Acute-on-chronic liver failure (ACLF) in the context of Budd-Chiari syndrome (BCS), or BCS-ACLF, can be classified into three types. Type A includes ACLF precipitated by acute hepatic vein (HV) thrombosis, extension of an existing HV thrombosis, re-occlusion of a previously recanalized vein, or occlusion of a stent, in patients with diagnosed or undiagnosed BCS. Type B encompasses ACLF precipitated by a non-thrombotic acute insult in patients with previously diagnosed or undiagnosed BCS. Type C involves ACLF precipitated by acute HV or inferior vena cava (IVC) thrombosis in patients with pre-existing non-vascular chronic liver disease.¹

Patients with BCS-ACLF exhibit a 10-year survival rate of 55%, in contrast to the survival rate of over 90% observed in other forms of BCS.² The management of type A and type C BCS-ACLF includes urgent attempts to recanalize the thrombosed veins, establish a transjugular intrahepatic portosystemic shunt (TIPS), or apply a direct intrahepatic portosystemic shunt (DIPS) to promote reversibility. Conversely, patients with type B BCS-ACLF should receive standard ACLF treatment, with failure to improve warranting liver transplantation.¹

A 21-year-old man presented with jaundice and a dull, aching pain in the right upper quadrant that had persisted for 10 days. Examination revealed icterus, grade II ascites accompanied by tenderness in the right hypochondrium, and hepatosplenomegaly.

The patient had been hospitalized 6 months earlier for abdominal pain and ascites. A computed tomography (CT) scan of the abdomen at that time had indicated severe narrowing of the intrahepatic IVC, along with mild ascites, moderate splenomegaly, and multiple portosystemic collaterals. Following this, the patient underwent vena cava angioplasty, as the contrast venogram revealed near-complete occlusion of the intrahepatic IVC. Further evaluation of his antiphospholipid profile revealed positive results for lupus anticoagulant, anti-cardiolipin immunoglobulin (Ig) G, and B2-glycoprotein IgG antibodies. In response to the apparent catastrophic antiphospholipid syndrome, the individual was treated with plasma exchange, intravenous steroids, and anticoagulant and antiplatelet agents. He recovered and was discharged with a prescription for warfarin, a tapering course of steroids, and aspirin due to seropositivity for antiphospholipid antibodies.

Evaluation during the patient’s current hospitalization (Table 1) revealed jaundice (with total serum bilirubin levels rising to 48 mg/dL), coagulopathy, acute kidney injury, and a positive antiphospholipid profile, indicated by a positive lupus anticoagulant test and the presence of anti-beta-2-glycoprotein I IgG antibodies.

Table 1 . Laboratory Results at Presentation and After DIPS, Antiviral, and Anticoagulation Therapy.

Test	At presentation			After DIPS, antiviral, and anticoagulation therapy
	Day 1	Day 7		Day 11	Day 18	Day 21	Day 28
Hemoglobin (g/dL)	10.1	-		9.9	10.4	10.8	9.4
Total leucocyte count (103/μL)	3,810	-		3,720	4,690	3,300	5,350
Platelet count (106/μL)	1.59	-		1.43	1.2	1.0	1.1
Total bilirubin (mg/dL)	12.3	48		24	8.6	6.6	3.9
Direct bilirubin (mg/dL)	7.9	19		10.9	4.6	3.1	1.9
Aspartate aminotransferase (IU/L)	18	263		170	273	128	95
Alanine aminotransferase (IU/L)	13	369		237	210	129	145
Alkaline phosphatase (IU/L)	179	198		171	102	176	110
Serum albumin (g/dL)	4.1	2.9		2.9	3.2	4	4.1
Blood urea nitrogen (mg/dL)	9	20		27	19	27	21
Serum creatinine (mg/dL)	1.8	1.4		1.3	1.6	1.7	1.4
Sodium (mEq/L)	140	131		133	131	137	145
International normalized ratio	> Vmax	1.4		2.1	2.7	2.7	2.6

DIPS, direct intrahepatic portosystemic shunt.

Viral serology showed reactivity for hepatitis B surface antigen—which had been non-reactive during the patient’s earlier hospitalization—and reactive IgM anti-HBc antibody. The hepatitis B quantitative viral load was 31,167 IU/mL (log 5.2 copies). Tests for hepatitis B e antigen (HBeAg), human immunodeficiency virus, anti-hepatitis C virus, IgM anti-hepatitis A virus, and IgM anti-hepatitis E virus were all non-reactive. According to the European Association for the Study of the Liver guidelines, serology was indicative of the HBeAg-negative chronic hepatitis B phase.³

During the current hospitalization, contrast-enhanced CT of the abdomen (Fig. 1) revealed hepatosplenomegaly with multiple regenerative nodules, a narrowed intrahepatic IVC with non-visualization of the right and middle HVs, and mild ascites. These findings suggest the presence of new-onset thrombosis of the HVs.

Figure 1. Contrast-enhanced computed tomography of the abdomen reveals an enlarged liver and spleen, mild ascites, and features including (A) the presence of intrahepatic veno-venous collaterals (red circle), (B) non-visualization of hepatic veins (black arrow), and (C) regenerative nodules.

Ascitic fluid analysis showed a high serum-ascites albumin gradient (2.3) and low protein content (0.7 g/dL), without spontaneous bacterial peritonitis. The patient’s prognostic scores on presentation—a Child-Turcotte-Pugh score of 10 (class C), a Model for End-Stage Liver Disease (MELD) score of 35, and a BCS-TIPS prognostic index score of 10.683—indicated a low (12%) chance of liver transplantation-free survival.⁴

The patient was diagnosed with ACLF based on the definition of the Asian Pacific Association for the Study of the Liver (APASL),⁵ accompanied by acute kidney injury. The underlying chronic event was identified as chronic BCS. Identifying the primary acute insult was challenging; therefore, treatment strategies for both potential etiologies were considered.

The patient was started on entecavir (1 mg orally) in conjunction with therapeutic doses of subcutaneous enoxaparin and aspirin (75 mg orally). In response to his rapidly deteriorating liver function, a DIPS procedure was performed, in which a 10 × 100 mm self-expandable stent was deployed across the tract between the right portal vein and the IVC (Fig. 2). Following stent placement, the portal pressure decreased to 15 mmHg, followed by the resolution of collaterals.

Figure 2. Fluoroscopic image captured after direct intrahepatic portosystemic shunt placement. A self-expandable stent, measuring 10 × 100 mm, has been deployed across the tract connecting the right portal vein to the inferior vena cava.

After treatment, the patient’s jaundice and liver function parameters (Table 1) improved, and his ascites resolved. However, his creatinine levels remained high despite volume expansion with intravenous human albumin. Urine analysis revealed an elevated fractional excretion of sodium at 5.6%, proteinuria in the nephritic range (1.9 g per 24 hours), and 4–5 red blood cells (RBCs) per high-power field. Additionally, the patient’s serum C3 levels were low at 80.9 mg/dL, while his C4 levels were normal at 14.8 mg/dL. Notably, no dysmorphic RBCs or casts were detected in the urine. Renal ultrasound revealed increased bilateral echotexture with the maintenance of corticomedullary differentiation, and a renal Doppler study yielded normal results. A nephrology consultation was sought, and transjugular renal biopsy was performed (Fig. 3), identifying mesangioproliferative glomerulonephritis with immune complex deposition and acute tubular injury. Subsequently, a sodium-glucose cotransporter 2 inhibitor (dapagliflozin) was incorporated into the medication regimen.⁶ The patient made an uneventful recovery (Table 1) and was discharged on entecavir, warfarin, aspirin, and dapagliflozin. He has been under regular follow-up for the past 4 months without any reported adverse events.

Figure 3. Light microscopy images reveal enlarged glomeruli characterized by increased mesangial cellularity and matrix, along with patchy thickening of the capillary walls. Additionally, foci of interstitial fibrosis, atrophy, and tubular injury are evident. The stains used are (A) Periodic acid-Schiff, (B) Hematoxylin & Eosin, and (C) methenamine silver. All images are in × 40 magnification.

Ethics committee approval is not applicable. Written informed consent was obtained from the patient.

Patients with BCS typically have subacute or chronic presentation^7,8 with only a small fraction exhibiting acute liver failure⁹ or ACLF.^10,11 In a study by Shalimar et al,¹² approximately 5% (n = 28) of 553 individuals with BCS were found to have ACLF according to the APASL definition. The same study identified several acute precipitating events of BCS-ACLF, which included thrombosis of a previously placed endovascular stent in 17.9% of cases, acute HV thrombosis in 10.7%, acute viral hepatitis in 7.1%, and multifactorial causes (such as antituberculosis drug therapy combined with hepatitis B virus reactivation) in 3.6%. However, in 60.7% of cases, no acute precipitants were identified.¹² Radha Krishna et al¹³ discussed the outcomes of acute viral hepatitis A and E in patients with cirrhosis. Among the 3.75% (n = 121) of 3,220 patients who developed ACLF triggered by acute hepatitis A and/or E, two cases reportedly had chronic BCS as the etiology of chronic liver disease.¹³ In this report, we present an unusual case of BCS-ACLF characterized by two acute insults—reactivation of hepatitis B (a non-thrombotic insult) and new vein thrombosis—in a patient previously treated for BCS.

In this case report, non-compliance with therapy and irregular follow-up were considered as potential contributing factors to the new thrombus development. The therapeutic range of the international normalized ratio could not be determined due to a lack of follow-up.

Traditionally, many physicians have been reluctant to offer TIPS to patients with high MELD scores (≥ 18) due to concerns about disproportionately high mortality risk associated with the procedure.¹⁴ However, a single-center study by Spengler et al¹⁵ demonstrated that TIPS does not independently increase mortality risk in patients with MELD scores of ≥ 18. In a study conducted by Shalimar et al¹² on the outcomes of endovascular interventions in patients with BCS-ACLF, the subgroup that underwent these interventions exhibited improved survival. Notably, both the presence of hepatic encephalopathy and endovascular intervention were identified as independent predictors of patient outcomes.¹² Furthermore, guidelines recommend liver transplantation for decompensated patients with BCS who do not respond to endovascular interventions.^1,16 Our case report highlights the safety and effectiveness of DIPS as a life-saving intervention in the management of BCS-ACLF, even with a high MELD score (≥ 18), in a non-transplant setting. However, the presence of multiple organ failures and infections complicates the decision to proceed with endovascular intervention. Therefore, the decision should be made through collaboration between the treating physician and the interventional radiologist, considering the severity of clinical presentation. In our case report, identifying the primary acute precipitating factor was challenging. Nevertheless, timely administration of DIPS alleviated hepatic congestion, and the combined use of DIPS and antivirals obviated the need for an urgent liver transplant. Prospective randomized controlled trials are warranted to further assess the role of endovascular intervention and liver transplantation in patients with BCS presenting as ACLF.

None.

The data that support the findings of this study are available from the corresponding author upon reasonable request.

No potential conflict of interest relevant to this article was reported.