バッド・キアリ症候群

BACKGROUND AND AIMS: Assessing liver congestion and portal hypertension (PHT) in Budd-Chiari syndrome (BCS) remains challenging. We evaluated liver and spleen stiffness measurements (LSM, SSM) obtained by transient elastography as non-invasive tools for identifying clinically meaningful liver congestion in BCS. METHODS: This retrospective study included consecutive patients with BCS followed at our unit. At each visit, patients were classified as having a controlled or uncontrolled clinical status based on clinical, biochemical, imaging and/or hemodynamic data, by absence or presence of clinically significant PHT. LSM and SSM were independently obtained at all visits and diagnostic performance for classifying clinical status was assessed using receiver operating characteristic (ROC) analysis. RESULTS: Sixty-six patients were included with a median follow-up of 65.5 months (range:2-182): 34 had persistently controlled status, 11 persistently uncontrolled, 14 initially uncontrolled improved to sustained controlled status and 7 showed fluctuating status. Two-hundred eighty-nine LSM were obtained during periods of controlled clinical status (median:15.1 kPa, IQR:10.9-19.9) and 203 during uncontrolled status (median: 41.1 kPa, IQR: 34.8-64.5). LSM discriminated controlled from uncontrolled status (AUC 0.985). LSM cut-off of 25 kPa yielded 97.5% sensitivity, 92.5% specificity, 97.6% negative predictive value and 90% positive predictive value. SSM showed good discrimination (AUC 0.854), with values ≤ 30 kPa ruling out and > 40 kPa ruling in uncontrolled status, but accuracy was inferior to LSM. LSM values rapidly decreased following liver congestion resolution after interventional procedures. CONCLUSIONS: In BCS, LSM shows excellent concordance with clinical status and periodic assessment may facilitate clinical management. SSM provides complementary information but does not outperform LSM.

Budd-Chiari syndrome (BCS) is a rare hepatic vascular disorder characterized by hepatic venous outflow obstruction with an incidence of 1-2 per million population annually. While dengue fever is primarily associated with hemorrhagic complications, thrombotic events are rarely reported. To our knowledge, this represents the first documented case of BCS occurring in association with dengue fever. A 22-year-old male from a rural area presented with a 4-day history of abdominal pain, fever, vomiting, and loose stools. Physical examination revealed hepatomegaly, ascites, and mild dehydration. Laboratory investigations confirmed dengue IgM positivity with thrombocytopenia (104,000/mm3) and elevated liver enzymes. Thrombophilia screening revealed deficiencies in protein C, protein S, and antithrombin III. Imaging studies, including ultrasonography, computed tomography with contrast, and color Doppler, demonstrated hepatic vein thrombosis, inferior vena cava narrowing, and caudate lobe hypertrophy, establishing the diagnosis of BCS. Upper gastrointestinal endoscopy revealed grade II esophageal varices consistent with portal hypertension. During admission, the patient also developed severe bilateral lower limb pain refractory to strong analgesics, and nerve conduction studies confirmed sensory polyneuropathy in both lower limbs. The patient was managed with supportive care and careful anticoagulation therapy using low-molecular-weight heparin (LMWH), followed by warfarin 4 mg daily. Despite initial thrombocytopenia, anticoagulation was successfully initiated with close monitoring for bleeding complications. The patient showed an excellent clinical response, with complete resolution of hepatic vein thrombosis, normalization of liver function, and resolution of ascites at follow-up. At 6-month follow-up, repeat thrombophilia assays performed after stopping warfarin and bridging with LMWH revealed normal levels of protein C, protein S, and antithrombin III, indicating no true inherited deficiency. This case highlights a novel association between dengue fever, BCS, and sensory polyneuropathy in a patient with apparent but transient thrombophilia. Early recognition, appropriate anticoagulation, and careful neurological evaluation can lead to favorable outcomes despite concurrent thrombocytopenia.

BACKGROUND AND AIMS: Vascular liver diseases such as porto-sinusoidal vascular disorder (PSVD), Budd-Chiari syndrome (BCS), and non-cirrhotic portal vein thrombosis (NCPVT) are rare causes of portal hypertension (PH) but share the same phenotype with parenchymal chronic liver disease (CLD). We assessed whether blood-based and elastography-based noninvasive tests (NITs) can: (i) differentiate vascular from parenchymal liver disease, (ii) detect specific signs of portal hypertension within etiologies and (iii) identify portal vein thrombosis. METHODS: Consecutive patients with PSVD, NCPVT, BCS, or CLD treated at a tertiary referral center between January 2022 and December 2024 were included. Assessed NITs included platelet count, liver stiffness measurement (LSM), spleen stiffness measurement (SSM), the SSM to LSM ratio, ANTICIPATE, and NICER. RESULTS: This study included 411 patients: PSVD n = 43, NCPVT n = 38, CLD n = 309, and BCS n = 21. Among patients without PVT, NIT patterns differed between etiologies. The PSVD showed low LSM despite elevated SSM, resulting in the highest SSM to LSM ratio. This ratio best discriminated PSVD from CLD and BCS (AUC ≥ 0.870); the proposed cut-off of > 2 showed good diagnostic performance. The ANTICIPATE also differentiated PSVD from CLD/BCS, whereas SSM alone did not. Detection of specific PH signs was etiology dependent. In PSVD, platelet count showed the highest accuracy (AUC 0.823). In CLD, several NITs were associated with specific PH signs but accuracy was limited. In BCS, differences of the tested NITs for specific PH signs were not statistically significant. Across etiologies, NITs showed limited accuracy for detecting PVT. CONCLUSION: Combined assessment of LSM and SSM, particularly the SSM to LSM ratio, supports differentiation of PSVD from parenchymal and posthepatic liver disease, whereas platelet counts was most informative to detect specific PH signs within PSVD.

BACKGROUND: Budd-Chiari syndrome (BCS) presents diagnostic and treatment challenges owing to its insidious onset. Genetic variants associated with BCS vary geographically; in Asian populations, the condition is primarily caused by membranous obstruction composed of endothelial cells (ECs). A better understanding of the genetic pathogenesis of membranous BCS may offer new insights into disease mechanisms. METHODS: This study employed whole-exome sequencing to identify candidate genes responsible for EC abnormalities in 485 patients with membranous BCS and 329 patients with vascular malformations (VaMs). Functional investigations were conducted to validate the selected genes in vitro and in vivo. RESULTS: Whole-exome data revealed that the frequency of variants in the vascular function-related KLHDC2 exceeded that of JAK2 in BCS. Knockdown of KLHDC2 promoted adhesion and suppressed proliferation of ECs. In addition, 92 genes enriched for rare variants overlapped between BCS and VaMs. Systems biology analysis revealed two gene clusters, including COMMD9, enriched in proteins intolerant to loss-of-function mutations. Furthermore, suppression of COMMD9 impaired EC migration and tube formation, inhibited subintestinal angiogenic sprouting in zebrafish, and elevated EC adhesion. Transcriptomic analysis linked COMMD9 to EC abnormalities via the PI3K-Akt pathway. Commd9 knockdown promoted venous hypercoagulability in vivo following drug or ligation-induced stenosis. CONCLUSIONS: These findings indicate that multiple rare genetic variants, particularly in COMMD9, are involved in the development of membranous BCS by regulating hypercoagulability induced by EC abnormalities. These findings may help guide future clinical research towards improved understanding and treatment of BCS.