasound-guided liver biopsy is increasingly being performed at several centers. It is also being promoted at endoscopy conferences. The currently available literature does not support the routine use of endoscopic ultrasound-guided liver biopsy as results are either inferior or comparable to percutaneous liver biopsy. We discuss the technical limitations of endoscopic ultrasound-guided liver biopsy when compared to percutaneous liver biopsy and the comparative studies in the current review. The routine use of endoscopic ultrasound-guided liver biopsy should be discouraged as it may get less tissue, the complication rate is similar and it is more costly.

Post-transplant Non-alcoholic Fatty Liver Disease and Metabolic Syndrome After Living Donor Liver Transplantation in Indians.

Background: Post-transplant non-alcoholic fatty liver disease (NAFLD) is common but is not well described in the living donor liver transplantation (LDLT) setting. Methods: The study was conducted at a large volume LDLT center in north India. Adult (age >18 years at the time of transplant) liver transplantation (LT) recipients were included. Patients with any history of alcohol use were excluded. The study was conducted prospectively from July 2022 to April 2023, and all patients with a minimum of 1-year follow-up after transplant attending outpatient services were included. NAFLD was diagnosed by ultrasound showing steatosis in the absence of other etiologies. Results: The study cohort included 103 males and 14 females, aged 48 ± 10 years at the time of LT and 53 ± 10 years at the time of inclusion in the study. The median follow-up from LT was 62 (32-97 months). A total of 39 (33%) patients suffered from post-LT NAFLD. NAFLD was recurrent in 9/23 (39%, in patients with NASH or cryptogenic cirrhosis as etiology of LT) and de novo in 30/94 (31%). Pre and post-LT higher body mass index, presence of diabetes and higher serum triglycerides values were associated with the development of post-LT NAFLD. Post-transplant metabolic syndrome was present in 58/95 (61%) LDLT recipients using HbA1c 5.7 to 6.4 as a marker of prediabetes. Conclusion: Post-LT NAFLD was present in one-third of the patients and metabolic syndrome in the majority of the patients at a median follow-up of 62 months after LDLT.

Cytomegalovirus Duodenitis Causing Persistent Hypoalbuminemia and Ascites After Liver Transplantation.

A 44-year-old male had persistent hypoalbuminemia and ascites after liver transplantation. Imaging of the liver and gastrointestinal system was normal. Urine examination was negative for proteinuria. A diagnosis of protein-losing enteropathy was suspected, and a duodenal biopsy was done. Duodenal biopsy was positive for cytomegalovirus (CMV). The patient improved with CMV treatment.

APASL clinical practice guidelines on the management of acute kidney injury in acute-on-chronic liver failure.

Acute-on-chronic liver failure (ACLF) is a syndrome that is characterized by the rapid development of organ failures predisposing these patients to a high risk of short-term early death. The main causes of organ failure in these patients are bacterial infections and systemic inflammation, both of which can be severe. For the majority of these patients, a prompt liver transplant is still the only effective course of treatment. Kidneys are one of the most frequent extrahepatic organs that are affected in patients with ACLF, since acute kidney injury (AKI) is reported in 22.8-34% of patients with ACLF. Approach and management of kidney injury could improve overall outcomes in these patients. Importantly, patients with ACLF more frequently have stage 3 AKI with a low rate of response to the current treatment modalities. The objective of the present position paper is to critically review and analyze the published data on AKI in ACLF, evolve a consensus, and provide recommendations for early diagnosis, pathophysiology, prevention, and management of AKI in patients with ACLF. In the absence of direct evidence, we propose expert opinions for guidance in managing AKI in this very challenging group of patients and focus on areas of future research. This consensus will be of major importance to all hepatologists, liver transplant surgeons, and intensivists across the globe.