2026 Hepatology Practice Board Questions

The stem describes a patient with a predominantly elevated AST, ALT, and ALP. She has a positive AMA as well as an elevated IgG level. The treatment plan describes pulsing with immunosuppression early and then transitioning to longer term immunosuppression with azathioprine. This is a treatment for autoimmune hepatitis. The elevated AMA and description of treating with ursodiol points towards PBC as well, making this AIH and PBC overlap. Option E shows pathologic features of PBC (florid duct lesion, granulomas) as well as features of autoimmune hepatitis (interface hepatitis), establishing AIH-PBC overlap and requiring the treatment plan as outlined in the question. Option A (interface hepatitis with submassive necrosis and hepatocellular collapse) describes AIH alone. Option B (ductopenia and onion skinning) describes PSC. Option C describes PBC alone. Option D would be compatible with drug induced liver injury.

The Paris Criteria have been used to identify patients with AIH and PBC overlap, although this may not capture all patients:

Two of the following criteria for PBC

• ALP ≥ 2x ULN or GGT ≥ 5x GGT
• Florid duct lesion on histology
• Presence of AMA

AND two of the following criteria for AIH

• ALT ≥ 5x ULN
• IgG ≥ 2x ULN or presence of smooth muscle antibodies
• Interface hepatitis on biopsy

Source:Mack, Cara L.*,1; Adams, David2; Assis, David N.3; Kerkar, Nanda4; Manns, Michael P.5; Mayo, Marlyn J.6; Vierling, John M.7; Alsawas, Mouaz8; Murad, Mohammad H.9; Czaja, Albert J.10. Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases. Hepatology 72(2):p 671-722, August 2020. | DOI: 10.1002/hep.31065 

The question stem suggests that this patient has an alcohol use disorder; his AUDIT-C score is well above 5. Naltrexone is safe and effective for treating AUD in liver disease and is most likely to improve outcomes for him. Previous concerns for naltrexone use in liver disease have largely been allayed by more recent data. While he has metabolic risk factors and may have Met-ALD, VCTE or MRI Elastography should be done prior to starting resmetirom, as it is only approved in patients with MASH and F2 or F3 fibrosis. Disulfiram is not recommended in liver disease. Budesonide can be used in autoimmune hepatitis, not alcohol related liver disease. Prednisolone may improve short term -- but not long term-- outcomes in acute alcohol related hepatitis; its use even in this setting is controversial. There is no evidence provided in the question stem that the patient has acute hepatitis presently. 

The lesion is concerning for HCC, especially in the setting of a new rise in AFP within the background of cirrhosis. The size and imaging characteristics of this lesion would technically classify it as LI-RADS 4, which indicate a high probability of HCC (60-70%); however, vascular disorders of the liver (for example BCS and Hereditary Hemorrhagic Telangiectasia) are specifically excluded from the LI-RADS system because the altered vascularity of the liver can lead to perfusion alterations such that benign lesions may be arterially perfused. While there is some suggestion that an alpha fetoprotein level of 15 ng/mL is predictive of HCC in BCS, this has not yet been validated in larger studies. Since the LI-RADS system cannot be readily applied here, the next best step is to confirm histologically if this lesion is indeed HCC before deciding on further management (Choices A and B). Given the findings are highly concerning for malignancy deferring biopsy for continued routine surveillance would be inappropriate (Choice D).

Sinusoidal Obstructive Syndrome (formerly Veno-occlusive disease) is a potential complication of SCT, especially early in the transplant course (“Classic SOS” typically presents within 21 days of transplantation). The pathophysiologic mechanism involves damage to the sinusoidal endothelial cells from the medications used in myeloablative therapy leading to obstruction of blood flow. This leads to post-sinusoidal portal hypertension. Refractory thrombocytopenia is often the first laboratory abnormality to be seen. Diagnosis can be challenging as there are no pathognomonic findings on labs or imaging.  Liver abnormalities can include mild elevations in transaminases with a cholestatic presentation. Imaging may show evidence of portal hypertension and/or reversal of portal flow. If performed, liver biopsy may show dilated sinusoids with erythrocytes in the space of Disse with later findings including fibrous obliteration of the central venules.

The modified Seattle criteria for diagnosing hepatic veno-occlusive disease (VOD/SOS) in adults, without requiring biopsy, requires the presence of at least two of the following findings within 20 days of transplant: 

• Hyperbilirubinemia: Total serum bilirubin > 2 mg/dl.
• Hepatomegaly: Increased over baseline, or right upper quadrant pain of liver origin.
• Weight gain:  >2 % of baseline body weight due to fluid accumulation.

Prophylactic treatment to prevent SOS includes ursodiol. Medical treatment is aimed at stopping the cycle of coagulation factor consumption and deposition of fibrin clots within the liver. While ursodiol is used prophylactically to prevent SOS, it is not effective for the treatment of SOS (Choice A). Defibrotide is currently the only FDA approved medication for SOS and the next best step (Choice D). If patients do not respond to at least 3 weeks of defibrotide therapy other management can be considered, however none have significant proven benefit. This could include high dose methylprednisolone (Choice C), but caution must be used given the risk of infection. Additionally, there have been small case reports/series of placement of TIPS in carefully selected patients, but long-term survival is uncommon. Finally, there are case reports of liver transplantation in patients with SOS, however, patient selection is difficult given underlying comorbidity. Heparin is not a guide-line directed therapy for SOS (B).

Living donor liver transplantation allows for earlier transplant for patients listed at low MELD scores, with decompensating events or QOL impairments not reflected in their MELD scores. After adjusting for donor characteristics, liver disease etiology and MELD scores, patient and graft survival is similar in long-term follow up. LDLT is associated with higher rates of biliary complications (up to 20%) and hepatic artery thrombosis, necessitating vigilant follow up.

Author: AS, Topic: Liver Donor Liver Transplant

Reference: AASLD AST Practice Guideline on Adult Liver Transplantation: Diagnosis and management of Graft-Related complications. Liver Transplantation. 2025. DOI:10.1097/LVT.0000000000000715

The use of DCD donors has increased dramatically with machine perfusion strategies now available to mitigate risks associated with early allograft dysfunction, but still represents a small minority of overall liver transplants in the United States and requires careful selection of both donors and recipients The 2021 ILTS consensus conference recommended increased scrutiny of DCD donor use in donors over 60 years old, with BMI over 30, with 30% or higher hepatic steatosis, or warm ischemia time over 8 hours. In this patient’s case, the International Liver Transplant Society (ILTS) also recommended against the use of DCD allografts in patients with complex portal vein thrombosis.

The Yerdel classification system grades portal vein thrombosis (PVT) severity (I-IV) based on thrombus extension and occlusion percentage, aiding surgical planning in liver transplantation. It classifies disease from partial thrombosis (Grade I) to complete, extensive thrombosis involving the superior mesenteric vein (Grade IV).

References:

Te HS, Agopian VG, Demetris AJ, Kwo PY, McGuire BM, Russo MW, Selzner N, Washburn WK, Winder GS, Schiano TD. AASLD AST Practice Guideline on Adult Liver Transplantation: Diagnosis and management of Graft-Related complications. Liver Transplantation. 2025. DOI: 10.1097/LVT.0000000000000715

Schlegel A, Foley DP, Savier E, Flores Carvalho M, De Carlis L, Heaton N, Taner CB. Recommendations for Donor and Recipient Selection and Risk Prediction: Working Group Report From the ILTS Consensus Conference in DCD Liver Transplantation. Transplantation.

2021;105(9):1892-903.

Patients with HBsAg positivity, HBeAg negativity, low-level HBV DNA (under 2,000 IU/mL), and normal ALT are classified as inactive HBV carriers. They do not require antiviral treatment, but ongoing monitoring is essential because some may transition into immune-active disease phases. Monitoring includes periodic ALT and HBV DNA testing in 3 months, and then in 6-12 months intervals after that if clinically stable.

Antiviral therapy is indicated for patients with chronic hepatitis B who have evidence of active disease: elevated HBV DNA (≥2,000 IU/mL if HBeAg– or over ;20,000 IU/mL if HBeAg+) and elevated ALT, or significant fibrosis/cirrhosis. This patient has low-level viremia (under<2,000 IU/mL), normal ALT, and only F1 fibrosis that is more likely related to underlying MAFLD given her obesity and diabetes. These features define the inactive carrier state, which does not warrant treatment (answer A is not correct).

Additionally, TAF is generally avoided as first line treatment in chronic hepatitis B patients with decreased bone density such as this patient, who carries a diagnosis of osteoporosis

B. Given her lack of cirrhosis, HCC screening is usually not required in this patient Population. In hepatitis B, HCC risk is elevated independently of the presence of cirrhosis (answer choice B is incorrect). For Asian women, HCC surveillance is recommended starting at age 50, even in the absence of cirrhosis. Since this patient is 51, screening every 6 months with imaging and +/- AFP levels would be indicated. Additional populations of HBV without cirrhosis who require screening include asian males over 40, individuals with a first degree relative with history of HCC, and those with co-infection with Hepatitis D virus.

D. A liver biopsy would be indicated in this patient. Biopsy is typically reserved for cases where fibrosis staging is unclear, where there is clinical suspicion despite noninvasive reassurance, or before initiating therapy when noninvasive testing is inconclusive. In this patient, elastography shows minimal fibrosis and labs are normal (answer D is not correct). A biopsy would not add useful information.

E. She has achieved functional cure of hepatitis B and does not need follow-up Functional cure of HBV is defined as loss of HBsAg with or without anti-HBs seroconversion. This patient remains HBsAg positive and HBsAb negative, meaning she has chronic infection and not a resolved infection (Answer E is not correct).  She requires ongoing monitoring for disease activity, HCC risk, and potential reactivation in the future.

References

1. Ghany, Marc G et al.  AASLD ISDA Practice Guideline on treatment of chronic hepatitis B. Hepatology. 2025. 
2. Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 Hepatitis B Guidance. Hepatology. 2018;67(4):1560-1599
3. European Association for the Study of the Liver (EASL). EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017
4. Heimbach JK, Kulik LM, Finn RS, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018.

This patient’s hypertension and proteinuria prior to delivery, as well as clear signs of hemolysis on lab work (elevated LDH, low haptoglobin, elevated indirect bilirubin) are suggestive of HELLP Syndrome. HELLP syndrome criteria include LDH > 600, PLT < 100, and AST/ALT  >2x ULN. Spontaneous subcapsular hepatic hemorrhage is a rare and severe complication of HELLP syndrome. 20% of HELLP syndrome cases occur within 48 hours of delivery. The pathophysiology includes decreased placental perfusion, ultimately leading to altered platelet aggregation and endothelial function. Within the liver, fibrin is deposited in the hepatic sinusoids, resulting in obstruction and subsequent ischemia that can in rare instances lead to hepatic rupture.  

TTP is incorrect because while it can cause hemolysis and low platelets, it would not be expected to cause subcapsular hemorrhage of the live. 

AFLP is incorrect because it typically presents with features of acute liver failure: severe coagulopathy (markedly elevated INR) and encephalopathy. While there is indeed some overlap in presentations, AFLP is not classically associated with hemolysis.

Eclampsia is incorrect because while this patient does have pre-eclampsia related findings, she does not have seizures.

Sarkar, Monika 1 ; Brady, Carla W. 2 ; Fleckenstein, Jaquelyn 3 ; Forde, Kimberly A. 4 ; Khungar, Vandana 4 ; Molleston, Jean P. 5 ; Afshar, Yalda 6 ; Terrault, Norah A. *,7 . Reproductive Health and Liver Disease: Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 73(1):p 318-365, January 2021. Chahine KM, Shepherd MC, Sibai BM. Association of Subcapsular Liver Hematoma With Preeclampsia, Eclampsia, or Hemolysis, Elevated Liver Enzymes, and Low Platelet Count Syndrome. Obstet Gynecol.2025 Mar 1;145(3):335-342. D

The essential detail to catch in this question is the intrahepatic biliary ductal dilatation. This is most consistent with intrahepatic cholangiocarcinoma and is further supported by the elevated CA19-9 and cholestatic lab profile. Also, the imaging pattern is classic for intrahepatic cholangiocarcinoma, which often presents as an ill-defined, infiltrative lesion rather than a discrete mass.

HCC is less likely in the setting of normal AFP and intrahepatic ductal dilatation. Furthermore, on imaging, HCC typically presents as a discrete mass with arterial phase hyperenhancement and venous washout on contrasted imaging.

Pancreatic cancer can present with liver metastases and elevated CA19-9; however the presence of a dominant hepatic mass and absence of pancreatic mass make this less likely. In addition, biliary ductal dilatation in pancreatic cancer is typically extrahepatic rather than isolated intrahepatic dilation. 

Colon cancer can also metastasize to the liver, but the metastases are typically rounded lesions with peripheral enhancement and would not cause biliary ductal dilation. We would also expect elevated CEA with primary colon malignancy.

Bridgewater J, Galle PR, Khan SA, et al.Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. Lancet. 2014;383(9935):2168–2179.

Razumilava N, Gores GJ. Cholangiocarcinoma. Lancet. 2014;383(9935):2168–2179.

Brancatelli G, Federle MP, Grazioli L, et al. Intrahepatic cholangiocarcinoma: spectrum of enhancement patterns and pitfalls at imaging. Radiographics. 2001;21(4):S101–S118.

Choi BI, Lee JM, Han JK. Imaging of intrahepatic and hilar cholangiocarcinoma. AJR Am J Roentgenol. 2008;191(3):755–763.

Chapman RW, Rosenberg WM. Cholangiocarcinoma: imaging and diagnosis. In: Boyer TD, Manns MP, Sanyal AJ, eds.

Zakim and Boyer’s Hepatology: A Textbook of Liver Disease. 7th ed. Philadelphia, PA: Elsevier; 2018.

Biliary atresia is nonsyndromic in >80% of cases. Patients with syndromic associations are classified into those with laterality defects, and those without. Those without laterality defects are most likely to have cardiovascular anomalies, followed by genitourinary, gastrointestinal, and pulmonary. Those with laterality defects are most likely to have gastrointestinal, splenic, and cardiac anomalies. Biliary atresia is not known to be associated with retinal abnormalities.

Schwarz KB, Haber BH, Rosenthal P, et al. Extrahepatic anomalies in infants with biliary atresia: results of a large prospective North American multicenter study. Hepatology. 2013;58(5):1724-1731. doi:10.1002/hep.26512

Fawaz R, Baumann U, Ekong U, et al. Guideline for the Evaluation of Cholestatic Jaundice in Infants: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr. 2017;64(1):154-168. doi:10.1097/MPG.0000000000001334

This patient has evidence of iron overloading. He has microcytic anemia, which is inconsistent with hereditary hemochromatosis. He has non-transfusion dependent thalassemia, which is suggested by the presence of extreme microcytosis (the Mentzer index can also be calculated if RDW is available) with hemolytic anemia (anemia with raised indirect bilirubin) and hepatosplenomegaly (which are due to extramedullary hematopoiesis). Haemoglobin electrophoresis would confirm the diagnosis of thalassemia. 

Iron overloading in the context of thalassemia most commonly occurs in the setting of chronic transfusion dependence. However, non-transfusion dependent thalassemia patients may still have secondary iron overloading due to ineffective erythropoiesis with inappropriate hepcidin suppression. MRI liver with R2* or T2* would confirm the diagnosis of liver iron overloading. 

Hepatitis B screening would be appropriate, as the patient has come from an endemic region and has received blood transfusions. HFE gene testing is of low yield in populations that are not of Western European descent. 

Since the AASLD 2011 and ACG 2019 guidelines on hemochromatosis, more updated guidance in hepatology have been published - EASL 2022, APASL 2023. Contemporary definitions of hemochromatosis and iron overloading have also been redefined in the BIOIRON 2022 recommendations. 

Prevalence of mutations involved in hemochromatosis in various cohort studies

Domenico G et al (2022). Hemochromatosis classification: update and recommendations by the BIOIRON Society. Blood (2022) 139 (20): 3018–3029.

EASL Clinical Practice Guidelines on haemochromatosis 2022. Journal of Hepatology 2022 vol. 77 j 479–502

Crawford DHG et al (2023) Clinical practice guidelines on hemochromatosis: Asian Pacific Association for the Study of the Liver. Hepatology International (2023) 17:522–541