Non-cirrhotic Portal Fibrosis Patients Research Articles

Splenectomy with endotherapy in non-cirrhotic portal fibrosis related portal hypertension: Can it be an alternative to proximal spleno-renal shunt?

Backgrounds/AimsProximal 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.MethodsThe 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.ResultsAmong 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.ConclusionsSplenectomy with endotherapy is alternative to PSRS in non-bleeder NCPF patients with indications for surgery.

Pathological abnormalities in splenic vasculature in non-cirrhotic portal hypertension: Its relevance in the management of portal hypertension.

BACKGROUNDPortal hypertension (PH) is associated with changes in vascular structure and function of the portosplenomesenteric system (PSMS). This is referred to as portal hypertensive vasculopathy. Pathological abnormalities of PSMS has been described in the literature for cirrhotic patients. Raised portal pressure and hyperdynamic circulation are thought to be the underlying cause of this vasculopathy. In view of this, it is expected that pathological changes in splenic and portal vein similar to those reported in cirrhotic patients with PH may also be present in patients with non-cirrhotic PH (NCPH).AIMTo investigate pathological abnormalities of splenic vein in patients with NCPH, and suggest its possible implications in the management of PH.METHODSA prospective observational study was performed on 116 patients with NCPH [Extrahepatic portal vein obstruction (EHPVO): 53 and non-cirrhotic portal fibrosis (NCPF): 63] who underwent proximal splenorenal shunt (PSRS), interposition shunt or splenectomy with devascularization in JIPMER, Pondicherry, India, a tertiary level referral center, between 2011-2016. All patients were evaluated by Doppler study of PSMS, computed tomography porto-venogram and upper gastrointestinal endoscopy. An acoustic resonance forced impulse (ARFI) scan and abdomen ultrasound were done for all cases to exclude cirrhosis. Intraoperative and histopathological assessment of the harvested splenic vein was performed in all. The study group was divided into delayed and early presentation based on the median duration of symptoms (i.e. 108 mo).RESULTSThe study group comprising of 116 patients [77 (66%) females and 39 (34%) males] with NCPH had a median age of 22 years. Median duration of symptoms was 108 mo. The most common presentation in both EHPVO and NCPF patients was upper gastrointestinal bleeding (hematemesis and melena). The ARFI scan revealed a median score of 1.2 (1.0-1.8) m/s for EHPVO and 1.5 (0.9-2.8) m/s for NCPF. PSRS was performed in 84 patients (two of whom underwent interposition PSRS using a 10 mm Dacron graft); splenoadrenal shunt in 9; interposition mesocaval shunt in 5; interposition 1st jejunal to caval shunt in 1 patient and devascularization with splenectomy in 17 patients. Median pre-splenectomy portal pressure was 25 (range: 15-51) mm Hg. In 77% cases, the splenic vein was abnormal upon intraoperative assessment. Under macroscopic examination, wall thickening was observed in 108 (93%), venous thrombosis in 32 (28%) and vein wall calcification in 27 (23%) cases. Upon examination under a surgical magnification loupe, 21 (18%) patients had intimal defects in the splenic vein. Histopathological examination of veins was abnormal in all cases. Medial hypertrophy was noted in nearly all patients (107/116), while intimal fibrosis was seen in 30%. Ninety one percent of patients with intimal fibrosis also had venous thrombosis. Vein wall calcification was found in 22%, all of whom had intimal fibrosis and venous thrombosis. The proportion of patients with pathological abnormalities in the splenic vein were significantly greater in the delayed presentation group as compared to the early presentation group.CONCLUSIONPathological changes in the splenic vein similar to those in cirrhotic patients with PH are noted in NCPH. We recommend that PH in NCPH be treated as systemic and pulmonary hypertension equivalent in the gastrointestinal tract, and that early aggressive therapy be initiated to reduce portal pressure and hemodynamic stress to avoid potential lethal effects.

High patency of proximal splenorenal shunt: A myth or reality ? – A prospective cohort study

BackgroundProximal splenorenal shunt (PSRS) is a well-accepted surgical procedure for non-cirrhotic portal hypertension (NCPH). Though a patent shunt is important for good long term outcome, there are very few studies on patency of these shunts. We analysed shunt patency using dynamic computed tomographic (CT) portography and compared it with other modalities. MethodsFrom 2004 to 2014, 50 patients with PSRS were evaluated prospectively for shunt patency using dynamic CT portography, clinical parameters and ultrasound Doppler. ResultsThe causes of NCPH were extrahepatic portal vein obstruction (EHPVO) in 38 patients and non-cirrhotic portal fibrosis (NCPF) in 12 patients. The shunt patency rate using clinical parameters, ultrasound Doppler and dynamic CT portography were 70%, 40% and 60% respectively. Clinical parameters overestimated while ultrasound Doppler underestimated the shunt patency rate. Dynamic portography had 100% correlation with conventional angiography in the five patients when this was done. The site of shunt could be demonstrated convincingly by dynamic CT portography. The shunt patency rate decreased over time. It was 64%, 60% and 43% in <1 year, 1–5 years and >5 years respectively. Our NCPF patients had a greater shunt patency rate compared to EHPVO patients (9/12 vs. 21/38) though the difference was not significant. Only size of the splenic vein had a significant impact on the shunt patency rate on statistical analysis. ConclusionsDynamic CT portography is useful for evaluation of shunt patency. Proximal splenorenal shunts have a high blockage rate which has hitherto not been reported.

Systemic and pulmonary hemodynamics in patients with non-cirrhotic portal fibrosis (NCPF) is similar to compensated cirrhosis.

Non-cirrhotic portal fibrosis (NCPF) is an important cause of portal hypertension (PHT) and variceal bleeding, especially in the developing countries. While the hepatic parenchyma and liver functions are normal, the patho-anatomic defect in these patients is pre- and peri-sinusoidal in nature. To study the systemic and pulmonary hemodynamic alterations in patients with NCPF and compare them with compensated cirrhotic patients. Patients with NCPF (n = 20, mean age 29.3 +/- 9.8 year) and matched Child's A cirrhotic patients (n = 17, age 34.1 +/- 9.8 year) who had bled in the past, underwent hemodynamic measurements using a balloon tipped catheter. In NCPF patients, the hepatic venous pressure gradient (HVPG) was significantly lower than in the cirrhotic patients (4.9 +/- 1.5 mmHg vs. 15.7 +/- 4.5 mmHg; P < 0.01). NCPF patients had hyperdynamic circulation and peripheral vasodilatation comparable to cirrhotic patients; cardiac output (8.0 +/- 1.2 l/min vs. 8.4 +/- 1.9 l/min; P = 0.4), cardiac index (5.4 +/- 0.8 l/min/m(2) vs. 5.5 +/- 1.9 l/min/m(2); P = 0.86), mean arterial pressure (88.2 +/- 14.1 mmHg vs. 89.9 +/- 17.3 mmHg; P = 0.73), systemic vascular resistance (852.8 +/- 204.3 dynes . s/cm(5) vs. 854.1 +/- 189.9 dynes . s/cm(5); P = 0.98) and pulmonary vascular resistance (41.6 +/- 18.1 dynes . s/cm(5) vs. 41.3 +/- 17.9 dynes . s/cm(5); P = 0.95) were comparable in the two groups. NCPF associated portal hypertension leads to a hyperdynamic state with high cardiac index and low systemic and pulmonary vascular resistance comparable to compensated cirrhosis. These novel observations suggest a primary role of portal hypertension in the development of hyperdynamic state.

NATURAL OR SPONTANEOUS PORTOSYSTEMIC SHUNTS PROTECT PATIENTS WITH NONCIRRHOTIC PORTAL HYPERTENSION FROM VARICEAL BLEEDING

Purpose: Extrahepatic portal venous obstruction (EHPVO) (Dilawari and Chawla, Gut 1988; 29:554-5) and noncirrhotic portal fibrosis (NCPF) or id-iopathic portal hypertension (Dhiman et al., J Gastroenterol Hepatol 2002; 17:6-16) are responsible for nearly 50% of patients with portal hypertension. Several patients develop natural or spontaneous portosystemic shunts (SPS), which may protect these patients from variceal bleeding. We, therefore, studied the frequency of SPS and their effect on incidence of variceal bleeding. Methods: We studied retrospectively 484 patients with EHPVO and 151 patients with NCPF over 15 years (1978–1993). All patients had undergone percutaneous splenoportovenography. A SPS was defined when the contrast, inj ected into the spleen, immediately revealed the inferior vena cava through splenorenal and umbilical vein shunts. The data were analyzed with reference to frequency of SPS and clinical findings. Complications due to SPV were minor and rare, however, this procedure was abandoned after the availability of noninvasive imaging such as, colour Doppler ultrasound and magnetic resonance splenoportovenography. Results: EHPVO patients were younger (mean ± SEM, 16.9 ± 10.2 year vs 30.5 ± 11.5 year, p <0.0001) and had male predominance (male: female, 361:123 vs 57: 94, p <0.0001). SPS were seen in 47 (9.7%) patients with EHPVO and in 24 (15.9%) patients with NCPF (p = NS). All 47 (100%) EHPVO patients had splenorenal shunts while in 24 NCPF patients, 15 (62.5%) patients showed splenorenal and 9 (37.5%) showed umbilical vein shunts. Twenty-nine of 47 (61.7%) EHPVO patients with SPS bled, while 396 of 437 (90.6%) patients without SPS bled (p = 0.0001). The incidence of bleeding was also significantly lower in NCPF patients with SPS; 10 of 24 (41.7%) patients with SPS bled while 86 of 127 (67.7%) patients without SPS bled (p = 0.015). Mean episode of bleeding per patient was significantly lower in patients with SPS than those without (EHPVO, SPS+ 1.77 ± 0.30 vs SPS- 2.59 ± 0.11, p = 0.015; NCPF, SPS+ 0.50 ± 0.13 vs SPS- 1.32 ± 0.12, p = 0.025). The mean hemoglobin concentration was higher in patients with SPS than those without (EHPVO, SPS+ 10.7 ± 0.36 vs SPS- 9.4 ± 0.24, p = 0.006; NCPF, SPS+ 10.5 ± 0.49 vs SPS- 8.9 ± 0.21, p = 0.006). Conclusions: SPS were seen frequently in a group of patients with EHPVO and NCPF. SPS protect these patients from variceal bleeding.

Coagulation profile and platelet function in patients with extrahepatic portal vein obstruction and non-cirrhotic portal fibrosis.

Coagulation disorders commonly develop in patients with cirrhosis of the liver. They have also been reported in patients with non-cirrhotic portal fibrosis (NCPF) and extra-hepatic portal venous obstruction (EHPVO); the two conditions with portal hypertension and near-normal liver functions. The spectrum and prevalence of coagulation abnormalities and their association with the pathogenesis of these diseases and with hypersplenism was prospectively studied. Eighteen EHPVO patients that included an equal number of NCPF patients and 20 healthy controls were prospectively studied. The coagulation parameters assessed included: international normalized ratio, partial thromboplastin time, and fibrinogen and fibrinogen degradation products. Platelet aggregation and malondialdehyde levels were measured. Both EHPVO (83%) and NCPF (78%) patients had a significantly prolonged international normalized ratio and a decrease in fibrinogen and platelet aggregation. The EHPVO patients had a significant prolongation in partial thromboplastin time (67% patients), with increased levels of fibrinogen degradation product levels occurring in all patients; these were normal in NCPF patients. Platelet malondialdehyde levels were normal in both groups. Hypersplenism was present in four EHPVO and seven NCPF patients. It did not significantly influence the coagulation profile in either NCPF or EHPVO patients. Coagulation anomalies are common and significant in both NCPF and EHPVO patients, suggestive of a mild disseminated intravascular coagulation disorder. These imbalances could be caused by chronic subclinical endotoxemia and cytokine activation after the initial portal thromboembolic event. The persistence of these abnormalities in adolescent patients indicates an ongoing coagulation derangement.

Increased incidence of glomerulonephritis following spleno-renal shunt surgery in non-cirrhotic portal fibrosis

In a prospective study of 200 non-cirrhotic portal fibrosis (NCPF) patients, 7% had mild proteinuria and their renal biopsies showed mild mesangial proliferative glomerulonephritis (mes-PGN). The remaining 93% biopsies were normal. However, following the insertion of a spleno-renal shunt (SRS) for portal hypertension 32% of these patients developed nephrotic syndrome in five years. Renal histology revealed mesangiocapillary glomerulonephritis (MCGN) (18.5%), mes-PGN (9%), minimal change nephropathy (3%), and chronic sclerosing GN (1.5%). Immunofluorescence showed granular deposition of IgA and C3. IgA2 was the predominant form of Ig in the glomerular deposits, indicating that IgA in the immune complexes was derived from the gastrointestinal tract. Electron microscopy revealed electron dense deposits in the mesangium. In contrast to the NCPF patients who underwent a SRS for portal hypertension, the 200 patients in our study who underwent spleno-renal shunting because of extra hepatic portal obstruction did not have renal disease, nor did they develop renal disease during the five-year post-operative follow-up. Fifty percent of the glomerulonephritis (GN) in the NCPF group progressed to renal failure in five years; 46.6% continued to have proteinuria. Low serum complement, C3 (40%) and circulating immune complexes (14.8%) were detected in the glomerulonephritis group. Our study shows that: (i) there is a high rate of the occurrence of GN following SRS in NCPF patients, but not in those with normal livers; (ii) the type of GN is primarily IgA nephropathy; and (iii) the GN could be the result of defective hepatic reticuloendothelial function in the NCPF group that is worsened by the shunting procedure.

Factors influencing development of portal hypertensive gastropathy in patients with portal hypertension

Portal hypertensive gastropathy (PGP) is an important cause of bleeding in portal hypertension patients. Although hyperdynamic congestion seems to be the underlying mechanism, the factors that influence the development of PGP are not understood. To investigate these, 107 patients [cirrhosis, 35; noncirrhotic portal fibrosis (NCPF), 24; extrahepatic portal vein obstruction (EHPVO), 46; Budd-Chiari syndrome, 2] were prospectively studied. Eighty-three patients had Child's A, 17 had Child's B, and 7 had Child's C liver disease. Before sclerotherapy, although intravariceal pressure was similar, 4 cirrhosis patients (3.7%) but no NCPF or EHPVO patients had PGP. After sclerotherapy, 21 additional patients (20.3%) developed PGP during a follow-up of 23.2 ± 3.4 months (range, 1–52). The incidence of PGP was higher in cirrhotic patients (37.1%) than in NCPF (16.7%; P < 0.05) or EHPVO (8.7%; P < 0.01) patients. The probability of developing PGP among all patients at the end of 52 months of follow-up was 30%, more in cirrhosis than in EHPVO (55% vs. 15%; P < 0.005). Only 2 patients bled from PGP during follow-up. Development of PGP correlated with severity of liver disease, being more common in Child's C than Child's A patients (87% vs. 13%; P < 0.001). PGP was seen more often in patients with gastroesophageal varices than in patients with esophageal varices alone (42% vs. 11%; P < 0.01). In conclusion, the results show that development of PGP is significantly influenced by sclerotherapy, severity of liver disease, etiology of portal hypertension and coexisting gastric varices and is not directly correlated with intravariceal pressure.

Characterization of peripheral blood lymphocytes in patients with non‐cirrhotic portal fibrosis: A comparison with cirrhotics and healthy controls

Non-cirrhotic portal fibrosis (NCPF) is a common cause of portal hypertension in India. Its aetiopathogenesis is not well understood. To investigate the possibility of an immune mediated injury, phenotypes of peripheral blood lymphocytes were studied in 15 NCPF patients and were compared with an equal number of compensated cirrhotics and matched healthy controls. The population of total peripheral T lymphocytes (T1) and suppressor/cytotoxic phenotype (T8) was significantly (P less than 0.01) decreased in NCPF patients compared with controls. The sub-populations of helper/inducer lymphocytes (T4) and total B lymphocytes, however, were comparable with controls. The ratio of T4 to T8 lymphocytes was significantly (P less than 0.01) increased in NCPF patients in comparison with controls. Similar changes in the lymphocyte population were also observed in cirrhotic patients. Further investigations are required to identify whether the cellular alterations seen in NCPF have a pathogenetic basis or are secondary to the disease process itself.

Immunological profile of patients with non‐cirrhotic portal fibrosis

The aetiopathogenesis of non-cirrhotic portal fibrosis (NCPF), a common cause of portal hypertension in India, is not known. To study the immune status of NCPF patients and to see whether immunological mechanisms have a role to play, humoral and cell-mediated immunological studies were carried out in 43 patients with NCPF and compared with equal number of matched healthy controls and 31 patients with compensated liver cirrhosis. Serum immunoglobulin A (IgA) and complement (C3, C4) levels were significantly (P less than 0.001) lower in NCPF patients compared with controls and cirrhotics. There was no significant difference between the total or the relative concentration of the immunoglobulins and complements between NCPF patients and healthy controls, but, in patients with cirrhosis, concentration of all the immunoglobulins was higher. The cutaneous response to dinitrochlorobenzene was poorer in patients with NCPF, but the difference between cirrhotics and controls was not significant. A decrease in the suppressor/cytotoxic (T8) phenotype of lymphocytes in the peripheral blood and an increase in the ratio of helper/inducer (T4) and T8 lymphocytes was seen in patients with NCPF and cirrhosis. Although these results indicate definite immunological abnormalities in NCPF patients, their role in the pathogenesis of NCPF remains to be investigated.

Measurement and correlation of wedged hepatic, intrahepatic, intrasplenic and intravariceal pressures in patients with cirrhosis of liver and non-cirrhotic portal fibrosis.

In order to examine the relationship of various haemodynamic parameters in two different liver diseases, 10 patients with cirrhosis of liver and 14 patients with non-cirrhotic portal fibrosis were studied. In cirrhotics, mean (+/- SD) wedged hepatic (25.8 +/- 6.4 mmHg), intrahepatic (24.5 +/- 6.2 mmHg) and intrasplenic (25.0 +/- 5.6 mmHg) pressures correlated significantly (p less than 0.001) with intravariceal (25.2 +/- 6.7) pressure measurements. In patients with NCPF, mean (+/- SD) wedged hepatic (9.1 +/- 3.7 mmHg) and intraphepatic (15.4 +/- 5.8 mmHg) pressures were significantly (p less than 0.01) lower than the intrasplenic (24.5 +/- 4.2 mmHg) and intravariceal (23.96 +/- 5.6 mmHg) pressures. Two independent pressure gradients, one between intrasplenic and intrahepatic pressure (8.9 +/- 6.5 mmHg) and another between intrahepatic and wedged hepatic venous pressure (6.2 +/- 5.6 mmHg) were seen in non-cirrhotic portal fibrosis patients, indicating the likelihood of both pre- and perisinusoidal resistance to flow of portal venous blood in these patients. A highly significant (p less than 0.001) correlation between intravariceal and intrasplenic pressures was found in patients with cirrhosis of liver (r = 0.93), as well as in patients with non-cirrhotic portal fibrosis (r = 0.85). No correlation was found between the size of oesophageal varices and wedged hepatic and intrahepatic pressures. Patients with grade 4 varices had significantly higher intravariceal (p less than 0.01) and intrasplenic (p less than 0.05) pressure than patients with grade 2 varices. It can be concluded that intravariceal pressure is representative of portal pressure in patients with cirrhosis of liver as well as in non-cirrhotic portal fibrosis patients and it can be recommended as the single haemodynamic investigation in patients with portal hypertension and oesophageal varices.

The use of two‐dimensional contrast echocardiography in patients with portal hypertension for the detection of cardiac chamber abnormalities and pulmonary arteriovenous shunts

To study the cardiac chamber abnormalities and presence of pulmonary arteriovenous shunts in patients with non‐cirrhotic portal fibrosis (NCPF), two‐diemensional echocardiography was carried out in 14 patients. Eleven patients with cirrhosis of the liver and seven patients with extrahepatic obstruction were also studied. No patient had organic heart disease, clinical cyanosis, significant anaemia, or features of hepatic decompensation. Significant enlargement of left atrial, left ventricular and right ventricular chambers was seen in 64%, 57% and 14% of NCPF patients, respectively. There was, however, no significant difference in the frequency of cardiac chamber enlargement in patients with NCPF compared with the other two groups of patients. Though reduced left ventricular ejection fraction (&lt; 60% normal) was more commonly seen in patients with NCPF (35.7%) than in patients with cirrhosis (18.2%), the difference was not significant. No patient with extrahepatic obstruction had reduced ejection fraction. Except for one patient with cirrhosis, echocardiography with saline infusion failed to reveal intrapulmonary shunts in any patient. It is concluded that cardiac chamber abnormalities were seen in a significant proportion of patients with NCPF, but, none of them showed pulmonary arteriovenous shunts as studied by contrast echocardiography.