Prevalence of non-cirrhotic portal hypertension among GIT bleeding patients at single center Alexandria governorate, Egypt

Noncirrhotic portal hypertension (NCPH) is a heterogeneous group of liver disorders of vascular origin, leading to PHT with near normal HVPG (4 & 5).

IN Western countries cirrhosis is the most common cause > 90%, otherwise non-cirrhotic causes are < 10% worldwide (6). NCPH commonest causes are Schistosomiasis, portal vein thrombosis and idiopathic (7).

NCPH is often asymptomatic until complications of portal hypertension develop which include: variceal hemorrhage, portal hypertensive gastropathy, ascites, hepatorenal syndrome, hepatopulmonary syndrome and cardiomyopathy (8).

The current study demonstrated the diversity of non-cirrhotic portal hypertension (NCPH) patients and their causes among GIT bleeding patients in our city. In addition, it demonstrated its novel aspect in exploring age and gender distribution among Alexandria fever hospital (AFH) patients. Among our 25 patients of NCPH, the study revealed that the most common cause is Schistosomal periportal fibrosis (PPF) 12 patients (48%) most of them were males between 40 – 55 years old, followed by Portal vein thrombosis (PVT) 7 patients (28%) most of them were adults between 21 – 35 years and 2 patients were children (4, 10 years), followed by Myeloproliferative diseases 3 patients (12%), then Budd-Chiari syndrome 2 patients (8%) and lastly Sarcoidosis 1 patient (4%).

Schitosomiasis PPF was the most common cause of NCPH in our study as other studies throughout the worldwide. Chronic hepatic schistosomiasis is characterized by features of portal hypertension: esophageal varices, gastric varices, gastropathy, splenomegaly with hypersplenism. In Indian and Uganda studies, Schitosomiasis was the most common cause of NCPH (8-9). Studies showed that 20% to 50% of adult patients diagnosed with hepatic schistosomiasis from an endemic area also have portal hypertension, varices, variceal upper gastrointestinal bleeding at the time of first diagnosis (10).

In our study we found 7 patients (28% of all NCPH patients) were diagnosed as portal vein thrombosis (PVT),  2 children patients (4 & 10 years) were diagnosed as Sickle cell anemia and Factor V Leiden mutation, 2 adult patients (20 & 23 years) were diagnosed as protein C deficiency and Factor V Leiden mutation, the remaining 3 adult patients of portal vein thrombosis (35, 43 & 48 years) were diagnosed by ultrasound and Contrast-enhanced computed tomography (CT) after abdominal surgery or infection; one post splenectomy, one post infected cholecystectomy and one patient of walled off necrosis pancreatic cyst underwent cysto-gastrostomy..

Patients with acute PVT have sudden onset of portal hypertension leading to GIT collaterals and bleeding. PVT may be complete or partial and clot may extend to the mesenteric veins or the splenic vein (11).

Extra-hepatic portal venous obstruction (EHPVO) is characterized by a chronic blockage of PV blood supply leading to PHT and its sequelae in the setting of a well-preserved liver function. EHPVO is a major cause of PHT (54%) and upper gastrointestinal bleeding in children (68–84%) from the developing world. In the West, non-cirrhotic non-tumoral PVT is the second most frequent cause of PHT in adults, whereas in children it constitutes a small proportion (11%) (12).

Like other studies of venous thrombosis, the factors leading to EHPVO can be grouped as those within the vessel lumen, within the wall and outside the vessel; and also, as prothrombotic states (inherited or acquired) and local factors (trauma, injury, inflammatory conditions). The most common prothrombotic states seen in children are methylene tetrahydrofolate reductase (MTHFR) deficiency and prothrombin gene mutations, whereas in adults, primary myeloproliferative disorders (MPN) (with or without janus kinase 2, JAK2 mutation are the commonest (13).

A previous Egyptian study performed to assess the prevalence of factor V Leiden mutation and other thrombophilic factors as risk factors in the development of PVT in the pediatric age group had detectable hereditary thrombophilia (62.5%), 12 had factor V  Leiden mutation (30%), 11 had protein C deficiency (27.5%), 6 had factor II mutation (15%) (14).

In our study, we found 3 patients (12%) of Myeloproliferative disorders or neoplasms (MPN) after hematologic and bone marrow evaluation.

Myeloproliferative disorders or neoplasms (MPN) diagnosis is based on the morphology of peripheral blood and bone marrow aspirate. Clinically, splenomegaly and hepatomegaly due to extramedullary hemopoiesis are common. The clinical symptoms and complications are primarily due thrombocytosis and polycythemia causing circulatory problems or thrombotic events as PVT (15). In a recent meta-analysis, the prevalence of MPD and JAK2 mutations in PVT was found to be 31.5% and 27.7%, respectively (16). On the other hand, in a patient with non-malignant non-cirrhotic PVT, the odds ratios of usage of oral contraceptives, or presence of prothrombin gene mutation, factor-V Leiden, or deficiencies of protein-C, protein-S and antithrombin-III are 50, 7, 1.5, 5, 3, and 1, respectively (16).

In our study, we found 2 patients (8%) of Budd Chiari syndrome, one patient (Male, 32 years) was diagnosed as polycythemia vera, the other patient (Female,35 years) was predisposed by contraceptive pills.

In our study, we found 1 patient (4%) of  Sarcoidosis diagnosed by liver biopsy.

Sarcoidosis is a multisystemic disease characterized by the presence of non-caseating granulomas in affected organs. Hepatic and pulmonary involvement is common (17). Long-standing sarcoid liver has been reported to result in portal hypertension in 3–18% of patients. This may be due initially to compression of portal venules by granulomas, and can result in variceal bleeding. Liver biopsy is usually required to confirm diagnosis (18). Similar to our case, Hitoshi Yoshiji and coworkers documented  a histologically proven case of progressive liver sarcoidosis with variceal rupture (19).