Schouten et al.

Orphanet Journal of Rare Diseases (2015) 10:67

DOI 10.1186/s13023-015-0288-8

REVIEW Open Access

Idiopathic non-cirrhotic portal

hypertension: a review
Jeoffrey NL Schouten1, Joanne Verheij2 and Susana Seijo3*

Abstract
Idiopathic non-cirrhotic portal hypertension (INCPH) is a rare disease characterized of intrahepatic portal hypertension
in the absence of cirrhosis or other causes of liver disease and splanchnic venous thrombosis. The etiology of
INCPH can be classified in five categories: 1) immunological disorders (i.e. association with common variable
immunodeficiency syndrome, connective tissue diseases, Crohn’s disease, etc.), 2) chronic infections, 3) exposure to
medications or toxins (e.g. azathioprine, 6- thioguanine, arsenic), 4) genetic predisposition (i.e. familial aggregation
and association with Adams-Oliver syndrome and Turner disease) and 5) prothrombotic conditions (e.g. inherited
thrombophilias myeloproliferative neoplasm antiphospholipid syndrome). Roughly, INCPH diagnosis is based on
clinical criteria and the formal exclusion of any other causes of portal hypertension. A formal diagnosis is based
on the following criteria: 1) presence of unequivocal signs of portal hypertension, 2) absence of cirrhosis, advanced
fibrosis or other causes of chronic liver diseases, and 3) absence of thrombosis of the hepatic veins or of the portal
vein at imaging. Patients with INCPH usually present with signs or symptoms of portal hypertension such as
gastro-esophageal varices, variceal bleeding or splenomegaly. Ascites and/or liver failure can occur in the context
of precipitating factors. The development of portal vein thrombosis is common. Survival is manly limited by
concomitant disorders. Currently, treatment of INCPH relies on the prevention of complications related to portal
hypertension, following current guidelines of cirrhotic portal hypertension. No treatment has been studied aimed
to modify the natural history of the disease. Anticoagulation therapy can be considered in patients who develop
portal vein thrombosis.
Keywords: Non-cirrhotic portal hypertension, Portal hypertension, Variceal bleeding, Portal vein thrombosis

Introduction HIV infection and antiretroviral treatment, trace metals,

Idiopathic non-cirrhotic portal hypertension (INCPH) is a certain medications and prothrombotic factors [1, 3, 7–9].
rare disease characterized by of intrahepatic portal hyper- The pathophysiological mechanisms causing INCPH re-
tension in the absence of cirrhosis, other causes of liver dis- main largely unknown. Patients with INCPH usually
ease and splanchnic venous thrombosis [1–7]. Histological present with signs and symptoms of portal hypertension
features of INCPH comprise a wide spectrum of nonspe- (PH) such as splenomegaly, thrombocytopenia and vari-
cific features, ranging from minor changes, sinusoidal dila- ceal bleeding [1, 2, 5]. Patients can develop additional
tation, phlebosclerosis and portal fibrosis to nodular liver-related complications such as ascites, hepatic en-
regenerative hyperplasia. It is still unclear whether this rep- cephalopathy, portal vein thrombosis (PVT) or liver fail-
ertoire of histological changes reflects different stages of the ure, that could eventually require liver transplantation
disease, or it could also be that INCPH comprises different (LT) [2, 3, 6, 10, 11].
nosologic entities that share the same clinical presentation. Orpha number: ORPHA64743
Different conditions have been associated to this disorder
including immune-based diseases, recurrent infections,
Epidemiology
Although INCPH has a worldwide distribution, it is par-
* Correspondence: [email protected] ticularly prevalent in Asia [4, 12, 13]. It is more frequent
3
Department of Medicine, CTO, Icahn School of Medicine at Mount Sinai,
New York, NY 10029, USA in socioeconomically disadvantaged individuals. Im-
Full list of author information is available at the end of the article provements in hygiene and living standards may explain
© 2015 Schouten et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution
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Schouten et al. Orphanet Journal of Rare Diseases (2015) 10:67 Page 2 of 8

the decreasing incidence of INCPH in Japan during the systemic lupus erythematosus, immunoglobulin interfer-
last decades, and the low prevalence of the disease in ence with prostacyclin formation has been found to in-
Western countries [7, 9, 14, 15]. Gender and age disparities crease microthrombosis vulnerability [19]. In patients with
have also been reported [4, 15]. In Western populations, celiac disease, an elevation of IgA anticardiolipin anti-
median age at diagnosis is 40 years, with predominance in bodies could be responsible for the obliteration of small
male gender. Conversely, Asian patients tend to be diag- vessels [1–7]. Interestingly, 70 % of patients with primary
nosed at a younger age. In summary, differences in socio- hypogammaglobulinemia have histological features of
economic status, living conditions, pathogen exposure and INCPH [1, 3, 7–9, 20].
ethnicity may play a role in INCPH development.
Chronic infections
Etiology and pathophysiology
Data indicate that intestinal infection with E. coli might
Etiology
cause recurrent septic embolization and subsequent ob-
The etiology of INCPH is unknown [1, 4, 9, 14, 16].
struction of small portal veins, a probable trigger of
Strikingly, small series and case studies show its associ-
INCPH. The high prevalence of INCPH in low socioeco-
ation with an array of rare disorders; whether these asso-
nomic areas with a high rate of abdominal infections in
ciations are more than fortuitous remains unclear.
early childhood lends credit to this theory [1, 2, 4, 5]. In
Roughly, the potential mechanisms involved in INCPH
addition, experimental studies demonstrate how E. coli
pathogenesis can be classified in five main categories:
injection into the portal vein results in the development
immunological disorders, chronic infections, exposure to
clinical and histological characteristics of INCPH [2, 3,
medications or toxins, genetic disorders and prothrom-
6, 10, 11, 21].
botic conditions (Table 1). A combination of these
In Western countries, INCPH has been reported in-
factors is also very likely. Associated conditions in 4 re-
creasingly in patients with human immunodeficiency
cently reported European series are described in Table 2
virus (HIV) infection [4, 9, 12–14, 17, 22–24]. Prolonged
[2, 6, 10, 11, 16].
monotherapy or short-term combination treatment with
didanosine and stavudine are independent risk factors
Immunological disorders
for the development of this disorder, suggesting a poten-
In Western countries, INCPH is frequently associated
tial role for mitochondrial toxicity in the development
with immunological disorders [3, 5, 7, 17, 18]. In patients
of INCPH [7, 9, 14, 15, 17, 22]. A recent multicenter
with systemic sclerosis, enhanced fibrogenesis seems to
study demonstrated a genetic predisposition to develop
have a major pathogenic role [8]. Also, in patients with
INCPH in HIV infected patients chronically exposed to
Table 1 Associated disorders of idiopathic non-cirrhotic portal didanosine [4, 15, 25]. Despite these data, it is difficult
hypertension to assign a definitive etiopathogenic role of didanosine,
Immunological disorders Common variable immunodeficiency as the drug has been widely used for the treatment of
syndrome [22, 54] HIV in the past. Alternatively, a high prevalence of pre-
Connective tissue diseases [55] existing hypercoagulability, mainly due to protein S defi-
Crohn’s disease [26, 27]
ciency, possibly leading to vascular obstruction, has also
been reported in patients with HIV-related INCPH [1, 4,
Solid organ transplant [56, 57]
9, 14, 16]. Hence, additional data will be needed to de-
Infections Bacterial intestinal infections [21] fine a causal role of didanosine exposure and HIV-
Human immunodeficiency virus (HIV) associated INCPH [2, 6, 7, 10, 11, 16, 17].
infection [2, 9, 14, 22]
Medications and toxins Thiopurine derivatives (didanosine,
azathioprine, cis-thioguanine) [27, 58] Exposure to medication and toxins
Arsenicals [28] Besides didanosine, exposure to other medications and
Vitamin A [59]
chemicals has been reported to be associated with
INCPH. Azathioprine, 6-thioguanine and arsenic as
Genetic disorders Adams-Olivier syndrome [32]
Fowler’s solution are the most frequently reported drugs
Turner syndrome [30] linked with this disorder [3, 5, 7, 17, 26–28]. Although it
Phosphomannose isomerase deficiency [60] is tempting to blame drug intake and chemical exposure
Familial cases [31, 61] as primary etiological factors, only a very small propor-
Prothrombotic conditions Inherited thrombophilias [2, 6, 10, 11, 62] tion of the patients treated with the above mentioned
Myeloproliferative neoplasm [2, 6, 10, 11, 62]
drugs or exposed to these chemicals develop clinical or
histological signs of INCPH. Clearly, additional factors
Antiphospholipid syndrome [2, 6, 10, 11, 62]
may play a pathogenic role in these patients.
Schouten et al. Orphanet Journal of Rare Diseases (2015) 10:67 Page 3 of 8

Table 2 Associated conditions in 4 recently reported series of European patients with idiopathic non-cirrhotic portal hypertension
Reference Hillaire et al. [6] Cazals-Hatem et al. [11] Schouten et al. [10] Siramolpiwat et al. [2]
Prothrombotic disorder 6 PS deficiency 3 PS deficiency 3 PS deficiency 1 PS deficiency
2 PC deficiency 3 PC deficiency 3 PC deficiency 2 FII Leiden
2 MTHFR mutation 1 MTHFR mutation 1 FV Leiden
3 FII Leiden 2 FV Leiden
Haematological malignancy 1 0 4 5
Myeloproliferative neoplasm 6 10 3 0
Chronic HIV infection 0 0 5 15
Autoimmune disorder 3 10 1 9
Crohn’s disease 0 0 3 0
Genetic disorder 0 0 4 0
Solid organ malignancy 0 0 1 0
Azathioprine treatment 0 0 8 0
Arsenicals - 0 4 0
No associated conditions 12 31 26 30
Incomplete evaluation 2 - - 9
a
Total 28 59 62 69
FII factor II, FV Leiden factor V Leiden, HIV human immunodeficiency virus, MTHFR metilentetrahydorfolate reductase, PC protein C, PS protein S
(a): Some patients have more than one associated condition

Genetic disorders Pathogenesis

Reports on familial aggregation of INCPH and presence A dual theory, implicating both intrahepatic vascular ob-
of its key histologic features in congenital disorders (e.g. struction and increased splanchnic blood flow, has been
Adams-Oliver syndrome, Turner disease) indicate a pos- suggested to explain portal hypertension in INCPH pa-
sible genetic component in INCPH [18, 29–33]. There is tients [1, 6, 39]. An increased intrahepatic resistance likely
evidence of an association between HLA-DR3 and results from the obstructed intrahepatic vessels (i.e. phle-
INCPH, what also supports an immunogenetic basis of bosclerosis) and distorted intrahepatic angioarchitecture
this disorder [8, 31]. (i.e. nodular regeneration). The mechanisms responsible
for the obliteration of portal venules remain unknown.
Several hypotheses have been proposed [1, 34, 39], includ-
Prothrombotic conditions ing aberrant coagulation activation or thrombosis, ac-
Thrombophilia seems invariable behind some clinical quired or inherited disorders of vascular remodeling, and
and histologic features of patients with INCPH. There endothelial injury from immune cells [40]. Similar to
are different pieces of evidence suggestive of this includ- cirrhosis, the imbalance of different vasoactive media-
ing the high prevalence (30-50 %) of pre-existing hyper- tors causing intrahepatic vasoconstriction could also be
coagulability commonly reported in INCPH patients [2, considered. Additionally to the increased intrahepatic
6, 10, 11, 19, 34]. Also, these patients tend to have a resistance, a portal venous overflow secondary to spleno-
relatively high incidence of portal vein thrombosis [2, 6, megaly has been linked to the development of portal
10, 11]. In addition, certain pathologic features in liver hypertension in INCPH patients [41, 42]. Overproduction
specimens of INCPH patients support a dominant role of nitric oxide, released in the sinus lining spleen cells,
of thrombophilia in the development of INCPH [6, 11, could also justify the dilatation of splenic sinuses and sub-
35, 36]. Presence of obliterative portal venopathy (i.e. lu- sequent massive splenomegaly frequently found in INCPH
minal narrowing or obliteration of small portal venous patients [1, 43].
branches accompanied by dense deposits of elastic fi-
bers) in liver specimens of INCPH patients is highly
suggestive of previous thrombotic episodes. Further- Clinical manifestations
more, the majority of liver explants from transplanted Complications related to portal hypertension dominate
INCPH patients demonstrate organized old thrombi in the signs and symptoms present in patients with INCPH
the large portal vein branches [37, 38]. [1, 2, 34, 39]. The liver function is usually preserved.
Schouten et al. Orphanet Journal of Rare Diseases (2015) 10:67 Page 4 of 8

Variceal bleeding is the most common clinical feature. veins or of the portal vein at imaging studies performed
Unlike cirrhotic patients, prognosis of variceal bleeding at diagnosis.
in INCPH is usually good due to the preserved liver Therefore, the current diagnostic work up for INCPH
function. In those patients without variceal bleeding at should include: 1) detailed medical history to investigate
diagnosis, over 75 % had varices at the initial endoscopy concomitant diseases and exposure to drugs, medica-
[2, 34]. A recent study has shown that the 1-year prob- tions or toxins, 2) liver imaging to evaluate the patency
ability of developing small and large varices was 10 % of the splanchnic venous axis, 3) laboratory tests to rule
and 13 %, respectively; this is similar to what is de- out other causes of liver diseases and/or PH and 4) a
scribed in cirrhotic patients [2]. This study also showed mandatory liver biopsy to discard cirrhosis and other
that in patients with large varices, the 1-year probability causes of chronic liver disease with or without PH. As a
of first bleeding episode despite primary prophylaxis was result, a diagnosis of INCPH can only be made upon the
9 %. In addition, the 1-year probability of re-bleeding exclusion of liver cirrhosis, portal vein thrombosis,
despite combined secondary prophylaxis (i.e. beta- Budd-Chiari syndrome, chronic liver diseases causing
blockers and endoscopic band ligation) was 22 % [2]. noncirrhotic portal hypertension (e.g. chronic viral hepa-
Ascites is reported in up to 50 % of cases, and it usually titis, primary biliary cirrhosis, non-alcoholic steatohepa-
develops in the context of precipitating factors such as titis, alcoholic steatohepatitis and autoimmune hepatitis)
variceal bleeding or infections. Generally, it is easily con- and conditions causing portal hypertension (congenital
trolled with low dose of diuretics and resolution of the liver fibrosis, sarcoidosis and schistomiasis).
trigger [1, 10]. Hepatic encephalopathy is a rare complica-
tion and it is also related to precipitating factors. There Liver function tests
are anecdotic reports of hepatopulmonary syndrome, por- Liver function tests are usually within normal range; jaun-
topulmonary hypertension and hepatocellular carcinoma. dice is rarely seen at diagnosis. Transient impairments in
Over 95 % of patients have splenomegaly and it can cause liver function may occur in the context of variceal bleeding
left upper quadrant’s abdominal pain. or infection. Anemia, leukopenia, and thrombocytopenia
Portal vein thrombosis (PVT) is also common, with a are common due to hypersplenism.
reported prevalence that ranges from 13-46 % [2, 6, 10].
A recent study found a 9 % annual probability of devel- Imaging
oping PVT. HIV infection and the presence of variceal Comprehensive liver imaging is required before INCPH
bleeding at diagnosis have been described as factors in- can be confidently diagnosed. The goals of liver imaging
dependently associated with a high risk of developing are twofold: 1) to determine the presence of radiological
PVT [2, 7]. Remarkably, most patients are asymptomatic signs of PH such as splenomegaly, collaterals or ascites,
at the time of PVT diagnosis. Therefore, it may be useful and 2) to evaluate the patency of the hepatic veins and
to screen for the presence of PVT in INCPH patients. It the porto-spleno-mesenteric venous axis. Of note, most
is unclear, however, the optimal frequency or best im- patients also present radiological signs of chronic liver
aging modality in this context. disease (i.e. liver surface nodularity) despite the lack of
histologic cirrhosis [45]. Doppler ultrasound in addition
Diagnosis to CT angiography or MRI angiography is the recom-
There is a lack of a specific positive test that leads to an mended strategy.
INCPH diagnosis. It is based on clinical criteria and the
formal exclusion of other causes of PH; this represents a Liver biopsy / liver pathology
clinical challenge, even in experienced liver units. Con- The morphological features associated with INCPH can
sequently, INCPH is frequently unrecognized, and in be sometimes subtle, what makes pivotal an adequate
many instances patients are misdiagnosed with liver cir- histological evaluation by expert liver pathologists. It is
rhosis [44, 45]. essential to systematically assess the different anatomical
structures in the liver, including their size, topography
Criteria and differential diagnosis and morphology. At the portal tracts, presence of a bile
The diagnosis of INCPH is a diagnosis of exclusion, duct, a branch of the hepatic artery and of a normally
based on the following previously reported criteria [1]: sized portal vein needs to be determined. Hypoplastic or
1) presence of unequivocal signs of portal hypertension minute portal tracts, with a lumen of the bile duct or ar-
(e.g., gastroesophageal varices, ascites, and/or spleno- tery smaller than the surrounding hepatocytes are typical
megaly); 2) absence of cirrhosis, advanced fibrosis or of INCPH (Fig. 1) [35]. These are thought to be portal
other causes of chronic liver diseases that can cause PH tract remnants, resulting from resorption of normal por-
by appropriate serological, biochemical tests and liver tal tract collagen [46]. Portal sclerosis or hepatoportal
biopsy and; 3) absence of thrombosis of the hepatic sclerosis is also a common feature. It consists of fibrous
Schouten et al. Orphanet Journal of Rare Diseases (2015) 10:67 Page 5 of 8

Fig. 1 a Paraportal shunting vessel (arrow), herniating into the liver parenchyma. The adjacent portal tract has a bile duct (*), hepatic artery (#)
and portal vein (+); PAS staining, 20x. b Phlebosclerosis. In a fibrotic portal tract (arrow), a bile duct (*), hepatic artery (#) and arterialised portal
vein (+) are present; haematoxylin and eosin, 20x. c Hypoplastic portal tract in which the lumen of the bile duct (*) is smaller than the diameter
of the surrounding hepatocytes; PAS-amylase staining, 40 x. d Nodular regenerative hyperplasia (NRH) with central hyperplasia and an atrophic
rim (arrow) in the absence of fibrosis; reticulin staining, 10x

thickening of the portal vein wall and may result from veins can be (partially) occluded associated with differ-
portal vein thrombosis and consequent organization, ei- ent toxic agents. A regenerative, compensatory response
ther from the larger portal vein branches or in the con- can be the result of a heterogeneous blood flow in the
text of local portal tract pathology. Some authors use presence of circulatory abnormalities at different levels
the term obliterative portal venopathy for this entity. of the microcirculation. This might lead to nodular re-
Other findings in the context of INCPH in the (peri)por- generative hyperplasia, showing micronodular trans-
tal area include dilated portal veins, abnormal spacing formation, with central hyperplasia and an atrophic rim
between portal tracts and veins, an increased number of in the absence of fibrosis [48, 49]. Pathologists should
vascular structures in the portal tracts, arterialization of become familiar with these features, in order to suggest
the wall of portal veins and the presence of paraportal or support the clinical diagnosis of INCPH in patients
shunting vessels and/or herniating in the liver paren- with non-cirrhotic portal hypertension.
chyma [38, 47, 48].
In the liver parenchyma, abnormalities that may be Other investigations
seen in the context of INCPH include sinusoidal dilata- INCPH is an intrahepatic presinusoidal cause of PH
tion, congestion and pericellular fibrosis, aberrant hep- [44, 50]. Hepatic venous pressure gradient (HVPG) is
atic vessels and dilatation of the central vein with or normal (≤5 mmHg) or slightly increased (5-10 mmHg)
without perivenular fibrosis. The lumen of the central but below the previously described cut-off for clinically
Schouten et al. Orphanet Journal of Rare Diseases (2015) 10:67 Page 6 of 8

significant portal hypertension in cirrhosis (CSPH; achieved some degree of recanalization [2]. Regarding
HVPG>10 mmHg) [37, 51]. Also, liver stiffness value on anticoagulation in these patients, some issues that need to
transient elastography (Fibroscan®) is lower than the de- be addressed: 1) which are the subgroup of PVT patients
scribed cut-off values for diagnosing cirrhosis, varices that benefit from anticoagulation, 2) which is the best
and CSPH [2, 7, 51]. Thus, lower values for HVPG and anticoagulantion modality (low molecular weight heparins
liver stiffness than those described for cirrhosis and vs vitamin-K antagonist vs new oral anticoagulants), 3)
CSPH can be helpful by ruling out cirrhosis in a patient which is the optimal duration of anticoagulation and 4)
with signs of PH. which are the early predictors of response. Another im-
portant point is whether anticoagulation may have a
Treatment role in the prevention of PVT. Based on the high preva-
Management of portal hypertension lence of thrombophilia, the frequent presence of throm-
Data on management and prophylaxis of variceal bleed- bosis of small intrahepatic and main portal veins in
ing in INCPH patients are scarce with a remarkable lack INCPH, it would be even more important to determine
of randomized controlled trials. There are no specific whether anticoagulation could play a role to prevent
guidelines for the management of PH in patients with disease progression.
INCPH. Nevertheless, expert opinion recommends fol-
lowing the guidelines of prophylaxis and management of Prognosis
PH in cirrhotic patients [1]. A recent cohort study re- Very few studies have evaluated the long-term prognosis
ported good long-term outcome by applying a manage- of INCPH patients. Overall, prognosis is generally better
ment strategy based on current guidelines for cirrhotic than in patients with cirrhosis and a similar degree of
variceal bleeding [2]. portal hypertension. As mentioned above, this may be
Briefly, primary and secondary prevention of variceal due to the fact that most INCPH patients have well pre-
bleeding includes the use of non-selective beta-blockers served liver function. However, a small subgroup of pa-
and endoscopic variceal ligation. Trans-jugular intrahepa- tients will develop liver failure and will require LT. Two
tic portosystemic shunting (TIPSS) is an effective alterna- recent European cohort studies evaluated prognosis of
tive in patients who fail to respond to medical and INCPH [2, 10, 32]. The Dutch study reported low overall
endoscopic therapy. Management of acute variceal bleed- and LT-free survival, 78 % and 72 % at 5 years, respect-
ing includes early pharmacological treatment with vaso- ively. However, it should be noted that only 13 % of pa-
active drugs, early endoscopic control of bleeding, careful tients died from liver-related causes. Conversely, the
blood product replacement, and prophylactic antibiotics Spanish cohort reported 86 % of LT-free survival at
[52]. Guidelines also recommend withdrawing any drug 5 years. Interestingly, ascites was identified as a poor
potentially associated with INCPH (e.g. azathioprine) and prognostic factor in both studies. The presence of a con-
treating any associated medical conditions [52]. comitant severe disorder such as an immunological dis-
ease or malignancy was also identified as a poor
Liver transplant prognostic factor in the Spanish study.
Even though INCPH patients usually have well preserved
liver function, and PH related complications are success- Conclusions and future perspectives
fully controlled, some patients may require a LT. Some of Over the last decade, numerous efforts have tried to
the reported indications for LT include unmanageable PH, clarify different aspects of INCPH. First, the nomencla-
progressive liver failure, chronic hepatic encephalopathy, ture concerning this clinical disorder has been ambigu-
hepatopulmonary syndrome and hepatocellular carcin- ous and highly depended on histological features. To
oma. Post-LT outcomes of INCPH patients are good and facilitate future studies and subsequently enhance our
the disease tends not to recur. However, data on this issue understanding of the disease, common terminology and
are limited and mostly based on small cohorts [1, 45]. diagnostic criteria have been developed [1]. Regarding
pathophysiology, some genetic traits have been identified
Management of PVT in HIV-associated INCPH [25]. Furthermore, cohort
The use of anticoagulation in the management of PVT studies performed in Europe provided new insights into
in INCPH is controversial, mainly due to the lack of the natural course and prognosis of these patients [2, 10,
prospective data. Nevertheless, we believe that anticoagu- 11]. Despite these improvements, several uncertainties
lation therapy must be considered in patients with under- related to its pathogenesis should be further addressed.
lying prothrombotic conditions and in patients who Large multicenter studies studying INCPH prevalence,
develop PVT. A recent retrospective series described 15 associated disorders, natural course and prognosis are
patients with INCPH and PVT that were treated with an- an unmet need. The diagnosis of INCPH still relies on
ticoagulants. At the end of follow-up, 54 % of patients clinical and histologic elements; future research should
Schouten et al. Orphanet Journal of Rare Diseases (2015) 10:67 Page 7 of 8

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Abbreviations compensatory nodular regenerative hyperplasia in HIV-infected patients.
CSPH: Clinically significant portal hypertension in cirrhosis; INCPH: Idiopathic AIDS. 2009;23:1511–8.
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Author details
1 21. Kono K, Ohnishi K, Omata M, Saito M, Nakayama T, Hatano H, et al.
Department of Gastroenterology, University Hospital Ghent, De Pintelaan
Experimental portal fibrosis produced by intraportal injection of killed
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University of Amsterdam, Amsterdam, The Netherlands. 3Department of
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Medicine, CTO, Icahn School of Medicine at Mount Sinai, New York, NY
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Received: 29 January 2015 Accepted: 20 May 2015
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