Non-selective β-blockers improve the correlation of liver stiffness and portal pressure in advanced cirrhosis

Background

Liver stiffness (LS) correlates with portal pressure (hepatic venous pressure gradient, HVPG). However, the dynamic components of portal hypertension (PHT) in advanced cirrhosis may not be adequately assessed by TE. The influence of treatment with non-selective β-blockers (NSBB) on the correlation of HVPG and LS has not been investigated.

Methods

One hundred and twenty-two patients with esophageal varices were included. LS, hemodynamic parameters, and HVPG were recorded at baseline (BL) and after 6?weeks of treatment with NSBB (FU). The correlation of LS and HVPG was compared to control patients with HVPG?≤?12?mmHg.

Results

Patients with higher Child-Pugh stages (A:88/B:25/C:9) had higher levels of liver stiffness (47.4?±?16.5 vs. 70.3?±?7.9 vs. 73.7 ± 2.1 kPa) and HVPG (21?±?5 vs. 26?±?5 vs. 26?±?4?mmHg). The correlation of LS and HVPG was stronger in controls with HVPG?≤?12?mmHg (R?=?0.951; P??12?mmHg (R?=?0.538; P?=?0.0004). The association of HVPG with LS became stronger under treatment with NSBB, which finally restored the linear correlation of HVPG and LS (R?=?0.930; P?R?=?0.864), but not in nonresponders (R?=?0.535), whereas changes in LS, heart rate, and MAP were similar in responders and nonresponders.

Conclusions

Targeting the hyperdynamic circulation and the increased splanchnic blood inflow by treatment with NSBB unmasks the linear (mechanical) correlation of HVPG and LS in patients with HVPG?>?12?mmHg. Measurement of LS by TE is not a feasible method to assess the dynamic components of PHT.     

Prognostic value of a single HVPG measurement and Doppler-ultrasound evaluation in patients with cirrhosis and portal hypertension

Background

In patients with cirrhosis the onset of clinically significant portal hypertension (CSPH; i.e., hepatic venous pressure gradient (HVPG) ???10?mmHg) is associated with an increased risk of complications. However, most cirrhotic patients already have CSPH at presentation, and limited information is available on further risk stratification in this population. This study assessed the prognostic value of a single HVPG measurement and Doppler-ultrasound (US) evaluation in patients with cirrhosis and CSPH.

Methods

Eighty-six consecutive patients with cirrhosis (73% compensated) and untreated CSPH (mean HVPG 17.8?±?5.1?mmHg) were included. All were studied by paired HVPG and US, and followed up for a minimum of 12?months (mean 28?±?20?months).

Results

Sixteen (25.3%) patients developed a first decompensation, and 11.6% died on follow-up. HVPG (per 1?mmHg increase OR 1.22, 95% CI 1.05?C1.40, p?=?0.007) and bilirubin (per 1?mg/ml increase OR 2.42, 95% CI 0.93?C6.26, p?=?0.06) independently predicted first decompensation, and Model for End-Stage Liver Disease (MELD) score (per 1 point increase OR 1.24, 95% CI 1.03?C1.51, p?=?0.03) and HVPG (per 1?mmHg increase OR 1.08, 95% CI 1.01?C1.26, p?=?0.05) independently predicted mortality. The best HVPG cutoff predicting these events was 16?mmHg. Ultrasonographic parameters lacked independent predictive value. The ultrasonographic detection of abdominal collaterals had a high positive likelihood ratio (7.03, 95% CI 2.23?C22.16) for the prediction of HVPG ???16?mmHg, implying an increase of the probability of belonging to this higher-risk population from 58 to 91%.

Conclusions

HVPG holds an independent predictive value for first decompensation and death in patients with CSPH. The ultrasonographic detection of collaterals allows the non-invasive identification of patients with HVPG ???16?mmHg, who are at higher risk.     

Hepatogenous Diabetes in Cirrhosis Is Related to Portal Pressure and Variceal Hemorrhage

Background and Aim

The clinical impact and complications of hepatogenous diabetes (HD) on cirrhosis have not been elucidated. This study aimed to evaluate the relationship of HD with portal hypertension (PHT) and variceal hemorrhage and to assess the prevalence of HD.

Methods

From July 2007 to December 2009, 75-g oral glucose tolerance test and insulin resistance (IR) were evaluated for 195 consecutive cirrhotic liver patients (M:F = 164:1, 53.0 ± 10.2 years) who had no history of diabetes mellitus. IR was calculated using the homeostasis model of assessment-insulin resistance (HOMA-IR) formula. Endoscopy for varices, hepatic venous pressure gradient (HVPG), and serologic tests were also conducted.

Results

HD was observed in 55.4 % (108/194) of the patients. Among them, 62.0 % required OGTT for diagnosis because they did not show an abnormal fasting plasma glucose level. The presence of HD showed a significant correlation with high Child–Pugh’s score, variceal hemorrhage, and HVPG (p = 0.004, 0.002, and 0.019, respectively). In multivariate analysis, Child–Pugh’s score (OR 1.43, 95 % CI 1.005–2.038) and HVPG (OR 1.15, 95 % CI 1.003–2.547) had significant relationships with HD. Patients with recent variceal hemorrhages (within 6 months) exhibited significantly higher glucose levels at 120 min in OGTT compared to patients without hemorrhages (p = 0.042). However, there was no difference in fasting glucose levels. The 120-min glucose level and HOMA-IR score were significantly and linearly correlated with HVPG (r ² = 0.189, p < 0.001 and r ² = 0.033, p = 0.011, respectively).

Conclusion

HD and IR have significant relationships with PHT and variceal hemorrhage. Postprandial hyperglycemia in particular had a significant relationship with variceal hemorrhage.     

Non-invasive aspartate aminotransferase to platelet ratio index correlates well with invasive hepatic venous pressure gradient in cirrhosis

Background

Hepatic venous pressure gradient (HVPG) is the best recommended tool to measure portal pressure, but is invasive. HVPG helps in prognosticating cirrhosis and predict its complications. Aminotransferase to platelet ratio index (APRI) is a simple non-invasive marker of hepatic fibrosis. We aimed to correlate APRI with HVPG and to determine the usefulness of APRI in predicting complication of cirrhosis.

Methods

APRI and HVPG were measured in consecutive patients of cirrhosis aged 18 to 70 years. Spearman’s rho was used to estimate their correlation; a cut-off value of APRI to predict severe portal hypertension (HVPG >?12 mmHg) was determined.

Results

This study, conducted between August 2011 and December 2014, included 277 patients, median age 51 (range: 16–90) years, 84% males. Etiology of cirrhosis was alcohol in 135 (49%), cryptogenic/nonalcoholic steatohepatitis (NASH) in 104 (38%), viral in 34 (12%), and others in 4 (1%). Median Child-Turcott-Pugh (CTP) and model for end-stage liver disease (MELD) scores were 7 (5–11) and 11 (6–33), respectively. Median HVPG was 17.0 (1.5–33) mmHg and median APRI was 1.09 (0.21–12.22). There was positive correlation between APRI and HVPG (Spearman’s rho 0.450, p?<?0.001). The area under the receiver operating characteristic (ROC) curve of APRI for predicting severe portal hypertension was 0.763 (p?<?0.01). Youden’s index defined the cut-off of APRI for predicting HVPG >?12 mmHg was 0.876 with a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 71%, 78%, 94%, 38%, and 73%, respectively. APRI also correlated well with CTP, variceal size, bleeding status, ascites but not with MELD.

Conclusions

APRI score of 0.876 has an acceptable accuracy to predict severe portal hypertension (HVPG >?12 mmHg). High APRI also correlated with severity of cirrhosis and its complications. Thus, APRI may be used as a simple, bedside, non-invasive, and inexpensive tool for evaluating portal hypertension and complications of cirrhosis.

     

Early primary prophylaxis with beta-blockers does not prevent the growth of small esophageal varices in cirrhosis: a randomized controlled trial

Background

The efficacy of portal pressure reduction by beta-blockers and the utility of serial hepatic venous pressure gradient (HVPG) measurements for the management of small (≤5 mm) esophageal varices in patients of cirrhosis are not clear.

Aims

The study had the following aims: to study (1) the effect of propranolol on the growth of small varices and (2) whether single or serial HVPG measurements result in a better outcome compared to no measurement in patients with small varices.

Methods

Consecutive cirrhosis patients with small varices, without any history of variceal bleed, were randomized to receive propranolol or placebo and to undergo no HVPG, only baseline HVPG, or serial HVPG measurements.

Results

A total of 150 cirrhotics (cirrhosis predominantly viral or alcohol induced) were included (77 in the beta-blocker and 73 in the placebo group). Baseline characteristics were similar. The actuarial 2-year risk of growth of varices (primary endpoint) was 11 and 16% in the propranolol and placebo group, respectively (P = 0.786). Variceal bleeding and mortality were also comparable in the two groups. Similarly, the outcome was not influenced by HVPG measurements (whether serial, only baseline, or no HVPG). A bilirubin level of ≥1.5 mg/dl was found to be an independent predictor of variceal progression.

Conclusions

In cirrhotics with small esophageal varices, nonselective beta-blockers are unable to prevent the growth of varices, variceal bleed, or mortality. HVPG monitoring of these patients did not change the outcome; however, the role of HVPG-guided therapy modification needs to be studied.     

Clinically Severe Portal Hypertension: Role of Multi-detector Row CT Features in Diagnosis

Background and Aim

To explore the CT signs which permit estimation of clinically severe portal hypertension (PH) [≥12 of hepatic vein pressure gradient (HVPG)].

Methods

One-hundred and seven consecutive patients who underwent HVPG measurement in the PH group and 52 controls were included. The diameters of main portal vein (øMPV), superior mesenteric vein (øSMV), splenic vein (øSV), and left gastric vein, øMPV/øSV, øSMV/øSV, as well as estimated spleen volumes were evaluated on the CT scan. The grade of varix and ascites were also evaluated semi-quantitatively. We explored the statistically significant CT features related to severe PH and performed a logistic regression analysis for an estimation model for severe PH.

Results

øMPV/øSV and øSMV/øSV tended to gradually increase as the PH became severer, and the difference between severe and not severe groups was statistically significant (p = 0.015 and 0.038, respectively). According to the regression analysis, øSMV/øSV and the grade of esophageal varix and ascites were finally included as related variables for predicting severe PH. The odds ratio (OR) of øSMV/øSV was 4.596, and large esophageal varix (OR 4.135) and mild (OR 3.051) and large amount of ascites (OR 21.781) were statistically significantly related to severe PH.

Conclusion

Changing diameters of portal system, the grades of esophageal varices and ascites on multi-detector row computed tomography might be indicative features for clinically severe PH.     

Portal hemodynamics and clinical outcomes of patients with gastric varices after balloon-occluded retrograde transvenous obliteration

Background

Long-term hemodynamic effects and clinical outcomes after balloon-occluded retrograde transvenous obliteration (B-RTO) remain unclear. The purpose of this study was to evaluate long-term clinical results and effects on portal hemodynamics after B-RTO for the treatment of gastric varices with spontaneous gastrorenal shunt.

Methods

A total of 21 patients with cirrhosis and gastric varices treated by B-RTO were evaluated. The cumulative survival rate was calculated, portal blood flow was measured by Doppler ultrasonography, and liver function was estimated on the basis of Child-Pugh classification before and 1 year after B-RTO.

Results

Gastric varices disappeared or decreased markedly in size in all patients. Overall cumulative survival rates at 1, 3 and 5 years were 90.48, 71.11 and 53.71%, respectively. Portal blood flow increased significantly from 681.9 ± 294.9 to 837.0 ± 279.1 ml/min (P = 0.0125) after B-RTO. Child-Pugh score was not significantly changed (P = 0.755) after obliteration, but serum albumin was elevated significantly from 3.49 ± 0.49 to 3.75 ± 0.53 g/dl (P = 0.0459). The ascites score was significantly increased (P = 0.0455) after B-RTO, but all cases of ascites could be controlled with medication.

Conclusions

Balloon-occluded retrograde transvenous obliteration is a safe and effective treatment for gastric varices with gastrorenal shunt. Portal blood flow and serum albumin parameters are increased, and liver function is unchanged after B-RTO.     

Effects of 1-year administration of olmesartan on portal pressure and TGF-beta1 in selected patients with cirrhosis: a randomized controlled trial

Background

The renin-angiotensin system plays an important role in hepatic fibrosis and portal hypertension. We evaluated the long-term effects of olmesartan, an angiotensin type 1 (AT1) receptor blocker, on hemodynamics and liver fibrosis.

Methods

Forty-eight selected patients with cirrhosis were randomly divided into two groups of 24 patients each, those who received and those who did not receive olmesartan treatment for 1?year. Hepatic hemodynamic studies, and measurements of transforming growth factor-beta1 (TGF-beta1) and blood markers of hepatic fibrosis, including serum hyaluronic acid (HA), type IV collagen, and procollagen III N-terminal propeptide levels, were also performed at the beginning and end of the study.

Results

The median dose of the final drug administration was 20?mg (range 10?C40?mg). Olmesartan reduced the hepatic venous pressure gradient (HVPG) by ?12.9?±?9.1% (p?=?0.035) after 1?year. No significant changes were seen in controls. Six of the 24 patients (25%) in the olmesartan group showed a >20% reduction of HVPG from baseline values. TGF-beta1 was significantly decreased in patients who received olmesartan (7.0?±?8.2 vs. 3.1?±?1.6?ng/mL, p?=?0.046) but there was no decrease in the controls. A significant trend was shown by correlating HA and TGF-beta1 variations in cirrhosis patients (p?=?0.018, r?=?0.377). Fibrosis markers were unchanged at the end of the study in both groups.

Conclusions

Olmesartan induced a mild reduction of portal pressure and TGF-beta1 for 1?year, but did not suppress hepatic fibrosis markers.     

Correlation of HVPG Level with CTP Score,MELD Score,Ascites, Size of Varices,and Etiology in Cirrhotic Patients

Background/Aim:

This study intends to determine the correlation of a patient''s hepatic venous pressure gradient (HVPG) measurement with six factors: Child–Turcotte–Pugh (CTP) score, model for end-stage liver disease (MELD) score, presence of ascites, size of varices, presence of variceal bleeding, and an etiology of cirrhosis. The study also aims to identify the predictors of higher HVPG measurements that can indirectly affect the prognosis of cirrhotic patients.

Patients and Methods:

Thirty patients diagnosed with cirrhosis were enrolled prospectively and each patient''s HVPG level was measured by the transjugular catheterization of the right or middle hepatic vein. The wedged hepatic venous pressure (WHVP) and free hepatic venous pressure (FHVP) were measured using a 7F balloon catheter. The HVPG level was calculated as the difference between the WHVP and FHVP measurements.

Results:

The mean HVPG level was higher in alcoholic than in nonalcoholic cirrhosis (19.5 ± 7.3 vs 15.2 ± 4.5 mm Hg, P = 0.13). The mean HVPG was also higher in bleeders compared with nonbleeders (18.5 ± 5.3 vs 10.7 ± 3.1 mmHg, P = 0.001). Patients with varices had a higher mean HVPG level than those without varices (17.4 ± 5.8 vs 11.7 ± 3.9 mmHg, P = 0.04). The difference among the three categories of varices (small, large, and no varices) was statistically significant (P = 0.03). In addition, the mean HVPG level was higher in patients with ascites than in those without ascites (18.7 ± 4.7 vs 11 ± 5.3 mmHg, P = 0.002), and it was significantly higher in patients in CTP class C (21.8 ± 5.5 mmHg) as compared with those in CTP class B (16.9 ± 2.9 mmHg) and CTP class A (10.5 ± 4.1 mmHg; P ≤ 0.001).

Conclusion:

HVPG levels were significantly higher in patients in CTP class C as compared with those in CTP classes A and B, thereby indicating that an HVPG measurement correlates with severity of liver disease. A high HVPG level signifies more severe liver disease and can predict the major complications of cirrhosis.     

Decreased Prohepcidin Levels in Patients with HBV-Related Liver Disease: Relation with Ferritin Levels

Background

Levels of prohepcidin, a homeostatic regulator of iron absorption, are altered in chronic hepatitis C and liver cirrhosis. However, data on the potential alterations of prohepcidin in patients with HBV-related liver disease are scarce. We investigated whether serum prohepcidin is related to iron overload and perenchymal dysfuction in HBV-related liver disease.

Methods

Three groups of subjects were studied: 66 patients with chronic hepatitis B, 32 patients with HBV-related cirrhosis, and 42 healthy controls without evidence of liver disease. Serum levels of prohepcidin were determined by enzyme-linked immunosorbent assay.

Results

Serum prohepcidin levels were significantly lower in patients with HBV-related cirrhosis (175.85 ± 71.5 ng/ml) than in patients with chronic hepatitis B (209.02 ± 62.7 ng/ml P < 0.05) and controls (222.4 ± 128.4 ng/ml, P < 0.05). After adjustment for potential confounders, prohepcidin was found to be an independent predictor of ferritin levels in multiple linear regression analysis (β = ?1.10, t = ?3.11, P < 0.01).

Conclusion

These results demonstrate that prohepcidin levels are reduced in patients with HBV-related cirrhosis and are an independent correlate of serum ferritin.     

The effect of continuous positive airway pressure therapy on blood pressure and arterial stiffness in hypertensive patients with obstructive sleep apnea

Aim

We aimed to evaluate the effect of continuous positive airway pressure (CPAP) therapy on blood pressure (BP) and arterial stiffness in hypertensive patients with obstructive sleep apnea (OSA).

Patients and methods

We studied 38 hypertensive patients who suffered from severe OSA. Ambulatory BP measurement was performed at baseline and after at least 3 months of uninterrupted CPAP therapy. In 19 of these patients, we also measured pulse wave velocity (PWV) at baseline, after the first night of CPAP therapy and at 3 months. Fifteen normotensive subjects without OSA comprised the control group.

Results

CPAP therapy reduced systolic BP from 141.5?±?12.1 to 133.5?±?9.7 mmHg (p?=?0.007) and diastolic BP from 87.8?±?6.8 to 83?±?5.4 mmHg (p?=?0.004). CPAP also reduced the PWV from 8.81?±?1.4 to 8.18?±?1 m/s after the first night of CPAP therapy (p?=?0.003) and to 7.37?±?1 m/s at 3 months (p?=?0.007).

Conclusions

To the best of our knowledge, this is the first study demonstrating that CPAP therapy in hypertensive patients with OSA improves arterial stiffness from the first night and that this favorable effect is maintained for at least 3 months of CPAP use. A reduction in BP was also observed, even though BP control was not always achieved.     

Incidence,predictors, and clinical course of atrial tachyarrhythmias in patients with pulmonary hypertension

Background

The prevalence and predictors of atrial tachyarrhythmias (ATa) in patients with pulmonary hypertension (PH) is less well understood.

Methods

We performed a retrospective study including 311 patients with PH, confirmed by right heart catheterization in our center between 2007 and 2011. Baseline characteristics, clinical, echocardiographic, and hemodynamic data were collected and compared between patients with and without ATa.

Results

The mean age was 61?±?13 years with 64 % females. The mean pulmonary artery pressure (mPAP) was 46?±?20 mmHg, mean left ventricular ejection fraction (LVEF) was 55?±?13 %, and mean pulmonary capillary wedge pressure (PCWP) was 19?±?9 mmHg. Of the 311 patients with PH, 121 (39 %) patients had ATa. Patients with ATa were older (p?p?=?0.03), diabetes (p?=?0.015), coronary artery disease (p?p?p?=?0.001), impaired LVEF (p?=?0.02), and left atrial enlargement (p?p?=?0.022). In multivariate analysis using Cox-proportional hazard model, the independent predictors of mortality were age (HR 1.05; p?=?0.003), coronary artery disease (HR 2.34; p?=?0.047), LVEF (HR 0.793; p?=?0.023), and mPAP (HR 1.023; p?=?0.003).

Conclusion

ATa are common in patients with PH. Left heart disease, left atrial enlargement, and elevated PCWP but not right atrial enlargement or mPAP predict the occurrence of ATa in patients with PH.     

The relationship between transient elastography and histological collagen proportionate area for assessing fibrosis in chronic viral hepatitis

Background

Collagen proportionate area (CPA) has a better correlation with hepatic venous pressure gradient (HVPG) than with Ishak stage. Liver stiffness measurement (LSM) is proposed as non invasive marker of portal hypertension/disease progression. Our aim was to compare LSM and CPA with Ishak staging in chronic viral hepatitis, and HVPG in HCV hepatitis after transplantation.

Methods

One hundred and sixty-nine consecutive patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections pre/post liver transplantation (LT), had a liver biopsy combined with LSM (transient elastography), CPA (biopsies stained with Sirius Red and evaluated by digital image analysis and expressed as CPA) and HVPG (measured contemporaneously with transjugular biopsies in LT HCV patients).

Results

LSM was dependent on CPA in HBV (r ² = 0.61, p < 0.0001), HCV (r ² = 0.59, p < 0.0001) and LT groups (r ² = 0.64, p < 0.0001). In all three groups, CPA and Ishak were predictors of LSM, but multivariately CPA was better related to LSM (HBV: r ² = 0.61, p < 0.0001; HCV: r ² = 0.59, p < 0.0001; post-LT: r ² = 0.68, p < 0.0001) than Ishak stage. In the LT group, multiple regression analysis including HVPG, LSM, aspartate aminotransferase to platelet ratio index (APRI) and Ishak stage/grade, showed that only CPA was related to HVPG (r ² = 0.41, p = 0.01), both for HVPG ≥6 mmHg (OR 1.34, 95 % CI 1.14–1.58; p < 0.0001) or ≥10 mmHg (OR 1.25, 95 % CI 1.06–1.47; p = 0.007).

Conclusion

CPA was related to LSM in HBV or HCV hepatitis pre/post-LT. CPA was better related to LSM than Ishak stage. In the LT HCV group, CPA was better related to HVPG than Ishak stage/grade, LSM or APRI. CPA may represent a better comparative histological index for LSM, rather than histological stages.     

Physiological and pharmacological properties of a modified Brooke ileostomy: justification for retaining the most distal ileum

Purpose

The traditional Brooke ileostomy removed the last 8–15 cm of the ileum due to concern of occurrence of terminal ileal Crohn’s disease, vide infra the ileocolic sphincter was removed. Retaining all the terminal ileum has the potential of retaining the ileocolic sphincter. Our aim was to investigate whether a high-pressure zone existed within the last few centimetres of the ileum and its response to pharmacological stimuli.

Methods

A balloon manometry catheter was introduced into the stoma of 16 patients who had formation of an end ileostomy (ileocolic sphincter retained, ICS). Recordings were made at 1 cm intervals from the meatus in order to identify the maximum intra-luminal resting and intra-abdominal pressure. At the point of maximum resting pressure, the response to phenylephrine (10 % gel) and glyceryl trinitrate (GTN) (0.2 % paste) was recorded. Results were recorded using an Ohmeda Oestiva 5 manometry system (in millimeter of mercury) and data were analysed using ANOVA. Results were compared with 13 historical controls (ileocolic sphincter removed).

Results

There was no significant difference in resting intra-abdominal pressure between the two groups (historical controls 8.5?±?3.0 mmHg; ICS 9.0?±?3.2 mmHg), p?=?NS. The maximum resting intra-luminal pressure in ICS patients exceeded historical controls 16?±?2.9 vs 10.0?±?2.5 mmHg, p?<?0.001. In ICS patients, phenylephrine increased the resting pressure to 26.0?±?3.5 mmHg, p?<?0.001. In historical controls, the pressure remained unchanged, 12?±?4.7 mmHg, p?=?NS. Subsequent addition of GTN to both groups lowered maximum intra-luminal pressure to pre-study values, 10?±?4.2 mmHg (ICS) and 7?±?3.5 mmHg (controls), p?=?NS.

Conclusion

Retention of the ileocolic sphincter in a modified Brooke ileostomy preserves a physiological high-pressure zone, the properties of which can be modified by pharmacological agents.     

Effect of endoscopic variceal obliteration by band ligation on portal hypertensive gastro-duodenopathy: endoscopic and pathological study

Introduction and aim

A few studies have shown that the degree of portal hypertensive gastropathy (PHG) and duodenopathy (PHD) has been worsening after the introduction of therapeutic endoscopic interventions. This study aimed to determine the impact of esophageal variceal eradication by endoscopic variceal ligation (EVL) on PHG and PHD using endoscopic and histopathologic assessment.

Methods

Fifty patients with esophageal varices for which EVL was indicated were included. EVL was carried out until complete variceal eradication was achieved. The degree of severity of PHG and PHD were recorded before and 4 weeks after variceal eradication. Biopsies were taken from various parts of the stomach and duodenum before and 4 weeks after variceal eradication.

Results

The whole Baveno score (4 vs. 2.5) increased significantly after variceal eradication when compared to those before eradication (p < 0.05). After obliteration, only 19 (38 %) patients had mild PHG versus 37 (74 %) before EVL, while severe PHG was found in 31 (62 %) patients versus 11 (22 %) before EVL and the difference was highly statistically significant. No significant changes were found regarding endoscopic PHD lesions before and after variceal eradication. Pathological changes as average blood vessel count, angiogenesis, ectasia and blood extravasation in stomach and duodenum significantly increased after EVL. Large esophageal varices (III–IV) and Baveno score (>1) at baseline endoscopy were independent risk factors for development of severe PHG after variceal obliteration (p < 0.05).

Conclusion

PHG increased significantly, endoscopically and pathologically, after variceal obliteration by EVL. Although PHD did not significantly change as documented by endoscopy, pathological examination documented statistically significant changes in the duodenum after EVL.

     

Reverse atrial electrical remodelling induced by continuous positive airway pressure in patients with severe obstructive sleep apnoea

Background

Obstructive sleep apnoea (OSA) is associated with cardiovascular morbidity and mortality, including atrial arrhythmias. Continuous positive airway pressure (CPAP) is the gold standard treatment for OSA; its impact on atrial electrical remodelling has not been fully investigated. Signal-averaged p-wave (SAPW) duration is an accepted marker for atrial electrical remodelling.

Objective

The objective of this study is to determine whether CPAP induces reverse atrial electrical remodelling in patients with severe OSA.

Methods

Consecutive patients attending the Sleep Disorder Clinic at Kingston General Hospital underwent full polysomnography. OSA-negative controls and severe OSA were defined as apnoea–hypopnea index (AHI)?<?5 events/hour and AHI?≥?30 events/hour, respectively. SAPW duration was determined at baseline and after 4–6 weeks of CPAP in severe OSA patients or without intervention controls.

Results

Nineteen severe OSA patients and 10 controls were included in the analysis. Mean AHI and minimum oxygen saturation were 41.4?±?10.1 events/hour and 80.5?±?6.5 % in severe OSA patients and 2.8?±?1.2 events/hour and 91.4?±?2.1 % in controls. At baseline, severe OSA patients had a greater SAPW duration than controls (131.9?±?10.4 vs 122.8?±?10.5 ms; p?=?0.02). After CPAP, there was a significant reduction of SAPW duration in severe OSA patients (131.9?±?10.4 to 126.2?±?8.8 ms; p?<?0.001), while SAPW duration did not change after 4–6 weeks in controls.

Conclusion

CPAP induced reverse atrial electrical remodelling in patients with severe OSA as represented by a significant reduction in SAPW duration.     

Real-life practice of antiviral therapy and disease patterns of patients with chronic hepatitis B: a single-center retrospective observation study

Purpose

To analyze the spectrum of diseases in patients with chronic hepatitis B virus (HBV) infection and their association with patient clinicopathologic characteristics and the effect of antiviral therapy on the spectrum of diseases in the study cohort.

Methods

We retrospectively reviewed the clinicopathologic and virologic records of patients with chronic HBV infection hospitalized at our institution during 2011. Demographic data, hepatitis B e antigen (HBeAg) status and HBV DNA (log₁₀ IU/ml) were obtained.

Results

A total of 1,619 patients were included; 272 (17.2 %) patients received antiviral therapy for a mean duration of 24.5 ± 18.3 months, and 71.0 % (198/279) patients were compliant with their antiviral therapy. HBeAg-positive patients had a markedly higher rate of moderate and severe CHB than HBeAg-negative patients (p < 0.001) but a significantly lower rate of liver cirrhosis (p < 0.001). The rate of severe and fulminant CHB was significantly lower in patients receiving antiviral therapy than in those not receiving antiviral therapy.

Conclusions

Patients receiving antiviral therapy exhibit a different spectrum of diseases from patients not receiving such therapy.     

The usefulness of transient elastography by FibroScan for the evaluation of liver fibrosis

Introduction

Liver stiffness measurement (LSM) is used for the assessment of liver fibrosis. However, there is limited data in Indian patients.

Aims and Objective

The aim of this study was to find the correlation of LSM, aspartate transaminase to platelet ratio index (APRI) with fibrosis as assessed by liver biopsy (LB), and predictors of discordance between LB and LSM.

Methods

One hundred and eighty-five consecutive patients who underwent liver biopsy and transient elastography (TE) were enrolled. Fibrosis was graded by two independent pathologists using the METAVIR classification. Area under receiver operating curves (AUROC) was used to evaluate the accuracy of transient elastography and APRI in diagnosing significant fibrosis (F>2) and cirrhosis (F4).

Results

Predominant etiologies were hepatitis B (46 %) and hepatitis C (26 %). LSM was unsuccessful in ten patients (5 %) because of small intercostal space (n?=?3) and obesity (n?=?7). Fibrosis is significantly correlated with LSM (r?=?0.901, p?=?0.001) and APRI (r?=?0.736, p?=?0.001). There was a significant difference in median LSM value in patients with no fibrosis (F0) in comparison to patients having mild fibrosis [mild portal fibrosis (F1)?+?fibrosis with few septa (F2)] (4.5 vs. 7.5 kPa, p?=?0.001) and advanced fibrosis [bridging fibrosis that is spreading and connecting to other areas that contain fibrosis (F3)?+?cirrhosis or advanced scarring of the liver (F4)] (4.5 vs. 19.4 kPa, p?=?0.001). Similarly, there was a significant difference in mean APRI value in patients with F0 in comparison to patients having mild fibrosis (F1?+?F2) (0.55?±?0.31 vs. 1.09?±?0.81, p?=?0.001) and advanced fibrosis (F3?+?F4) (2.3?±?1.3, p?=?0.001). AUROC for diagnosis of significant fibrosis was 0.98 (95 % confidence interval (CI) 0.963–0.999) for TE and 0.865 (95 % CI 0.810–0.920) for APRI. Optimal TE value was 10.0 kPa for diagnosis of significant fibrosis and 14.7 kPa for cirrhosis with specificity and sensitivity of 89 %, 98 % and 96 %, and 97 %, respectively. On multivariate analysis, total bilirubin and histological activity index (HAI) were identified as an independent predictor of TE inaccuracy.

Conclusion

LSM is a reliable predictor of hepatic fibrosis in Indian patients. LSM is superior to APRI for noninvasive diagnosis of hepatic fibrosis and cirrhosis, and high bilirubin (10.5 mg/dL) and Ishak HAI grade (>11) were independent predictors of discordance between LB and LSM.     

Portal hypertensive polyps: distinct entity

Introduction

Gastric mucosal changes in portal hypertension (PH) are well known, but gastroduodenal polyps in PH are rarely described.

Aim

This study aims to estimate prevalence of upper gastrointestinal (GI) polyps in patients with PH of any etiology and to evaluate the role of angiogenesis in portal hypertensive polyps.

Material and Methods

This is a retrospective analysis of all patients undergoing upper GI endoscopy to compare the etiology of the polyps in the portal hypertensive group vs. those without PH. The diagnosis of polyps was done using standard histological criteria. Another part of the study consisted of prospective analysis of vascular proliferative marker CD 34 and morphometry in 47 patients.

Results

A total of 3,811 upper GI endoscopies were done of which 121 patients (3.2 %) had polyps in upper GI tract. In patients with PH (=631), polyps were noted in 16, portal hypertensive polyps in 9, hyperplastic in 6, and fundic gland polyp in 1. In the patients without PH (n?=?3,180), polyps of various etiologies were noted in 105 patients. The prevalence of polyps of all causes was similar in both groups (2.5 % vs. 3.3 %, p?=?0.3957). Prevalence of hyperplastic polyps was similar in PH (0.95 %) and non-PH group (1.3 %). On immunohistochemistry, PH polyps and PH gastric mucosa had significantly higher vessel diameter of >50 μm, increased vascular density as compared to non-portal hypertensive polyps (PHP) and normal gastric mucosa.

Conclusion

PHP are definite identifiable lesion in patients of cirrhosis with PH. PHP are probably related to increased angiogenesis in gastric mucosa.     

Effect of Mosapride Combined with Esomeprazole Improves Esophageal Peristaltic Function in Patients with Gastroesophageal Reflux Disease: A Study Using High Resolution Manometry

Background

Whether addition of prokinetics to proton pump inhibitors improves esophageal peristalsis and symptoms in patients with gastroesophageal reflux disease (GERD) remains unknown.

Aim

We evaluated the effect of mosapride, a 5-HT₄ agonist, and PPI cotherapy in patients with GERD on esophageal motility using high-resolution manometry (HRM).

Method

This study was designed as a double-blind, randomized, placebo-controlled trial. Patients with GERD were allocated to a group either taking 40 mg esomeprazole plus 30 mg mosapride or taking esomeprazole plus placebo. Symptom assessment and the HRM study were conducted before drug treatment and after 4 weeks.

Results

Of 50 patients enrolled, 24 in the mosapride group (49 years old, 15 males) and 19 in the placebo group (43 years old, nine males) completed the study. Approximately 79 % of the patients had normal peristaltic function. Treatment response was not different between the two groups (79 vs. 68 %). Mosapride cotherapy tended to yield better response in patients with dyspepsia than those without dyspepsia (92 vs. 67 %). Lower esophageal sphincter pressure didn’t change in both groups. Intrabolus pressure decreased in the mosapride group (3.4 ± 3.5 mmHg to 1.4 ± 4.1 mmHg, P < 0.05). Distal esophageal amplitude increased in the mosapride group and not in the placebo group (81 ± 34 to 89 ± 29 mmHg vs. 82 ± 32 to 83 ± 31 mmHg).

Conclusion

Adding mosapride on esomeprazole improved esophageal contractability and lowered intrabolus pressure in patients with GERD. Mosapride and esomeprazole cotherapy tended to yield better response in patients with concomitant dyspepsia.