[Show abstract][Hide abstract] ABSTRACT: Background
There is limited data on celiac disease in patients with cryptogenic cirrhosis or idiopathic noncirrhotic intrahepatic portal hypertension (NCIPH). Our objective was to evaluate for celiac disease in patients with portal hypertension in India.
Consecutive patients with portal hypertension having cryptogenic chronic liver disease (cases) and hepatitis B- or C-related cirrhosis (controls) were prospectively enrolled. We studied tissue transglutaminase (tTG) antibody and duodenal histology in study patients.
Sixty-one cases (including 14 NCIPH patients) and 59 controls were enrolled. Celiac disease was noted in six cases (including two NCIPH patients) as compared to none in controls. In a significant proportion of the remaining study subjects, duodenal biopsy showed villous atrophy, crypt hyperplasia, and lamina propria inflammation, not accompanied by raised intraepithelial lymphocytes (IELs); this was seen more commonly in cases as compared to controls. An unexpectedly high rate of tTG antibody positivity was seen in study subjects (66 %) of cases as compared to 29 % in controls (p-value
Full-text · Article · Sep 2014 · Indian Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: Chronic microangiopathy of portal venules results in idiopathic non-cirrhotic intrahepatic portal hypertension (NCIPH). Recent data suggest a role for vasoactive factors of portal venous origin in the pathogenesis of this ‘pure’ vasculopathy of the liver. Enteropathies (often silent), are an important ‘driver’ of this disease. NCIPH is under-recognized and often mis-labeled as cryptogenic cirrhosis. Liver biopsy is needed to prove the diagnosis of NCIPH. In these patients, with advancing disease and increased porto-systemic shunting, the portal venous vasoactive factors bypass the liver filter and contribute to the development of pulmonary vascular endothelial disorders—porto-pulmonary hypertension and hepato-pulmonary syndrome as well as mesangiocapillary glomerulonephritis. Prognosis in NCIPH patients is determined by presence, recognition and management of associated disorders. With better understanding of the pathogenesis of NCIPH, newer treatment options are being explored. Imbalance in ADAMTS 13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13): vWF (von-Willebrand factor) ratio is documented in NCIPH patients and may have a pathogenic role. Therapeutic interventions to correct this imbalance may prove to be important in the management of NCIPH.
No preview · Article · Jul 2014 · Journal of Clinical and Experimental Hepatology
[Show abstract][Hide abstract] ABSTRACT: Introduction Patients with BCS and short stenosis of the hepatic vein or the upper IVC can be treated with recanalisation by percutaneous venoplasty ± hepatic vein stent insertion. Recent data suggests >60% failure rate (PMID 23389867). We studied the long-term outcomes of this approach in our institution.
Methods Retrospective analysis of patients referred from 1987 to 12/2012 for radiological intervention. Of 161 patients treated for BCS, 60 patients were selected.
Results Median age, 34.5 years (19–65), M:F ratio 23:37. Mean follow up, 8 ± 6.6 years (0.1–26 years). 60% of patients had ≥1 haematological risk factor. Percutaneous recanalisation was technically successful in all patients. The obstruction was at the level of hepatic vein (s) (86.6%), IVC (6.6%) and both IVC and HV (6.6%). 30 patients were managed with venoplasty alone. Of the 30 who had stent placement, 15 had venoplasty prior to stent placements, ranging from 1–11 venoplasty episodes. Due to failure of recanalisation, 26.66% patients required TIPSS (16.7%), surgery (8.3%) and liver transplantation (6.7%). Actuarial survival at 1, 5, 10 was 95%, 93%, and 83% respectively (kaplan meier survival Graph 1). All patients maintained Child’s A status throughout follow up and there was no incidence of Hepatocellular Carcinoma.
Conclusion BCS patients due to short stenosis of the hepatic vein or the upper IVC can be successfully managed with percutaneous recanalisation alone with good outcomes over a long period of follow up. Our data supports the stepwise approach to the managements of BCS, with better results than recent series.
Disclosure of Interest None Declared.
[Show abstract][Hide abstract] ABSTRACT: We have reported A disintegrin and metalloprotease with thrombospondin type 1 motif, member 13 (ADAMTS13) deficiency in noncirrhotic intrahepatic portal hypertension (NCIPH) patients of European origin with preserved liver function. We aimed to study ADAMTS13-von Willebrand factor (vWF) imbalance in Indian patients with NCIPH.
Twenty-nine cases with NCIPH [22 males; 29 years (13-58); Child's A, 23; B, 6], 22 disease controls with cryptogenic chronic liver disease [15 males; 46 years (18-74); Child's A, 9; B, 9; C, 4] and 17 healthy controls [14 males; 32 years (27-45)] were enrolled in the study. We measured ADAMTS13 antigen and activity (by collagen binding assay (CBA) and by fluorescence resonance energy transfer [FRET] assay), and vWF antigen levels in plasma of study patients.
ADAMTS13 activity by CBA in NCIPH patients (32 %, 5 % to 100 %; median, range; p-value <0.001) and disease controls (36 %, 5 % to 144 %; p = 0.001) was significantly lower than in healthy controls (87 %; 60 % to 148 %). ADAMTS13 antigen and activity by FRET assay were also lower in cases and disease controls. ADAMTS13 activity (by CBA) to antigen ratio was lower in NCIPH and disease controls than in healthy controls. Of 29 NCIPH patients, 3 (all in Child's A) had severe ADAMTS13 deficiency (<10 % ADAMTS13 activity), and 8 (Child's A, 7; B, 1) had moderate ADAMTS13 deficiency (10 % to 25 % activity). Conversely, vWF antigen and vWF:ADAMTS13 ratio were higher in patients with NCIPH and in disease controls than in healthy controls.
This study validates the finding of ADAMTS13 deficiency in NCIPH despite preserved liver functions in an Indian population suggesting its involvement in pathogenesis of NCIPH.
Preview · Article · Apr 2014 · Indian Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: There have been encouraging reports on transjugular intrahepatic portosystemic stent-shunt (TIPSS) for Budd-Chiari syndrome (BCS). Long-term data are lacking.
To assess long-term outcomes and validate prognostic scores following TIPSS for BCS.
A single centre retrospective study. Patients underwent TIPSS using bare or polytertrafluoroethane (PTFE)-covered stents.
Sixty-seven patients received successful TIPSS between 1996 and 2012 using covered (n = 40) or bare (n = 27) stents. Patients included had a Male: Female ratio of 21:46, and were characterised (mean ± s.d.) by age 39.9 ± 14.3 years, Model of end stage liver disease (MELD) 16.1 ± 7.0 and Child's score 8.8 ± 2.0. Seventy-eight percent had haematological risk factors. Presenting symptoms were ascites (n = 61) and variceal bleeding (n = 6). Nine patients underwent hepatic vein dilatation or stenting prior to TIPSS. Mean follow-up was 82 months (range 0.5-184 months). Fifteen percent had post-TIPSS encephalopathy. Two have been transplanted. Primary patency rates (76% vs. 27%, P < 0.001) and shunt re-interventions (22% vs. 100%, P < 0.001) significantly favoured covered stents. Secondary patency was 99%. Six-, 12-, 24-, 60- and 120-month survival was 97%, 92%, 87%, 80% and 72% respectively. Six patients had liver related deaths. Two patients developed hepatocellular carcinoma. The BCS TIPS PI independently predicted mortality in the whole cohort, but no prognostic score was a significant predictor of mortality after subgroup validation.
Long-term outcomes following TIPSS for Budd-Chiari syndrome are very good. PTFE-covered stents have significantly better primary patency. The value of prognostic scores is controversial. TIPSS should be considered as first line therapy in symptomatic patients in whom hepatic vein patency cannot be restored.
No preview · Article · Feb 2014 · Alimentary Pharmacology & Therapeutics
[Show abstract][Hide abstract] ABSTRACT: Background & objectives:
There are only a few studies on aetiology of portal hypertension among adults presenting to tertiary care centres in India; hence we conducted this study to assess the aetiological reasons for portal hypertension in adult patients attending a tertiary care centre in southern India.
Causes of portal hypertension were studied in consecutive new adult patients with portal hypertension attending department of Hepatatology at a tertiary care centre in south India during July 2009 to July 2010.
A total of 583 adult patients (>18 yr old) were enrolled in the study. After non-invasive testing, commonest causes of portal hypertension were cryptogenic chronic liver disease (35%), chronic liver disease due to alcohol (29%), hepatitis B (17%) or hepatitis C (9%). Of the 203 patients with cryptogenic chronic liver disease, 39 had liver biopsy - amongst the latter, idiopathic non cirrhotic intrahepatic portal hypertension (NCIPH) was seen in 16 patients (41%), while five patients had cirrhosis due to non alcoholic fatty liver disease. Fifty six (10%) adult patients with portal hypertension had vascular liver disorders. Predominant causes of portal hypertension in elderly (>60 yrs; n=83) were cryptogenic chronic liver disease (54%) and alcohol related chronic liver disease (16%).
Interpretation & conclusions:
Cryptogenic chronic liver disease was the commonest cause of portal hypertension in adults, followed by alcohol or hepatitis B related chronic liver disease. Of patients with cryptogenic chronic liver disease who had liver biopsy, NCIPH was the commonest cause identified. Vascular liver disorders caused portal hypertension in 10 per cent of adult patients. Cryptogenic chronic liver disease was also the commonest cause in elderly patients.
No preview · Article · May 2013 · The Indian Journal of Medical Research
[Show abstract][Hide abstract] ABSTRACT: Unlabelled:
Budd-Chiari syndrome (BCS) is a rare, life-threatening disease caused by obstruction of hepatic venous outflow. The aim of the study was to assess long-term outcome and identify prognostic factors in BCS patients managed by a step-wise approach using anticoagulation, angioplasty/thrombolysis, transjugular intrahepatic portosystemic shunting (TIPS), and orthotopic liver transplantation (OLT). We reviewed long-term data on 157 patients previously included by the European Network for Vascular Disorders of the Liver, a multicenter prospective study of newly diagnosed BCS patients in nine European countries. Patients were followed for a median of 50 months (range, 0.1-74.0). During the study, 88 patients (56%) received at least one invasive intervention (22 patients angioplasty/thrombolysis, 62 TIPS, and 20 OLT) and 36 (22.9%) died. Most interventions and/or deaths occurred in the first 2 years after diagnosis. The Rotterdam score was excellent in predicting intervention-free survival, and no other variable could significantly improve its prognostic ability. Moreover, BCS-TIPS prognostic index (PI) score (based on international normalized ratio, bilirubin, and age) was strongly associated with survival and had a discriminative capacity, which was superior to the Rotterdam score.
The current study confirms, in a large cohort of patients with BCS recruited over a short period, that a step-wise treatment approach provides good long-term survival. In addition, the study validates the Rotterdam score for predicting intervention-free survival and the BCS-TIPS PI score for predicting survival.
[Show abstract][Hide abstract] ABSTRACT: Budd-Chiari syndrome is a rare disorder caused by hepatic venous outflow obstruction and resulting hepatic dysfunction. Despite a lack of prospective randomized trials, much progress has been made in its management over the last 20 years. The main goals of treatment are to ameliorate hepatic congestion and prevent further thrombosis. The selective use of anticoagulation, vascular stents, transjugular intrahepatic portosystemic stent-shunt and liver transplant has resulted in a significant increase in survival. The diagnosis, initial management and long-term follow-up of patients with Budd-Chiari syndrome is reviewed. The concept of individualization of treatment and a stepwise approach to invasive procedures is also discussed.
No preview · Article · Dec 2012 · Expert review of gastroenterology & hepatology
[Show abstract][Hide abstract] ABSTRACT: We propose that porto-pulmonary hypertension (PPH) may arise as a consequence of deficiency of ADAMTS13 (a plasma metalloprotease that regulates von Willebrand factor size and reduces its platelet adhesive activity) and provide a clinical case history to support our hypothesis A patient with non-cirrhotic intrahepatic portal hypertension (NCIPH), ulcerative colitis and celiac disease developed symptoms of PPH which had advanced beyond levels which would have made her an eligible candidate for liver transplantation (mean pulmonary artery pressure (PAP) 49 mm Hg). She was known to have severe ADAMTS13 deficiency, which we considered to be causative of, or contributory to her NCIPH. We postulated that increasing porto-systemic shunting associated with advancing portal hypertension would make the next encountered vascular bed, the lung, susceptible to the pathogenic process that was previously confined to the portal system, with pulmonary hypertension as its consequence. Her pulmonary artery pressures fell significantly during the next year on weekly replacement of plasma ADAMTS13 by infusions of fresh frozen plasma and conventional drug treatment of her pulmonary hypertension. Her pulmonary artery pressures had fallen to acceptable levels when, in response to platelet infusion, it rose precipitously and dangerously. The sequence strongly supports our hypothesis that PPH is a consequence of ADAMTS13 deficiency and is caused by platelet deposition in afferent pulmonary vessels.
Preview · Article · Nov 2012 · Journal of Hepatology
[Show abstract][Hide abstract] ABSTRACT: Background and aims:
Idiopathic non-cirrhotic intrahepatic portal hypertension (NCIPH) is often mis-diagnosed as cryptogenic cirrhosis. Serum vitamin B12 levels can be raised in cirrhosis, probably because of excess release or reduced clearance. Because NCIPH is characterised by long periods of preserved liver function, we examined whether serum B12 level could be used as a marker to differentiate NCIPH from cryptogenic cirrhosis.
We analysed serum B12 levels in 45 NCIPH and 43 cryptogenic cirrhosis patients from January 2009 to September 2011.
Serum B12 levels were significantly lower in NCIPH patients than in cryptogenic cirrhosis patients (p < 0.001) and were useful in differentiating the two disorders (area under ROC: 0.84; 95% C.I: 0.76-0.93). Low serum B12 level (≤250 pg/ml) was noted in 25/72 (35%) healthy controls, 14/42 (33%) NCIPH patients, and 1/38 (3 %) cryptogenic cirrhosis patients. In patients with intrahepatic portal hypertension of unknown cause, serum B12 level ≤ 250 pg/ml was useful for diagnosing NCIPH (positive predictive value: 93 %, positive likelihood ratio 12.7), and serum B12 level >1,000 pg/ml was useful in ruling out NCIPH (negative predictive value: 86 %, negative likelihood ratio: 6.67). Low serum B12 levels (≤250 pg/ml) correlated with diagnosis of NCIPH after adjusting for possible confounders (O.R: 13.6; 95% C.I:1.5-126.2). Among patients in Child's class A, serum B12 level was ≤250 pg/ml in 14/35 NCIPH patients compared with 1/21 cryptogenic cirrhosis patients (O.R: 13.3; 95% C.I: 1.6-111).
Serum vitamin B12 level seems to be a useful non-invasive marker for differentiation of NCIPH from cryptogenic cirrhosis.
No preview · Article · Aug 2012 · Digestive Diseases and Sciences
[Show abstract][Hide abstract] ABSTRACT: Non alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. NAFLD represents a spectrum of liver disease ranging from reversible hepatic steatosis, to non alcoholic steato-hepatitis (NASH) and cirrhosis. The potential role of glucocorticoids (GC) in the pathogenesis of NAFLD is highlighted in patients with GC excess, Cushing's syndrome, who develop central adiposity, insulin resistance and in 20% of cases, NAFLD. Although in most cases of NAFLD, circulating cortisol levels are normal, hepatic cortisol availability is controlled by enzymes that regenerate cortisol (F) from inactive cortisone (E) (11β-hydroxysteroid dehydrogenase type 1, 11β-HSD1), or inactivate cortisol through A-ring metabolism (5α- and 5β-reductase, 5αR and 5βR).
[Show abstract][Hide abstract] ABSTRACT: ADAMTS13 deficiency leading to excess ultralarge von Willebrand factor (VWF) multimers and platelet clumping is typically found in thrombotic thrombocytopenic purpura (a type of thrombotic microangiopathy). Idiopathic noncirrhotic intrahepatic portal hypertension (NCIPH) is a microangiopathy of portal venules associated with significant thrombocytopenia and predisposing gut disorders.
To determine whether the portal microangiopathy in NCIPH is associated with ADAMTS13 deficiency.
Plasma levels of ADAMTS13, anti-ADAMTS13 antibodies, and VWF were compared between cases (NCIPH patients) and controls (with chronic liver diseases of other etiology) matched for severity of liver dysfunction. Eighteen NCIPH patients [median (range) MELD score 12 (7-25)] and 25 controls [MELD score 11 (4-26)] were studied.
ADAMTS13 activity was reduced in all 18 NCIPH patients and significantly lower than controls (median, IQR: 12.5%, 5-25% and 59.0%, 44-84%, respectively, P<0.0001) [normal range for plasma ADAMTS13 activity (55-160%)]. ADAMTS13 activity was <5% in 5/18 NCIPH patients (28%) and 0/25 controls (P=0.009). ADAMTS13 antigen levels were also decreased. Sustained low ADAMTS13 levels were seen in four NCIPH patients over 6 weeks to 11 months (highest ADAMTS13 level in each patient: <5%, 6%, 6%, and 25%), despite two patients having MELD score 12. Although nine cases had low titer anti-ADAMTS13 antibodies, there was no significant difference between cases and controls. Abnormally large VWF multimers were observed in 4/11 NCIPH patients (36%) and in 0/22 controls (P=0.008).
Sustained deficiency of ADAMTS13 appears characteristic of NCIPH, irrespective of severity of liver disease.
No preview · Article · May 2011 · Digestive Diseases and Sciences
[Show abstract][Hide abstract] ABSTRACT: Budd-Chiari syndrome (BCS) is a rare vascular liver disorder caused by thrombosis of the hepatic veins. In some patients, no known thrombophilic factor can be identified. This study aimed to identify novel factors that might play a role in thrombosis in BCS-patients by using a proteomic approach.
The abundance of plasma clot-bound proteins was compared between nine BCS-patients and nine controls by using two-dimensional difference gel electrophoresis. The protein with the most significant decrease in patients was identified by mass spectrometry. Plasma levels of this protein were measured and the results were validated in a large cohort of BCS-patients.
A total of 26 protein spots significantly differed (p<0.001). The spot that decreased with the highest statistical significance in patients was identified by mass spectrometry as apolipoprotein A1 (apo A1). The mean level of apo A1 in the plasma of these BCS-patients (0.74 g/L) was also significantly lower than in controls (1.45 g/L, p=0.002). This finding was validated in a large cohort of 101 BCS-patients and 101 controls (0.97 g/L vs. 1.32 g/L, p<0.0001). There was no major correlation between plasma levels of apo A1 and various liver function tests.
BCS-patients show decreased clot-bound protein abundance and plasma levels of apo A1. Decreased levels of apo A1 may play a role in the etiology of thrombosis in BCS-patients and possibly in other patients with venous thrombosis.
No preview · Article · May 2011 · Journal of Hepatology