OVERVIEW
Hepatic small vein occlusive disease (HVOD), also known as sinusoidal gap obstruction syndrome, is a nonthrombotic obstruction of the hepatic circulation with centrilobular sinusoidal gap fibrosis and fibrotic stenosis or occlusion of the common small hepatic veins. Clinical appearance of liver enlargement, pain, ascites, etc., more than half of the patients can be recovered, 20% of patients die of liver failure, a few patients develop cirrhosis portal hypertension.
Etiology
Ingestion of plants, herbs or tea products containing pyrrolizidine alkaloids is the most common cause of the disease. Other factors may be: (1) toxic substances such as arsenic and mercury; (2) preoperative high-dose chemotherapy and radiotherapy in stem cell transplant patients; (3) estrogen and so on.
Symptoms
The main manifestations include increased liver size, weight gain due to fluid retention in the body and hyperbilirubinemia. Most patients may have gastrointestinal, respiratory and systemic symptoms before the onset of the disease. The acute phase starts rapidly, with severe pain in the epigastrium, abdominal distension, rapid enlargement of the liver, tenderness, ascites may be accompanied by loss of appetite, nausea, vomiting, etc. Jaundice, edema of the lower limbs are less common, and there are often abnormalities in liver function. The subacute phase is characterized by persistent liver enlargement and recurrent ascites, and the chronic phase is characterized by portal hypertension, the same as other types of cirrhosis.
Examination
CT and MRI, as an important clinical test, are characterized by the detection of small lesions, while enhanced examination and image post-processing techniques are more helpful for early diagnosis of the disease. In hepatic small vein occlusive disease, this feature is fully utilized.
Spiral CT and magnetic resonance imaging both show different degrees of liver volume increase and large amount of ascites, etc. In addition, due to the uneven density, the image signal uneven phenomenon is obvious; in magnetic resonance T2WI, there are flaky high signals, and “cloudy” shadows appear on the image. Dynamic enhancement scans of spiral CT and magnetic resonance imaging show uneven enhancement in the arterial and venous phases, with “splotchy” changes; the enhancement is more obvious in the delayed phase.
Diagnosis
The diagnosis of HVOD is difficult, and patients with the above typical manifestations should be carefully searched for the relevant causes or triggers. Because of the characteristic manifestations of liver histopathology, the diagnosis of HVOD mainly relies on liver tissue biopsy.
Ultrasound and other imaging tests may reveal enlarged liver, ascites, exclude bile duct dilatation and hepatic liver-occupying changes, and reduced hepatic venous flow may be observed in early stages, and slowing of portal venous flow or change in direction of flow may be seen in late stages, but a diagnosis of the disease cannot be made on this basis.
Other techniques that may be helpful in obtaining a diagnosis are transvenous liver biopsy, which allows both the acquisition of liver tissue and the determination of the pressure gradient in the hepatic veins, which exceeds 10 mm Hg and is considered to be diagnostically specific.
Differential diagnosis
The most easily confused with HOVD is Buerger’s syndrome (B-CS), and the following points help to differentiate it: ① HOVD has been associated with the consumption of plants containing wild larkspur alkaloids, such as herbal bush and grass teas, and with the receipt of radiation, chemotherapy, or immunosuppressive medications, whereas there is no corresponding medical history for B-CS. (ii) The acute phase of B-CS is rarely accompanied by fever, vomiting, and diarrhea, although symptoms such as abdominal distension and pain in the liver region may also be present. In the acute phase, more than half of them are accompanied by inferior vena cava hypertension syndrome, such as chest and abdominal wall vein rage, lower extremity edema, perineal and superficial lower extremity varicose veins, and foot and ankle ulcer formation, which is not found in HOVD. (iii) Inferior vena cava and hepatic venography can clarify the site, degree and extent of obstruction of the hepatic vein and inferior vena cava and the formation of collateral circulation in the case of B-CS, while there is no positive finding in HOVD. ④ Ultrasound can find out whether the inferior vena cava is narrowed, occluded, the degree of obstruction, thrombosis and intrahepatic side-branch formation in B-CS, whereas HOVD mostly shows only hepatomegaly. ⑤ Liver biopsy is the most important differentiation between B-CS and HOVD. In B-CS, there may be thrombosis in the hepatic vein, while in HOVD, there is no hepatic vein thrombosis, and the lesions mainly involve the central vein and the sublobular vein, and they are edematous stenosis or fibrous stenosis. Acute HOVD should also be differentiated from acute hepatitis and acute severe hepatitis.
Prognosis
It is related to the severity of the disease. Mild patients usually recover on their own without special treatment; moderate patients require general and symptomatic supportive treatment and most of them also recover successfully; however, severe patients have a very high mortality rate and often die from multi-organ failure of the kidneys and cardiorespiratory function. Poor prognostic factors include aminotransferase levels above 750 U/L, high hepatic venous pressure gradient, portal vein thrombosis, blood creatinine more than twice the normal value, and decreased oxygen saturation.
Treatment
1. Acute stage
Comprehensive treatment program in acute stage: For early suspected cases, exposure, ingestion and application of hepatotoxic substances should be stopped in time. The following comprehensive treatment program should be adopted in the acute stage:
(1) Supportive therapy Intravenous drip of polarizing fluid and application of supportive therapy can be used in the acute stage;
(2) Specialized therapy Mainly anticoagulation and depolymerization therapy: the combined application of fibrinogen activator and heparin therapy can benefit about 30% of patients, but not in patients who have already bled and have renal and pulmonary failure. Patients with bleeding in the brain and lungs are not candidates for this treatment. Dextrose 40 (low molecular dextrose) should also be administered intravenously to improve microcirculation in the liver, lungs and kidneys.
(3) Other symptomatic therapeutic measures include abdominal septal compartment syndrome when the amount of ascites is large and stubborn, which should be purified by ultrafiltration of ascites and then infused intravenously with the cooperation of blood purification center. In case of ascites, diuretic drugs should be used, and pain relieving drugs should be given in case of abdominal pain.
(4) Preventing and controlling infections: Apply broad-spectrum antibiotics to patients with combined infections.
(5) Intermittent oxygen inhalation Hyperbaric oxygen therapy is given to those who have the condition, which is more beneficial to the severely ill patients. It can promote the elimination of hypoxemia in the circulatory system, reduce liver edema, and improve the whole body energy metabolism process, especially the regeneration process of hepatocyte mitochondria.
2.Chronic stage
In the chronic stage, the liver becomes sclerotic and portal hypertension syndrome occurs, and appropriate portal-corporeal or portal-lung shunt can be selected. Partial splenectomy is performed for markedly enlarged spleens, and only splenic artery ligation is performed for mildly or moderately enlarged spleens. However, surgery to preserve the spleen is only performed additionally in the presence of gastrointestinal bleeding requiring decompression and hemostasis with combined shunting and weaning. In-situ liver transplantation may be performed at the discretion of the patient with liver failure.