AIM: To assess the lifetime cumulative incidence of portal venous thrombosis (PVT) in the general population.

METHODS: Between 1970 and 1982, 23 796 autopsies, representing 84% of all in-hospital deaths in the Malmö city population, were performed, using a standardised protocol including examination of the portal vein. PVT patients were characterised and the PVT prevalence at autopsy, an expression of life-time cumulative incidence, assessed in high-risk disease categories and expressed in terms of odds ratios and 95% CI.

RESULTS: The population prevalence of PVT was 1.0%. Of the 254 patients with PVT 28% had cirrhosis, 23% primary and 44% secondary hepatobiliary malignancy, 10% major abdominal infectious or inflammatory disease and 3% had a myeloproliferative disorder. Patients with both cirrhosis and hepatic carcinoma had the highest PVT risk, OR 17.1 (95% CI 11.1 - 26.4). In 14% no cause was found; only a minority of them had developed portal-hypertension-related complications.

CONCLUSION: In this population-based study, PVT was found to be more common than indicated by previous clinical series. The markedly excess risk in cirrhosis and hepatic carcinoma should warrant an increased awareness in these patients for whom prospective studies of directed intervention might be considered.

Extrahepatic portal vein thrombosis (PVT) may be caused by a variety of conditions including cirrhosis, cancer and abdominal infectious and inflammatory processes. In the wake of thrombus organisation and vessel involution follows development of tortuous collaterals, so called cavernous transformation[1]. Symptom development is often insidious and related to the progression of portal hypertension. The concept of PVT as a rare disease is mainly based on clinical series and case reports[2-7]. Estimates of frequency and of distribution of etiological fractions vary widely between studies[2,4,5,6,8,9,10,11]. To some extent this may be explained by lack of precision in these small series, but a contribution of case selection and ascertainment bias should also be considered.

For several decades, the city of Malmö in southern Sweden has been a centre for epidemiological research, including clinical and autopsy-based studies of cardiovascular diseases[12,13,14,15]. Between 1970 and 1982, close to 24 000 autopsies, comprising 84% of all in-hospital deaths in the city, were performed. All procedures followed a standardised protocol including examination of the portal vein and its major tributaries. In consequence with the course in PVT, the prevalence at autopsy can be regarded as a proxy for the cumulative incidence during lifetime to develop PVT. The size of the cohort together with the high autopsy rate thus provides a unique opportunity to yield a robust estimate of risk in the general population. Further aims have been to evaluate likely causes to PVT and clinical characteristics related to portal hypertension, and to estimate the absolute risk of PVT in high-risk disease categories as characterised by autopsy findings.

Our finding of an overall risk in the general population of 1 % to develop PVT during lifetime does not corroborate the concept of PVT being a rare disease. The figure might even be an underestimation, since it cannot be ruled out that in some cases of partial thrombosis earlier in life a spontaneous resolution may have occurred. It should therefore be relevant to view these patients with renewed interest.

Among the major causes of PVT in adults, cirrhosis is generally named the most common, followed by neoplasia[5-6]. In this study the order of magnitude was reversed, with cancer in two thirds of the patients. By nature of being an autopsy study it is a selection of the sickest patients, and in some of these the thrombosis may be a late event in advanced cancer disease. Discrepancies in proportion of cirrhosis patients compared with previously published case series might also reflect patient selection and ascertainment bias resulting from an increased diagnostic activity in high-risk categories, but one should also consider the impact of disease duration. An intriguing finding was the heterogeneity of risk within the group of metastatic malignancy, with a significantly higher risk with pancreatic cancer in comparison with other major gastrointestinal adenocarcinomas.

When assessing the risk for a patient with a certain condition to develop an infrequent complication like PVT, knowledge from case series on the distribution of causes to that complication may be helpful and is sometimes the only available information. It may be misguiding, though. In this study, secondary malignancies accounted for a twice as large fraction of PVT cases as primary hepatobiliary cancer, but the actual risk of PVT in patients with secondary malignancies was less than half of that associated with primary hepatic cancer. In patients with both cirrhosis and hepatic cancer the risks appeared to be additive resulting in a prevalence of 14%. Whether increased diagnostic and therapeutic activities would be effective to reduce this rate is to be considered for further studies. A recent study, though, indicates that even hepatocellular cancer patients, who have developed portal vein tumour thrombosis, may benefit from an active treatment if timely diagnosed with respect to hepatic function[16].

In one sixth of the PVT patients no explanation could be found despite the thorough examination. This group differed from the other patients by a low frequency of complications typical to portal hypertension. A cross-sectional study like the present has obvious limitations for assessment of previous diseases, and this group may harbour some cases of juvenile PVT, though recent longitudinal studies indicate that PVT is an infrequent complication to umbilical vein sepsis, and in the western world the risk of this complication to umbilical vein catheterisation has declined considerably over time[5,17-18]. Similarly, it cannot be ruled out that the thrombosis in the odd case might have been caused by surgical trauma not evident from the recent patient history. With increasing possibilities to detect various trombophilic disorders the proportion of non-explainable, so called idiopathic PVT has gradually become smaller[5,10,19-22]. The present study does not allow an investigation of markers of the haemostatic system, but it is not unreasonable that the PVT in some of these cases may be an expression of a hypercoagulability state.

Autopsy rates have declined considerably also in Malmö, following changes in legislation, and it is unlikely that a similar study will ever be performed again. With regards to the setting in time, some limitations should be discussed. Apart from aspects of the design previously viewed, the potential effects on the epidemiology of an increasing use of antithrombotic therapies should be considered. The study does not allow an assessment of actual medications, but even today the majority of these conditions would not warrant primary or secondary anticoagulant prophylaxis according to guidelines[23].

From this first population-based study we conclude that PVT is more common than previously indicated by clinical series. The greatly increased risk in patients with cirrhosis and hepatic carcinoma should warrant an increased awareness in these patients. While anticoagulation therapy might be considered for certain patient categories, this remains to be evaluated in prospective studies.