Liver Transplantation: Protocol for Recipient Selection, Evaluation, and Assessment

Liver transplantation (LT) is the definitive therapy for patients with end-stage liver disease, acute failure, acute-on-chronic hepatocellular carcinoma, and metabolic diseases. The acceptance of LT in Asia has been gradually increasing so expertise to perform LT. Preparing a patient cirrhosis most important aspect successful preparation begins first index decompensation cirrhosis. Patients planned should undergo thorough screening infections, complete cardiac, pulmonology, psychosocial evaluation pre-LT. In this review, we discuss indications contraindications assessment disease treatment failure (ALF). humans was attempted 1963 Colorado, USA, by Starzl et al. However, human performed only 1967.1Starzl T.E. Marchioro T.L. Vonkaulla K.N. Hermann G. Brittain R.S. Waddell W.R. Homotransplantation humans.Surg Gynecol Obstet. 1963; 117: 659-676PubMed Google Scholar,2Starzl Groth C.G. Brettschneider L. al.Orthotopic homotransplantation liver.Ann Surg. 1968; 168: 392-415Crossref PubMed Scholar 1980s, moved be therapeutic approach rather than an experimental modality. outcomes remained dismal, 1-year survival rate about 25% till invention calcineurin inhibitors, now widely used post-LT.3Haddad E.M. McAlister V.C. Renouf E. Malthaner R. Kjaer M.S. Gluud L.L. Cyclosporin versus tacrolimus transplanted patients.Cochrane Database Syst Rev. 2006; 2006Cd005161PubMed improved more 80%, along improvement overall morbidities.4Kim M. Hwang S. Ahn C.S. al.Twenty-year longitudinal follow-up after transplantation: single-center experience 251 consecutive patients.Korean J Transplant. 2022; 36: 45-53Crossref Scopus (2) India, Human Organ Transplantation Act passed 1994, deceased donor transplant (DDLT) 1998, followed shortly living (LDLT) 1998.5Narasimhan Living India.Hepatobiliary Surg Nutr. 2016; 5: 127-132PubMed Data from Indian Transplant Registry (ILTR, www.iltr.org), which went live August 2019, suggest that close 1800 LTs are every year around 90–100 centers. contrast Western world, where DDLT common, LDLT predominant India.6Choudhary N.S. Bhangui P. Soin A.S. India.Clin Dis (Hoboken). 19: 32-35Crossref Recent literature published large-volume centers India reports 3-year adult between 80–85% 61–75%, respectively, viral hepatitis alcoholic being common LT.6Choudhary Scholar,7Nidoni Kandagaddala Agarwal Dey Chikkala B.R. Gupta aged 60 years or older: large volume centre India.J Clin Exp Hepatol. 2021; 11: 3-8Abstract Full Text PDF (0) Several unique challenges loom field our country. number on wait-lists disproportionate organs available donors. major hindrance population lack access healthcare, indigent national policies, financial support precluding LT.8Kulkarni A.V. Premkumar Reddy D.N. Rao P.N. ascites management: perspective.Clin 234-238Crossref (3) often present high model (MELD) scores. Multiple hospital admissions before increase risk multidrug-resistant infections poorer post-LT.5Narasimhan Scholar,9Mah A. Wright Infectious considerations pre-transplant cirrhotic awaiting orthotopic transplantation.Curr Infect Rep. 18: 4Crossref (7) Scholar,10Kulkarni Gora B.A. al.Patients require higher healthcare utilization adequate optimization prior transplantation.Hepatology. 76 (Wiley 111 River St, Hoboken 07030-5774, NJ USA): S53-S54Google Poor management B C, as well apathy dealing nonalcoholic steatohepatitis (NASH), contributor late referrals. Successful public-sector programs registry organ allocation lacking. Despite several constraints, private institutes performing LT, significantly recent years.11Nagral Nanavati Nagral India: at crossroads.J 2015; 329-340Abstract A sick potentially inappropriate candidate may have fewer 3 months not suitable LT.12Petrowsky H. Rana Kaldas F.M. al.Liver highest acuity recipients: identifying factors avoid futility.Ann 2014; 259: 1186-1194Crossref (134) Therefore, post-LT dependent appropriate selection recipient selection, evaluation, protocol. Common include decompensated cirrhosis, (ACLF), carcinoma (HCC), ALF, diseases (Table 1).Table 1Indications Transplantation.CausesAcute (ALF)-Viral hepatitis- Hepatitis (young), B, E (elderly)-Drug induced (Ex. ATT, CAM, Acetaminophen)-Wilson's disease-Autoimmune hepatitis-Amanita phalloides (mushroom) poisoning-Budd-Chiari syndrome-Other viruses- Dengue, EBV, CMV-Acute fatty pregnancy-Hemophagocytic lymphohistiocytosisMetabolic diseases-Wilson's disease-Familial amyloid polyneuropathy-Primary hyperoxaluria-Cystic fibrosis-Alpha-1 antitrypsin deficiency-Glycogen storage (type I type IV)-Tyrosinemia-Hemochromatosis-Acute intermittent porphyriaChronic disease/Cirrhosis due any cause-MELD >15-Child Cirrhosis portal hypertension-Standard MELD exception pointsCMV, cytomegalovirus; Epstein Barr Virus; MELD, disease; antitubercular treatment; UKELD, United KIngdom End-stage Disease; D-Delta MELD; HIV, immunodeficiency virus. Open table new tab CMV, prioritize since 2002. It initially modeled predict 3-month prognosis undergoing transjugular intrahepatic portosystemic shunt (TIPS) procedure.13Kamath P.S. Kim (MELD).Hepatology. 2007; 45: 797-805Crossref (1169) who <1 poor quality life without Weisner demonstrated ability score correctly rank mortality candidates aid prioritization.14Wiesner Edwards Freeman al.Model livers.Gastroenterology. 2003; 124: 91-96Abstract (2000) Three-month those scores <9, 10–19, 20–29, 30–39, >40 2%, 6%, 19.6%, 52.6, 71.3%, respectively.14Wiesner Implementing reduced median waiting time 981 days pre-MELD 564 2007.15Berg C.L. Steffick D.E. E.B. intestine States 1998-2007.Am 2009; 9: 907-931Abstract (138) observed very (≥35) had comparable fulminant hepatic failure.16Sharma Schaubel Gong Q. Guidinger Merion R.M. wait-list status-1A candidates.Hepatology. 2012; 55: 192-198Crossref (72) latter considered system confound geographical boundaries procurement.17Washburn K. Harper Klintmalm Goss J. Halff Regional sharing status 1 candidates: reduction waitlist mortality.Liver Transpl. 12: 470-474Crossref (18) Share 35 policy launched 2013, ensured cirrhotics advanced (MELD ≥ 35) given same failure.18Kwong A.J. Goel Mannalithara Improved posttransplant share 2018; 67: 273-281Crossref (33) With implementation policy, increased; however, contradictory, especially racially underprivileged sections HCC.18Kwong Scholar, 19Massie A.B. Chow E.K. Wickliffe C.E. al.Early changes distribution following 35.Am 15: 659-667Abstract (98) 20Croome K.P. Lee D.D. Harnois D. Taner C.B. Effects rule carcinoma.PLoS One. 2017; 12e0170673Crossref 21Goyes Danford C.J. Nsubuga J.P. Bonder Waitlist free Hispanic listed using UNOS database.Ann 23100304Crossref guidelines proposed Clinical Severity Score tool prioritizing LT.22Reddy Mathur S.K. Sudhindran al.National Allocation Policy (N-LAP) - consensus document Society nationally uniform grafts.J 2023; 13: 303-318https://doi.org/10.1016/j.jceh.2022.12.001Abstract This complex score, including modifiable clinical variables period, requires further validation. There were caveats initial system. Serum sodium level, easily measurable objective variable, correlates complications ascites, hepatorenal syndrome (HRS), mortality.23Ruf A.E. Kremers W.K. Chavez Descalzi V.I. Podesta L.G. Villamil F.G. Addition serum into predicts list better alone.Liver 2005; 336-343Crossref (350) study reported unit decrease levels 140 125, increases 5%.24Kim Biggins S.W. al.Hyponatremia among liver-transplant list.N Engl Med. 2008; 359: 1018-1026Crossref (974) Network Sharing (UNOS) included cutoff 137 capped 125. 7% each Thus, finding significant predictors 6-month candidates, incorporated “MELD-Na” score.25Biggins Terrault N.A. al.Evidence-based incorporation concentration MELD.Gastroenterology. 130: 1652-1660Abstract (548) latest modification, 3.0, addition female sex albumin capping creatinine mg/dl (instead 4 previously). 3.0 reclassifying approximately 9% individuals tier, chances women26Kim Heimbach J.K. al.MELD 3.0: updated modern era.Gastroenterology. 161: 1887-1895.e1884Abstract (55) 2).Table 2Modifications MELD.Name MELDYear introductionModificationsCommentsMELD XI2007Included bilirubin-Suited anticoagulationIntegrated (iMELD)2007Includes age-Increased accuracy predicting mortalityMELD Na2008Sodium-Serum predictor survivalD-MELD2009Donor age x score-<1600 survivalUKELD2011Similar Na, UK.Different coefficients-UKELD >49 >9% year-UKELD >60 = 50% mortalityRecalibrated MELD2013Multivariate recalibration-Predicting 6-week variceal bleedingReFit MELDReFit Na2017Updated coefficients, change upper lower bounds, incorporate sodium-improved predictionMELD Na LFI2017C-statistic 0.77 mortality.-Reclassify appropriately 19% non-delistingsMELD Lactate2020Lactate-Early inpatient 3.02021Albumin, Female added-More accurate prediction-Addresses disparityLFT, frailty index; sodium. LFT, Key message: scoring remains gold standard listing date. ALF covered detail elsewhere.27Biswas Shalimar Review article: failure- indication, prioritization, timing, referral.J Abstract incidence ACLF increased years.28Allen A.M. Moriarty Shah N.D. Larson J.J. Kamath Time trends health care burden chronic States.Hepatology. 64: 2165-2172Crossref (104) Although advances made these ill patients; remain absence Development multiorgan preclude ACLF, irrespective etiology, early improve survival.29Choudhury Vijayaraghavan Maiwall al.‘First week’ crucial period deciding failure.Hepatol Int. 1376-1388Crossref validity limited. having MELD-Na during admission, 0.7% ACLF-1, 1.9% ACLF-2, 2.7% ACLF-3 merely 3.5%, 7.3%, 4.2% 6 months.30Hernaez Liu Y. Kramer J.R. El-Serag H.B. Kanwal F. Model disease-sodium underestimates 90-day failure.J 2020; 73: 1425-1433Abstract (53) similar (33–40%) low (<25) compared <10% <25 no ACLF.31Chang Matheja Krzycki transplantation.Dig Dis. 54: 784-790Abstract Scholar,32Sundaram V. Jalan Wu T. al.Factors associated severe transplantation.Gastroenterology. 2019; 156: 1381-1391.e1383Abstract (160) valuable identified Asian Pacific Association Study Disease (APASL) criteria, mainly failure.33Laique S.N. Zhang N. Hewitt Bajaj Vargas H.E. Increased Rule: analysis 23100288Crossref 34Kumar Krishnamoorthy Tan H.K. Lui H.F. W.C. Change two weeks, indicator failure.Gastroenterol Rep (Oxf). 3: 122-127Crossref 35Lin B.Y. Zhou Geng al.High neutrophil-lymphocyte ratio indicates transplantation.World Gastroenterol. 21: 3317-3324Crossref (21) An ≥2 points 2 weeks can days, useful settings commonly performed.34Kumar Scholar,36Choudhary Saraf Saigal Factors unanswered questions.Gastroenterology. 157: 1162-1163Abstract assessed suitability sensitized regarding visit. HCC India.37Kumar Acharya Singh S.P. al.The National (INASL) prevention, diagnosis Puri recommendations.J (S3–s26)Abstract (41) 38Kumar al.2019 Update Consensus Prevention, Diagnosis, Management Hepatocellular Carcinoma II 10: 43-80Abstract (30) 39Kulkarni Fatima Sharma al.Lenvatinib unresectable carcinoma: experience.GastroHep. 407-408Crossref Milan criteria current LT.40EASL Practice Guidelines: carcinoma.J 69: 182-236Abstract (4453) Mazzaferro 4-year 75%, less 10–15% recurrence, when HCC: one nodule ≤5 cm ≤3 lesions, none >3 gross vascular invasion, metastases lymph nodes involvement.41Mazzaferro Regalia Doci small carcinomas cirrhosis.N 1996; 334: 693-699Crossref (5762) American (AASLD) recommends bridging meet criteria.42Heimbach Kulik L.M. Finn al.AASLD carcinoma.Hepatology. 358-380Crossref (2239) These modalities like resection, percutaneous ethanol injection (PEI), radiofrequency ablation (RFA), transarterial chemoembolization (TACE), radioembolization, radiotherapy. Some techniques also “downstage” HCC, is, reducing tumor such it recurrence 20%.43Yao F.Y. Expanded carcinoma.Hepatol Res. 37: S267-S274Crossref usually selected other LDLT.44Pamecha Sinha P.K. Rajendran al.Living patients- scenario different?.Indian 40: 295-302Crossref (1) Currently, (LTSI) suggests satisfying University California, San Francisco (UCSF) (single ≤6.5 tumors largest diameter ≤4.5 total ≤8 cm) AFP <1000 ng/ml invasion extrahepatic spread.22Reddy Scholar,45Bhangui Gautam al.Incorporating biology expanded criteria.Liver 27: 209-221Crossref (10) models, French model, Metroticket 2.0 Kyoto surrogates Des-gamma-carboxy prothrombin (DCP) reliably negative outcomes; universal use lacking.46Mehta management.Clin 17: 332-336Crossref curative and/or lifesaving various inherited liver. Metabolic uncommon indication India. conditions Wilson glycogen disorders, hemochromatosis, tyrosinemia, urea cycle defects. presence manifestations shown affect all ages.47McKiernan P.J. Ganoza Squires J.E. al.Evolving States.Liver 25: 911-921Crossref (24) Excellent long-term achieved careful conditions, though they minor adults, children.48Alam Lal B.B. presenting children.Indian Pediatr. 53: 695-701Crossref Dietary must ignored.49Kaenkumchorn T.K. Patel Berenhaut al.Dietary disease.Curr Hepatol 22: 24-32https://doi.org/10.1007/s11901-023-00599-3Crossref Scholar,50Kulkarni Vinu Lingala M.R. al.Not citrullinemia transplant.J 708-710Abstract One center 5-year 95% 97% pediatric recipients.29Choudhury there exist few contraindicated. Frequent reasons delaying active sepsis dyselectrolytemia, hyponatremia. Age itself criterion exclude candidacy. Studies comparing geriatric (70 older) graft function outcomes.51Aduen J.F. Sujay B. Dickson R.C. al.Outcomes 70 older younger years.Mayo Proc. 84: 973-978Abstract (92) Scholar,52Lipshutz G.S. Hiatt Ghobrial al.Outcome septuagenarians: experience.Arch 142 (discussion 781-774): 775-781Crossref (66) cardiopulmonary disproportionately elevated perioperative might eligible detailed testing. four failures LT.53Gustot Fernandez Garcia al.Clinical course effects prognosis.Hepatology. 62: 243-252Crossref (405) Terminal encephalopathy (HE), brain death, nonreversible absolute contraindication while stages reversed stage IV HE.54Tzakis A.G. Gordon R.D. Makowka transplantation.Radiol North Am. 1987; 289-297PubMed Furthermore, intracranial bleeding dismal offered LT.55Lagman C. Nagasawa D.T. Azzam al.Survival hemorrhage disease.Oper Neurosurg (Hagerstown). 16: 138-146Crossref Other offset need work ongoing substance disorders social support. issues addressed extensive counseling, encouraged follow-up. Pretransplantation referred hepatology clinic their >15. All essential blood obtained, count differential, comprehensive panel, urinalysis, coagulation group cross-matching, typing. Additional lab includes calcium, vitamin D levels, alpha-fetoprotein, markers infectious serology (discussed further). Imaging tests done identify lesions biliary anatomy 3). Basic assessment, workup, vaccinations, varices, bone density evaluation. required emergency minimal basic biochemical tests, ultrasonography abdomen, cardiac evaluati