Non-cirrhotic portal fibrosis (NCPF)Non-cirrhotic Portal Fibrosis (NCPF) variously called as Idiopathic PHT (IPH), hepatoportal sclerosis and obliterative venopathy, is a disorder of unknown etiology, clinically characterized by features of PHT; moderate to massive splenomegaly, with or without hypersplenism, preserved liver functions, and patent hepatic and portal veins [, ] (Table 2).The disease has been reported from all parts of the world, more so from the developing countries [, , , , , , , , , , ]. According to the consensus statement of the Asia Pacific Association for the Study of the Liver (APASL) on NCPF, the disease accounts for approximately 10–30% of all cases of variceal bleed in several parts of the world including India . It is more common in young males in third to fourth decades belonging to low socioeconomic groups [, , , , , ]. A disease mimicking NCPF, known as IPH in Japan and idiopathic non-cirrhotic PHT in the West, has female preponderance and presents around the fifth decade [, , , ] (Table 3). Such demographic variations could be due to differences in the living conditions, ethnicity, average life span, reporting bias as well as on the diagnostic criteria utilized. There are speculations of decreasing incidence of the disease, which is possibly related to improved standards of hygiene and perinatal care leading to reduction in incidences of umbilical sepsis and diarrheal episodes in early childhood .
EtiopathogenesisThe precise etiopathogenesis of NCPF/IPH is an area of ongoing research. Infections and prothrombotic states are commonly incriminated in the eastern and western patients, respectively .
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Etiological factorsRarity of the disease in the west, a declining trend with improved standards of living and hygienic conditions support the role of infections, of imprecise nature, at an early age in the disease pathogenesis [, ]. Endotoxin mediated injury with or without induced autoimmunity is the proposed hypothesis . Role of prothrombotic disorders in the pathogenesis is supported by autopsy studies showing high prevalence of PV thrombosis (PVT) and studies from the west indicating association with prothrombotic states [, ]. However, PVT being not a universal event, absence of acute manifestations of PVT and presence of increased blood flow in the splenic vein are pointers, which negate this hypothesis. Prolonged exposure to several medications and toxins especially arsenic has also been incriminated as a cause [, , , ]. Immunological basis is propagated due to female preponderance, association with various immunological and autoimmune disorders, and presence in serum of various autoantibodies . Lastly, familial clustering, association with human leukocyte antigen (HLA)-DR3 and with some genetic syndromes suggest a genetic basis [, ].
Animal studiesVarious animal models suggesting an infective and immune basis are shown in Fig. 1 [, , ]. NCPF animals develop splenomegaly, high portal pressures, low mean arterial pressures with normal liver functions and histology, demonstrating the role of vascular compartment in causing PHT. Also, in the chronic arsenic exposure model, there is increased hydroxyproline and collagen without significant hepatic fibrosis .
PathogenesisVarious theories to explain the pathogenesis of NCPF/IPH have been proposed and are mentioned in Fig. 2 [, , ].
PathologyLiver pathology is characterized by phlebosclerosis, fibroelastosis, periportal, and perisinusoidal fibrosis, aberrant vessels in portal tract (portal angiomatosis), preserved lobular architecture, and differential atrophy [, , ]. Main PV trunk is dilated with thick sclerosed walls, along with thrombosis in medium and small PV branches – the histological hallmark termed “obliterative portal venopathy” [, ]. Nakanuma et al. had proposed a staging system based on gross and imaging features: stages I–IV, stage I being absence of peripheral parenchymal atrophy; stage IV showing presence of obstructive thrombosis in intrahepatic large branches or trunk of PV . Spleen is disproportionately large (average weight 723 g) at portal pressures comparable to other conditions of PHT .