Here, we present a case series of BCS, a rare vascular disease of the liver. We found a low incidence rate of 28.6 cases per million inhabitants, which was still higher than that of other European studies [3, 10, 11] at 2–10 cases per million inhabitants [3, 10, 11]. Most of the information available in the academic literature to date comes from case reports or small cohort studies. In our series, cancer was present in 6 of 15 patients (40%), which was higher than previously reported. Most of the studies focused on primary BCS, excluding cases attributed to neoplasms. The relationship between neoplasms and BCS has been previously reported [12, 13], with BCS being related to both solid and haematological cancers. Cancer can cause BCS through various mechanisms, such as direct compression of the hepatic veins, metastases, vessel infiltration, or the induction of venous embolisms. In our series, 4 of the 6 cases of cancer-related BCS were attributed to solid neoplasms located in the abdomen. While hepatocarcinoma has previously been reported as a cause of BCS , we found no previous reports of ovarian cancer associated with BCS.
The second most common cause of BCS in our series was liver abscesses. Interestingly, the coexistence of portal vein thrombosis (PVT) and a liver abscess was relatively frequent , but BCS secondary to abdominal infections was rarely reported . Only a few such cases have been described, and some of these were attributed to amoebic infections , although our case series did not include any of these cases. Amoebic infections, including liver abscesses, are rare in western countries, with most of the reported cases being from low-income regions . Isolation of 2 or more microorganisms, including bacteria and fungi, is common in liver abscesses , while the presence of Candida spp. and other fungi have previously been reported as a rare cause of liver abscesses . In our case series, two or more microorganisms were isolated from liver or peritoneal samples in 2 patients.
Lastly, prothrombotic factors rather than cancer or infection were detected in 3 patients. Paroxysmal nocturnal haemoglobinuria, a factor V Leiden mutation, and antiphospholipid syndrome have been identified as risk factors for several thrombotic diseases, including BCS [21, 22]. Of note, previous studies showed around a 25% prevalence of mutated factor V in BCS, while in this work, we found a prevalence of only 6.7% . This could perhaps be explained by the distribution of the factor V mutation around the world. In Spain, the prevalence of this mutation in the general population is around 3.3% , while in other European countries such as Sweden, it exceeds 10%.
Regarding the treatment of BCS, most of patients received anticoagulation as the primary therapy. There are currently no ongoing clinical trials comparing BCS management options, and so, most information arises from observational studies and clinical experience. Anticoagulation with heparin seems to be the treatment of choice, although no clinical trials have compared UH to LMWH in this context . In addition, no clinical trials have evaluated anti-vitamin K or direct oral anticoagulants in these patients. The second line of BCS management is treatment of the underlying cause. In our case series, 5 out of 6 patients with neoplasms received chemotherapy. Patients with hypercoagulable disorders rather than an infection should receive indefinite anticoagulation unless contraindicated.
BCS is related to liver cirrhosis through several mechanisms. Firstly, liver cirrhosis has been identified as a risk factor for venous thrombosis (e.g. BCS and portal vein thrombosis). Secondly, liver cirrhosis may develop after BCS as the result of chronic liver damage and fibrosis. In our series, 2 patients were previously diagnosed with liver cirrhosis and another 2 developed cirrhosis after the diagnosis of BCS. According to clinical guidelines, screening for hepatocarcinoma and oesophageal varices is mandatory in both settings .
Interventional therapy for BCS is also controversial. No clinical trials have compared different treatments for BCS and most of the data available to date has come from observational studies. The interventional approach has 2 major goals. Firstly is to restore the circulation through thrombosed veins using thrombolytics or by placing a stent. Secondly, in some selected cases, the placement of TIPS or shunts may reduce pressure on hepatic circulation. In our centre, two patients underwent a mechanical thrombectomy, although no clinical trials have yet compared this procedure with the use of thrombolytics. In contrast, the safety and efficacy of TIPS has been demonstrated in several observational cohorts. In our series, this procedure was conducted in 2 patients in combination with LWMH therapy. Finally, in some cirrhotic patients, liver transplant may be indicated, although none of the patients at our centre were referred to the liver transplant unit.
The mortality rate in the first 6 months post-diagnosis was remarkably high in these patients (46.7%) and was closely related to the underlying cause of the BCS. Case-series or cohorts focused on primary BCS found a mortality of between 10 and 20% . However, the mortality rate was higher in secondary BCS, mostly because of the underlying disease . In previous series, cancer-related BCS was less common than primary BCS [27,28,29] while in our study, secondary BCS was more frequent. Importantly, the incidence, mortality, and causes of BCS seem to vary in different geographical areas, probably in relation to patient age and genetic factors.