Optimal recipient outcomes in DDLT depend on comprehensive donor evaluation and meticulous intensive care unit (ICU) management aimed at preserving organ function. Donor evaluation should include comprehensive medical and behavioral history, physical examination, and laboratory workup. Core tests encompass ABO blood typing, complete blood count (CBC), electrolytes, renal and hepatic function tests, coagulation profile, glucose, and a comprehensive infectious screening panel (HBsAg, anti-HBc, anti-HBs, anti-HCV, anti-HIV, CMV, EBV, VDRL, toxoplasmosis, varicella-zoster virus, HTLV-I/II, HSV-I/II, Trypanosoma cruzi, and SARS-CoV-2).

Depending on the donor's origin and local epidemiology, expanded screening for endemic pathogens, such as Strongyloides stercoralis, West Nile virus, malaria, and Leptospira species, may be warranted. Additional evaluations include arterial blood gases, urinalysis, chest radiography, abdominal ultrasound, and, when hospitalization exceeds 72 h, blood, and urine cultures (10–12). Pre-procurement liver biopsy (LB) and computed tomography (CT) Imaging are recommended when steatosis, focal lesions, or vascular abnormalities are suspected.

Most DDLT grafts originate from donors after brain dead (DBD). Brain death is defined as the complete and irreversible cessation of all brain activity, including the brainstem (13). Diagnosis is based primarily on clinical criteria and bedside neurological examination, while ancillary testing is reserved for cases with diagnostic uncertainty (14). Legal and ethical requirements for death certification and consent vary by jurisdiction and must be strictly observed before any procurement procedure (13, 14).

Goal-directed donor management is essential to maintain hemodynamic and metabolic homeostasis, thereby preserving graft quality (15, 16). Recommended targets include: mean arterial pressure >60 mmHg, urine output >1 ml/kg/h, temperature >35 °C, serum sodium <150 mEq/L, lactate normalization, PaO2 > 80 mmHg, hemoglobin >7 g/dl, hematocrit >30%, glucose <180 mg/dl, central venous pressure <10 mmHg, pH 7.35–7.45, caloric intake 70%–85% of baseline needs, fibrinogen >100 mg/dl, platelets >80,000/mm³, and hormonal support (e.g., thyroid and corticosteroids) (17–21).

In many regions, effective donor evaluation relies on Organ Procurement Organizations (OPOs) or equivalent procurement networks that operate independently from the recipient team. This organizational separation ensures transparency, minimizes conflicts of interest, and allows specialized personnel to focus exclusively on donor optimization (22).

Beyond DBD, donation after circulatory death (DCD) has become an increasingly relevant source of grafts, particularly with the advent of machine perfusion technologies. Although DCD donation presents unique challenges related to warm ischemia and early graft dysfunction, advances in hypothermic and normothermic perfusion have markedly improved outcomes, enabling the safe expansion of this donor pool (23, 24).

Given the shortage of organs, the use of marginal or extended criteria donors (ECDs) has increased. Although there is no universally accepted definition of ECDs, they are generally associated with higher risks of early allograft dysfunction (EAD), suboptimal graft function, or transmission of donor-derived diseases (25). Emerging and developing liver transplant programs, apply varying acceptance criteria depending on local policies, access to LDLT, and the risk of patient mortality (5, 6, 25).

Key donor risk factors include:

Age: No strict upper limit exists, but donors >60 years require meticulous evaluation (25–29).

Advances in dynamic preservation have reshaped the evaluation of ECD and DCD grafts. Hypothermic oxygenated perfusion (HOPE) reduces ischemia–reperfusion injury by restoring mitochondrial respiration and promoting metabolic recovery prior to implantation, consistently lowering rates of early allograft dysfunction (80). Normothermic machine perfusion (NMP), by maintaining physiological temperature, allows real-time functional assessment through lactate clearance, glucose metabolism, bile production, and bile quality (pH or bicarbonate content), and perfusate transaminase trends (24, 81). Both modalities have demonstrated improved outcomes in DCD grafts and enable prolonged preservation beyond traditional cold-storage limits, facilitating broader graft utilization while supporting objective viability assessment (24, 80).

At the time of organ retrieval, there is no standardized criterion for determining when a LB is necessary; this decision remains center- and surgeon-dependent (82, 83). The pathologist plays a key role in interpreting histological findings within the broader donor risk context (84, 85).

Historically, the concept of donor–recipient risk matching has guided allocation strategies in LT. Although no randomized controlled trial has definitively established a rigid algorithm, recent evidence supports aligning graft quality with recipient condition, that is, allocating higher-risk or ECD livers to physiologically robust, typically lower-MELD recipients, while reserving optimal grafts for those with higher urgency or comorbid burden. This risk-balancing approach aims to maximize graft utility and overall survival across the waiting list (86).

Ultimately, graft acceptance should be determined by a multidisciplinary team, balancing graft quality, recipient urgency, and center experience. Informed consent should include disclosure of any allograft-specific risks (25).

Although volumetric considerations are traditionally emphasized in LDLT, graft- recipient size mismatch also represents an important risk factor in DDLT. Oversized grafts may be difficult to implant in smaller recipients and have been associated with impaired venous outflow, increased intra-abdominal pressure, and abdominal compartment syndrome, particularly in pediatric or sarcopenic adults (87). Pre-procurement CT volumetry and anthropometric assessment can assist in anticipating mismatch, while intraoperative measures, such as temporary abdominal closure or delayed fascial closure, may mitigate mechanical constraints. Incorporating basic size-matching principles into DDLT evaluation adds an additional layer of safety and may improve implantation outcomes in selected recipients (Table 1).

The first step in LDLT is identifying a suitable donor, with donor safety as the overriding priority (88, 89). A multidisciplinary transplant team should perform a comprehensive assessment encompassing ethical, psychosocial, medical, and anatomical evaluations (vascular and biliary integrity) (89, 90). The donor team should be separate and distinct from the recipient team to minimize any potential conflicts of interest or bias. Institutional protocols vary depending on local resources and experience, and only about 40% of potential donors ultimately qualify for donation (91) (Table 2).

Living donor liver transplantation (LDLT) represents a unique scenario in which the donor undergoes major surgery for purely altruistic reasons without any direct medical benefit. The foundational ethical principles of autonomy, beneficence, non-maleficence, and justice must be upheld, and the donor's risk must be carefully balanced against the recipient's potential benefit under the concept of clinical equipoise (88, 92, 93).

The Vancouver Forum established key tenets to optimize donor safety (94). It specifies that: a) the risk to the donor must be justified by a predictable and acceptable outcome in the recipient; b) graft and patient survival should be comparable to outcomes achieved with DDLT; and c) LDLT should provide a clear advantage over remaining on the DDLT waiting list.

Living-donor surgery carries an overall complication rate of approximately 10%–40% and a mortality rate of <1% (95–97). LDLT also entails a significant learning curve, with most programs achieving procedural consistency after 15–20 consecutive donor hepatectomies (90). Consequently, informed consent is paramount: donors must clearly understand potential risks, and center-specific outcome and complication data should be transparently disclosed.

A licensed mental-health professional should assess each donor's psychological readiness and document full informed consent (9, 89, 90, 98). Donors retain the absolute right to refuse or withdraw consent at any time before surgery (93, 99).

The International Liver Transplantation Society (ILTS) and the International LDLT Group recently convened the ILTS-iLDLT Consensus Conference on Living Donor Safety. Although its formal publication is pending, this global initiative provides updated recommendations on ethical, psychosocial, and procedural safeguards, further strengthening donor protection within LDLT programs.

A thorough clinical history, physical examination, and initial laboratory testing are essential to exclude contraindications. Common baseline studies include hematologic, biochemical, and serologic panels for viral hepatitis (HBsAg, anti-HBc, anti-HCV, anti-HIV, CMV, EBV), chronic liver disease (ANA, ferritin/iron saturation, ceruloplasmin, α1-antitrypsin, IgG), and infectious disease screening adapted to geographic endemicity (VDRL, toxoplasmosis, varicella-zoster virus, HTLV-I/II, HSV-I/II, Chagas disease, tuberculosis screening with QuantiFERON or PPD), as well as pregnancy testing in women under 50 years (9, 11, 100, 101).

Although not universally standardized, screening for hypercoagulable states (factor V Leiden, prothrombin G20210A mutation, antithrombin III, protein C and S deficiency, antiphospholipid antibodies, homocysteine) is advisable (9, 90, 102, 103). When cost is a concern, testing can be performed in phases, starting with basic serologies and expanding as indicated. There should be a low threshold for screening for genetic liver diseases, especially among related donor-recipient pairs (9, 104, 105).

If initial testing is acceptable, further evaluation guided by center-specific protocols may include chest radiography, electrocardiography, abdominal imaging (ideally CT and MRI/MRCP), cardiovascular assessment (echocardiography, stress testing, or CT angiography in selected cases), pulmonary function testing (in smokers, asthmatics, or donors >40 years), and age- or risk-adapted cancer screening (11, 12, 90).

Multidisciplinary assessment by hepatology, surgery, anesthesiology, psychiatry, social work, nutrition, and transplant coordination teams is also standard (11, 12, 90). LB is reserved for selected cases, such as unexplained abnormal liver function tests, suspected metabolic disease (e.g., Wilson's disease, α1-antitrypsin deficiency), or when imaging suggests significant steatosis and advanced noninvasive modalities are unavailable (106–108).

While donor age limits vary by region and center, most programs accept candidates between between 18 and 60 years (7, 28, 109). Although younger donors typically offer more favorable vascular characteristics—reduced atherosclerosis, less vascular tortuosity, and larger, more uniform vessel calibers—age alone is not an absolute contraindication (110–112). Outcomes among donors over 55–60 years are variable and associated with reduced regenerative capacity and higher complication rates; therefore, more rigorous evaluation is warranted in this group (28, 97). Donation beyond age 60 should generally be limited to high-volume centers with extensive LDLT experience.

Ideal living donors should have no significant comorbidities, or only well-controlled mild conditions, and no evidence of major end-organ dysfunction, including cardiopulmonary disease or active malignancy. For donors with metabolic risk factors (prediabetes, hypertension, hyperlipidemia, obesity), metabolic syndrome should be optimized, and further evaluation should include screening for metabolic dysfunction–associated steatohepatitis (MASH), fibrosis, and cardiac risk assessment (89).

Body mass index (BMI) thresholds vary internationally, ranging from >25 kg/m² (Indian guidelines) to >40 kg/m² (absolute contraindication in some U.S. centers), but there is no universally accepted cutoff (109, 113). Most Western and Latin American programs set an upper limit of 30–32 kg/m², with select acceptance up to 35 kg/m² only in isolated obesity without metabolic abnormalities and in centers with extensive LDLT experience (7, 9). Donors with BMI >30 kg/m² should undergo non-invasive quantification of hepatic steatosis [MRI-Proton Density Fat Fraction (PDFF) or CAP] and, when uncertainty persists, LB to exclude steatohepatitis or fibrosis (9, 89, 100, 114, 115).

ABO compatibility remains the standard criterion; however, emerging desensitization protocols (rituximab, plasmapheresis, intravenous immunoglobulin) have yielded acceptable outcomes in carefully selected ABO-incompatible cases (116–123). Final decisions depend on institutional expertise, available resources, and local experience.

Once donor physical and psychological suitability is confirmed, a comprehensive evaluation of graft anatomy, size, and function is essential. This includes assessment of liver volume, vascular and biliary anatomy, and hepatic parenchymal quality (e.g., exclusion of fibrosis, significant steatosis, or liver injury), using imaging modalities such as CT, MRI/MRCP, angiography, cholangiography, transient elastography, and, when indicated, LB (89, 124).

Expert consensus recommends MRI/MRCP and CT angiography as preferred modalities for biliary and vascular mapping, respectively, with adaptation to local expertise and resource availability (108). For graft selection (right lobe, left lobe, left/caudate lobe, or dual grafts), 3D reconstructions are advised to optimize volumetric planning and detect anatomical variations that may influence surgical strategy (9).

MRI, ideally incorporating PDFF, provides superior sensitivity and negative predictive value for detecting low-grade steatosis and can often reduce the need for biopsy (108). LB may be considered in high-risk candidates, those with metabolic syndrome, suspected MASH, elevated liver enzymes, or uncertainty in MRI-PDFF accuracy.

Although no universal threshold for acceptable macrovesicular steatosis exists, most centers adopt a <10% cutoff on LB (90, 101). Importantly, MRI-PDFF and histologic steatosis do not correlate linearly; in the study by Qadri et al., PDFF and biopsy estimates were comparable at 5%, however, PDFF values beyond this level consistently underestimated histologic steatosis with up to a 3.5-fold difference (125) Hence, if aiming for <10% macrosteatosis on biopsy, these intermodality differences must be considered. High-volume Asian centers may accept 10%–30% steatosis in young, otherwise ideal donors (9, 126).

The extent of hepatectomy is guided by recipient volume requirements, donor remnant liver volume (RLV), and anatomic feasibility. The right lobe (≈60% of total liver volume) is most used for adult LDLT, followed by the left lobe (≈40%), while left lateral segment grafts (≈20%) are reserved for pediatric recipients. Adequate graft size is critical to avoid small-for-size syndrome (SFSS). Graft adequacy is determined using the graft-to-recipient weight ratio (GRWR) and the graft volume-to-standard liver volume ratio (GV/SLV). A GRWR ≥0.8% or GV/SLV ≥40% is generally recommended, though high-risk recipients may require higher targets (1.0%–1.2% or >45%) (127).

SFSS manifests as early post-transplant dysfunction with hyperbilirubinemia, coagulopathy, ascites, and/or encephalopathy in the absence of technical or vascular causes (90). It is associated with graft hyperperfusion, portal hypertension, and inadequate venous outflow (90, 128). Portal inflow modulation (PIM), through splenic embolization, ligation, splenectomy, or shunting, can mitigate this risk. With careful PIM, successful LDLT using smaller grafts (GRWR ≥0.6% or GV/SLV ≥25%) has been reported in high-volume Asian centers when donor quality is excellent and urgency is high (129–131). Each case should be evaluated individually, particularly when flow-modulation strategies are applied (132, 133).

Donor safety requires maintaining a residual liver volume (RLV/TLV) ≥30%, although factors such as donor age, sex, and steatosis may influence this threshold (101, 108). Selected low-risk donors (<50 years, minimal steatosis, preserved middle hepatic vein) may tolerate slightly lower remnants, but these should be exceptions in highly experienced centers with advanced intraoperative monitoring (134–136). Most programs adopt a strict ≥30% cutoff. As graft size increases, recipient benefit rises but donor risk escalates proportionally; hence, the global trend favors greater utilization of left lobe grafts to enhance donor safety (90, 128, 137–140). However, left lobe graft should be avoided in recipients with BMI >30, MELD >20, age >45 years, or severe portal hypertension (128, 141–144).

When a single partial graft is insufficient, dual-graft LDLT (e.g., two left lobes or a left and right lobe) may be an option in select high-volume centers. Though effective, this technique involves substantial technical and logistical complexity and should be limited to institutions with extensive experience (145, 146).

In transplant oncology, LDLT plays an increasingly pivotal role—particularly for patients undergoing downstaging or bridging therapies for hepatocellular carcinoma (HCC), or for those with limited access to deceased donor grafts, such as cases of colorectal liver metastases (CRLM). The elective and planned nature of LDLT allows time-sensitive coordination crucial for patients requiring documented tumor control before transplantation.

Given its voluntary nature, some centers cautiously extend LDLT indications beyond those of DDLT, including selected cases of cholangiocarcinoma, CRLM, or HCC beyond conventional criteria (Milan, UCSF), when favorable tumor biology (low AFP, PET-negativity, sustained response to therapy) suggests a meaningful survival benefit (147, 148).

Several high-volume Asian centers have reported positive outcomes in high-urgency settings such as acute liver failure or acute-on-chronic liver failure patients. Although consensus is lacking, decisions should be guided by multidisciplinary risk-benefit analysis and supported by expedited donor-recipient evaluation protocols (149–155). Success depends on appropriate risk matching between donor and recipient and robust perioperative planning.

In summary, LDLT offers a life-saving alternative where deceased donor organs are scarce. Nonetheless, donor selection criteria should remain conservative, particularly in developing or mid-volume centers. Thresholds for age, BMI, steatosis, and remnant liver volume must prioritize donor safety rather than expansion. Any deviation from these standards should occur only in experienced, high-volume programs with multidisciplinary expertise and structured mentorship.