Authors: Shuangshuang Sun, Qingchun Fu

Shanghai Public Health Clinical Center

Editor's Note: Hepatic sinusoidal obstruction syndrome (HSOS), also known as hepatic veno-occlusive disease, is a common secondary vascular liver disease caused by various factors leading to damage to sinusoidal endothelial cells, resulting in sinusoidal obstruction and hepatic congestion. Clinically, it primarily presents with abdominal distension, liver pain, rapid ascites accumulation, hepatomegaly, and jaundice, which can lead to severe liver dysfunction, multi-organ failure, and even death. Professor Qingchun Fu's team from the Shanghai Public Health Clinical Center shares a clinical case and their experience in diagnosing and treating a patient with HSOS induced by combined drug and alcohol use.

Case Presentation

Patient: Male, 38 years old, admitted for “skin and scleral jaundice for over two months.”

History of Present Illness: In September 2023, the patient developed skin and scleral jaundice without apparent cause, with no symptoms of poor appetite, fatigue, abdominal distension, or pain, and did not seek treatment. Ten days before admission, he experienced a fever with a maximum self-measured temperature of 38°C, and self-medicated twice with “999 Cold Remedy Granules”, after which the fever subsided. In November 2023, he visited a tertiary hospital in Shanghai. Test results were: blood routine: WBC 15.34×10^9/L, PLT 99×10^9/L; liver enzymes: ALT/AST 20/104 U/L, ALP/GGT 245/493 U/L, TBIL 291 μmol/L, PT 15.2s; AFP 2.6 ng/mL. Abdominal ultrasound suggested a suspicious solid hypoechoic area near the gallbladder (no mass on enhancement), cholecystitis, fatty liver, splenomegaly, and ascites.

Past Medical History: Bilateral hip replacement for bilateral femoral head necrosis four years ago.

Personal Habits: 20-year smoking history, 20 cigarettes/day, not quit; 20-year drinking history, initially half a jin of white wine, 2-3 times a week, occasionally beer; switched to 2 jin of yellow wine/day; since 2018, daily intake of two bottles (125 ml each) of 35° medicinal wine containing Huai Shan Yao, Xian Mao, Rou Cong Rong, Gou Qi Zi, Huang Qi, Rou Gui, Ding Xiang, and Yin Yang Huo, totaling 70 g of alcohol/day, not quit.

Examination on Admission

Blood Routine: WBC 17.45×10^9/L, RBC 3.19×10^12/L, HB 116 g/L, PLT 368×10^9/L, N 87.20%, RET 2.28%; hypersensitive CRP 37.72 mg/L, ESR 65 mm/h; liver function: ALT/AST 16.20/79.50 U/L, TB/DB 409.3/365 umol/L, AKP/GGT 216/297 U/L, ALB 33.3 g/L, Cr 37 μmol/L; coagulation function: PT 16 s, APTT 58.3 s, INR 1.32, D-D 8.62 μg/mL; other tests normal.

Imaging:

• Upper abdominal enhanced CT: (1) Liver enlargement with inflammatory changes, slight ascites, splenomegaly. (2) Cholecystitis, abnormal perfusion near the right lobe of the liver. (3) Portal hypertension with mild cavernous transformation, multiple collateral circulations in the esophagus, gastric fundus, and abdominal cavity; slender hepatic veins; segmental stenosis of the intrahepatic inferior vena cava.

• Upper abdominal CTA/CTV: (1) Liver enlargement with inflammatory changes, splenomegaly, ascites. Portal hypertension with mild cavernous transformation, multiple collateral circulations in the esophagus, gastric fundus, and abdominal cavity; slender hepatic veins; segmental stenosis of the intrahepatic inferior vena cava. (2) Liver enlargement, liver damage, cholecystitis. (3) Abnormal enhancement area near the gallbladder fossa, liver island possibility, mass to be ruled out.

• MRI enhancement: Liver damage, liver enlargement, weak echo mass in the right lobe (MT to be ruled out), splenomegaly, gallbladder wall edema, gallbladder bile stasis, ascites, portal vein system dilation, slender hepatic veins.

Treatment Process

The initial consideration for the cause of jaundice was pending (drug-induced? alcohol-related?). Multiple imaging checks suggested the possibility of a mass. Tumor markers showed no significant abnormalities, leading to a re-evaluation by imaging specialists, excluding a tumor diagnosis and considering HSOS based on chronic liver damage manifestations.

Due to the complexity of the patient’s condition, a multidisciplinary team (MDT) discussion was held, leading to the final diagnosis of:

1. HSOS (possibly drug-induced)

1. Portal hypertension (esophageal and gastric varices, splenomegaly)

1. Alcoholic liver disease; Maddrey discriminant function score = 53

1. Post bilateral hip replacement

Medical recommendations included enhanced anticoagulation therapy, with Transjugular Intrahepatic Portosystemic Shunt (TIPS) considered if necessary to reduce hepatic sinusoidal pressure. As medical anticoagulation showed poor results and jaundice progressed, the patient was referred for TIPS + transjugular intrahepatic liver biopsy. Post-surgery, continued anticoagulation resulted in rapid jaundice improvement, with second pathology review suggesting alcohol and drug-induced factors.

Expert Second Review Conclusions

Chronic liver damage was characterized by extensive perisinusoidal fibrosis, potential post-sinusoidal obstruction, bile lakes, significant neutrophil infiltration in portal areas, Mallory bodies, and coarse fibrous scars, consistent with alcoholic liver disease. Chronic drug-induced liver damage, including vascular damage, was also suspected, though acute SOS signs were absent, suggesting chronic SOS.

Treatment-Related Safety Analysis

Following admission, the patient’s blood routine indicated gradually increasing white cells and neutrophils, with no significant improvement after treatment with Piperacillin Sodium and Tazobactam Sodium and Meropenem. Antibiotic treatment was discontinued, and following TIPS surgery, liver sinusoidal pressure and blood flow improved, correlating with jaundice resolution, likely due to alcohol-related liver disease and drug-induced inflammation. During treatment, platelet count dropped, likely an adverse reaction to the anticoagulant Rivaroxaban, which improved upon discontinuation.

Case Summary

The patient, a 38-year-old male with a significant drinking history, exhibited marked jaundice unresponsive to medical treatment. After comprehensive examination and MDT discussion, the final diagnosis was:

1. HSOS (induced by drugs and alcohol)

1. Alcoholic cirrhosis

1. Post bilateral hip replacement

Common Causes of HSOS

Common HSOS inducers include pyrrolizidine alkaloids (PAs) found in certain herbs or wild plants, prevalent in Asteraceae, Fabaceae, and Boraginaceae families. These can be ingested via traditional herbal remedies, teas, grains, or the food chain. The patient’s herbal medications did not clearly contain PAs, but geographic and compositional differences might have contributed to hepatotoxicity.

Despite liver biopsy lacking typical HSOS pathology, imaging matched “Nanjing Criteria” for HSOS diagnosis: CT showed ascites, reduced heterogeneous liver density, characteristic “map-like” enhancement post-contrast, and MRI depicted heterogeneous liver parenchyma enhancement in portal and delayed phases with poor contrast agent filling in liver veins. The patient responded well to TIPS, validating the HSOS diagnosis. Follow-up showed good general condition.

Expert Commentary

Alcoholic liver disease was the primary condition, with drug-induced damage contributing to HSOS clinical presentation. The etiology involved both alcohol and medication, diagnosed using “Nanjing Criteria” and supported by expert MDT consultation.

Drug-induced vascular liver damage is not limited to commonly known Tusanqi; the patient’s herbal history warrants further investigation. Drug damage can affect sinusoids, portal, and hepatic veins. Typical drugs like Oxaliplatin can initially present as HSOS and later lead to portal sinusoidal vascular disease (PSVD) with significant portal hypertension and normal liver function, often overlooked.

Enhanced clinical research, multidisciplinary collaboration, and public education on drug-induced vascular liver damage are crucial to prevent such cases.