Editor’s Note
Hepatic sinusoidal obstruction syndrome (HSOS) is a hepatic vascular disease characterized by edema, necrosis, and detachment of the endothelial cells in the hepatic sinusoids, hepatic venules, and interlobular veins, leading to microthrombi formation, intrahepatic congestion, liver injury, and portal hypertension. Clinical manifestations include abdominal distension, liver pain, ascites, jaundice, and hepatomegaly. In cases of sudden liver enlargement, liver pain, jaundice, and ascites, HSOS should be suspected. This article features a classic HSOS case shared by Professor Shao Ming's team from Shanxi Yuncheng Huiren Hospital, detailing their diagnosis and treatment experience.Case Introduction
Patient Kou, male, 59 years old, farmer, native of Shanxi.
Chief Complaint: Abdominal distension for 10 days.
Present Illness: The patient experienced abdominal distension 10 days ago without an obvious cause, with no fever, nausea, or vomiting. Local clinic diagnosed “gastritis” and provided symptomatic treatment with no improvement. One day ago, he sought care at another hospital, where an abdominal ultrasound suggested liver cirrhosis with ascites. He came to our hospital for further diagnosis and treatment on September 1, 2023. He was admitted to our department with “decompensated liver cirrhosis.” Since the onset, the patient’s appetite decreased, but his mental state, sleep, and bowel movements were normal.
Past Medical History: Treated with compound glycyrrhizin for a skin condition two years ago. Immunization history is unknown.
Personal History: Born in his hometown, no alcohol consumption habit, smoked for 30 years with an average of 60 cigarettes per day. No long-term residence in other areas, no exposure to endemic areas, no history of contact with industrial toxins, dust, or radioactive substances. No history of travel.
Marital and Reproductive History: Married at the appropriate age, has two children, and his wife and sons are healthy.
Family History: No relevant family disease history.
Physical Examination: Vital signs normal, mild jaundice in sclera, coarse breath sounds in both lungs, heart (-). Abdominal distension, liver palpable 1 cm below the costal margin, moderate texture; spleen not palpable. Negative fluid wave test, positive shifting dullness. Bilateral lower limb edema.
Admission Test Results:
- Liver Function: TB 32.3 µmol/L, DB 18.70 µmol/L, IB 13.60 µmol/L, ALT 86.0 U/L, AST 146.0 U/L, ALP 110.0 U/L, GGT 209.0 U/L, ChE 2790.5 U/L, TP 62.9 g/L, Alb 25.0 g/L, Glo 37.9 g/L.
- Lipid Profile and Renal Function: Normal.
- Electrolytes: K+ 4.2 mmol/L, Na+ 140.34 mmol/L, Cl- 104.7 mmol/L, Ca2+ 1.08 mmol/L.
- Infection Markers: HBsAg (-), Anti-HBs (+), HBeAg (-), Anti-HBe (-), Anti-HBc (-), Anti-HBc-IgM (-); Anti-HCV (-), Anti-HIV (-), RPR (-).
- Blood Count: WBC 3.37×10^9/L, RBC 4.57×10^12/L, HGB 141.0 g/L, PLT 35.0×10^9/L, NEUT% 71.80%.
- Coagulation Profile: Normal.
- Urinalysis: Hematuria 3+, Proteinuria 3+, Urobilinogen 1+; others normal.
- ECG: Normal.
- Chest CT: Mild centrilobular emphysema in the upper right lobe, interstitial changes in the subpleural region of the lower lobes, atherosclerosis of the aorta, a small amount of pleural effusion on the right, and fatty liver.
- Abdominal Ultrasound: Enlarged liver with uneven distribution of hepatic echo, suspected diffuse liver cancer for further examination; small amount of ascites; gallbladder wall edema.
An enhanced abdominal CT on September 3, 2023, showed fatty liver or hepatitis with decreased enhancement in the liver parenchyma (excluding HSOS, recommended further examination); a small amount of ascites; small amount of right pleural effusion; atherosclerosis of the abdominal aorta and iliac arteries; bilateral renal cysts.
A gastroscopy on September 20, 2023, showed mild esophageal varices and portal hypertensive gastropathy. MRI suggested Budd-Chiari syndrome, suspecting small hepatic venous occlusive disease. However, there was no relevant medication history, and personal and family history was unremarkable. The patient refused low molecular weight heparin and warfarin anticoagulation therapy.
For further diagnosis, the patient visited a tertiary hospital out of the province on October 6, 2023, where hepatic angiography showed: narrowing of the intrahepatic segment of the inferior vena cava, the right, middle, and left hepatic veins near the second hepatic hilum were slender and not clearly visible; liver enlargement, uneven enhancement in the liver parenchyma with diffuse reticular high-density shadow enhancement; these signs suggested Budd-Chiari syndrome or small hepatic venous occlusive disease. Liver biopsy pathology indicated: nodular cirrhosis with “Budd-Chiari syndrome” suspected based on imaging findings.
Due to abdominal distension, the patient sought care at a tertiary hospital in Beijing in January 2024. The abdominal ultrasound indicated: three hepatic veins were slender with unobstructed blood flow, and unobstructed blood flow in the inferior vena cava with local compression. Gastroscopy showed mild esophageal varices and portal hypertensive gastropathy. Fibroscan results: liver stiffness 68.7 kPa, spleen stiffness 87.3 kPa. Another transjugular liver biopsy revealed: liver tissue showed changes suggestive of HSOS, with hepatocyte degeneration, sinusoidal inflammation, endothelial cell proliferation, and new small vessel formation, with large nuclei cells and a suspicion of vascular-origin tumor. Bone marrow biopsy showed active proliferation with poor megakaryocyte platelet production.
The patient did not respond well to oral diuretics, was hospitalized twice more at our hospital, and underwent abdominal paracentesis and drainage. Repeated inquiries revealed no related medication history, no exposure to toxins, health products, or dietary supplements. Anticoagulation treatment was ineffective.
Preoperative examination for TIPS on March 1, 2024, showed: severe esophagogastric varices and portal hypertensive gastropathy. Clinical diagnosis: HSOS; ascites; pleural effusion; hypoalbuminemia; esophagogastric varices; portal hypertensive gastropathy.
On March 7, 2024, a TIPS procedure was performed through the hepatic vein to the left branch of the portal vein. One month post-operation, an enhanced abdominal CT on April 16, 2024, showed reduced liver congestion and resolution of ascites. Follow-up gastroscopy indicated the disappearance of esophagogastric varices, and abdominal wall varices also disappeared.
Discussion
HSOS, also known as hepatic veno-occlusive disease (HVOD), is a hepatic vascular disorder caused by various factors leading to edema, damage, and detachment of endothelial cells in the hepatic sinusoids, hepatic venules, and interlobular veins, forming microthrombi, resulting in intrahepatic congestion, liver injury, and portal hypertension. Clinical manifestations include abdominal distension, liver pain, ascites, jaundice, and hepatomegaly. In China, HSOS is often reported due to the consumption of plants containing pyrrolizidine alkaloids, with Tusanqi (or Jin Sanqi) being the most common.
Imaging examinations are essential for suspected HSOS, including:
- Typical 2D ultrasound findings show diffuse liver enlargement; coarsened and denser liver parenchymal echo with uneven distribution, patchy hypoechoic areas along the hepatic veins, and ascites;
- Abdominal ultrasound reveals normal diameter of the portal and splenic veins with reduced blood flow velocity (<25 cm/s);
- Contrast-enhanced ultrasound shows heterogeneous enhancement in the arterial phase, slow portal vein filling, prolonged transit time between hepatic artery and vein;
- Abdominal CT shows diffuse liver enlargement, with unenhanced liver parenchyma presenting reduced, uneven density. In the venous and equilibrium phases, the liver parenchyma exhibits characteristic “map-like” or “patchy” enhancement, with low-density edema bands around the portal vein, known as “halo sign”; caudate lobe and left lateral segment are less affected, with higher enhancement around hepatic veins showing characteristic “cloverleaf sign,” and narrowed or obscured hepatic vein lumens; typically associated with ascites, pleural effusion, gallbladder wall edema, and gastrointestinal wall edema. Acute phase rarely associates with splenomegaly or esophagogastric varices;
- MRI shows liver enlargement and massive ascites with heterogeneous liver signals, slender or obscured hepatic veins, T2-weighted imaging (T2WI) shows patchy high signals like “cotton wool”; dynamic MRI scan shows heterogeneous enhancement in arterial and venous phases, more prominent in the delayed phase.
Typical liver pathology of HSOS shows predominantly zone III hepatic sinusoidal endothelial cell swelling, damage, detachment, significant sinusoidal dilatation and congestion; varying degrees of hepatocyte swelling and necrosis, erythrocyte infiltration into Disse’s space, thickening and narrowing of small hepatic venous walls, and absence of fibrosis or mild portal area fibrosis.
Expert Commentary
Clinicians should suspect HSOS in patients with sudden liver enlargement, liver pain, jaundice, and ascites, and inquire about medication history in detail. CT or MRI showing characteristic “patchy” uneven enhancement of the liver parenchyma, after excluding other diseases, can confirm the diagnosis. HSOS’s main differential diagnosis is Budd-Chiari syndrome, as both have similar clinical presentations. HSOS also causes hepatic vein narrowing due to liver enlargement compressing the inferior vena cava, but the lack of interconnecting vessels between hepatic veins is a key distinguishing feature. Histological examination also helps in differentiation. Early anticoagulation is crucial in treatment, with TIPS considered if medical therapy is ineffective.
