Assessment of portal hypertension severity using machine learning models in patients with compensated cirrhosis

1. Download : Download high-res image (255KB)
2. Download : Download full-size image

     

Haemodynamic effects of enalaprilat on portal hypertension in patients with HBsAg-positive cirrhosis

Abstract It has been suggested that enalaprilat inhibits the renin-angiotensin-aldosterone system in plasma and tissue; it may therefore reduce portal vascular pressure owing to secondary hyperaldosteronism in patients with liver cirrhosis. In order to evaluate this concept, 20 patients with hepatitis B surface antigen (HBsAg)-positive liver cirrhosis and portal hypertension received an intravenous infusion of 2.5 mg of enalaprilat. Wedged hepatic venous pressure, free hepatic venous pressure and cardiac index were measured before, immediately after, and then 15 min, 30 min and 1 h after intravenous enalaprilat infusion. The mean pressure gradient between wedged hepatic venous pressure and free hepatic venous pressure was significantly decreased, by 13% immediately after, 18% at 15 min, 23% at 30 min and 13% at 1 h after infusion of enalaprilat. Thirteen patients experienced a decrease of hepatic venous pressure gradient (HVPG) greater than 5 mmHg, another three 3-5 mmHg and the remaining four patients exhibited no significant change in HVPG. Systemic haemodynamic indices, including pulmonary arterial pressure, pulmonary capillary wedge pressure and central venous pressure, decreased significantly at 15 and 30 min after enalaprilat infusion ( P < 0.01). Liver function, renal function and blood routine before and after enalaprilat infusion showed no significant changes. There were no adverse effects during or after enalaprilat infusion. We conclude that enalaprilat infusion can quickly and safely reduce the hepatic venous pressure gradient in patients with HBsAg-positive cirrhosis.     

Assessment of liver stiffness in patients after living donor liver transplantation by transient elastography

Objective. Recurrence of hepatitis and progression of fibrosis are major problems in liver transplantation (LT) for patients with hepatitis C. Liver stiffness measurement (LSM) by transient elastography correlates well with histologic liver fibrosis stages in chronic liver diseases. The aim of this study was to evaluate the usefulness of transient elastography for the assessment of fibrosis in patients after living donor LT. Material and methods. Seventy-nine patients who visited our institution, and in whom LSM was successfully evaluated, were enrolled in the study. The patients were divided into three groups according to positivity for hepatitis C antibody and hepatitis B surface antigen as the hepatitis C virus (HCV) group (n=37), the hepatitis B virus (HBV) group (n=10), and the NBNC (negative for both hepatitis B and C) group (n=32). The correlation between LSM and histologic fibrosis stage was assessed in 36 patients. LSM was also compared with regard to the effect of interferon therapy in HCV patients. Results. The median value for liver stiffness was 6.8 kPa and the median time from LT was 3.1 years. In patients who underwent liver biopsy, stiffness was significantly correlated with the stages of fibrosis (p<0.001, rho = 0.848). In patients who received interferon therapy after LT, the LSM decreased over time in those with a sustained virological response, whereas LSM increased in patients without a response. Conclusion. Transient elastography may be an appropriate non-invasive procedure to sequentially assess the progression of liver fibrosis in patients after LT.     

Comparison of Doppler ultrasonography and the hepatic venous pressure gradient in assessing portal hypertension in liver cirrhosis

BACKGROUND AND AIM: This prospective study aimed to determine whether Doppler ultrasonography can represent the hepatic venous pressure gradient (HVPG) as an assessment of the severity of portal hypertension and the response to terlipressin, which reduces the portal pressure in liver cirrhosis. METHODS: The HVPG and the Doppler ultrasonographic parameters, such as the portal venous velocity and the splenic venous velocity, the pulsatility and the resistive index of the hepatic, splenic and renal arteries were measured in 138 patients with liver cirrhosis. The changes in the HVPG and the portal venous velocity after administering terlipressin were evaluated in 43 of the 138 patients. The patients who showed a reduction in the HVPG of more than 20% of the baseline were defined as responders to terlipressin. RESULTS: None of the Doppler ultrasonographic parameters correlated with the HVPG. Both the HVPG (28.0 +/- 19.8%) and the portal venous velocity (29.7 +/- 13.2%) showed a significant reduction after terlipressin administration. However, the portal venous velocity decreased significantly, not only in the responders (31.0 +/- 12.0%) but also in the non-responders (25.2 +/- 16.4%). CONCLUSIONS: Doppler ultrasonography does not represent the HVPG, and is therefore not suitable for replacing HVPG as a means of assessing the severity of portal hypertension and the response to drugs which reduce the portal pressure in liver cirrhosis.     

A placebo-controlled clinical trial of nadolol in the prophylaxis of growth of small esophageal varices in cirrhosis

BACKGROUND & AIMS: Beta-blockers are extensively used to prevent variceal bleeding in patients with large esophageal varices. It is not established if beta-blockers delay the growth of small varices. METHODS: A total of 161 patients with cirrhosis and small esophageal varices (F1 according to the classification of Beppu et al.) without previous bleeding were enrolled. A total of 83 patients were randomized to nadolol (dose adjusted to decrease resting heart rate by 25%; mean dose given, 62 +/- 25 mg/day) and 78 to placebo. The principal end point was occurrence of large esophageal varices (F2 or F3 according to the classification of Beppu et al.). Endoscopic examination was performed after 12, 24, 36, 48, and 60 months of follow-up. Mean follow-up was 36 months. RESULTS: The 2 groups were well matched for demographic and clinical characteristics. During the study period, 9 patients randomized to nadolol and 29 randomized to placebo had growth of esophageal varices. At the end of follow-up, the cumulative risk was 20% versus 51% (P < 0.001) (absolute risk difference, 31%; 95% confidence interval, 17%-45%). When possible confounding factors were taken into account, treatment was a significant factor predicting growth of varices (odds ratio, 4.0; 95% confidence interval, 1.95-8.4). The cumulative probability of variceal bleeding was also lower in patients randomized to nadolol (P = 0.02). Survival was not different (P = 0.33). Adverse effects resulting in withdrawal of drug occurred in 9 in the nadolol group and one in the placebo group (P = 0.01). CONCLUSIONS: This study suggests that beta-blocker prophylaxis of variceal bleeding in patients with compensated cirrhosis should be started when small esophageal varices are present.     

Modified spleen stiffness measurement by transient elastography is associated with presence of large oesophageal varices in patients with compensated hepatitis C virus cirrhosis

To evaluate the accuracy of liver transient elastography (TE), spleen TE and other noninvasive tests (AAR, APRI score, platelet count, platelet/spleen ratio) in predicting the presence and the size of oesophageal varices in compensated hepatitis C virus (HCV) cirrhosis, we studied 112 consecutive patients with compensated HCV cirrhosis who underwent biochemical tests, gastrointestinal endoscopy, liver TE and spleen TE by Fibroscan^® (Echosens, Paris, France) using a modified software version with a range between 1.5 and 150 kPa. Spleen TE was not reliable in 16 patients (14.3%). Among the 96 patients with a valid measurement (69.8% men, mean age: 63.2 ± 9.5 years), 43.7% had no oesophageal varices, 29.2% had grade 1% and 27.1% had grade 2 or grade 3 oesophageal varices. Patients with values of 75 kPa by standard spleen TE had mean values of modified spleen TE of 117 kPa (range: 81.7–149.5). Linear regression revealed a significant correlation between modified spleen TE and oesophageal varix size (r = 0.501; beta: 0.763, SE: 0.144; P < 0.001). On univariate analysis, the variables associated with grade 2/grade 3 oesophageal varices were AAR score, APRI score, platelet/spleen ratio, liver TE and modified spleen TE. On multivariate analysis, only modified spleen TE (OR: 1.026; 95% CI: 1.007–1.046; P = 0.006) and AAR (OR: 14.725; 95% CI: 1.928–112.459; P = 0.010) remained independently associated with grade 2/grade 3 oesophageal varices. Platelet/spleen ratio was the best predictor of oesophageal varices area under the ROC curve (AUROC: 0.763, cut‐off: 800, sensitivity: 74%, specificity: 70%), while modified spleen TE was more accurate in predicting grade 2/grade 3 oesophageal varices (AUROC: 0.82, cut‐off: 54.0 kPa, sensitivity: 80%, specificity: 70%). Portal hypertension increases spleen stiffness, and the measurement of modified spleen TE is an accurate, noninvasive tool for predicting the presence of large oesophageal varices in patients with compensated HCV cirrhosis.     

The stratification of cirrhosis

Cirrhosis is traditionally seen as an irreversible stage of chronic liver disease although its clinical course may last several years. Overall, the clinical management of patients with cirrhosis is based on the observation of clinical events mostly related to complications of portal hypertension. Each event of cirrhosis decompensation has clear prognostic implications although it is not precisely predictable. In practice, the advancement in the knowledge of the mechanisms responsible for disease progression is not yet translated in clinical tools allowing the stratification of the cirrhotic stage according to pathophysiological mechanisms. This article provides a review of the main clinical and histopathological features of liver cirrhosis that are relevant for its clinical stratification together with the advancements provided by the introduction of non‐invasive measures of portal hypertension. Other clinical aspects that have a major impact on the quality of life and the possibility of liver transplantation are also discussed.     

瞬时弹性扫描诊断肝纤维化准确性研究

目的验证瞬时弹性扫描（FibroScan）诊断肝纤维化的准确性。方法选取141例慢性肝病患者,每例均进行肝脏活体组织检查,并应用瞬时弹性扫描仪测量肝脏硬度,以病理检查结果为金标准,验证FibroScan诊断肝纤维化的准确性。结果肝脏硬度与肝纤维化程度密切相关,Kendall相关系数为0．74（P=0．001）。FibroScan诊断肝纤维化F1～F4、F2～F4、F3～F4、F4期的受试者工作特征曲线下面积分别为0．97、O．96、0．99、0．97。结论FibroScan诊断肝纤维化有较好的准确性。     

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.     

Non-invasive assessment of liver fibrosis by transient elastography in post transfusional iron overload

Background: Liver fibrosis, assessed by biopsy, is the main complication of post transfusional liver iron overload. Transient elastography (TE) is a new, non invasive method able to measure liver stiffness (LS) caused by fibrosis. Method: We prospectively evaluated the predictive value of LS measurement for liver fibrosis evaluation in 15 chronically transfused patients and compared these results with the METAVIR histological fibrosis stage from liver biopsies. Results: Mean TE values significantly differed in patients with severe fibrosis (METAVIR F3, F4): 9.1 (±3.7 SD) kPa from those with mild or no fibrosis (METAVIR F0, F1, F2): 5.9 (±1.8 SD) kPa (P = 0.046). TE value above 6.25 kPa (Se = 80%; Sp = 70%; AUROC = 0.820) identified patients at risk for severe fibrosis (Negative Predictive Value 88%; Positive Predictive Value 57%). Conclusion: Transient elastography appears to be a reliable tool to evaluate liver fibrosis in post‐transfusional iron overload.