Effect of laparoscopic splenectomy on portal hypertensive gastropathy in cirrhotic patients with portal hypertension

Aim:  This study investigated the relationship between portal hypertensive gastropathy (PHG) and splenomegaly, and the effect of laparoscopic splenectomy on PHG in cirrhotic patients with portal hypertension.
Methods:  Seventy patients with liver cirrhosis and portal hypertension were prospectively studied. Indication for laparoscopic splenectomy was bleeding tendency in 10 patients, induction of interferon in 45, treatment of hepatocellular carcinoma in seven, and treatment for endoscopic injection sclerotherapy-resistant esophagogastric varices in eight. The severity of PHG was classified into none, mild, or severe according to the classification by McCormack et al. The severity of liver disease was classified using the Child–Pugh score. All patients underwent upper gastrointestinal endoscopy before and 1 month after the operation.
Results:  The prevalence of PHG was significantly correlated with the severity of liver disease using the Child–Pugh score. The severity of PHG was significantly correlated with the resected spleen volume. One month after the operation, PHG was improved in 16 of 17 patients with severe PHG and in 12 of 32 with mild PHG. The Child–Pugh score showed a significant improvement (6.8 ± 1.4 to 6.2 ± 1.2) at 3 months after laparoscopic splenectomy ( P  < 0.0001).
Conclusions:  PHG may be associated with splenomegaly, and laparoscopic splenectomy may have a beneficial effect on PHG, at least for a short time.     

Correlation of routinely used coagulation parameters and presence of portal vein thrombosis in patients with liver cirrhosis

Aim:  Portal vein thrombosis (PVT) is a serious complication in patients with liver cirrhosis. In patients with advanced stages of liver cirrhosis plasmatic coagulation and platelet count are often reduced. However, patients with normal coagulation status might carry a high risk for developing PVT. A correlation between coagulation status used in clinical routine and the incidence of PVT in patients with liver cirrhosis has been evaluated in the present retrospective analysis.
Methods:  88 patients with liver cirrhosis were identified by screening a database. Of these patients, 23 suffered from PVT. Patients were classified according to the Child–Pugh classification. Patients were subdivided into early stages (Child A) and advanced stages (Child B/C) of liver cirrhosis.
Results:  In patients with Child–Pugh A cirrhosis, there was no difference in activated partial thromboplastin time (apTT), international normalized ratio (INR), and platelet count between the PVT ( n  = 7) and the control group ( n  = 35). In contrast, the median apTT and INR were significantly lower in patients with Child B/C cirrhosis and PVT ( n  = 16) in comparison with patients without PVT (37 s vs 43 s [ P  = 0.017] and 1.25 vs 1.40 [ P  = 0.022]), respectively. Platelet count did not differ significantly in patients with advanced liver cirrhosis and PVT from those without PVT.
Conclusion:  Patients with advanced liver cirrhosis and PVT displayed lower apTT and INR compared with those without PVT. Therefore, patients with advanced liver cirrhosis and almost normal coagulation parameters might be at particular risk of developing PVT. The results suggest that regular monitoring using Doppler-ultrasound should be carried out in these patients, especially when liver transplantation is intended.     

Portal Hypertensive Gastropathy: Correlation with Portal Hypertension and Prognosis in Cirrhosis

Background

Portal hypertensive gastropathy (PHG) is a common endoscopic finding in patients with cirrhosis. However, the relationship between PHG and portal hypertension is controversial. Furthermore, nothing is known regarding the correlation between PHG and prognosis in patients with cirrhosis.

Methods

The hepatic venous pressure gradient (HVPG), endoscopic PHG grade, Child–Pugh score, and model for end-stage liver disease (MELD) score were assessed at baseline and were followed prospectively in 331 cirrhotic patients (284 males, 85.8%; mean age, 52.16 ± 9.05 years) from January 2001 to April 2009. The relationship between PHG with HVPG and survival was investigated.

Results

The HVPG was significantly higher in patients with severe PHG than in those with mild or no PHG (absent, 4.9 ± 1.7 mmHg; mild, 10.7 ± 4.1 mmHg; severe, 15.6 ± 4.6 mmHg; P < 0.001). During follow-up, 28 patients (8.5%) died from liver-related disease. In the Cox regression analysis, severe PHG (none and mild vs. severe) (hazard ratio 1.153, 95% confidence interval: 1.048–1.269) showed a significantly high relative risk of mortality, and in the Kaplan–Meier analysis, severe PHG showed a significantly shorter expected survival time than none or mild PHG (median survival time, 77.6 ± 9.6 months in severe PHG; log-rank test, P = 0.030).

Conclusions

PHG was associated with portal hypertension severity and prognosis in patients with cirrhosis.     

Reappraisal of repeated transarterial chemoembolization in the treatment of hepatocellular carcinoma with portal vein invasion

Background and Aim:  This study aimed to evaluate the therapeutic efficacy and safety of repeated transarterial chemoembolization (TACE) with additional radiation therapy (RT) in hepatocellular carcinoma (HCC) with portal vein (PV) invasion.
Methods:  We performed survival analysis of consecutive HCC patients with PV invasion according to the treatment modalities after stratification by the degree of PV invasion and liver function retrospectively.
Results:  During 2005, 281 patients were newly diagnosed to have HCC with PV invasion at our institution. Repeated TACE or transarterial chemoinfusion (TACI) was performed in 202 (71.9%) patients and additional RT was performed for PV invasion in 43 of them. A total of 281 patients had a median survival of 5.2 months and a 2-year survival rate (YSR) of 19.2%. Repeated TACE showed significant survival benefits compared with conservative management in patients with PV branch invasion; median survival and 2-YSR was 10.2 vs 2.3 months and 33.7% vs 0% in Child–Pugh A categorized patients and 5.5 vs 1.3 months and 10.3 vs 0% in Child–Pugh B categorized patients, respectively ( P  < 0.001). In patients with PV branch invasion, the survival rate was significantly longer with TACE/TACI plus RT than with TACE/TACI alone both in Child–Pugh A categorized patients (1-YSR: 63.6 vs 35.6%, P  = 0.031) and Child–Pugh B categorized patients (1-YSR: 66.7 vs 7.7%, P  = 0.007). Repeated TACE was well tolerated in our patients, with only one dying within one month after TACE.
Conclusion:  Repeated TACE with additional RT can be performed safely and showed a significant survival benefit in HCC patients with PV branch invasion with conserved liver function.     

Abnormality of the hepatic vein waveforms in cirrhotic patients with portal hypertension and its prognostic implications

Background and Aim:  We investigated the prognostic significance of changes in the Doppler hepatic vein (HV) waveforms in cirrhotic patients with portal hypertension and the mechanisms of these changes.
Methods:  A total of 103 consecutive patients were included in this study and their HV waveforms were classified into four types: type I, triphasic waveform; type II, biphasic waveform; type III, biphasic waveform with reduced phasic oscillations; and type IV, a flat waveform.
Results:  Type I was observed in 34, type II in 40, type III in 23, and type IV in six patients. The 5-year survival rates were 90%, 89%, 41%, and 0% in type I, II, III, and IV, respectively. Five variables including the Child–Pugh score, albumin, bilirubin, ascites, and HV waveform significantly correlated with the survival in a univariate analysis. A multivariate analysis only identified the HV waveform (type III and IV) to be an independent prognostic value. Even in Child–Pugh class B patients, the 5-year survival rate for type III or IV was as poor as 26% in comparison to 92% for type I or II. In contrast, in Child–Pugh class C patients, the 5-year survival rate for type I or II was as good as 63% in comparison to 25% for type III or IV. Furthermore, the changes in HV waveforms correlated with the extent of hepatic fibrosis, the increase in portal perfusion per liver volume, or the decrease in portal vascular resistance.
Conclusions:  Analyzing the HV waveforms was thus found to be a simple method for accurately assessing the prognosis in cirrhotic patients with portal hypertension.     

Irbesartan plus low-dose propranolol versus low-dose propranolol alone in cirrhosis: a placebo-controlled, double-blind study

OBJECTIVES:  Angiotensin II receptor antagonists have been shown to moderately lower portal pressure in some patients with cirrhosis but may have adverse effects on kidney function. This study aimed at comparing the effects of a combined treatment using irbesartan plus propranolol with propranolol monotherapy on portal pressure and kidney function in patients with cirrhosis.
METHODS:  Thirty-two patients were included (Child A/B/C: 13/18/1, etiology: 16 alcohol, 13 viral, 3 other; bilirubin 1.4 ± 1.1 mg/dL, creatinine 0.86 ± 0.20 mg/dL, baseline hepatic venous pressure gradient 18.7 ± 5.3 mmHg). All patients received 20 mg propranolol b.i.d. Additionally, they randomly received either placebo (N = 15) or irbesartan (step-up dosage titration up to 300 mg/d, N = 17). Patients were followed at weekly intervals, re-evaluation of hepatic venous pressure gradient (HVPG) was performed after 8 wk.
RESULTS:  One patient in the propranolol/irbesartan group was excluded due to variceal bleeding. No other adverse events occurred. Portal pressure declined in both groups (propranolol/irbesartan group 19.6 ± 1.5 mmHg to 16.6 ± 1.2 mmHg, P = 0.037, propranolol/placebo group 17.8 ± 1.1 mmHg to 15.1 ± 1.2 mmHg, P = 0.019). Sodium excretion significantly increased in the propranolol/irbesartan group (from 122 ± 20 mmol/d to 230 ± 23 mmol/d, P = 0.045), but not in the propranolol/placebo group.
CONCLUSIONS:  Combination treatment of propranolol plus irbesartan is well tolerated in cirrhotic patients when titrating the angiotensin II antagonist in a step-up manner, and it increases sodium excretion in patients with compensated or moderately decompensated cirrhosis. Addition of irbesartan has no effect on portal pressure.     

Clinical features and survival in Chinese patients with hepatitis B e antigen-negative hepatitis B virus-related cirrhosis

Aim:  To compare the clinical features of hepatitis B e antigen (HBeAg)-negative and HBeAg-positive cirrhosis, and to define the survival and prognostic indicators of Chinese HBeAg-negative hepatitis B virus (HBV)-related cirrhosis.
Methods:  Two hundred and seventeen patients with chronic hepatitis B cirrhosis were studied. Survival was calculated using the Kaplan–Meier method. Proportional hazards Cox regression procedure was used to identify independent predictors of survival. The relationship between HBV-DNA viral load and prognosis was also investigated.
Results:  The mean follow-up time was 35 months (3–47 months). HBeAg-negative liver cirrhosis patients comprised the greatest number of cirrhosis patients. Median alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, median total leukocytes (WBC), hemoglobin (Hb), platelet (Plt) and HBV-DNA levels and the proportion of HBV-DNA > 10⁵ copies/mL were lower in HBeAg-negative patients. There were fewer complications in patients treated with lamivudine than in other patients. Survival rates were significantly reduced in patients with HBeAg-negative cirrhosis ( P  = 0.0024). The baseline Child–Pugh scores and more than one decompensation during follow up were independent variables correlated with survival of HBeAg-negative liver cirrhosis patients ( P  = 0.006 and P  = 0.001, respectively). The HBV-DNA viral load did not correlate with any complications or mortality rates of HBeAg-negative patients.
Conclusions:  The clinical features of HBeAg-negative and -positive liver cirrhosis differ. Survival was significantly reduced for Chinese patients with HBeAg-negative than -positive cirrhosis. Factors contributing to the prognosis were baseline Child–Pugh scores and the presence of more than one decompensation during follow up.     

Evaluation of Quantitative Portal Venous, Hepatic Arterial, and Total Hepatic Tissue Blood Flow Using Xenon CT in Alcoholic Liver Cirrhosis: Comparison With Liver Cirrhosis C

Background/Aims: Xenon computed tomography (Xe-CT) is a noninvasive method of quantifying and visualizing tissue blood flow (TBF). For the liver, Xe-CT allows separate measurement of hepatic arterial and portal venous TBF. The present study evaluated the usefulness of Xe-CT as a noninvasive diagnostic procedure for measuring hepatic TBF in alcoholic liver cirrhosis (AL-LC), compared with liver cirrhosis C (C-LC).
Methods: Xenon computed tomography was performed on 12 patients with AL-LC and 17 patients with C-LC. The severity of LC was classified according to Child–Pugh classification. Correlations between hepatic TBF and Child–Pugh classification were examined. Correlations of hepatic TBF in Child–Pugh class A to C-LC and AL-LC were also examined.
Results: The mean portal venous TBF (PVTBF) was significantly lower in AL-LC than in C-LC ( p =0.0316). Similarly, the mean total hepatic TBF (THTBF) was significantly lower in AL-LC than in C-LC ( p =0.0390). PVTBF displayed a significant negative correlation with Child–Pugh score ( r =−0.396, p =0.0368).
Conclusions: Measurement of hepatic TBF using Xe-CT is useful as a noninvasive, objective method of assessing the state of the liver in chronic liver disease.     

Urinary bile acid sulfate levels in patients with hepatitis C virus-related chronic liver diseases

Aim:  Urinary bile acids are mainly conjugated with sulfuric acid, and urinary sulfated bile acid (USBA) levels in hepatobiliary diseases have been reported. However, the relationship between USBA and fasting serum total bile acid (TBA) has not been studied in hepatobiliary diseases. In the present study, we measured USBA levels in patients with hepatitis C virus-related chronic liver diseases, and the relationship between TBA and various laboratory tests was studied.
Methods:  USBA was measured using an automatic assay kit in 66 patients with chronic hepatitis and 28 patients with liver cirrhosis, and its relationship between TBA and various laboratory tests was studied.
Results:  The median USBA level was 10.7 µmol/g creatinine in patients with chronic hepatitis and 41.1 µmol/g creatinine in liver cirrhosis ( P  = 0.000). More patients with chronic hepatitis had elevated USBA levels (61%) compared to TBA level (39%) ( P  = 0.002). USBA level was well correlated with TBA (r_s = 0.680), and negatively correlated with albumin (r_s = −0.488), prothrombin time (r_s = −0.385) and platelet counts (r_s = −0.394). In patients with liver cirrhosis, USBA was significantly elevated in Child–Pugh class B compared to Child–Pugh class A ( P  = 0.036).
Conclusion:  Although the metabolic pathways of USBA and TBA are different, these levels correlated very well, and USBA is considered to be a useful indicator of hepatic function like TBA in patients with chronic hepatitis C.     

Relationships between the severity of cirrhosis and haemodynamic values in patients with cirrhosis

Abstract The relationship between the severity of cirrhosis and systemic and hepatic haemodynamic values was evaluated in 193 patients with cirrhosis, most of whom were diagnosed with post-necrotic cirrhosis. It was found that the hepatic venous pressure gradient and cardiac output in Pugh's A patients (13.6 ± 4.8 mmHg and 6.2 ± 1.6 L/min, mean ± s.d.) were significantly lower than in both Pugh's B (16.8 ± 4.3 mmHg and 7.3 ± 2.1 L/min) and Pugh's C (18.8 ± 5.5 mmHg and 7.4 ± 2.3 L/min) patients ( P < 0.01), respectively. In contrast, the systemic vascular resistance in Pugh's A patients (1232 ± 369 dyn/s per cm⁵) was significantly higher than in both Pugh's B (1016 ± 345 dyn/s per cm⁵) and Pugh's C (935 ± 234 dyn/s per cm⁵) patients ( P < 0.01), respectively. Additionally, not only was there a positive correlation found between Pugh's score and cardiac output and hepatic venous pressure gradient, but a negative correlation was found between Pugh's score and systemic vascular resistance. It was also confirmed that the degree of portal hypertension and the hyperdynamic circulation were more severe in patients with ascites than in those without ascites. However, there were no statistically significant differences in hepatic venous pressure gradient among patients with F1, F2 and F3 esophageal varices (15.7 ± 4.0, 17.0 ± 4.8 and 18.0 ± 4.8 mmHg, respectively). It is concluded that in those patients with cirrhosis, the severity of cirrhosis is closely related to the degree of the hyperkinetic circulatory state and portal hypertension.     

The effects of transjugular intrahepatic portosystemic shunt on portal hypertensive gastropathy

In addition to variceal bleeding, haematemesis may occur due to haemorrhagic gastritis in patients with portal hypertension. This has been known as portal hypertensive gastropathy (PHG). We have evaluated the effects of the transjugular intrahepatic portosystemic shunt (TIPS) on portal venous pressure (PVP) and endoscopic gastric mucosal changes observed in patients with portal hypertension. We performed TIPS in 12 patients with complications due to portal hypertension as follows: variceal bleeding in nine patients (bleeding from oesophageal varices in seven and gastric varices in two), refractory ascites in three and haemorrhage from severe PHG in one. Endoscopic examinations were performed before and after TIPS for all patients. Changes of PVP and gastric mucosal findings on endoscopy were analysed. Before TIPS, PHG was seen in 10 patients. Portal venous pressure decreased from an average of 25.1 ± 8.8 to 17.1 ± 6.2 mmHg after TIPS ( P < 0.005). On endoscopy, PHG improved in nine of 10 patients. Oesophagogastric varices improved in eight of 11 patients. In one patient with massive haematemesis, haemorrhage from severe PHG completely stopped after TIPS. Because TIPS effectively reduced PVP, this procedure appeared to be effective for the treatment of uncontrollable PHG.     

Norfloxacin treatment for clinically significant portal hypertension: results of a randomised double‐blind placebo‐controlled crossover trial

Background: While selective intestinal decontamination (SID) can alter the hyperdynamic circulatory state of cirrhosis, the impact of SID on portal pressure remains unclear especially in the setting of clinically significant portal hypertension. Aims: To examine the impact of SID with norfloxacin on portal pressure in subjects with clinically significant portal hypertension and explore the potential mechanisms by which norfloxacin exerts its haemodynamic effects. Methods: Randomised, double blind, placebo‐controlled, crossover trial of norfloxacin 400 mg twice daily for 4 weeks. The portal pressure was assessed by hepatic venous pressure gradient (HVPG). Endotoxaemia was assessed by the Limulus amebocyte lysate (LAL) assay. l ‐arginine (l ‐Arg) transporter function was assessed in peripheral blood mononuclear cells (PBMCs). Plasma levels of urotensin II (UII) and tumour necrosis factor were measured before and after therapy. Results: Sixteen subjects with clinically significant portal hypertension (16.5±1.1 mmHg) completed the study. Norfloxacin therapy was not superior to placebo in reducing HVPG (13.8±1.0 mmHg vs 13.6±1.2 mmHg, P=0.3). Furthermore, no alteration in l ‐Arg transport was detected after 4 weeks of norfloxacin therapy. Plasma UII levels correlated positively with HVPG (P=0.01) and the Child–Pugh score (P<0.05). However, UII levels following therapy did not parallel HVPG changes. Conclusions: Norfloxacin is not superior to placebo in reducing HVPG in subjects with clinically significant portal hypertension. Furthermore, norfloxacin does not appear to modulate the l ‐Arg transporter mechanism in this patient population. Although plasma UII correlates positively with HVPG, UII does not appear to have a direct role in modulating HVPG.     

Quantitation of tissue polypeptide antigen (TPA) in hepatic and systemic circulation in patients with chronic liver diseases

Background and Aim: Abnormal serum tissue polypeptide antigen (TPA) values are commonly found in patients with chronic liver damage and liver cirrhosis even in the absence of malignancies. The aim of this study was to compare serum TPA levels in patients with cirrhosis, to examine correlations between TPA levels and the degree of portal hypertension, and to evaluate TPA concentrations in paired hepatic and peripheral blood samples. Methods: A total of 128 patients with chronic liver disease of various severity were studied prospectively. TPA concentrations in hepatic vein and peripheral blood were determined, and Hepatic Vein Pressure Gradient (HVPG) was measured. Results: TPA levels were significantly higher in patients with cirrhosis than in those with chronic hepatitis, and in systemic circulation than in hepatic vein blood. Peripheral but not hepatic TPA levels did correlate with the HVPG. Subjects with clinically significant portal hypertension (HVPG > 10 mmHg) showed significantly higher peripheral TPA levels than those with HVPG < 10 mmHg. Conclusions: Our data suggest that the increased TPA levels observed in cirrhotic patients and the high systemic‐to‐hepatic blood TPA gradient are probably due to the presence of portal‐systemic shunts rather than to hepatic necro‐inflammatory activity. In clinical practice, TPA determination could help us to identify and to follow up cirrhotic patients with more severe portal hypertension.     

Prevalence of gastric ulcer in cirrhotic patients and its relation to portal hypertension

The prevalence of gastric ulcer and its relationship to the severity of cirrhosis and degree of portal hypertension was evaluated in 245 cirrhotic patients, and compared with 245 age- and sex-matched healthy subjects. Portal and systemic haemodynamic studies were performed in cirrhotic patients. The prevalence of gastric ulcer in cirrhotic patients was 20.8%, which was significantly higher than the 4.0% found in healthy controls. Using a multivariate logistic regression model, the hepatic venous pressure gradient was found to be the only predictor of the prevalence of gastric ulcer in cirrhotic patients to present with gastric ulcer. The hepatic venous pressure gradient was significantly higher in cirrhotic patients with gastric ulcer than in those without (17.3 ± 4.4 vs 15.5 ± 5.0 mmHg, P= 0.01). Other variables, including sex, smoking, cardiac output and severity or aetiology of cirrhosis did not show significant differences between the two patient groups. The prevalence of gastric ulcer in cirrhotic patients whose hepatic venous pressure gradient was below 12 mmHg (4.5%) was similar to that observed in the healthy controls (4.0%). However, when the hepatic venous pressure gradient was > 12 mmHg, the prevalence of gastric ulcer (24.4%) was significantly higher than that in control subjects. However, the incidence of gastric ulcer was not related to the degree of portal hypertension. In conclusion, the prevalence of gastric ulcer in cirrhotic patients was found to be significantly higher than in the age- and sex-matched healthy subjects. Portal hypertension with a hepatic venous pressure gradient > 12 mmHg may be an important factor contributing to the increased prevalence of gastric ulcer observed in patients with liver cirrhosis.     

Increased plasma nitric oxide, L-arginine, and arginase-1 in cirrhotic patients with progressive renal dysfunction

Background and Aims:  Increased levels of nitric oxide (NO) are hypothesized to contribute to renal dysfunction in patients with decompensated cirrhosis. In this study, we examined whether splanchnic and/or peripheral NO levels and L-arginine (L-Arg) correlate with progressive renal dysfunction in cirrhotics.
Methods:  Serum NO metabolites (NOx) and L-Arg were measured in: controls ( n  = 10); organ donors ( n  = 12); compensated cirrhotics ( n  = 17), cirrhotics with ascites ( n  = 25), refractory ascites ( n  = 11) or hepatorenal syndrome type II (HRS) ( n  = 11) and chronic renal failure patients ( n  = 18).
Results:  Plasma NOx and L-Arg levels rose progressively with worsening renal function in decompensated cirrhotics. Both NOx and L-Arg levels were highest in patients with HRS ( P  < 0.001 and P  < 0.025, respectively). While there were no differences in NOx levels related to the site of sampling, L-Arg levels were lowest in hepatic venous blood. There were significant relationships of NOx and L-Arg with Model for End-Stage Liver Disease score and Child–Pugh scores ( P  < 0.04 and P  < 0.01, respectively). Multivariate analysis showed a significant relationship between NOx, L-Arg and HRS.
Conclusion:  Worsening renal function in decompensated cirrhosis is accompanied by progressive elevation in plasma NOx and L-Arg. These findings support the hypothesis that NO-mediated vasodilation is probably linked with the mechanism of progressive renal failure in decompensated cirrhotics.     

Is portal hypertension associated with protein-losing enteropathy?

Background and Aim:  Hypoalbuminemia in patients with decompensated cirrhosis has traditionally been assumed to be a result of to impaired liver synthesis; however, protein-losing enteropathy (PLE) may also contribute. The aim of this study was to assess whether hypoalbuminemic cirrhotic patients with portal hypertension had evidence of PLE.
Methods:  Sixteen patients with alcoholic cirrhosis, hypoalbuminemia and portal hypertension underwent whole gut lavage with polyethylene glycol solution. The effluent obtained was analyzed for albumin, immunoglobulin (Ig)G and α1-antitrypsin (α1-AT). Serum C-reactive protein (CRP) was also measured to assess the systemic inflammatory response.
Results:  Twelve of the 16 enrolled patients had a persistently low albumin concentration at the time of lavage. Only one patient (who was subsequently found to have celiac disease) had elevated concentrations of lavage albumin, α1-AT and IgG levels. There was a significant correlation between lavage albumin and α1-AT ( r  = 0.671, P  = 0.024), and between lavage albumin and IgG ( r  = 0.614, P  = 0.045). There was no correlation between serum albumin and lavage proteins. Six patients had elevated serum CRP levels, but serum albumin or lavage protein concentrations did not correlate with serum CRP.
Conclusion:  There is no evidence of a significant PLE in patients with alcoholic cirrhosis, hypoalbuminemia and portal hypertension.     

Predictors of microscopic portal vein invasion by hepatocellular carcinoma: Measurement of portal perfusion defect area ratio

Objective:  Microscopic portal vein invasion (PVI) by cancer cells is a poor prognostic factor after hepatic resection for hepatocellular carcinoma (HCC). The aim of this study is to predict PVI preoperatively in patients with HCC.
Methods:  We studied 46 hepatectomized patients who had HCC without any portal venous invasion detected during preoperative radiographic evaluation. We defined the portal perfusion defect area ratio (PPDAR) as the following: the quotient of the maximal portal perfusion defect area, on computed tomography during arterio-portography (CTAP) is divided by the maximal tumor area on magnetic resonance imaging (MRI) or CT.
Results:  The median PPDAR was 1.3 (mean 1.4 ± 1.1; ranged from 0.7 to 5.8). The incidence of PVI was 4.5% in patients with a PPDAR <1.3, 35.7% in those with a PPDAR of 1.3–1.6, 70% in those with a PPDAR ≥1.6 ( P  = 0.0005). When analyzing the preoperative value of different cut-off points for the PPDAR, the lowest P -value by Fisher's exact test was achieved when the PPDAR threshold was 1.6 ( P  = 0.0012). The sensitivity was 58%, and specificity was 91% with this cut-off value. On univariate analyses, factors that significantly correlated with PVI were PPDAR ( P  = 0.0012), serum levels of des-gamma-carboxy prothrombin ( P  = 0.033), and tumor size ( P  = 0.0126). On multivariate analysis, PPDAR was the only significant independent predictor of PVI.
Conclusion:  Our study shows that PPDAR is a new concept, which is useful in predicting PVI and that a value ≥1.6 is predictive of PVI.     

Frequency and factors influencing portal hypertensive gastropathy and duodenopathy in cirrhotic portal hypertension

Portal hypertensive gastropathy and duodenopathy are distinct clinical and endoscopic entities. Data on factors influencing the development of these lesions are still emerging. Data on portal hypertensive duodenopathy are scarce. We prospectively studied 230 patients with liver cirrhosis and oesophageal varices attending the liver clinic of the Sanjay Gandhi Post Graduate Institute of Medical Sciences. One hundred and forty-two patients had no history of upper gastrointestinal bleeding, while the remainder had bled in the past. Endoscopic appearances were recorded before starting patients on a sclerotherapy programme. Forty-four patients were re-evaluated after variceal eradication. The frequency of portal hypertensive gastropathy (PHG) and duodenopathy (PHD) was 61 and 14%, respectively. Mild PHG was present in 85% and was severe in the rest. Portal hypertensive duodenopathy was mild in 50%, while in the other half it was severe. There was no relationship of PHG and PHD to: (i) a history of upper gastrointestinal bleed; (ii) size of oesophageal varices; (iii) aetiology of liver cirrhosis; or (iv) liver function status as assessed by Child Pugh's scores (P=NS for all). The prevalence of PHG was higher in those patients with oesophagogastric varices (74 of 107; 69%) compared with patients with oesophageal varices alone (68 of 123; 55%; P<0.05). However, no such increase in frequency of PHD was noted in patients with oesophagogastric varices. Sclerotherapy increased the frequency of PHG. Twenty-four patients had PHG before starting sclerotherapy, while it was noted in 33 patients 1–3 months after variceal eradication (P< 0.05). In contrast, there was no increase in the prevalence of portal hypertensive duodenopathy after sclerotherapy (P=NS). There was no correlation between endoscopic and histological changes of PHG and PHD. In conclusion, PHG is quite frequent in patients with cirrhosis and its frequency increases with the presence of oesophagogastric varices and after sclerotherapy. However, the frequency of PHD is low and is not affected by the factors studied.     

Effect of viral suppression on hepatic venous pressure gradient in hepatitis C with cirrhosis and portal hypertension

Portal hypertension is a predictor of liver‐related clinical events and mortality in patients with hepatitis C and cirrhosis. The effect of interferon‐free hepatitis C treatment on portal pressure is unknown. Fifty patients with Child‐Pugh‐Turcotte (CPT) A and B cirrhosis and portal hypertension (hepatic venous pressure gradient [HVPG] >6 mm Hg) were randomized to receive 48 weeks of open‐label sofosbuvir plus ribavirin at Day 1 or after a 24‐week observation period. The primary endpoint was sustained virologic response 12 weeks after therapy (SVR12) in patients who received ≥1 dose of treatment. Secondary endpoints included changes in HVPG, laboratory parameters, and MELD and CPT scores. A subset of patients was followed 48 weeks posttreatment to determine late changes in HVPG. SVR12 occurred in 72% of patients (33/46). In the 37 patients with paired HVPG measurements at baseline and the end of treatment, mean HVPG decreased by ‐1.0 (SD 3.97) mm Hg. Nine patients (24%) had ≥20% decreases in HVPG during treatment. Among 39 patients with pretreatment HVPG ≥12 mm Hg, 27 (69%) achieved SVR12. Four of the 33 (12%) patients with baseline HVPG ≥12 mm Hg had HVPG <12 mm Hg at the end of treatment. Of nine patients with pretreatment HVPG ≥12 mm Hg who achieved SVR12 and completed 48 weeks of follow‐up, eight (89%) had a ≥20% reduction in HVPG, and three reduced their pressure to <12 mm Hg. Patients with chronic HCV and compensated or decompensated cirrhosis who achieve SVR can have clinically meaningful reductions in HVPG at long‐term follow‐up. (EudraCT 2012‐002457‐29).     

Hepatic venous pressure gradient measurement: is it mandatory in the management of portal hypertension?

Abstract   Portal hypertension can be evaluated by hepatic vein catheterization and measurement of wedged and free hepatic vein pressures. The hepatic venous pressure gradient (HVPG) is the difference between both pressures and its normal value is lower than 5 mmHg. The technique is safe and reliable provided several requirements are fulfilled to get accurate results. HVPG measurement is useful to determine the site of increased resistance either presinusoidal, sinusoidal or postsinusoidal. If HVPG is normal in the presence of clinical signs of portal hypertension, evaluation of the portal venous system and direct measurement of portal vein pressure is required. HVPG measurement may also be used as a prognostic marker to evaluate the risks of developing complications such as ascites or variceal bleeding; in addition, it has been suggested that it could provide prognostic information for variceal rebleeding or survival. Primary and secondary prophylaxis of variceal bleeding can be achieved with a pharmacological treatment using beta blockers and/or nitrates. Repeated HVPG measurements are probably useful to monitor the treatment; it has been suggested that decreasing HVPG by 20% or below 12 mmHg is a reasonable target to define a good hemodynamic response and hopefully a low risk of bleeding; endoscopic therapy can be used in non-responders. Repeated hemodynamic evaluation, however, is invasive and must be performed in specialized liver units; therefore, future clinical trials must demonstrate unequivocally the clinical usefulness of this approach prior to recommending repeated HVPG measurement on a routine basis.