Clinical and laboratory differentiation of cirrhosis and extrahepatic portal venous obstruction in children

BACKGROUND AND AIM: Differentiation between cirrhosis and extrahepatic portal venous obstruction (EHPVO) in children presenting with features of portal hypertension is important for cost-effective management and proper resource utilization. We undertook this study to differentiate clinical and laboratory features between these two groups of patients. METHODS: Clinical features and laboratory parameters at presentation of children with portal hypertension and cirrhosis of the liver were analyzed. The variables analyzed were age at presentation, duration of symptoms, incidence and frequency of upper gastrointestinal (GI) bleeding, encephalopathy, jaundice, ascites, splenomegaly, and presence of dilated abdominal veins. The laboratory parameters studied were hemoglobin, prothrombin time, serum bilirubin, albumin, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase. Two groups were compared using appropriate statistical methods; and the differentiating features were analyzed using logistic regression analysis. RESULTS: Of the total of 120 cases, cirrhosis was diagnosed in 28.3% and EHPVO in 71.6%. Children with EHPVO, in comparison to cirrhosis, had significantly higher frequency of upper GI bleeding (61.6%vs 14.7%), increased number of previous bleeding episodes (2.7 +/- 0.5 vs 1.2 +/- 0.4), longer duration of symptoms (25.7 +/- 4.6 vs 12.3 +/- 3 months) and a lower frequency of jaundice (2%vs 76.4%). Low hemoglobin (6.4 +/- 2.7 g/dL) and preserved liver functions characterized by normal bilirubin, albumin levels and prothrombin time were observed in EHPVO cases. Cirrhosis patients had higher hemoglobin (8.8 +/- 2.8 g/dL) and abnormal liver function tests. CONCLUSION: Presence of UGI bleeding and the absence of jaundice are 97.5% accurate in predicting diagnosis of EHPVO.     

Consensus on extra-hepatic portal vein obstruction.

The Asian Pacific Association for the Study of the Liver (APASL) had set up a working party on portal hypertension in 2002 with a mandate to develop consensus on various aspects of portal hypertension. The first of these consensuses has been developed on extra-hepatic portal vein obstruction (EHPVO). It was discussed and prepared by the experts in this field from the Asian region and was presented at the annual meeting of the APASL, at Bali in August 2005. This article summarizes all the consensus statements approved by the APASL on various aspects of EHPVO.     

Portographic changes with time in patients with extrahepatic portal venous obstruction

Portographic changes of successive splenoportovenograms in 27 patients with extrahepatic portal venous obstruction (EHPO) over a mean period of 27 months have been studied. No extension of the portal vein thrombus was observed either in 20 patients with EHPO who had variceal obliteration by endoscopic sclerotherapy or in the 12 patients who remained without treatment for a mean period of 33.4 months (five of them were later subjected to sclerotherapy). There was no evidence of spread of thrombosis in the portal veins with time.     

Fifteen-year follow up of endoscopic injection sclerotherapy in children with extrahepatic portal venous obstruction

BACKGROUND AND AIM: Endoscopic sclerotherapy has emerged as an effective treatment for bleeding esophageal varices both in adults and children but the long-term outcome is poorly defined in children. The authors report a 15-year follow up of sclerotherapy in children with extrahepatic portal venous obstruction. METHODS: Between June 1982 and February 1992, 69 children with bleeding esophageal varices underwent sclerotherapy; variceal eradication was achieved in 63 (91.3%) patients, with procedure-related morbidity of 28.9% and mortality of 1.4%. Fifty-nine patients with variceal eradication were followed for between 10.4 and 20.1 years (mean, 15.1 +/- 3.1 years). RESULTS: After a median period of 3 years (range, 1.2-12.8 years), seven (11.9%) patients presented with recurrent bleeding (esophageal varices, four; gastric varices, two; and duodenal ulcer, one). Recurrent bleeding occurred in six of seven (85.7%) patients within the first 4 years of initial variceal eradication. Esophageal varices recurred in eight (13.6%) patients. Five of the seven patients with recurrent bleeding and all eight with recurrent varices were effectively treated with further sclerotherapy. Two patients with gastric variceal bleeding unresponsive to sclerotherapy underwent shunt surgery. Elective surgery was required in eight additional patients for reasons other than recurrent varices or bleeding. CONCLUSIONS: The authors conclude that (i) sclerotherapy is the ideal, safe and effective treatment for bleeding esophageal varices, that it prevented bleeding in 88.1% patients after variceal eradication and hence, should be included in primary management strategies; (ii) follow-up endoscopy should be performed on a yearly basis for the first 4 years after variceal eradication; and (iii) surgery is required as a complementary technique for patients with uncontrolled bleeding, painful splenomegaly, growth retardation and symptomatic portal biliopathy.     

Rectal varices in extrahepatic portal hypertension

Abstract Rectal varices, as distinct from haemorrhoids, occur due to high pressure in the inferior mesenteric venous system in patients with portal hypertension. The exact prevalence of rectal varices in extrahepatic portal hypertension is unknown. To determine this, 116 patients with extrahepatic portal hypertension were studied for the presence of rectal varices. These lesions were found in 103 (88.8%) patients. Bleeding from rectal varices occurred in 14.6% of patients. Massive bleeding requiring hospitalization and blood transfusion was not encountered. It is concluded that rectal varices are common in extrahepatic portal hypertension. Bleeding from them is uncommon, and often mild and self-limiting. The available literature is reviewed and the importance of recognizing the condition stressed.     

Frequency of gastropathy and gastric varices in children with extrahepatic portal venous obstruction treated with sclerotherapy

BACKGROUND: There are limited reports of the effect of endoscopic sclerotherapy (EST) on portal hypertensive gastropathy (PHG) and gastric varices (GV) in children with extrahepatic portal venous obstruction (EHPVO). We have studied the prevalence of PHG and GV in children with EHPVO and assessed the effect of EST on them on long-term follow-up. METHODS: From January 1992 to June 2002, consecutive children presenting with variceal bleeding due to EHPVO were included in this study. All children underwent EST at presentation and at 2-3 week intervals thereafter. During each session of endoscopy, gastric mucosa and fundus of the stomach was screened carefully to detect PHG and GV. Gastric varices were classified as gastroesophageal (GOV) and isolated gastric varices (IGV). RESULTS: In total, 274 cases of EHPVO were managed during the study period. The mean age was 7.4 +/- 3.5 years with a male to female ratio of 2.3:1. Of these 274 cases, 186 completed the EST program (study population), 60 were lost to follow-up, five died and 23 underwent surgery. At presentation (n = 274) 27% cases had PHG (3.6% severe) and 68.6% had GV (GOV 66.8%, IGV 1.8%). Following EST (n = 186) there was a significant (P < 0.001) decrease in GOV (45% from 64%) but an increase in IGV (14% from 1%) and PHG (51.6% from 24.7%).There was also a significant increase in severe PHG (15.6% from 3.2%, P < 0.05). On follow-up (mean follow-up 38 +/- 30 months) 19% children with IGV bled while none with PHG bled. CONCLUSIONS: Portal hypertensive gastropathy and gastric varices are quite common in children with EHPVO. Following EST, there is a chance of developing isolated gastric varices.     

Meso-Rex bypass for the management of extrahepatic portal vein obstruction in adults (with video)

Background:Extrahepatic portal vein obstruction(EHPVO)results in severe portal hypertension(PHT)leading to severely compromised quality of life.Often,pharmacological and endoscopic management is unable to solve this problem.Restoring hepatic portal flow using meso-Rex bypass(MRB)may solve it.This procedure,uncommon in adult patients,is considered the treatment of choice for EHPVO in children.Methods:From 1997 to 2018,8 male and 6 female adults,with a median age of 51 years(range 22-66)underwent MRB procedure for EHPVO at the University Hospitals Saint-Luc in Brussels,Belgium.Symp-toms of PHT were life altering in all but one patient and consisted of repetitive gastro-intestinal bleedings,sepsis due to portal biliopathy,and/or severe abdominal discomfort.The surgical technique consisted in interposition of a free venous graft or of a prosthetic graft between the superior mesenteric vein and the Rex recess of the left portal vein.Results:Median operative time was 500 min(range 300-730).Median follow-up duration was 22 months(range 2-169).One patient died due to hemorrhagic shock following percutaneous transluminal interven-tion for early graft thrombosis.Major morbidity,defined as Clavien-Dindo score≥III,was 35.7%(5/14).Shunt patency at last follow-up was 64.3%(9/14):85.7%(6/7)of pure venous grafts and only 42.9%(3/7)of prosthetic graft.Symptom relief was achieved in 85.7%(12/14)who became asymptomatic after MRB.Conclusions:Adult EHPVO represents a difficult clinical condition that leads to severely compromised quality of life and possible life-threatening complications.In such patients,MRB represents the only and last resort to restore physiological portal vein flow.Although successful in a majority of patients,this procedure is associated with major morbidity and mortality and should be done in tertiary centers expe-rienced with vascular liver surgery to get the best results.     

Comparative efficacy of emergency endoscopic sclerotherapy for active variceal bleeding due to cirrhosis of the liver, non-cirrhotic portal fibrosis and extrahepatic portal venous obstruction

Patients with continued variceal bleeding due to portal hypertension (n = 202) were treated by endoscopic injection sclerotherapy after resuscitation. Portal hypertension was due to hepatic cirrhosis in 123, non-cirrhotic portal fibrosis (NCPF) in 49 and extrahepatic portal venous obstruction (EHO) in 30 patients. Polidocanol 1% was injected intravariceally. An adequate sclerotherapy was carried out in 97% of patients. Immediate haemostasis was achieved in 177 (88%) patients. Rebleeding occurred in 31 (17.5%) of 177 patients. By reinjection of varices, definitive control of bleeding occurred in 160 (79%) patients. There was no significant difference in terms of immediate control of bleeding in patients with different aetiologies of portal hypertension and hepatic functional status (Child's grade). Rebleeding episodes were lower in patients with EHO than cirrhosis of the liver and NCPF. Similarly, the Child's status significantly influenced the recurrence of bleeding which was lower in Child's A than B and B than C. The in-hospital mortality was 18.6%. This was also significantly related to Child's status and aetiology of portal hypertension. Minor complications occurred in 10.4% of patients. It is concluded that endoscopic sclerotherapy as the first line of treatment is an effective and technically feasible procedure for the control of active variceal bleeding, regardless of the cause of portal hypertension. Furthermore, the results were influenced by the aetiology of portal hypertension and hepatic functional status.     

Percutaneous transhepatic catheterization of the portal venous system

During recent years, percutaneous transhepatic catheterization of the portal venous system has become the most accurate procedure for investigation of the portal system. The procedure can be performed under local analgesia, is relatively simple, and complications are rare. The success rate is high, approximately 90%, especially when the liver hilum is localized by ultrasonography prior to catheterization. The free portal pressure can be measured. Selective catheterization of all portal tributaries can be performed. The indications are: portography in patients with cirrhosis of the liver and portal hypertension for delineation of collateral vein systems including gastro-oesophageal varices; visualization of veins that may be used for portosystemic shunt operations; postoperative control of shunt patency; diagnosis of portal and hepatic vein thrombosis; localization of stenosis in the portal vein system; pre-operative evaluation of patients with tumours in the biliary tract and pancreas; obliteration of bleeding oesophageal varices; and verification and localization of endocrine pancreatic tumours making curative resection possible. Further, transhepatic catheterization of the portal system may be used in research on the development of portal hypertension, collateral veins, variceal bleeding, and for haemodynamic, metabolic and pharmacologic studies in the gastrointestinal tract.     

Study of portal vein thrombosis in patients with idiopathic portal hypertension in Japan.

BACKGROUND/AIMS: The aim of this study was to elucidate the incidence and clinical manifestations of portal vein thrombosis (PVT) in patients with idiopathic portal hypertension (IPH) in Japan during long-term follow-up. PATIENTS AND METHODS: Twenty-two patients with IPH were examined for PVT by sonography during a follow-up of 12+/-6 years. Clinical manifestations and patient outcome related to PVT were studied. Seventy patients with liver cirrhosis were examined by sonography as an incidence control of thrombosis. RESULTS: Nine IPH patients had portal thrombosis (9/22, 41%), a higher incidence than in liver cirrhosis patients (7/70, 10%). Those with thrombosis showed ascites, marked hypersplenism, and low serum albumin. Four patients with thrombosis died. Patients without thrombosis showed less clinical problems after long-term follow-up. Plasma antithrombin III and protein C activity decreased in almost half of the patients. However, there were no differences in these parameters between patients with and without thrombosis. CONCLUSIONS: In Japan, IPH patients had a high incidence of portal thrombosis, a significant factor for poor prognosis. Whether the management of PVT contributes to an improvement of a clinical course of IPH or not should be clarified in further study.     

Hepatic hemodynamics in 24 patients with nodular regenerative hyperplasia and symptomatic portal hypertension

Background and Aim: To evaluate hepatic hemodynamics in patients with nodular regenerative hyperplasia of the liver (NRH) with portal hypertension (PHT). Methods: We retrospectively reviewed the charts of 24 patients referred for PHT related to biopsy‐proven NRH. Hemodynamic measurements included wedged hepatic vein (WHVP) and inferior vena cava (IVCP), and, in 12 patients, portal vein pressure (PVP). Hepatic vein pressure gradient (HVPG: WHVP–IVCP) and portal vein pressure gradient (PVPG: PVP–IVCP) were calculated. Results: Nodular regenerative hyperplasia was associated in 24 patients with various diseases (oxaliplatin chemotherapy, treatment with purine antagonists, post liver transplantation, hematologic and rheumatologic conditions and HIV infection). Liver function parameters were either completely normal or slightly impaired. Patients were referred for gastroesophageal varices (n = 18), and/or ascites (n = 11), and/or splenomegaly (n = 20). In patients with varices or ascites, HVPG was lower than 10 mmHg (a cut‐off point for the presence of varices and/or ascites) in 15/21, suggesting a pre‐sinusoidal component to their PHT confirmed by a PVP higher than 12 mmHg in 12/12 patients. The mean difference between HVPG and PVPG was 8.7 mmHg in these patients. Ten patients were treated by transjugular intrahepatic portosystemic shunt. None of them re‐bled, and one presented transient hepatic encephalopathy. Conclusions: Presinusoidal PHT associated with NRH is probably related to compression of portal venules by the regenerative nodules. In patients with HTP and a HVPG < 10 mmHg, the diagnosis of NRH must be suspected and PVP measured, which is important in the management of these patients.     

Captopril reduces portal pressure effectively in portal hypertensive patients with low portal venous velocity

Background The effect of an angiotensin II blockade in lowering the portal pressure in patients with liver cirrhosis and portal hypertension is controversial. This prospective study was undertaken to evaluate the portal hypotensive effect of captopril compared to that of propranolol, and to determine the factors that contribute to a successful reduction in the portal pressure after longterm captopril administration in patients with liver cirrhosis.Methods The hepatic venous pressure gradient (HVPG) and portal venous velocity (PVV) were measured both before and 3 months after initiation of the administration of captopril (n = 29) or propranolol (n = 29) in cirrhotic patients with a variceal bleeding episode. Patients who showed a reduction in the HVPG of more than 20% of the baseline were defined as being responders.Results At 3 months, the mean reduction in the HVPG after captopril was less than that after propranolol (–3.0 ± 9.3% vs –28.5% ± 4.1%; P 0.05). However, of the 29 patients receiving captopril, 9 were classified as being responders. On multivariate analysis with parameters including age, cause, Child-Pugh score, HVPG, and PVV, only low PVV was found to be a significant independent factor for responders (PVV 12cm/s; odds ratio [OR], 12.2; 95% confidence interval [CI], 1.47–102.40) in the captopril group.Conclusions Longterm captopril administration reduces the portal pressure effectively in cirrhotic patients with a low PVV. This suggests that the reduction in portal pressure after captopril administration is a result of improved portal venous outflow brought about by a decrease in the intrahepatic vascular resistance. When the PVV is below 12cm/s, a captopril trial might be useful in preventing variceal bleeding in portal hypertensive patients.Part of this work has appeared in abstract form, in J Hepatol 2002;36 (Suppl 1):64     

Systemic and pulmonary hemodynamics in patients with extrahepatic portal vein obstruction is similar to compensated cirrhotic patients

Background  Patients with cirrhosis and portal hypertension exhibit a hyperdynamic circulation manifesting as increased cardiac output, heart rate and plasma volume; and decreased arterial blood pressure, systemic vascular resistance, and pulmonary vascular resistance. It is believed that these changes are related to both hepatocellular dysfunction and portal hypertension. However, the role of portal hypertension per se in producing these changes in circulation has not been clear. Extrahepatic portal vein obstruction (EHPVO), a vascular disorder of the liver characterized by cavernomatous transformation of the main portal vein, is an excellent model to study the role of portal hypertension per se in producing these changes because there is no hepatic dysfunction in EHPVO. The main aim of our study was, therefore, to evaluate alterations of systemic and pulmonary vascular systems in patients with EHPVO and compare them with patients with compensated cirrhosis. Patients and methods  Consecutive patients of EHPVO, 15 years or older, and past variceal bleeders were studied. For comparison, consecutive patients with compensated cirrhosis and history of variceal bleed, matched for variceal status, and body surface area were included. The hemodynamic studies included the measurements of cardiac index (by Fick’s oxygen method), and systemic and pulmonary vascular resistance indices. Results  Fifteen patients of EHPVO and same number of controls (compensated cirrhotics) were included in the study. The baseline parameters in the two groups were comparable. Both EHPVO patients and cirrhotics had similar values in all the measured systemic and pulmonary hemodynamic parameters. The median (range) cardiac index in EHPVO was 3.8 (2.3–7.7) l min⁻¹ m⁻², whereas it was 4.4 (2.8–8.9) l min⁻¹ m⁻² in cirrhosis (P = 0.468). The median (range) systemic vascular resistance index in EHPVO was 1,835 (806–3400) dyne s cm⁻⁵ m⁻², which was similar to that in cirrhotic patients (1,800 [668–3022], P = 0.520). Similarly, the values of median (range) pulmonary vascular resistance index were comparable in the two groups (71 [42–332] vs. 79 [18–428], P = 0.885). A subgroup analysis was done for 8 patients of EHPVO and 8 age-matched compensated cirrhotic patients, which also revealed similar values of cardiac index, cardiac output, systemic vascular resistance index, systemic vascular resistance, pulmonary vascular resistance index, and pulmonary vascular resistance in the two groups. Conclusions  EHPVO patients have hyperdynamic circulation manifested by high cardiac index and low systemic and pulmonary vascular resistance indices. These hemodynamic changes are comparable with compensated cirrhotic patients who have similar grade of portal hypertension. This suggests a predominant role of portal hypertension per se in the genesis of systemic and pulmonary hemodynamic alterations.     

Prognosis in patients with cirrhosis and mild portal hypertension

Objective. Sixty to 70% of upper gastrointestinal bleeding episodes in patients with cirrhosis are caused by oesophageal varices. Prophylaxis is indicated in patients with varices and a hepatic venous pressure gradient (HVPG) above 12 mmHg. The study of the natural history of patients with lower HVPG has been sparse. In this study, long-term survival and the risk of complications in mild portal hypertension were analysed. Material and methods. Sixty-one patients with cirrhosis and HVPG below 10 mmHg were included in the study. Data were collected from medical files and National Patient Registries. Variceal bleeding, hepatic encephalopathy and death related to cirrhosis were registered. Thirty-nine patients were graded as Child class A, 19 as class B and 3 as class C. Median survival time was 11 years. Results. Twenty-eight patients (46%) developed one or more complications: variceal bleeding in 10 (16%) and hepatic encephalopathy in 18 patients (30%). Twenty-three patients (38%) died from complications of cirrhosis. Two patients (3%) died from variceal bleeding, another two (3%) from gastrointestinal bleeding of unidentified source. Survival rate was significantly decreased compared with that in the background population. Conclusions. The frequency of complications in patients with mild portal hypertension is considerable, and guidelines for follow-up or medical prophylaxis are warranted. The risk of bleeding from oesophageal varices is low and bleeding-related deaths rare.