Liver Transplantation

Liver transplantation is often the best treatment for advanced cirrhosis, acute hepatic failure, and some liver cancers. It is the only definitive therapy for end-stage liver disease.

Types are deceased-donor transplantation (whole or split graft), living-donor transplantation (usually right lobe from a near relative), auxiliary transplantation, and domino transplantation. In India the large majority of liver transplants are living-donor, because of the shortage of deceased donors.

Indications are: decompensated cirrhosis of any cause; acute liver failure; hepatocellular carcinoma within Milan criteria (a single lesion ≤5 cm, or up to three lesions each ≤3 cm, with no vascular invasion or extrahepatic spread); metabolic liver disease; and intractable complications such as refractory pruritus or recurrent cholangitis.

The commonest indications in older recipients are now metabolic dysfunction-associated steatohepatitis (MASH/NASH), alcohol-related liver disease and hepatocellular carcinoma. Hepatitis C as an indication has fallen sharply since direct-acting antivirals.

The decision on when to offer transplantation is based on the Model for End-stage Liver Disease (MELD), a mathematical formula that grades life expectancy in a cirrhotic patient.

MELD parameters are creatinine, sodium, bilirubin and INR. Multiple online calculators exist.

At a MELD score of 17, a patient is likely to do better with a transplant than without one. Practice is to refer to a transplant clinic once MELD exceeds 15, provided the patient is a reasonable candidate.

A 'reasonable candidate' is one who is otherwise healthy — with no cancer, no dementia and no cardiovascular disease. Kidney disease is not a bar, as such patients can be listed for a combined liver–kidney transplant.

In patients over 70, additional requirements are a good performance status, a stable and supportive home life, and a reasonable likelihood of living 10 years with the transplant.

Referral should also be triggered by the first episode of decompensation — ascites, variceal bleeding, hepatic encephalopathy or spontaneous bacterial peritonitis — even if MELD is still low.

Carefully selected patients over 65 have a good prognosis, with about 80% five-year survival.

In the Mayo Clinic study comparing 42 patients over 70 with 42 matched patients under 60, five-year survival was identical. Chronological age alone is therefore not a contraindication.

Donor age is likewise not an absolute bar — Eurotransplant data show that using livers from donors older than 70 should not be discouraged, because survival rates are good. The liver is less affected by age than other organs.

Geriatric patients who are otherwise healthy should be considered for liver transplantation — under-referral on grounds of age alone is a recognised failure of care. Pre-transplant Evaluation in the Older Candidate

The work-up must cover: cardiac assessment (echocardiography, stress testing, coronary angiography where indicated — coronary disease is the commonest reason for exclusion), pulmonary assessment for hepatopulmonary syndrome and portopulmonary hypertension, renal function, malignancy and infection screening, dental clearance, bone density, and psychosocial and caregiver assessment.

Assess nutrition, sarcopenia and frailty formally — these predict waitlist mortality and post-transplant recovery better than age. Assess cognition, because dementia is an exclusion, and confirm abstinence, insight and social support in alcohol-related disease.

Immunosuppression uses induction (basiliximab or anti-thymocyte globulin) and maintenance with a calcineurin inhibitor (tacrolimus), an antimetabolite (mycophenolate) and tapering steroids; mTOR inhibitors (everolimus, sirolimus) are used to spare renal function and in HCC.

Older recipients need less immunosuppression because of immunosenescence — they have less acute rejection but more infection, more de novo malignancy and more calcineurin-inhibitor nephrotoxicity. Drug–drug interactions with tacrolimus (azoles, macrolides, calcium channel blockers, statins) are a major practical hazard in the polypharmacy setting.

Complications: primary non-function, hepatic artery thrombosis, biliary strictures and leaks, acute and chronic rejection, CMV and opportunistic infection, post-transplant lymphoproliferative disorder, recurrence of the original disease, chronic kidney disease, metabolic syndrome, osteoporosis and de novo malignancy.

In India, transplantation is governed by the Transplantation of Human Organs Act 1994, amended in 2011 (Transplantation of Human Organs and Tissues Act, THOTA) with Rules 2014. It defines brain-stem death, requires certification by a board of four medical experts, permits near-relative and swap donation, requires authorisation committee approval for non-near-relative (altruistic) donation, and makes commercial dealing in organs a punishable offence.

The organisational network is NOTTO at national level, ROTTOs regionally and SOTTOs at state level, under the National Organ Transplant Programme.

For patients who are not candidates, the alternatives are optimal medical management of cirrhosis (beta-blockers and band ligation for varices, diuretics and albumin for ascites, TIPS for refractory ascites or bleeding, lactulose and rifaximin for encephalopathy), locoregional therapy for HCC (TACE, radiofrequency ablation, SBRT), and early palliative care with advance care planning. Median survival in untreated decompensated cirrhosis is about two years.

MELD 3.0 was implemented for organ allocation in 2023. It adds female sex and serum albumin to the existing variables, updates the creatinine ceiling and the interactions between components. It corrects the systematic disadvantage that MELD-Na imposed on women, who were being under-prioritised because of lower muscle mass and hence lower creatinine.

Machine perfusion has transformed organ preservation. Normothermic machine perfusion (NMP) allows ex-vivo perfusion at body temperature with viability testing before implantation; hypothermic oxygenated perfusion (HOPE) reduces ischaemia–reperfusion injury and biliary complications.

UNOS/OPTN analyses (Transplantation Direct 2024; World J Transplant 2025) show that NMP increases the use of donation-after-circulatory-death and extended-criteria grafts, and is associated with better two-year patient and graft survival in DCD recipients after propensity matching.

Machine perfusion is directly relevant to older recipients — matched analyses show that despite receiving more marginal grafts (older donors, more DCD), elderly NMP recipients had similar graft survival and a shorter length of stay, so NMP may mitigate donor risk factors that would otherwise be relative contraindications.

Normothermic regional perfusion (NRP) in the donor before retrieval, alone or combined with NMP, is now an established DCD strategy.

The Liver Frailty Index (grip strength, timed chair stands, balance testing) is now a standard, validated waitlist assessment; CT-measured sarcopenia at the L3 level independently predicts waitlist and post-transplant mortality. Structured prehabilitation before transplantation is increasingly offered.

Early liver transplantation for severe alcohol-associated hepatitis is now accepted in carefully selected patients, replacing the rigid six-month abstinence rule; selection is by psychosocial assessment rather than by a fixed time interval.

Allocation reform: the United States has moved from regional boundaries to acuity circles and is moving towards continuous distribution, reducing geographic inequity.

Expanded donor pool: HCV-viraemic donors are now used for HCV-negative recipients with short-course DAA prophylaxis, and anti-HBc-positive donors are used with antiviral prophylaxis — both are especially valuable for older candidates who cannot afford a long wait.

MASH/MASLD is now among the leading indications for liver transplantation in high-income countries and is rising rapidly in India; these recipients are older and carry more cardiovascular and metabolic risk, so cardiac work-up standards have tightened.

Indian context: India performs roughly 3,000–4,000 liver transplants a year, the great majority living-donor, and is second only to the USA in absolute LDLT numbers. Deceased-donation rates remain below one per million population. Recent national policy changes have removed the upper age limit of 65 years for registration for deceased-donor organs, removed the domicile requirement so a patient may register in any state, and removed the registration fee — all of which improve access for older Indian patients.