Clinical Profile and Pathogenesis of Idiopathic Non Cirrhotic Intrahepatic Portal Hypertension

Abstract

Idiopathic non-cirrhotic intra-hepatic portal hypertension (NCIPH) is a disorder characterized by occlusion of small intra-hepatic portal venous radicles (3rd/ 4th order branches). It is thus a cause of pre-sinusoidal intra-hepatic portal hypertension. NCIPH is clinically characterized by portal hypertension (gastro-oesophageal varices and subsequent bleeding), hypersplenism (low blood counts secondary to peripheral destruction) and liver functions that deteriorate, albeit much later in comparison to cirrhosis. A proportion of NCIPH patients develop liver failure and require liver transplant. Even the explant liver at the time of transplant grossly gives the appearance of cirrhosis. newline1. Non-cirrhotic intra-hepatic portal hypertension (NCIPH) remains a common cause of portal hypertension in 21st century India.2. The overall prognosis in these patients remains good, but these patients are prone to decompensation, hepatocellular carcinoma and portal vein thrombosis. 3. Imbalance of von-Willebrand factor and its cleaving protease (ADAMTS-13), despite normal liver function, suggests a possibility of micro-angiopathy involving small portal venous radicles as the pathogenetic mechanism involved in NCIPH causation. 4. Over-representation of gut disorders, often non-specific inflammation which is clinically silent, suggests the important role of GI tract in the pathogenesis of NCIPH. This may also partly explain the increased prevalence of NCIPH in India, esp. in the lower socio-economic strata. 5. Continued ingestion of arsenic contaminated groundwater may be one of the pathogenic mechanisms in NCIPH, esp. in patients hailing from regions near Ganges. IMPLICATIONS FOR FUTURE RESEARCH: 1. Role of gastrointestinal tract has been postulated and this needs to be studied further. Role of gut microbiome in pathogenesis and disease modification needs to be clarified. 2. Role of primary haemostasis has been hypothesised and needs to be further studied. The genetic predisposition of Indians needs to be explored.