Table 2.

Diagnostic Pointers and Line of Management of Various Causes of Elevated Liver Function Tests After Transplantation.

Differential diagnosis	Timing and clinical pointers	Diagnostic tests	Management approach
Ischemia reperfusion injury14,31	First week Hepatocellular pattern Donor-recipient risk factors	Clinical diagnosis Rule out structural causes	80% resolve with supportive management35 No long-term impact 10–20% may progress to EAD36
Early allograft dysfunction37,38	First week Moderate-massive rise in aminotransferases in hepatocellular pattern Presence of donor and recipient risk factors (Table 1) Suspect if: •Worsening negative base excess •Unresolving coagulopathy •Persisting synthetic dysfunction •Persistent hyperammonaemia •Reduced-pale bile in the drain, if present	Clinical diagnosis of exclusion Rule out structural causes Diagnostic criteria: Presence of ≥1 of the following parameters in the first week after the LT39 1. Total bilirubin ≥10 mg/dl or INR ≥1.6 on postoperative day 7, or 2. Aminotransferases >2000 U/L within the first week after LT.	Supportive management Plasma exchange on case-to-case basis. Complete resolution and liver regeneration eliminates risk of long-term adverse outcomes. Re-transplantation if progresses to primary non-function.
Hepatic artery thrombosis40,41	Overall incidence: 5–6% Early HAT: <14 days •Massive elevation in AST/ALT in hepatocellular pattern Late HAT: Later period •Ischemic, multifocal NAS-biliary strictures	USG Abdomen with doppler Confirm with Angiography (CT or MRI)	Early HAT: Surgical or IR guided revascularization/thrombolysis Late HAT: Biliary drainage Re-transplantation if above measures fail.
Biliary leak42, 43, 44	Incidence: 5–15% Mostly occur in the first 1–3 months. Can present as pain abdomen, fever, cholangitis, intraabdominal/cut surface collections	USG Abdomen and/or cross- sectional imaging (CT/MRI)	Image guided (USG/CT/EUS) drainage of collections ERCP and biliary stenting.
Portal vein thrombosis45, 46, 47	Incidence: 2–3% More common in early post-operative period but can occur later also. Hepatocellular pattern. Persistent or new onset portal hypertension (ascites, variceal bleeding)	USG Abdomen with doppler Confirm with dynamic cross-sectional imaging (CT or MRI)	Surgical or IR guided revascularization/stenting Anticoagulation
Small for size syndrome48,49,50	Living donor/split grafts. Risk factors: •GRWR <0.8 •Graft steatosis •Older donor •Sick recipient (MELD >30) with high portal pressures, Insufficient outflow Present as prolonged cholestasis and features of hepatic insufficiency	Diagnosis of exclusion Diagnostic criteria: •Bilirubin >10 mg/dl on POD7 and •Features of hepatic insufficiency such as intractable ascites, daily production of >1L ascites on POD28, persistent coagulopathy, and/or high-grade hepatic encephalopathy.	Supportive Rule out structural causes Splanchnic vasoconstrictors may be tried.51,52 Plasma exchange in selective cases
Anastomotic biliary stricture14,15,42	Incidence: 15–25% Living donor > Deceased donors Most present 2–6 months after LT Cholestatic jaundice with/without Cholangitis	Cross-sectional imaging (MRI)	ERCP and stenting
Rejection2,33,34	10–30% recipients develop rejection Acute TCMR: •Hepatocellular pattern •Early TCMR: 80%; most occur in first 90 days; >80% respond to treatment •Late TCMR: 11–20%; most occur later (>180 days); 20–40% may fail to respond to first line treatment. •Repeated early TCMR predispose to late TCMR and CR. Chronic TCMR (CR): •1–3% incidence •Cholestatic pattern •60–70% respond to treatment AMR: Suspect when TCMR does not respond to adequate treatment Limited data	Liver biopsy is mandatory to diagnose type of rejection, to assess its severity and to rule out other possible etiologies. Repeat liver biopsy not needed to ascertain response if biochemical improvement seen.	Mild acute TCMR: Increase in baseline immunosuppression Moderate-severe TCMR (early and late): Intravenous methylprednisolone pulse therapy, concomitant up titration of baseline maintenance immunosuppression CR: Shift from cyclosporin to Tacrolimus; addition of mTOR inhibitors AMR: Limited data; steroid boluses, DSA depleting strategies.
Recurrent autoimmune liver diseases53,54	Incidence at 5-years •AIH: 20–30% •PBC: nearly 20% •PSC: 15–20% Clinical presentation similar to pre-LT	Diagnostic criterion similar to pre-LT criteria. Liver biopsy for AIH, PBC and overlap syndromes MRI Abdomen for suspected PSC	Limited data Modulation of immunosuppression
NAFLD55,56	Overall incidence •Recurrent NAFLD: >80% •NASH/fibrosis in 20–25% •De-novo NAFLD: 20–30% Metabolic syndrome and immunosuppressive agents predispose.	Ultrasound Abdomen Liver biopsy	Lifestyle changes Manage risk factors and comorbidities Immunosuppression drug modulation

AIH, Autoimmune hepatitis; AMR, Antibody mediated rejection; CR, Chronic rejection; CT, Computed tomography; DSA, Donor specific antibodies; EAD, Early allograft dysfunction; EUS, Endoscopic ultrasound; ERCP, Endoscopic retrograde cholangiopancreatography; GRWR, Graft to recipient weight ratio; HAT, Hepatic artery thrombosis; IR, Interventional radiology; INR, International normalized ratio; LT, Liver transplantation; MELD, Model for end stage liver disease; MRI, Magnetic resonance imaging; NAFLD, Non-alcoholic fatty liver disease; NASH, Non-alcoholic steatohepatitis; NAS, Non-anastomotic biliary stricture; PBC, Primary biliary cholangitis; POD, Post operative day; PSC, Primary sclerosing cholangitis; SFSS, Small for size syndrome; TCMR, T-cell mediated rejection; USG, Ultrasonography.