BCS is a rare vascular disease of the liver with heterogeneous clinical manifestations caused by obstruction of hepatic venous outflow. According to the etiology of the disease, BCS is classified as primary and secondary. Primary BCS is caused by acquired conditions such as myeloproliferative neoplasms, hereditary conditions such as Factor V Leiden, and systemic prothrombotic conditions. Secondary BCS is caused by vascular compression due to pyogenic infectious process or benign and malignant tumors [1, 2]. Regardless of the cause of the venous outflow obstruction, increased hepatic sinusoidal pressure and portal hypertension occur rapidly, leading to ischemic damage to the hepatocytes, followed by nodular regeneration, fibrosis, and eventually cirrhosis. In addition, large regenerative nodules may in turn lead to compression of intrahepatic veins [1, 4].
This study is the first report to compare the clinical features, laboratory parameters, and outcomes between acute and chronic BCS from Iran. This cross-sectional study showed that spontaneous bacterial peritonitis and jaundice were significantly associated with the chronic group compared with the acute group. The study also showed that levels of MELD score, INR, and BUN in chronic BCS was significantly higher than in the acute group. There was no significant difference between the outcomes of the two groups in terms of hospital LOS and mortality. In our patients the most common predisposing factor for BCS were myeloproliferative neoplasms, paroxysmal nocturnal hemoglobinuria, and systemic lupus erythematosus (Table 1)
The definitions of acute and chronic of BCS are not clearly defined [9]; however, most studies have classified the BCS with an onset of less than 6 months as acute and more than 6 months as chronic [3, 5, 6]. When BCS is suspected, color Doppler ultrasound is typically the first imaging procedure with high sensitivity and specificity [8]. Doppler ultrasound, MRI, and computed tomography are usually sufficient to diagnose BCS. Liver biopsy is only useful if the thrombosis is limited to the small intrahepatic veins and the large vessels appear normal on imaging [2, 7]. In our study, most patients were in the chronic BCS group.
The clinical manifestations of BCS are heterogeneous and depend on the extent and speed of the obstruction of the hepatic venous outflow and the presence of collateral venous ducts. All of our participants were symptomatic, although the literature reported that up to 20% of patients with BCS were asymptomatic [1]. This difference may be due to the fact that all of our participants were referred from other centers for diagnostic and therapeutic procedures and were hospitalized, so we did not evaluate outpatients. Although the classic triad of abdominal pain, ascites, and hepatomegaly is common in BCS patients, other clinical features, including fever, pedal edema, truncal hepatic veins, GI bleeding, and hepatic encephalopathy, may be seen in this disease [1].
In a study by Darwish Murad et al. [10], they found that 61% and 83% of patients with BCS had ascites and abdominal pain, while esophageal bleeding and hepatic encephalopathy have been reported in approximately 5% and 9% of their patients, respectively. The frequency of all of these manifestations was higher in our results. 76.7% of our patients had abdominal pain, while GI bleeding and hepatic encephalopathy in our participants was about 15%, but there was no significant difference in terms of these manifestations between acute and chronic BCS. Another complication of liver failure is spontaneous bacterial peritonitis, which was significantly higher in our study in the chronic group than in the acute group.
In a study conducted by Mahmoud et al. [11] on BCS patients, the frequency of abdominal pain (84%) and hepatic encephalopathy (36%) was higher than our results, while the frequency of peripheral edema (4%), GI bleeding (9%), jaundice 4 (9%), and vomiting (27%) was less than our study. According to clinical manifestations, in our research, the presence of jaundice in chronic BCS was significantly higher than acute group, but there was no significant difference in other clinical features including peripheral edema, and fever between two groups (Tables 2 and 4).
Serum aminotransferases, alkaline phosphatase, serum albumin, serum bilirubin, and prothrombin may be normal or high in patients with BCS [12]. In our participants, although the mean ALT, AST, bilirubin, INR, and PTT were high in both acute and chronic groups, the differences between the two groups were significant only in bilirubin, INR, and PTT. In a study by Rautou et al. [13], in 96 BCS patients, they concluded that high levels of ALT reflected acute and severe but potentially reversible ischemic liver cell necrosis. Another study of 45 BCS patients who were admitted to four medical centers concluded that serum ALT appeared to be a prognostic indicator [14]. Serum creatinine levels can also be high, usually due to pre-renal dysfunction [12], and may be associated with patient death [15]. The levels of BUN and creatinine in the chronic group of our patients were higher than acute, which was significant in terms of BUN.
The classic composition of ascitic fluid in BCS is high SAAG (> 1.1 g/dL) [1, 12]. All patients with acute BCS in our study had high SAAG ascites, but 7% of patients in the chronic group had low SAAG ascites (Table 3); the reason for this difference was unclear and requires further research with higher sample size. Although standard laboratory analyzes are of little help in diagnosing BCS, they are useful in predicting the severity of the disease, the likelihood of death, and the possible response to treatment. One of the common prognostic indices in BCS is the MELD score [1, 7]. MELD score and INR in chronic BCS group of our patients were significantly higher than the acute group (Table 5).
An important limitation in our research was that only symptomatic hospitalized participants were studied, so the results of this study may not be generalizable to asymptomatic patients. Another limitation of our study was that it was conducted in a single center, but the main strength of our research was the optimal evaluation of clinical features as well as the detailed assessment of laboratory parameters in acute and chronic BCS patients.
