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.

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.

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.

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.

Post Living Donor Liver Transplantation Small-for-size Syndrome: Definitions, Timelines, Biochemical, and Clinical Factors for Diagnosis: Guidelines From the ILTS-iLDLT-LTSI Consensus Conference.

BACKGROUND: When a partial liver graft is unable to meet the demands of the recipient, a clinical phenomenon, small-for-size syndrome (SFSS), may ensue. Clear definition, diagnosis, and management are needed to optimize transplant outcomes. METHODS: A Consensus Scientific committee (106 members from 21 countries) performed an extensive literature review on specific aspects of SFSS, recommendations underwent blinded review by an independent panel, and discussion/voting on the recommendations occurred at the Consensus Conference. RESULTS: The ideal graft-to-recipient weight ratio of ≥0.8% (or graft volume standard liver volume ratio of ≥40%) is recommended. It is also recommended to measure portal pressure or portal blood flow during living donor liver transplantation and maintain a postreperfusion portal pressure of <15 mm Hg and/or portal blood flow of <250 mL/min/100 g graft weight to optimize outcomes. The typical time point to diagnose SFSS is the postoperative day 7 to facilitate treatment and intervention. An objective 3-grade stratification of severity for protocolized management of SFSS is proposed. CONCLUSIONS: The proposed grading system based on clinical and biochemical factors will help clinicians in the early identification of patients at risk of developing SFSS and institute timely therapeutic measures. The validity of this newly created grading system should be evaluated in future prospective studies.

The Renal Histological Correlates of Refractory Renal Dysfunction After Liver Transplantation.

Background: Kidney dysfunction is common after liver transplantation (LT) and is often attributed to calcineurin inhibitors (CNIs). Very few studies have looked at histological causes. Material and methods: The study is a retrospective analysis of histological findings and diagnosis in all patients who underwent a kidney biopsy after LT from 2010 to 2020. Data are shown as mean ± standard deviation or medians (25-75 interquartile range). Results: The study cohort consisted of 26 patients (25 males, 1 female), aged 55 ± 7 years at the time of the kidney biopsy. Kidney biopsies were done at 27.5 (6.7-60.7) months after LT. At the time of the kidney biopsy, the median serum creatinine was 2.10 (1.50-2.86) mg/dl and proteinuria was 3.8 (1.8-5.9) gm/day. Twenty-four (92%) patients were on CNIs. The diagnoses on kidney biopsies were diabetic nephropathy (n = 7), focal segmental glomerulosclerosis (n = 4), CNI nephrotoxicity (n = 3), IgA nephropathy (n = 4), chronic glomerulonephritis (n = 3), hypertensive nephropathy (n = 1), membranous glomerulonephritis (n = 1), acute on chronic interstitial nephritis (n = 1), and C1q nephropathy (n = 1), and the sample was inadequate in one patient. A total of sixteen patients had progression of kidney disease. The kidney function remained stable/improved in 6 (23%) patients, follow-up data were not available for 4 patients. Fourteen (53.8%) patients (including one with CNI nephrotoxicity) required hemodialysis at 13.5 (5.7-29) months after the kidney biopsy. Conclusion: Although the kidney biopsy diagnosed the cause of unexplained renal insufficiency in LT recipients, the majority of patients progressed to end-stage renal disease despite treatment modifications. The use of CNIs was an uncommon cause of renal impairment.

LTSI Consensus Guidelines: Preoperative Pulmonary Evaluation in Adult Liver Transplant Recipients.

The relationship between chronic liver disease and respiratory symptoms and hypoxia is well recognized. Over the last century, three pulmonary complications specific to chronic liver disease (CLD) have been characterized: hepatopulmonary syndrome, portopulmonary hypertension, and hepatic hydrothorax. Apart from that coexisting pulmonary disease like chronic obstructive lung disease and interstitial lung disease also complicate the outcomes after liver transplantation (LT). Assessment for evaluation of underlying pulmonary disorders is essential to improve outcomes in patients with CLD, posted for LT. This consensus guideline of the Liver Transplant Society of India (LTSI) provides a comprehensive review of pulmonary issues in CLD, related and unrelated to underlying liver disease and gives recommendations for pulmonary screening in specific clinical scenarios in adults with chronic liver disease planned for LT. This document also aims to standardize the strategies for preoperative evaluation of these pulmonary issues in this subset of patients. Proposed recommendations were based on selected single case reports, small series, registries, databases, and expert opinion. The paucity of randomized, controlled trials in either of these disorders was noted. Additionally, this review will highlight the lacunae in our current evaluation strategy, challenges faced, and will provide direction to potentially useful futuristic preoperative evaluation strategies.

Indian National Association for Study of the Liver (INASL) Guidance Paper on Nomenclature, Diagnosis and Treatment of Nonalcoholic Fatty Liver Disease (NAFLD).

Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease globally and in India. The already high burden of NAFLD in India is expected to further increase in the future in parallel with the ongoing epidemics of obesity and type 2 diabetes mellitus. Given the high prevalence of NAFLD in the community, it is crucial to identify those at risk of progressive liver disease to streamline referral and guide proper management. Existing guidelines on NAFLD by various international societies fail to capture the entire landscape of NAFLD in India and are often difficult to incorporate in clinical practice due to fundamental differences in sociocultural aspects and health infrastructure available in India. A lot of progress has been made in the field of NAFLD in the 7 years since the initial position paper by the Indian National Association for the Study of Liver on NAFLD in 2015. Further, the ongoing debate on the nomenclature of NAFLD is creating undue confusion among clinical practitioners. The ensuing comprehensive review provides consensus-based, guidance statements on the nomenclature, diagnosis, and treatment of NAFLD that are practically implementable in the Indian setting.

South Asian Transplant Infectious Disease Guidelines for Solid Organ Transplant Candidates, Recipients, and Donors.

These guidelines discuss the epidemiology, screening, diagnosis, posttransplant prophylaxis, monitoring, and management of endemic infections in solid organ transplant (SOT) candidates, recipients, and donors in South Asia. The guidelines also provide recommendations for SOT recipients traveling to this region. These guidelines are based on literature review and expert opinion by transplant physicians, surgeons, and infectious diseases specialists, mostly from South Asian countries (India, Pakistan, Bangladesh, Nepal, and Sri Lanka) as well as transplant experts from other countries. These guidelines cover relevant endemic bacterial infections (tuberculosis, leptospirosis, melioidosis, typhoid, scrub typhus), viral infections (hepatitis A, B, C, D, and E; rabies; and the arboviruses including dengue, chikungunya, Zika, Japanese encephalitis), endemic fungal infections (mucormycosis, histoplasmosis, talaromycosis, sporotrichosis), and endemic parasitic infections (malaria, leishmaniasis, toxoplasmosis, cryptosporidiosis, strongyloidiasis, and filariasis) as well as travelers' diarrhea and vaccination for SOT candidates and recipients including travelers visiting this region. These guidelines are intended to be an overview of each topic; more detailed reviews are being published as a special supplement in the Indian Journal of Transplantation .

Liver Stiffness Values in Persons with Normal Histology.

Background and aims: Most studies to date have focused on liver stiffness measurement (LSM) in patients with different chronic liver diseases, and normal LSM is defined based on normal liver function tests or the absence of fibrosis. Very few studies have defined LSM based on completely normal liver biopsies. The current study was done to define the distribution of LSM values in individuals with normal liver biopsies. Methods: All prospective liver donors presenting to Medanta, the Medicity hospital between September 2020 and September 2021 fulfilling the eligibility criteria were included in this study. Results: A total of 63 donors (36 females and 27 males) were included in the study, 37 (58.7%) donors had normal liver biopsies, and 26 (41.2%) donors showed the presence of non-alcoholic fatty liver disease. LSM values in the normal liver histology group were 5.01 ± 1.99 kPa by the M probe and 5.34 ± 2.25 kPa by the XL probe. Even though the correlation was weak (r = 0.29, P = 0.03), M probe LSM correlated positively with body mass index. There was a good correlation between the LSM measured by the M probe and the XL probe (r = 0.73, P = <0.001). Conclusions: LSM value in the biopsy-proven normal liver histology group was 5.01 ± 1.99 by the M probe and 5.34 ± 2.25 by the XL probe.

Nonalcoholic Fatty Liver Disease in Living Donor Liver Transplant Recipients: A Histology-Based Study.

Background: Recurrent or de novo nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are common after liver transplantation (LT) and may be associated with rapid progression to fibrosis; however, there is limited data in this regard after living donor liver transplantation (LDLT). Material and methods: This is a retrospective study at a high volume LDLT center of all liver biopsies performed in patients with post-transplant NAFLD diagnosed on ultrasound of the abdomen. Liver biopsy was indicated for raised transaminases and/or high liver stiffness on TE. The association between these prebiopsy parameters and inflammation and fibrosis on histology was analyzed. Data are shown as mean ± standard deviation or median (25-75 interquartile range). Results: The study cohort consisted of 31 males and 3 females, aged 43 ± 10 years. The LT to liver biopsy interval was 44 (28-68) months. The prebiopsy AST and ALT were 71 (38-119) and 66 (50-156), respectively. The histology suggested no nonalcoholic steatohepatitis (NASH) in 7 (20%), borderline NASH in 15 (44%), and NASH in 12 (35%) patients. A total of 15 patients (44%) had stage 1 or stage 2 fibrosis. The proportion of patients having fibrosis was significantly higher in patients with NASH (83%) compared to patients with borderline NASH (33%) or no NASH (none had fibrosis, P = 0.001). Among 18 patients who underwent TE (on FibroScan), liver stiffness was significantly higher in patients with fibrosis [18.1 (9.7-22.5)] than in those without fibrosis [9.7 (4.0-12.7); P = 0.043]. Conclusion: Over a third of the LDLT recipients with post-transplant NAFLD developed NASH, and nearly half, borderline NASH 3-5 years after transplant. Most with established NASH also had fibrosis on histology. Prevention of risk factors and early diagnosis is warranted in these patients.

Diagnostic Accuracy and Optimal Cut-off of Controlled Attenuation Parameter for the Detection of Hepatic Steatosis in Indian Population.

Background and aims: Ultrasound of the liver is not good to pick up mild steatosis. Controlled attenuation parameter (CAP) evaluated in transient elastography (FibroScan) is widely available in India. However, data regarding the diagnostic accuracy and optimal cut-off values of CAP for diagnosing hepatic steatosis are scarce in Indian population. MRI-PDFF is an accurate technique for quantifying hepatic steatosis. Thus, this study examined the diagnostic accuracy and optimal cut-off values of CAP for diagnosing steatosis with MRI-PDFF as reference standard. Methods: A total of 137 adults underwent CAP and MRI-PDFF measurements prospectively. A subset of participants (n = 23) underwent liver biopsy as part of liver transplantation evaluation. The optimal cut-off values, area under the receiver operating characteristic (AUROC) curves, sensitivity, and specificity for CAP in detecting MRI-PDFF ≥5% and ≥10% were assessed. Results: The mean age and body mass index (BMI) were 44.2 ±10.4 years and 28.3 ±3.9 kg/m2, respectively. The mean hepatic steatosis was 13.0 ±7.7% by MRI-PDFF and 303 ±54 dB/m by CAP. The AUROC of CAP for detecting hepatic steatosis (MRI-PDFF ≥5%) was 0.93 (95% CI, 0.88-0.98) at the cut-off of 262 dB/m, and of MRI-PDFF ≥10% was 0.89 (95% CI, 0.84-0.94) at the cut-off of 295 dB/m. The CAP of 262 dB/m had 90% sensitivity and 91% specificity for detecting MRI-PDFF ≥5%, while the CAP of 295 dB/m had 86% sensitivity and 77% specificity for detecting MRI-PDFF ≥10%. Conclusions: The optimal cut-off of CAP for the presence of liver steatosis (MRI-PDFF ≥5%) was 262 dB/m in Indian individuals. This CAP cut-off was associated with good sensitivity and specificity to pick up mild steatosis.

Poor Outcomes after Recidivism in Living Donor Liver Transplantation for Alcohol-Related Liver Disease.

BACKGROUND: Recidivism in patients who underwent liver transplantation for alcohol-related liver disease (ALD) is shown to be associated with poor survival in some studies. METHODS: Living donor liver transplantation (LDLT) recipients for ALD with at least 2 years of follow-up and history of significant alcohol relapse were included. The recipients underwent LDLT from June 2010 to December 2016, and data were analyzed until June 2019. The cohort had a median follow-up of 54 (33-78 IQR) months. Recidivism (significant alcohol intake) was defined as >21 units per week. RESULTS: A total of 27 of 463 (5.8%) LDLT recipients (all men), aged 43.5 ± 9.6 years, had significant alcohol intake. A liver biopsy was performed on demand in 14 patients (in the presence of raised levels of liver enzymes or jaundice). The histological diagnoses in these patients were as follows: alcoholic hepatitis in 7 (50%), alcoholic hepatitis and acute cellular rejection or chronic rejection in 4 (28.5%), cirrhosis in 2 (14.2%), and acute cellular rejection and cirrhosis in 1 (7.1%) patient. Four of 5 patients with a biopsy diagnosis of acute or chronic rejection were noncompliant with immunosuppression. Six of these patients died. The mortality after 1 year of transplant was significantly more in patients with recidivism. CONCLUSION: Recidivism was associated with significant morbidity and mortality after liver transplantation.