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.     

Correlation of hepatic venous pressure gradient with variceal bleeding, size of esophageal varices, etiology, ascites and degree of liver dysfunction in cirrhosis of liver

An elevated hepatic venous pressure gradient (HVPG) has been associated with risk of variceal bleeding, and outcome and survival after variceal bleeding. In this pilot study, we measured HVPG in 40 patients with liver cirrhosis and studied its relationship with etiology of liver disease, esophageal variceal size, history of variceal bleeding or ascites, biochemical liver tests and Child-Pugh class. There was no procedurerelated complication. The mean (SD) HVPG was similar in patients who had history of variceal bleeding as compared to those who did not (15.4 [2.8] mmHg vs. 13.9 [2.7] mmHg, p=0.1); HVPG had no significant association with etiology of cirrhosis (p=0.4). HVPG levels were significantly higher in patients with larger esophageal varices (grade III/IV vs. I/II: 15.2 [2.7] mmHg vs.13.1 [2.8] mmHg, p=0.04), poorer Child-Pugh class (B or C versus A), and presence of ascites (p=0.04). Thus, HVPG correlated with variceal size, Child-Pugh class, and presence of ascites, but not with variceal bleeding status.     

Use of portal pressure studies in the management of variceal haemorrhage

Portal hypertension occurs as a complication of liver cirrhosis and complications such as variceal bleeding lead to significant demands on resources. Endoscopy is the gold standard method for screening cirrhotic patients however universal endoscopic screening may mean a lot of unnecessary procedures as the presence of oesophageal varices is variable hence a large time and cost burden on endoscopy units to carry out both screening and subsequent follow up of variceal bleeds. A less invasive method to identify those at high risk of bleeding would allow earlier prophylactic measures to be applied. Hepatic venous pressure gradient (HVPG) is an acceptable indirect measurement of portal hypertension and predictor of the complications of portal hypertension in adult cirrhotics. Varices develop at a HVPG of 10-12 mmHg with the appearance of other complications with HPVG > 12 mmHg. Variceal bleeding does not occur in pressures under 12 mmHg. HPVG > 20 mmHg measured early after admission is a significant prognostic indicator of failure to control bleeding varices, indeed early transjugular intrahepatic portosystemic shunt (TIPS) in such circumstances reduces mortality significantly. HVPG can be used to identify responders to medical therapy. Patients who do not achieve the suggested reduction targets in HVPG have a high risk of rebleeding despite endoscopic ligation and may not derive significant overall mortality benefit from endoscopic intervention alone, ultimately requiring TIPS or liver transplantation. Early HVPG measurements following a variceal bleed can help to identify those at risk of treatment failure who may benefit from early intervention with TIPS. Therefore, we suggest using HVPG measurement as the investigation of choice in those with confirmed cirrhosis in place of endoscopy for intitial variceal screening and, where indicated, a trial of B-blockade, either intravenously during the initial pressure study with assessment of response or oral therapy with repeat HVPG six weeks later. In those with elevated pressures, primary medical prophylaxis could be commenced with subsequent close monitoring of HVPG thus negating the need for endoscopy at this point. All patients presenting with variceal haemorrhage should undergo HVPG measurement and those with a gradient greater than 20 mmHg should be considered for early TIPS. By introducing portal pressure studies into a management algorithm for variceal bleeding, the number of endoscopies required for further intervention and follow up can be reduced leading to significant savings in terms of cost and demand on resources.     

Pharmacological reduction of portal pressure and long-term risk of first variceal bleeding in patients with cirrhosis

OBJECTIVES: A reduction in hepatic venous pressure gradient (HVPG) of > or =20% of baseline or to < or =12 mmHg (responders) is associated with a reduced risk of first variceal bleeding. The aim of this study was to evaluate whether this protective effect is maintained in the long term and if it extends to other portal hypertension complications. METHODS: Seventy-one cirrhotic patients with esophageal varices and without previous variceal bleeding who entered into a program of prophylactic pharmacological therapy and were followed for up to 8 yr were evaluated. All had two separate HVPG measurements, at baseline and after pharmacological therapy with propranolol +/- isosorbide mononitrate. RESULTS: Forty-six patients were nonresponders and 25 were responders. Eight-year cumulative probability of being free of first variceal bleeding was higher in responders than in nonresponders (90% vs 45%, p= 0.026). The lack of hemodynamic response and low platelet count were the only independent predictors of first variceal bleeding. Additionally, reduction of HVPG was independently associated with a decreased risk of spontaneous bacterial peritonitis (SBP) or bacteremia. No significant differences in the development of ascites, hepatic encephalopathy, or survival were observed. CONCLUSIONS: The hemodynamic response in cirrhotic patients is associated with a sustained reduction in the risk of first variceal bleeding over a long-term follow-up. Reduction of HVPG also correlate with a reduced risk of SBP or bacteremia.     

Perendoscopic variceal pressure measurement: A reliable estimation of portal pressure in patients with cirrhosis?

OBJECTIVES: In patients with cirrhosis, the hepatic venous pressure gradient (HVPG) is the reference method for the assessment of portal hypertension (PHT). Variceal pressure (VP) may be measured at endoscopy, but its relationship to the HVPG remains controversial. The aim of the study was to retrospectively compare HVPG and VP values obtained in a cohort of patients with cirrhosis and PHT. METHODS: Within 8 days (range: 6-10 days), 64 patients in a stable condition with biopsy-proven cirrhosis [alcoholic: 47; other 17; mean age: 56.5 yrs (35-70); mean Child-Pugh's score: 9.4 +/- 1.9; ascites: 37/64; previous variceal bleeding (="bleeders"): 24/64) and oesophageal varices (grade 2: 49; grade 3: 15)] underwent both measurement of the HVPG during transjugular liver biopsy and VP at endoscopy using a "home made" pressure sensitive gauge in the absence of needle puncture of the varix. Alcoholic hepatitis was present in 28 patients with alcoholic cirrhosis. RESULTS: The pressure sensitive gauge was well tolerated. The mean HVPG and VP values were 18.5 +/- 3.4 mmHg and 19 +/- 3.7 mmHg, respectively. A significant difference was observed between "bleeders" (n=24) and non "bleeders" (n=40) in terms of VP values (21.4 +/- 3.3 vs 17.2 +/- 3.2 mmHg, P<0.001), but not for HVPG values (19.4 +/- 4.1 vs 17.9 +/- 2.8 mmHg, P=0.075). A positive correlation was observed between VP and HVPG values (r=0.62, P<0.0001). CONCLUSIONS: In this group of patients with cirrhosis and oesophageal varices, a "home-made" pressure sensitive gauge allowed a non invasive perendoscopic measurement of VP. The positive correlation between VP and HVPG values suggests that measurement of VP may be a reliable estimate of portal pressure in these patients.     

Prognostic usefulness of hepatic vein catheterization in patients with cirrhosis and esophageal varices.

Clinical and anamnestic data, Pugh score, and size of esophageal varices were obtained in 129 cirrhotics. Hepatic vein catheterization was performed to measure hepatic venous pressure gradient (HVPG), indocyanine green (ICG) intrinsic hepatic clearance, and hepatic plasma flow. During a follow-up period of up to 60 months, 44 patients experienced gastrointestinal bleeding and 54 died. Applying Cox regression analysis, ICG intrinsic hepatic clearance, Pugh score, previous variceal bleeding, and HVPG were the only significant prognostic determinants of survival. In addition, Cox's regression analysis showed that HVPG, Pugh score, size of varices, and previous variceal bleeding all contained significant prognostic information regarding risk of gastrointestinal bleeding. The models were validated using a split-sample technique, and prognostic indexes for death and gastrointestinal bleeding were calculated. The prognostic index predicting death had significantly improved prognostic accuracy over a prognostic index calculated excluding the data obtained from hepatic vein catheterization (P less than 0.05). In conclusion, prognostic accuracy in cirrhosis with portal hypertension is significantly improved by information obtained from hepatic vein catheterization.     

Intrahepatic heterogeneity of hepatic venous pressure gradient in human cirrhosis

BACKGROUND: The hepatic venous pressure gradient (HVPG) is used to evaluate portal hypertension. METHODS: We measured HVPG in two separate liver veins in 169 liver vein catheterizations in 102 cirrhosis patients and in 27 patients with no liver disease (controls). RESULTS: In the controls, the two measurements differed by 0.0 +/- 1.8 mmHg (mean +/- s, n = 27), upper 95% confidence limit 3.6 mmHg (mean + 2 s). HVPG ranged from -0.1 to 8.3 mmHg, upper 95% confidence limit 6.7 mmHg. In cirrhosis, the two measurements agreed within +/- 3.6 mmHg in 39%. In 61%, the measurements differed by 4-34 mmHg. In 35%, fluoroscopy demonstrated hepatic vein-to-hepatic-vein shunting in veins with low HVPG values. In some patients with HVPG measurements above 30 mmHg, Doppler ultrasound examination showed arterialization of the hepatic vasculature. DISCUSSION: Our results demonstrate a hitherto unrecognized notable heterogeneity of the intrahepatic vasculature and HVPG measurements in cirrhosis. The presumption of interposition of non-flowing blood between the catheter tip and the portal system for the measurement of HVPG may thus be violated in about one-third of the cirrhosis cases because of abnormal outlet into hepatic venous shunts and in a minor fraction because of abnormal arterial inlet. In 26%, one measurement was below 12 mmHg, the other measurement above. If the HVPG had been measured in only one liver vein, 13% of the cases would have been classified in a lower risk group than appropriate according to the 12 mmHg concept of risk of bleeding from oesophageal varices.     

Hepatic venous pressure gradient determination in patients with hepatitis C virus-related and alcoholic cirrhosis

OBJECTIVES: Few data exist regarding the degree of portal hypertension in hepatitis C virus (HCV)-related cirrhosis, as the majority of studies have included mainly patients with alcoholic cirrhosis. This study was aimed at comparing the severity of portal hypertension in patients with HCV-related or alcoholic cirrhosis. METHODS: In total, 59 cirrhotic patients with portal hypertension (HCV-related in 34 cases and alcoholic in 25) underwent main right hepatic vein catheterization, with determination of the wedged and free hepatic venous pressures, and of hepatic venous pressure gradient (HVPG). RESULTS: HVPG values did not differ between the two groups of patients (19.4 +/- 6.0 mmHg vs 18.5 +/- 3.5 mmHg; P = 0.51). The prevalence and degree of oesophageal and gastric varices and portal hypertensive gastropathy did not correlate with the aetiology. Patients with viral cirrhosis had a lower prevalence of previous bleeding than those with alcoholic cirrhosis, despite a similar proportion of large varices in the two groups and similar HVPG levels. In both groups of patients, HVPG did not differ between patients with previous bleeds and those without. CONCLUSIONS: The degree of portal hypertension in cirrhotic patients does not correlate with the cause of the disease. Thus, current statements on the management of portal hypertension, although based upon studies including mainly patients with alcoholic cirrhosis, can be applied also to patients with viral-related cirrhosis.     

Intrahepatic Heterogeneity of Hepatic Venous Pressure Gradient in Human Cirrhosis

Background: The hepatic venous pressure gradient (HVPG) is used to evaluate portal hypertension. Methods: We measured HVPG in two separate liver veins in 169 liver vein catheterizations in 102 cirrhosis patients and in 27 patients with no liver disease (controls). Results: In the controls, the two measurements differed by 0.0 ± 1.8 mmHg (mean ± s , n = 27), upper 95% confidence limit 3.6 mmHg (mean + 2 s ). HVPG ranged from-0.1 to 8.3 mmHg, upper 95% confidence limit 6.7 mmHg. In cirrhosis, the two measurements agreed within ± 3.6 mmHg in 39%. In 61%, the measurements differed by 4-34 mmHg. In 35%, fluoroscopy demonstrated hepatic vein-to-hepatic-vein shunting in veins with low HVPG values. In some patients with HVPG measurements above 30 mmHg, Doppler ultrasound examination showed arterialization of the hepatic vasculature. Discussion: Our results demonstrate a hitherto unrecognized notable heterogeneity of the intrahepatic vasculature and HVPG measurements in cirrhosis. The presumption of interposition of non-flowing blood between the catheter tip and the portal system for the measurement of HVPG may thus be violated in about one-third of the cirrhosis cases because of abnormal outlet into hepatic venous shunts and in a minor fraction because of abnormal arterial inlet. In 26%, one measurement was below 12 mmHg, the other measurement above. If the HVPG had been measured in only one liver vein, 13% of the cases would have been classified in a lower risk group than appropriate according to the 12 mmHg concept of risk of bleeding from oesophageal varices.     

Hepatic venous pressure gradient measurement: Time to learn!

Portal hypertension is a clinical syndrome defined by a pathological increase in portal pressure. The development of cirrhosis of the liver is characterized by clinical manifestations related to portal hypertension like esophageal varices, ascites, bleeding, and encephalopathy. Direct measurement of portal pressure is invasive, inconvenient, and clinically impractical. Currently, the most commonly used parameter is the Hepatic Venous Pressure Gradient (HVPG), i.e., the difference between the wedged (WHVP) and the free hepatic venous pressures. HVPG represents the gradient between pressures in the portal vein and the intra-abdominal portion of inferior vena cava. When blood flow in a hepatic vein is stopped by a wedged catheter, the proximal static column of blood transmits the pressure from the preceding communicated vascular territory (hepatic sinusoids) to the catheter. Thus, WHVP reflects hepatic sinusoidal pressure and not the portal pressure itself. In the normal liver, due to pressure equilibration through interconnected sinusoids, wedged pressure is slightly lower than portal pressure, though this difference is clinically insignificant. In liver cirrhosis, the static column created by balloon inflation cannot be decompressed at the sinusoidal level due to disruption of the normal intersinusoidal communications; therefore, WHVP gives an accurate estimation of portal pressure in cirrhosis. The normal HVPG value is between 1 to 5 mmHg. Pressure higher than this defines the presence of portal hypertension, regardless of clinical evidence. HVPG >/= 10 mmHg (termed clinically significant portal hypertension) is predictive of the development of complications of cirrhosis, including death. HVPG above 12 mmHg is the threshold pressure for variceal rupture. The main advantages of HVPG are its simplicity, reproducibility, and safety. This review summarizes the technique of the HVPG measurement.     

New angiotensin II type 1 receptor blocker olmesartan improves portal hypertension in patients with cirrhosis

Aim: To evaluate the effect of the new oral angiotensin II type 1 receptor blocker olmesartan on portal hemodynamics in patients with cirrhosis. Methods: From January 2005 to March 2006, 18 cirrhosis patients treated with endoscopic band ligation for primary esophageal variceal bleeding were included in the present study. Hepatic venous pressure gradient (HVPG) of the patients was >/=12 mmHg at baseline measurement. The patients were given 10 mg olmesartan orally once daily for 2 weeks. Eighteen cirrhosis patients with esophageal variceal bleeding who did not receive any antihypertensive agents were included in the study as control. On day 14, HVPG, blood pressure, heart rate, and parameters of hepatic and renal function were examined after the treatment. Responders were defined as those with HVPG reduction of >20% versus baseline. Results: Olmesartan significantly reduced HVPG by -16.8 +/- 22.0% (P = 0.031) and mean arterial pressure by -13.1 +/- 10.8% (P = 0.0041). Six of 18 (33.3%) patients in the olmesartan group showed >20% reduction of HVPG from baseline values. None of the patients treated with olmesartan had any complications. Conclusion: Olmesartan reduces portal pressure and may be safe and highly effective in the treatment of portal hypertension.     

A cost-effectiveness study of hepatic venous pressure gradient measurement in the secondary prevention of variceal bleeding

OBJECTIVE: variceal rebleeding is common following a first episode of hemorrhage in cirrhotic patients. The objective of this study was to determine the cost-effectiveness of monitoring hepatic venous pressure gradient (HVPG) to guide secondary prophylaxis. METHODS: we created a Markov decision model to calculate cost-effectiveness for two strategies: Group 1: HVPG monitoring to decide treatment -when portal pressure was reduced by at least 20 percent or HVPG was less than 12 mmHg after beta-blocker administration, patients received beta-blockers; when portal pressure did not meet these criteria therapy was endoscopic band ligation. Group 2: in this group there was no monitoring of HVPG. Patients with large varices received treatment with beta-blockers combined with EBL; patients with small varices received beta-blockers plus isosorbide mononitrate. RESULTS: there was no recurrent variceal bleeding in group 1 for good responders, and for 17% of poor responders. In group 2 a 25% rebleeding rate was detected in patients with small varices and 13% for those with big varices. Overall cost in group 1 was 14,100.49 euros, and 14,677.16 in group 2. CONCLUSIONS: HVPG measurement is cost-effective for the secondary prophylaxis of variceal bleeding.     

Long-term follow-up study of adult patients with non-cirrhotic obstruction of the portal system: comparison with cirrhotic patients.

Thirty-two patients with non-cirrhotic portal system obstruction and oesophageal varices of non-malignant etiology were recruited over 13 years. Diagnosis was based on the presence of oesophageal varices at endoscopy, minor alterations in liver function tests and liver histology, a low hepatic venous pressure gradient, and pertinent angiographic patterns. Twenty-three had portal vein thrombosis, nine had splenic vein thrombosis. Twenty-one had idiopathic portal vein obstruction, 11 had secondary obstruction. The outcome was compared with a group of 32 patients with cirrhosis and portal hypertension, matched for age, Child-Pugh class, previous history of gastrointestinal bleeding, and size of oesophageal varices. Patients with non-cirrhotic obstruction of the portal system were followed for up to 171 months (mean 94 months). During follow-up ten patients had gastrointestinal bleeding, and eight died (five of gastrointestinal bleeding). After 6 years of follow-up, the cumulative risk of gastrointestinal bleeding was 24%, the cumulative risk of death was 17%, and the cumulative risk of death from gastrointestinal bleeding was 14%. Cumulative probability of death by any cause and the probability of gastrointestinal bleeding were significantly lower in patients with non-cirrhotic obstruction of the portal system than in patients with cirrhosis comparable for liver function and portal hypertension (p = 0.04 for both). The cumulative probability of death by gastrointestinal bleeding was not significantly different. In conclusion, the prognosis for non-cirrhotic obstruction of the portal system is significantly better than for patients with cirrhosis with comparable levels of liver function impairment and severity of portal hypertension.     

Maintenance of hemodynamic response to treatment for portal hypertension and influence on complications of cirrhosis

BACKGROUND/AIMS: Following treatment with beta blockers in patients with cirrhosis and portal hypertension, reduction of hepatic venous pressure gradient (HVPG) to <12 mmHg or by >20% of baseline induces an extremely low risk of variceal bleeding. However, several factors such as compliance to therapy or alcohol abstinence may change the initial response after a long follow-up, and the effect of response on other complications of cirrhosis is less clear. The aim of this study was to assess the long-term maintenance of hemodynamic response and its influence on complications of cirrhosis. METHODS: One hundred and thirty two cirrhotic patients received nadolol and isosorbide mononitrate to prevent variceal rebleeding. HVPG was measured at baseline, after 1 to 3 months under treatment and again 12 to 18 months later. RESULTS: Sixty four patients were responders. After a longer follow-up, earlier response did not change in 81% of cases. Changes of response were mainly related to modifications in medication dose or in alcohol intake. As compared with poor-responders, responders had a lower probability of developing ascites (P<0.001) and related conditions, a greater improvement of Child-Pugh score (P=0.03), and a lower likelihood of developing encephalopathy (P=0.001) and of requiring liver transplantation (P=0.002). Eleven responders and 22 poor-responders died (P=0.029). CONCLUSIONS: Hemodynamic response to treatment of portal hypertension is usually sustained after a long-term follow-up. Response decreases the probability of developing complications of cirrhosis and the need for liver transplantation, and significantly improves survival.     

Management of acute bleeding from portal hypertension

Gastrointestinal bleeding is a frequent and severe complication of portal hypertension. The most frequent cause of the bleeding is variceal rupture. Despite improvements in prognosis after variceal bleeding over the past two decades, the 6-week mortality rate remains high, ranging from 15 to 30%. Patients die from uncontrolled bleeding, early rebleeding, infection, or renal failure within the first weeks of a bleeding episode. Poor hepatic function, severe portal hypertension with a hepatic venous pressure gradient (HVPG) >20 mmHg, and active bleeding at endoscopy are independently associated with poor prognosis. First-line treatment includes resuscitation, prophylactic antibiotic therapy, the combined use of vasoactive drugs (started as soon as possible), and an endoscopic procedure. Reconstitution of blood volume should be done cautiously to maintain the haematocrit between 25 and 30%. Terlipressin, somatostatin, or octreotide can be used, and drug therapy is maintained from 48 h to 5 days. Ligation is the endoscopic treatment of choice in bleeding oesophageal varices; in gastric varices, obturation with cyanoacrylate is preferable. Uncontrolled bleeding should be an indication for a salvage transjugular portosystemic shunt (TIPS). In patients with Child-Pugh score A, shunt surgery might be an alternative to TIPS. Trials are currently ongoing into the precise indications of early TIPS in selected patients with an HVPG >20 mmHg, and into the usefulness of administration of recombinant activated factor VII when there is an active bleeding at endoscopy.     

Clinical significance and prediction factors of gastric varices in patients with hepatocellular carcinoma

BACKGROUND/AIMS: Hepatocellular carcinoma is part of the natural history of liver cirrhosis. Gastrointestinal bleeding and hepatic failure are the leading causes of death in hepatocellular carcinoma patients. With gastrointestinal bleeding, variceal bleeding is the most prominent, and most variceal bleeding is of esophageal origin. Gastric varices bleeding is often a massive and severe bleeding episode. The role of gastric varices among patients with hepatocellular carcinoma remains to be clarified. In this study, we aimed to evaluate the prevalence, clinical significance and prediction of gastric varices in patients with hepatocellular carcinoma. METHODOLOGY: From 1998 to 2000, we reviewed 304 patients with hepatocellular carcinoma receiving upper gastrointestinal endoscopic examinations. Patients' clinical characteristics, physical findings, laboratory data, image studies, endoscopic examinations and treatment were reviewed. RESULTS: Among 304 patients with HCC, twenty-one (6.9%) had gastric varices among 304 patients with hepatocellular carcinoma. The location of gastric varices were the posterior wall in 12 (57%), the lesser curvature in 1 (5%), the greater curvature in 4 (19%) and the fundus in 4 (19%). Three (14%) of these 21 patients with hepatocellular carcinoma and gastric varices had clinical evidence of bleeding. One of them died due to uncontrollable bleeding. Child-Pugh classification, hepatic encephalopathy, portal vein or splenic vein dilatation, ascites, splenomegaly, albumin level, prothrombin time and platelet count were significantly different between hepatocellular carcinoma patients with gastric varices and without gastric varices under the univariate analysis. Ascites (Odds ratio: 5.45; 95% confidence interval: 2.12-14.01) and portal vein or splenic vein dilatation (Odds ratio: 4.38; 95% confidence interval: 1.77-10.86) were the two most important predictors under the stepwise logistic regression analysis. CONCLUSIONS: The prevalence of gastric varices in patients with hepatocellular carcinoma is 6.9% and the risk of bleeding is low in this study. The Predictors of gastric varices among hepatocellular carcinoma are related to liver cirrhosis, Child-Pugh classification, hepatic encephalopathy, portal vein or splenic vein dilatation, ascites, splenomegaly, albumin level, prothrombin time and platelet count.     

Predicting portal hypertension and variceal bleeding using non-invasive measurements of metabolic variables

Background & aim. This study assessed the involvement of metabolic factors (anthropometric indices, insulin resistance (IR) and adipocytokines) in the prediction of portal hypertension, esophageal varices and risk of variceal bleeding in cirrhotic patients.Material and methods. Two prospective and retrospective cohorts of cirrhotic patients were selected (n = 357). The first prospective cohort (n = 280) enrolled consecutively in three centers, underwent upper gastrointestinal endoscopy, seeking evidence of esophageal varices. Clinical, anthropometric, liver function tests, ultrasonographic, and metabolic features were recorded at the time of endoscopy, patients were followed-up every 6 months until death, liver transplantation or variceal bleeding. The second retrospective cohort (n = 48 patients) had measurements of the hepatic venous pressure gradient (HVPG). Statistical analyses of the data were with the SPSS package.Results. The presence of esophageal varices was independently associated with lower platelet count, raised HOMA index and adiponectin levels. This relationship extended to subset analysis in patients with Child A cirrhosis. HOMA index and adiponectin levels significantly correlated with HVPG. Beside Child-Pugh class, variceal size and glucagonemia, HOMA index but not adiponectin and leptin plasma levels were associated with higher risk of variceal bleeding.Conclusion. In patients with cirrhosis, HOMA score correlates with HVPG and independently predict clinical outcomes. Three simple markers i.e. platelet count, IR assessed by HOMA-IR and adiponectin significantly predict the presence of esophageal varices in cirrhotic patients.     

Treatment of portal hypertension

Portal hypertension is the main complication of cirrhosis and is defined as an hepatic venous pressure gradient (HVPG) of more than 5 mmHg. Clinically significant portal hypertension is defined as HVPG of 10 mmHg or more. Development of gastroesophageal varices and variceal hemorrhage are the most direct consequence of portal hypertension. Over the last decades significant advancements in the field have led to standard treatment options. These clinical recommendations have evolved mostly as a result of randomized controlled trials and consensus conferences among experts where existing evidence has been reviewed and future goals for research and practice guidelines have been proposed. Management of varices/variceal hemorrhage is based on the clinical stage of portal hypertension. No specific treatment has shown to prevent the formation of varices. Prevention of first variceal hemorrhage depends on the size/characteristics of varices. In patients with small varices and high risk of bleeding, non-selective β-blockers are recommended, while patients with medium/large varices can be treated with either β-blockers or esophageal band ligation. Standard of care for acute variceal hemorrhage consists of vasoactive drugs, endoscopic band ligation and antibiotics prophylaxis. Transjugular intrahepatic portosystemic shunt (TIPS) is reserved for those who fail standard of care or for patients who are likely to fail ("early TIPS"). Prevention of recurrent variceal hemorrhage consists of the combination of β-blockers and endoscopic band ligation.     

Hepatic Venous Pressure Gradient: Worth Another Look?

Portal hypertension is one of the most important complications of chronic liver disease and accounts for significant morbidity and mortality. Measurement of the hepatic venous pressure gradient (HVPG) is a simple, invasive, and reproducible method of assessing portal venous pressure. Measurement of HVPG provides the clinician an estimate of the degree of intrahepatic portal flow resistance, guides therapy for variceal bleeding (primary and secondary prophylaxis), assesses feasibility of resection in patients with hepatocellular cancer, and predicts response to therapy of patients with chronic hepatitis C. Achieving hemodynamic targets of reducing the HVPG to <10 mmHg or a 20% reduction from baseline virtually eliminates complications related to portal hypertension from chronic liver disease. This review explores the role of HVPG measurement in the contemporary treatment of patients with cirrhosis and portal hypertension.     

Hepatic venous pressure gradient predicts clinical decompensation in patients with compensated cirrhosis

BACKGROUND AND AIMS: Our aim was to identify predictors of clinical decompensation (defined as the development of ascites, variceal hemorrhage [VH], or hepatic encephalopathy [HE]) in patients with compensated cirrhosis and with portal hypertension as determined by the hepatic venous pressure gradient (HVPG). METHODS: We analyzed 213 patients with compensated cirrhosis and portal hypertension but without varices included in a trial evaluating the use of beta-blockers in preventing varices. All had baseline laboratory tests and HVPG. Patients were followed prospectively every 3 months until development of varices or VH or end of study. To have complete information, until study termination, about clinical decompensation, medical record review was done. Patients who underwent liver transplantation without decompensation were censored at transplantation. Cox regression models were developed to identify predictors of clinical decompensation. Receiver operating characteristic (ROC) curves were constructed to evaluate diagnostic capacity of HVPG. RESULTS: Median follow-up time of 51.1 months. Sixty-two (29%) of 213 patients developed decompensation: 46 (21.6%) ascites, 6 (3%) VH, 17 (8%) HE. Ten patients received a transplant and 12 died without clinical decompensation. Median HVPG at baseline was 11 mm Hg (range, 6-25 mm Hg). On multivariate analysis, 3 predictors of decompensation were identified: HVPG (hazard ratio [HR], 1.11; 95% confidence interval [CI], 1.05-1.17), model of end-stage liver disease (MELD) (HR, 1.15; 95% CI, 1.03-1.29), and albumin (HR, 0.37; 95% CI, 0.22-0.62). Diagnostic capacity of HVPG was greater than for MELD or Child-Pugh score. CONCLUSIONS: HVPG, MELD, and albumin independently predict clinical decompensation in patients with compensated cirrhosis. Patients with an HVPG <10 mm Hg have a 90% probability of not developing clinical decompensation in a median follow-up of 4 years.