Noncirrhotic portal hypertension (NCPH) comprises a diverse group of vascular liver disorders characterized by elevated portal pressure without cirrhosis. Due to overlapping clinical features, distinguishing NCPH from cirrhosis and porto-sinusoidal vascular disorder (PSVD) remains challenging. This review explores recent advancements in diagnosis, differentiation, and evolving treatment strategies.

NCPH is characterized by preserved liver function and near-normal hepatic venous pressure gradients (HVPG). It shares risk factors with PSVD, including infections, drugs, toxins, and prothrombotic conditions. Diagnostic advancements, such as liver stiffness measurement (LSM) and splenic stiffness measurement (SSM), offer noninvasive differentiation from cirrhosis, while liver biopsy remains crucial for confirming PSVD and noncirrhotic portal fibrosis (NCPF). Imaging is reliable for diagnosing extrahepatic portal vein obstruction (EHPVO). Transjugular intrahepatic portosystemic shunts (TIPS) for refractory variceal bleeding or ascites, achieving rebleeding control in 72-80% of cases. Surgical shunts and splenectomy remain essential for uncontrolled bleeding and portal biliopathy, demonstrating excellent variceal control (93-95%).

NCPH requires a high index of suspicion for diagnosis. Differentiation from cirrhosis and PSVD relies on clinical, histological, and hemodynamic assessments. Management focuses on endoscopic, interventional, and surgical strategies tailored to disease severity. Future research should standardize diagnostic criteria, explore targeted therapies, and refine prognostic tools to improve outcomes.

Idiopathic portal hypertension (IPH) is a subtype of portal hypertension that arises in the absence of cirrhosis. IPH frequently manifests with clinical features typical of portal hypertension, including splenomegaly and esophagogastric fundal varices, along with other associated symptoms. Imaging studies may indicate portal hypertension; however, they typically do not provide evidence of cirrhosis. There are no standardized diagnostic criteria for IPH, and diagnosis is often established by excluding other hepatic diseases. Liver biopsy remains the most reliable approach to verify the diagnosis of IPH.

A patient previously diagnosed with "hepatitis B cirrhosis" at an external hospital presented to our facility with gastrointestinal bleeding. Initial assessment revealed minor liver injury, splenomegaly, esophagogastric varices, and portal hypertension. Imaging studies did not indicate cirrhosis and repeated hepatitis B serology tests yielded negative results. After excluding various causes of cirrhosis and other non-cirrhotic etiologies of portal hypertension, liver biopsy confirmed the diagnosis of IPH. The patient was managed with regular endoscopic therapy and long-term carvedilol administration.

Currently, there are no standardized diagnostic criteria for IPH, and its diagnosis is generally established by excluding other conditions. Liver biopsy remains the most reliable method for IPH diagnosis.

Since the Asian Pacific Association for the Study of the Liver (APASL) published guidelines on non-cirrhotic portal fibrosis/idiopathic portal hypertension in 2007, there has been a surge in new information, especially with the introduction of the term porto-sinusoidal vascular disorder (PSVD). Non-cirrhotic intra-hepatic causes of portal hypertension include disorders with a clearly identifiable etiology, such as schistosomiasis, as well as disorders with an unclear etiology such as non-cirrhotic portal fibrosis (NCPF), also termed idiopathic portal hypertension (IPH). This entity is being increasingly recognized as being associated with systemic disease and drug therapy, especially cancer therapy. An international working group with extensive expertise in portal hypertension was assigned with formulating consensus guidelines to clarify the definition, diagnosis, histological features, natural history, and management of NCPF/IPH, especially in the context of PSVD. The guidelines were prepared based on evidence from existing published literature. Whenever there was paucity of evidence, expert opinion was included after detailed deliberation. The goal of this manuscript, therefore, is to enhance the current understanding and help create global consensus on the issues surrounding NCPF/IPH.

Both noncirrhotic portal fibrosis (NCPF) and extrahepatic portal venous obstruction (EHPVO) are important causes of noncirrhotic portal hypertension (PH) in the Asian region. In this study, we analyzed the histopathological changes of liver needle-core biopsies from patients with NCPF and EHPVO.

The patients were diagnosed as per the Asia Pacific Association for the Study of Liver (APASL) criteria. Minimum adequacy criteria for liver core biopsies were defined, and finally, 69 liver biopsies from patients with NCPF and 100 liver biopsies from patients with EHPVO were analyzed. All histological parameters were predefined, and three experienced pathologists analyzed the biopsies after reaching consensus. Institute ethics committee clearance was taken.

Although some histological features were overlapping, phlebosclerosis of intra-hepatic branches of the portal vein (PV), periportal aberrant vascular channels, remnant portal tracts, and hepatic fibrosis beyond the portal tracts without the formation of complete hepatic nodules (P < 0.001 for all) were common histological characteristics of NCPF on core-needle liver biopsies; while maintained lobular architecture, nonspecific dilatation of PV branches, absence of intra-hepatic PV phlebosclerosis, aberrant vascular channels, and significant fibrosis were characteristics of EHPVO.

Despite the considerable histological overlap between NCPF and EHPVO, careful histological evaluation, supplemented by clinical features, radiological and biochemical findings can help in making a conclusive diagnosis. Patients with NCPF and EHPVO with clinical jaundice show transaminitis, high serum alkaline phosphatase level, more variceal bleed, and histological evidences of nodular regenerative hyperplasia.

To determine the concordance of liver explants with the pretransplant diagnosis.

This was a retrospective analysis of 251 liver explants. Patient information included demography, comorbidity, and etiological diagnosis. Final diagnosis was based on morphological and histological findings. For non-alcoholic steatohepatitis (NASH) and cryptogenic cirrhosis, we investigated comorbid states such as obesity, hypertension, and diabetes. Chi square test and Cohen's Kappa value were used. A P value of <0.05 was considered significant.

A total of 192 patients (76.5%) were males. A significant concordance of explant diagnosis with pretransplant diagnosis was present in 225 (89.6%) patients. It was 100% for alcohol-related disease, hepatitis B, hepatitis C, autoimmune (AI) liver disease, biliary cirrhosis, and Budd-Chiari syndrome. Of 37 patients with a pretransplant diagnosis of cryptogenic cirrhosis, major discordance was observed in 23 (62.1%). On explant, seven patients each had hemochromatosis 5 (13.5%), AI hepatitis, and NASH (18.9%); two had noncirrhotic fibrosis (5.4%); and one each had Wilson's disease and congenital hepatic fibrosis (2.7%). Of the 20 explants, 3 with pretransplant diagnosis of NASH had a diagnosis of cryptogenic cirrhosis on explant specimens. Cohen's Kappa for the concordance of pretransplant diagnosis and explant diagnosis in NASH and cryptogenic cirrhosis patients was 0.75 and 0.47, respectively. An incidental hepatocellular carcinoma was picked up in 16 explants, and 18 had granulomas.

Concordance between pretransplant and explant diagnosis is lower for NASH and cryptogenic cirrhosis. The true prevalence of cryptogenic cirrhosis in our study was 5.6%.

In India, an unexplained enteropathy is present in a majority of non-cirrhotic intrahepatic portal hypertension (NCIPH) patients. Small intestinal bacterial contamination and tropical enteropathy could trigger inflammatory stimuli and activate the endothelium in the portal venous system. Groundwater contaminated with arsenic is an environmental factor of epidemic proportions in large areas of India which has similar consequences. Von Willebrand factor (a sticky protein) expressed by activated endothelium may promote formation of platelet microthrombi and occlusion of intrahepatic portal vein branches leading to NCIPH. Environmental factors linked to suboptimal hygiene and sanitation, which enter through the gastrointestinal (GI) tract, predispose to platelet plugging onto activated endothelium in portal microcirculation. Thus, NCIPH, an example of poverty linked thrombophilia, is a disease mainly affecting the lower socio-economic strata of Indian population. Public health measures to improve sanitation, provide clean drinking water and eliminate arsenic contamination of drinking water are urgently needed. Till such time as these environmental factors are addressed, NCIPH is likely to remain 'an Indian disease'.

Idiopathic portal hypertension (IPH) and extrahepatic portal venous obstruction (EHPVO) are prototype noncirrhotic causes of portal hypertension (PHT), characterized by normal hepatic venous pressure gradient, variceal bleeds, and moderate to massive splenomegaly with preserved liver synthetic functions. Infections, toxins, and immunologic, prothrombotic and genetic disorders are possible causes in IPH, whereas prothrombotic and local factors around the portal vein lead to EHPVO. Growth failure, portal biliopathy, and minimal hepatic encephalopathy are long-term concerns in EHPVO. Surgical shunts and transjugular intrahepatic portosystemic shunt resolve the complications secondary to PHT. Meso-Rex shunt is now the standard-of-care surgery in children with EHPVO.

Idiopathic portal hypertension (IPH) and extrahepatic portal venous obstruction (EHPVO) are non-cirrhotic vascular causes of portal hypertension (PHT). Variceal bleed and splenomegaly are the commonest presentations.

The present review is intended to provide the existing literature on etiopathogenesis, clinical profile, diagnosis, natural history and management of IPH and EHPVO.

IPH and EHPVO are both characterized by normal hepatic venous pressure gradient, moderate to massive splenomegaly with preserved liver synthetic functions. While the level of block in IPH is presinusoidal, in EHPVO it is at prehepatic level. Infections, autoimmunity, drugs, immunodeficiency and prothrombotic states are possible etiological agents in IPH. Contrastingly in EHPVO, prothrombotic disorders and local factors around the portal vein are the incriminating factors. Diagnosis is often clinical, supported by simple radiological tools. Natural history is defined by episodes of variceal bleed and symptoms related to enlarged spleen. Growth failure, portal biliopathy and minimal hepatic encephalopathy are additional concerns in EHPVO. Long-term survival is reasonably good with endoscopic surveillance; however, parenchymal extinction leading to decompensation is seen in a minority of patients in both the disorders. Surgical shunts revert the complications secondary to PHT. Meso-Rex shunt has become the standard surgery in children with EHPVO.

This review gives a detailed summary of these two vascular conditions of liver-IPH and EHPVO. Further research is needed to understand the pathogenesis and natural history of these disorders.

Noncirrhotic portal fibrosis (NCPF) has been classically described as a disease of young to middle age with limited literature regarding its occurrence, onset, or clinical presentation in children. We hereby present a series of 19 patients diagnosed and managed as NCPF in pediatric age group.

A retrospective review of all the patients presenting to the pediatric hepatology department (age <18 years) and diagnosed as NCPF was done and data were evaluated.

A total of 19 patients were diagnosed as NCPF with median age at onset of symptoms and diagnosis as 10 years and 13.8 years respectively. Majority presented with left upper quadrant discomfort or mass. Laboratory parameters showed hypersplenism in majority with preserved liver synthetic functions. Median values for hepatic venous pressure gradient and liver stiffness measurement were 13.5 mmHg and 10.6 kPa, respectively. Classical hepatic histopathological features seen were maintained lobular architecture, atretic portal tracts, approximation of portal-portal and portal-central areas, and aberrant peripheral portal channels. During follow-up, majority of the patients did not show disease progression.

NCPF is not an uncommon entity in pediatric population with age of onset in early second decade. Hepatic histopathology must be used to exclude cirrhosis and to confirm the diagnosis. Hepatic venous pressure gradient and liver stiffness measurement values, in some cases, may overlap with those in patients with cirrhosis and may not be diagnostic in isolation. Any patient presenting with evidence of portal hypertension with preserved hepatic functions, irrespective of the age, should be evaluated for possible NCPF.

Non-cirrhotic portal fibrosis (NCPF) is one of the important causes of upper gastrointestinal haemorrhage in patients in tropical countries. The aim of this study was to describe the clinical and laboratory profile of 68 patients with NCPF.

NCPF is defined as liver disease with: (1) evidence of portal hypertension; (2) a liver biopsy showing no cirrhosis or a Tc-labelled sulphur colloid scan showing a pattern suggestive of NCPF; and (3) a patent splenoportal axis. The clinical, laboratory and demographic features of 68 patients with such criteria were studied and analysed.

NCPF was common in women (73.5%) in the fourth decade of life. The median duration of illness was 24 months (range, 1 month-28 years). Patients presented to hospital with the sensation of a mass in the abdomen (50%) or with haematemesis (26.5%). They had splenomegaly (95.6%) and thrombocytopenia (88.2%). The majority of patients had normal liver function tests. Abdominal ultrasonography showed increased periportal and peri gallbladder echoes (72%), spontaneous collaterals (41.2%) and ascites (19.1%). Liver biopsy revealed portal venous sclerosis (76.3%) and periportal fibrosis (55.3%). Tc-labelled sulphur colloid scan was suggestive of NCPF in the remaining 30 cases.

NCPF is common in South India. Transient ascites occurs due to decompensation of liver function after variceal bleeding and in long standing cases of NCPF. Our study used Tc-sulphur scan for diagnosing NCPF in patients where liver biopsy was contraindicated in view of severe thrombocytopenia; however, the diagnostic utility of Tc-sulphur nuclear scan to diagnose NCPF in patients with severe hypersplenism needs to be further evaluated in future studies.

Long-term prehepatic portal hypertension in the rat produces a low-grade splanchnic inflammation with liver steatosis and dyslipidemia. It has been suggested that in this experimental model these inflammatory alterations could represent a risk factor of vascular disease. Therefore, our aim was to investigate whether long-term prehepatic portal hypertension (PH) induces vascular pathology, fundamentally inflammatory aortopathy. Male Wistar sham-operated (SO) rats and rats with triple partial portal vein ligation in the very long-term (22 months) of postoperative evolution were used. Serum lipid profile, pro- and anti- inflammatory cytokines and ACTH and corticosterone were assayed by spectrophotometric and ELISA techniques. Aorta mRNA expression of oxidative and nitrosative stress enzymes, NFκB e IκB, immune-related cytokine production and vascular fibrosis parameters, were evaluated by real time RT-PCR. In addition, aortic p22phox subunit immunostaining, morphometry and vascular fibrosis in aorta were analyzed. PH rats have increased serum cholesterol, triglyceride, low-density lipoproteins (LDL) and very low-density lipoproteins (VLDL), while high-density lipoproteins (HDL) were lower than in SO rats. Serum ACTH and corticosterone decreased in PH rats. Also, serum TNF-α, IL-1β and IL-6 were significantly higher in PH-rats. Portal hypertensive-rats showed aortic oxidative stress with increased mRNA expressions of NAD(P)H oxidase p22phox, XDh, SOD and eNOS; higher aortic levels of pro-inflammatory cytokines, including TNF-α, IL-1β and IL-6; remodeling markers, like collagen I, CTGF and MMP-9; and finally, higher protein production of p22phox and collagen and extracellular matrix density were significantly higher in rats with PH. The results from the current study suggest that very long-term prehepatic portal hypertension in rats induces an abdominal aortic inflammatory and fibrotic response. Therefore, it could be considered that portal hypertension aggravates aortic inflammaging and one of its more severe complications, which is remodeling by a wound healing reaction.

Treatment for portal hypertension (PHT) has evolved from surgery being the only option during the 1970s to the wide range of options currently available. Surgery has not vanished from the therapeutic armamentarium, but its role has changed and is constantly evolving. The present review primarily focuses on the role of surgery in tackling patients with PHT and varices with regard to the Indian scenario and also looks at its relevance, given the availability of a host of other therapeutic options.