Non-cirrhotic portal hypertension (NCPH), also known as idiopathic non-cirrhotic portal hypertension (INCPH) and porto-sinusoidal vascular disorder (PSVD), is a rare disease characterized by intrahepatic portal hypertension (IPH) in the absence of cirrhosis. The precise etiopathogenesis of IPH is an area of ongoing research. NCPH diagnosis is challenging, as there are no specific tests available to confirm the disease, and a high-quality liver biopsy, detailed clinical information, and an expert pathologist are necessary for diagnosis. Currently, the treatment of NCPH relies on the prevention of complications related to portal hypertension, following current guidelines of cirrhotic portal hypertension. No treatment has been studied that aimed to modify the natural history of the disease; however, transjugular intrahepatic porto-systemic shunt (TIPS) placement, shunt and liver transplantation are considerable symptomatic options. In this review, we discuss the heterogeneity of NCPH as well as its etiopathogenesis, clinical presentation and management issues. Starting from the assumption that portal hypertension does not always mean cirrhosis, cooperative studies are probably needed to clarify the issues of etiology and the possible genetic background of this rare disease. This knowledge might lead to better treatment and perhaps better prevention.

Porto-sinusoidal vascular disorder (PSVD) is one of the common causes of portal hypertension and has overlapping features with early cirrhosis. The differentiation of PSVD from cirrhosis requires a liver biopsy, which is invasive and has potential complications. This systematic review aimed at summarizing the current evidence on the performance of noninvasive modalities for differentiating PSVD from cirrhosis.
A comprehensive search of electronic databases of MEDLINE, Embase, and Scopus was conducted from 2000 to October 2022 for the studies comparing the elastographic and radiological features of PSVD and cirrhosis, using liver biopsy as the gold standard.
A total of 12 studies were included in the systematic review. Transient elastography (TE) as a modality was studied in five studies, MR elastography (MRE) in two, contrast CT in two, Contrast CT and MRI in two, and ARFI in only one. Both TE and MRE showed a significantly lower liver stiffness measurement and a higher splenic stiffness measurement with a higher SSM/LSM ratio with PSVD, compared to cirrhosis. Among the radiological features, focal nodular hyperplasia-like lesions, portal vein abnormalities (intrahepatic and extrahepatic), and a larger spleen size favored a diagnosis of PSVD. In contrast, surface nodularity and atrophy of segment IV with a segment I hypertrophy favored a diagnosis of cirrhosis.
Elastography and cross-sectional imaging can help differentiate PSVD from early cirrhosis with good accuracy. Further studies are required to assess the diagnostic role of a combination of both modalities.

BACKGROUND: Portal hypertension is secondary to either cirrhotic or non-cirrhotic causes, and complicating pregnancy poses a challenge to the treating team. A systematic review was performed to determine maternal and perinatal outcomes in women with portal hypertension. Outcomes were compared among those with cirrhotic (CPH) with non-cirrhotic portal hypertension (NCPH) as well as non-cirrhotic portal fibrosis (NCPF) with extra-hepatic portal vein obstruction (EHPVO).
METHODS: Medline and EMBASE databases were searched for studies reporting outcomes among pregnant women with portal hypertension. Reference lists from relevant papers and reviews were hand-searched for appropriate citations. Data were extracted to describe maternal complications, obstetric and neonatal outcomes. A random-effects model was used to derive pooled estimates of various outcomes, and final estimates were reported as percentages with a 95% confidence interval (CI). Cumulative, sequential and sensitivity analysis was studied to assess the temporal trends of outcomes over the period.
RESULTS: Information on 895 pregnancies among 581 patients with portal hypertension was included from 26 studies. Portal hypertension was diagnosed during pregnancy in 10% (95% CI 4-24%). There were 22 maternal deaths (0%, 95% CI 0-1%), mostly following complications from variceal bleeding or hepatic decompensation. Variceal bleeding complicated in 14% (95% CI 9-20%), and endoscopic interventions were performed in 12% (95% CI 8-17%) during pregnancy. Decompensation of liver function occurred in 7% (95% CI 3-12%). Thrombocytopenia was the most common complication (41%, 95% CI 23-60%). Miscarriages occurred in 14% (95% CI 8-20%), preterm birth in 27% (95% CI 19-37%), and low birth weights in 22% (95% CI 15-30%). Risk of postpartum hemorrhage was higher (RR 5.09, 95% CI 1.84-14.12), and variceal bleeding was lower (RR 0.51, 95% CI 0.30-0.86) among those with CPH compared to NCPH. Risk of various outcomes was comparable between NCPF and EHPVO.
CONCLUSIONS: One in ten pregnancies complicated with portal hypertension is diagnosed during pregnancy, and thrombocytopenia is the most common complication. Hepatic decompensation and variceal bleeding remain the most common cause of maternal deaths, with reduced rates of bleeding and its complications reported following the introduction of endoscopic procedures during pregnancy. CPH increases the risk of postpartum hemorrhage, whereas variceal bleeding is higher among NCPH.

Non-cirrhotic portal hypertension (NCPH) forms an important subset of portal hypertension in children. Variceal bleed and splenomegaly are their predominant presentation. Laboratory features show cytopenias (hypersplenism) and preserved hepatic synthetic functions. Repeated sessions of endoscopic variceal ligation or endoscopic sclerotherapy eradicate esophageal varices in almost all cases. After variceal eradication, there is an increased risk of other complications like secondary gastric varices, cholangiopathy, colopathy, growth failure, especially in extra-hepatic portal vein obstruction (EHPVO). Massive splenomegaly-related pain and early satiety cause poor quality of life (QoL). Meso-Rex bypass is the definitive therapy when the procedure is anatomically feasible in EHPVO. Other portosystemic shunt surgeries with splenectomy are indicated when patients present late and spleen-related issues predominate. Shunt surgeries prevent rebleed, improve growth and QoL. Non-cirrhotic portal fibrosis (NCPF) is a less common cause of portal hypertension in children in developing nations. Presentation in the second decade, massive splenomegaly and patent portal vein are discriminating features of NCPF. Shunt surgery is required in severe cases when endotherapy is insufficient for the varices. Congenital hepatic fibrosis (CHF) presents with firm palpable liver and splenomegaly. Ductal plate malformation forms the histological hallmark of CHF. CHF is commonly associated with Caroli\'s disease, renal cysts, and syndromes associated with neurological defects. Isolated CHF has a favourable prognosis requiring endotherapy. Liver transplantation is required when there is decompensation or recurrent cholangitis, especially in Caroli\'s syndrome. Combined liver-kidney transplantation is indicated when both liver and renal issues are present.

OBJECTIVE: To assess the maternal and perinatal outcomes of pregnant women with non-cirrhotic portal hypertension (NCPH).
METHODS: This was an observational study done by retrieving the records of pregnant women with non-cirrhotic portal hypertension admitted to a tertiary hospital in South India, over a 9-year study period. Data regarding the clinical course, complications during pregnancy, labor, and delivery details were reviewed. We also compared the outcomes among women with non-cirrhotic portal fibrosis (NCPF) with extrahepatic portal vein obstruction (EHPVO).
RESULTS: During the study period, portal hypertension was noted in 0.07%(n = 108) of the pregnancies and 74.1% of them had NCPH. The diagnosis was made for the first time in 54.7% of them when presented with pancytopenia or splenomegaly. Variceal bleeding complicated 25% of the pregnancies in women with NCPH pregnancies, with three among them having a massive bleed. Eighteen among them underwent endoscopy following bleeding; variceal banding procedure was performed in nine of them without any complications. Preterm birth was the most common (20.6%) obstetric complication. There was one maternal death from severe sepsis, acute kidney injury, and disseminated intravascular coagulation, following a massive variceal bleed. Obstetric outcomes and medical complications were similar in women with NCPF and EHPVO. Perinatal loss was comparable in both the groups (14.3% vs. 9.6%, p = 0.417) CONCLUSION: Multidisciplinary team approach, with optimal and timely intervention with intensive monitoring, can reduce the morbidity and help achieve an optimal maternal-perinatal outcome in pregnancies complicated with portal hypertension.

UNASSIGNED: Proximal splenorenal shunt (PSRS) is usually done in symptomatic non-cirrhotic portal fibrosis (NCPF). The outcomes of splenectomy with endotherapy in non-bleeder NCPF patients has not been well studied. We here by aimed to study the post-surgical outcomes on short and long-term basis between PSRS and splenectomy among non-bleeder NCPF patients.
UNASSIGNED: The consecutive non-bleeder NCPF patients whom underwent either splenectomy or PSRS from 2008 to 2016 were enrolled. The patients were followed up post-surgery clinically and biochemical investigations, Doppler ultrasound and upper gastrointestinal endoscopy were done as required. The peri-operative parameters compared were operative time, blood loss, hospital stay and morbidity. The long-term outcome measures compared were incidence of portal hypertension (PHTN) related bleed, change in grade of varices, shunt patency, shunt complications and thrombosis of spleno-portal axis.
UNASSIGNED: Among 40 patients with non-bleeder status, 24 underwent splenectomy and 16 underwent PSRS. The baseline characteristics including indication of surgery, biochemical investigations and grade of varices were comparable between PSRS and splenectomy. The peri-operative morbidity was not significantly different between two groups. The median follow up duration was 42 months (12-72 months), the decrement in grade of varices was significantly higher in PSRS group (p=0.03), symptomatic PHTN related UGIB was non-significant between PSRS and splenectomy (p=0.5). In PSRS group, 3 (18.3%) patients had shunt thrombosis (n=1) & encephalopathy (n=2) while in splenectomy group two patients developed thrombosis of splenoportal axis.
UNASSIGNED: Splenectomy with endotherapy is alternative to PSRS in non-bleeder NCPF patients with indications for surgery.

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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\'.

OBJECTIVE: Non-cirrhotic portal fibrosis (NCPF) is a clinical disorder characterized by features of portal hypertension in the absence of significant fibrosis. It is one of the commonest causes of portal hypertension in India. This study aimed to analyze histomorphological spectrum of NCPF in detail.
RESULTS: There were 67 specimens from 66 patients which included 43 (65.2%) male and 23 (34.8%) female patients with a mean age of 31 years (range: 7-61 years). The liver function tests showed only a mild derangement. The average length of biopsy was 1.4 cm (median: 1.2 cm, range: 0.8-3.4 cm) and the mean number of portal tracts per biopsy was 11.1 (median: 10, range: 5-30). Most cases showed a combination of histological features; the mean number of histological features per biopsy was 7.4 (median: 7, range: 3-12). Obliterative portal venopathy was seen in 47.8% cases. Portal angiomatosis (61.2%), paraportal shunt vessels (61.2%), portal vein dilatation (74.6%), hypoplastic portal tracts (56.7%), megasinusoids (64.1%), and abnormally dilated central veins (64.1%) were other prevalent features. Portal/periportal fibrosis and perisinusoidal fibrosis were seen in 77.6% and 61.2% cases; none showed bridging fibrosis or cirrhosis. The median hepatic venous pressure gradient (HVPG) and liver stiffness (LS) values were 8 mm of Hg (range: 5-20 mm of Hg) and 9.2 kPa (range: 4.4-26.3 kPa). There was no correlation of HVPG or LS with either portal/periportal fibrosis or perisinusoidal fibrosis.
CONCLUSIONS: Due to relatively non-specific and non-pathognomonic nature, a combination of different histological features in the absence of significant fibrosis and appropriate clinico-radiological background is needed for diagnosing NCPF.

BACKGROUND: Non-cirrhotic intrahepatic portal hypertension (NCIPH) is characterized by thrombotic microangiopathy of the portal venous system, low ADAMTS13 (a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs-13), and high vWF (von Willebrand factor) levels. This study aimed to screen for ADAMTS13 mutations, focusing on the CUB domain, in these patients.
METHODS: Prospectively recruited NCIPH patients and healthy volunteers underwent tests for plasma vWF-ADAMTS13 balance. Sanger sequencing of the CUB domain of ADAMTS13 was done in a subset of the NCIPH patients, and the detected mutation was screened for in all the study participants. Next-generation sequencing of clinically relevant exome and liver immunostaining for ADAMTS13 was done in patients with detected ADAMTS13 mutation.
RESULTS: Plasma vWF-ADAMTS13 balance was significantly altered in 24 NCIPH patients (Child\'s class A:23, B:1) as compared to 22 controls. On initial sequencing of the CUB domain (17 cases and 3 controls), one NCIPH patient showed a rare missense variant (SNV) at position c.3829C >T resulting in p.R1277W (rs14045669). Subsequent RFLP analysis targeted to the R1277W variant did not detect this in any other NCIPH patient, nor in any of the 22 controls. The NCIPH patient with the R1277W variant had severe ADAMTS13 deficiency, consistently high vWF, other missense SNVs in ADAMTS13, vWF, and complement genes. Immunostaining of his liver biopsy revealed globules of ADAMTS13 within stellate cells.
CONCLUSIONS: We report missense variants in ADAMTS13, vWF, and complement genes in a patient with NCIPH who had decreased secretion and activity of ADAMTS13 protein. Further studies are needed in NCIPH patients in this regard.