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.     

Influence of hepatic venous pressure gradient on the prediction of survival of patients with cirrhosis in the MELD Era

Measurements of portal pressure, usually obtained via the hepatic venous pressure gradient (HVPG) may be a prognostic marker in cirrhosis. The aim of this study was to evaluate the impact of HVPG on survival in patients with cirrhosis in addition to the Model for End-Stage Liver Disease (MELD) score. We also examined whether inclusion of HVPG in a model with MELD variables improves its prognostic ability. Retrospective analyses of all patients who had HVPG measurements between January 1998 and December 2002 were considered. Proportional hazards Cox models were developed. Prognostic calibrative and discriminative ability of the model was evaluated. In this period, 693 patients had a hepatic hemodynamic study, and 393 patients were included. Survival was significantly worse in those patients with greater HVPG value (univariate HR, 1.05; 95% CI, 1.02-1.08; P = .001). HVPG remained as an independent variable in a model adjusted by MELD, ascites, encephalopathy, and age (multivariate HR, 1.03; 95% CI, 1.00-1.06; P = .05) so that each 1-mmHg increase in HVPG had a 3% increase in death risk. In addition, HVPG as well as MELD score variables and age, significantly contributes to the calibrative predictive capacity of the prognostic model; however, discriminative ability improved only slightly (overall C statistic [95% CI]; MELD score variables: 0.71 [0.62-0.80], MELD score variables, age, and HVPG 0.76: [0.69-0.83]). In conclusion, HVPG has an independent effect on survival in addition to the MELD score. Although inclusion of HVPG and age in a survival predicting model would improve the calibrative ability of MELD, its discriminative ability is not significantly improved.     

Von Willebrand factor as new noninvasive predictor of portal hypertension, decompensation and mortality in patients with liver cirrhosis

von Willebrand factor antigen (vWF-Ag) is elevated in patients with liver cirrhosis, but the clinical significance is unclear. We hypothesized that vWF-Ag levels may correlate with portal pressure, measured by hepatic venous pressure gradient (HVPG), and predict clinically significant portal hypertension (CSPH; HVPG ≥10 mmHg), decompensation and mortality. Portal hemodynamics were assessed by HVPG measurement, whereas vWF-Ag levels were measured by enzyme-linked immunosorbent assay. During follow-up, complications of liver cirrhosis, death or transplantation were recorded. Two hundred and eighty-six patients (205 male and 81 female; mean age, 56 years) with liver cirrhosis were included. vWF-Ag correlated with HVPG (r = 0.69; P < 0.0001) and predicted CSPH independently of Child Pugh score. Higher vWF-Ag levels were associated with varices (odds ratio [OR] = 3.27; P < 0.001), ascites (OR = 3.93; P < 0.001) and mortality (hazard ratio: 4.41; P < 0.001). Using a vWF-Ag cut-off value of ≥241%, the AUC for detection of CSPH in compensated patients was 0.85, with a positive predictive value and negative predictive value of 87% and 80%, respectively. Compensated patients had 25% mortality after 53 months if the vWF-Ag was <315% compared to 15 months in patients with vWF-Ag >315% (P < 0.001). Decompensated patients had a mortality of 25% after 37 and 7 months if their vWF-Ag was <315% and >315%, respectively (P = 0.002). In compensated patients with a vWF-Ag >315% median time to decompensation or death was 32 months compared with 59 months in patients with vWF-Ag <315%. vWF-Ag equals Model for End-Stage Liver Disease (MELD) in mortality prediction (area under the curve [AUC] = 0.71 for vWF-Ag versus AUC = 0.65 for MELD; P = 0.2). Conclusion: vWF-Ag is a new, simple and noninvasive predictor of CSPH. A vWF-Ag cut-off value at 315% can clearly stratify patients with compensated and decompensated liver cirrhosis in two groups with completely different survival. vWF-Ag may become a valuable marker for the prediction of mortality in patients with liver cirrhosis in clinical practice. (HEPATOLOGY 2012).     

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).     

Alcohol Abstinence Improves Prognosis Across All Stages of Portal Hypertension in Alcohol-Related Cirrhosis

Background and AimsAlcohol-related liver disease is a leading cause of liver-related mortality. The effect of alcohol abstinence on the natural history of alcohol-related cirrhosis across distinct stages of portal hypertension has not been thoroughly investigated. In this study, we assessed the clinical implications of abstinence in patients with alcohol-related cirrhosis and clinically significant portal hypertension.MethodsAlcohol abstinence, hepatic decompensation, and mortality were assessed in patients with alcohol-related cirrhosis who underwent a baseline hepatic venous pressure gradient (HVPG) measurement and were diagnosed with clinically significant portal hypertension (HVPG ≥10 mm Hg).ResultsA total of 320 patients with alcohol-related cirrhosis (median age: 57 [interquartile range (IQR), 49.7-63.1] years; 75.6% male; 87.5% decompensated) and a median HVPG of 20 (IQR, 17-23) mm Hg were followed up for a median of 36 (IQR, 14-80) months. Overall, 241 (75.3%) patients remained abstinent, while 79 (24.7%) patients had active alcohol consumption. Alcohol abstinence was linked to a significantly reduced risk of hepatic decompensation (adjusted hazard ratio [aHR], 0.391; P < .001), as well as liver-related (aHR, 0.428; P < .001) and all-cause (aHR, 0.453; P < .001) mortality, after adjusting for baseline HVPG, MELD, and previous decompensation. Importantly, alcohol abstinence significantly reduced the cumulative incidence of hepatic decompensation in both groups with HVPG 10–19 mm Hg (P < .001) and HVPG ≥20 mm Hg (P = .002). The 3-year decompensation probability was 32.4% vs 60.0% in HVPG 10–19 mm Hg and 57.5% vs 82.6% in HVPG ≥20 mm Hg for abstinent patients vs active drinkers, respectively.ConclusionsAlcohol abstinence improves prognosis across all stages of portal hypertension in alcohol-related cirrhosis, including in patients who have already progressed to high-risk portal hypertension. (ClinicalTrials.gov, Number: NCT03267615).     

Hepatic Venous Pressure Gradient in Cirrhosis: Correlation with the Size of Varices, Bleeding, Ascites, and Child's Status

The hepatic venous pressure gradient (HVPG) clearly reflects portal pressure in cirrhotic portal hypertension. Its relation with variceal bleeding has been well studied. We undertook to study the relation of HVPG to variceal size, Child's status, and etiology of cirrhosis. Patients with cirrhotic portal hypertension with esophageal varices underwent HVPG measurement as part of a prospective evaluation. One hundred seventy-six cirrhotics with varices (M:F, 140:36; mean age, 42.6 ± 13.4 years), 104 with CLD related to viral etiology, 40 with alcoholic liver disease, 26 cryptogenic with cirrhosis, and 6 with miscellaneous causes of CLD underwent HVPG measurement. The mean HVPG was lower in patients with small varices (n = 77; 14.6 ± 5.9 mm Hg) than in patients with large varices (n = 99; 19.2 ± 6.6 mm Hg; P < 0.01). In patients with large varices, the mean HVPG in bleeders (n = 37) was higher than in nonbleeders (n = 62) (21.7 ± 7.2 vs 17.9 ± 6.2 mm Hg; P < 0.01). The mean HVPG was significantly higher in Child's B (n = 97; 17.4 ± 6.9 mm Hg) and C (n = 56; 19.0 ± 5.7 mm Hg) compared to Child's A cirrhotics (n = 23; 12.2 ± 5.9 mm Hg; P < 0.01), and Child's C compared to Child's B cirrhotics (P = 0.05). HVPG was higher in alcoholic compared to nonalcoholic cirrhotics (20.8 ± 7.3 vs 16.4 ± 6.3 mm Hg; P < 0.05), but this was not significant in multivariate analysis. The HVPG was comparable between hepatitis B- and hepatitis C virus-related cirrhotics (P = 0.8). Cirrhotics with ascites had a higher HVPG than those without ascites (18.5 ± 5.6 vs 16.6 ± 7.6 mm Hg; P = 0.02). In multivariate analysis, only Child's status, size of varices, and variceal bleed predicted higher HVPG. HVPG is higher in cirrhotics with large varices and a history of bleed. There is a good correlation between HVPG and large varices, bleeder status, and ascites. A higher HVPG reflects more severe liver disease. The etiology of liver disease did not influence the portal pressure.     

Obesity is an independent risk factor for clinical decompensation in patients with cirrhosis

Obesity is associated with an aggressive course in chronic viral hepatitis; however, its impact in the development of clinical decompensation (CD) in patients with established cirrhosis is uncertain. We evaluated the role of obesity, in relationship to other recognized predictors, in the development of CD in patients with compensated cirrhosis. The study population, a subset of patients included in a randomized trial of beta-blockers in the prevention of varices in whom data on body mass index (BMI) was available, consisted of 161 patients with compensated cirrhosis. Laboratory tests and portal pressure (assessed by the hepatic venous pressure gradient or HVPG) were assessed on inclusion. Patients were followed until CD (ascites, hepatic encephalopathy, or variceal hemorrhage), or until September 2002. Altogether, 29% had a normal BMI, 40% were overweight, and 30% were obese. In a median follow-up of 59 months, CD occurred in 48/161 (30%) patients with an increasingly higher rate according to BMI group (15% in those with normal BMI; 31% in overweight; 43% in obese patients, P=0.011). The actuarial probability of developing CD was significantly higher in the abnormal BMI groups (P=0.022). In a multivariate model that included parameters previously identified as being predictive of CD (HVPG, albumin, Mayo endstage liver disease score), etiology, and treatment group, BMI (hazard ration 1.06; 95% confidence interval 1.01-1.12), P=0.02] was an independent predictor of decompensation, together with HVPG and albumin. CONCLUSION: Obesity has a deleterious effect on the natural history of compensated cirrhosis of all etiologies, independent of portal pressure and liver function. Weight reduction may be a valuable therapeutic measure in this patient population.     

Long-term survival and clinical outcomes following direct-acting antiviral (DAA) treatment in HCV decompensated cirrhosis in Brazil: a real-world study

IntroductionThe outcomes regarding portal hypertension-related complications and infections after HCV cure in decompensated cirrhosis are scarcely reported. We aimed to identify the predictors of survival and to evaluate the frequency of decompensation events of cirrhosis, including hepatocellular carcinoma (HCC), portal hypertension complications and infections in a cohort of decompensated cirrhotic with sustained virological response (SVR) in a real-world scenario.Patients and methodsThis was a prospective study in consecutive HCV-infected patients with decompensated cirrhosis who achieved SVR after direct-acting antiviral (DAA) treatment. At baseline, clinical and laboratory data were recorded. Patients were followed until development of outcomes regarding further decompensation, death, or liver transplant. A Cox-regression analysis was performed and survival curves were constructed using the Kaplan Mayer method.ResultsOne hundred and thirty patients (age 60 ± 9 years, 64% female, 70% genotype 1) were included and followed-up through three years. SVR was associated with a lower prevalence of ascites and an improvement in Child-Pugh and MELD scores. One and three-year probability of transplant-free survival was 93% and 66%, respectively. Variables related to three-years survival were MELD < 11 (HR 1.24, 95% CI 1.13-1.37) and absence of ascites (HR 2.03, 95% CI 0.99-4.13) after the end of treatment (91% versus 37% in patients with ascites and a higher MELD, p < 0.001).ConclusionsDecompensated cirrhotics with SVR and a low MELD without ascites have an excellent long-term prognosis. On the contrary, those with higher MELD and ascites have a low probability of survival even in the short term and might be evaluated for liver transplantation.     

Prognostic Factors in Compensated and Decompensated Cirrhosis

There are an increasing number of studies that evaluate predictive factors, mostly of death, in cirrhosis. These are different depending on the presence of compensated or decompensated cirrhosis. In compensated cirrhosis the main event to predict is decompensation. The degree of portal hypertension as determined by the hepatic venous pressure gradient (HVPG) and serum albumin levels are the most relevant predictors of decompensation. Since HVPG determination is obtained through an invasive procedure, recent studies have examined alternative non-invasive methods to establish the presence of clinically significant portal hypertension. In decompensated cirrhosis the main event to predict is death and “further decompensation”, the event that most commonly occurs prior to death. The Child and MELD scores are the most important predictors of death in decompensated disease. Child score continues to be a useful stratifying tool in all patients with cirrhosis. Specific predictive factors in each type of clinical decompensation are discussed.     

Primary and secondary prophylaxis of esophageal variceal bleeding

Cirrhosis is a chronic condition with high-mortality. Portal hypertension (PH) is the initial and main consequence of cirrhosis and is responsible for most of its complications, including esophageal varices. A portal pressure, as determined by the hepatic venous pressure gradient (HVPG) >5 mm Hg defines PH. When the HVPG reaches 10 mm Hg or greater, the patient with compensated cirrhosis has developed clinically significant PH and is at a higher risk of developing varices and clinical decompensation. Patients with varices that have not bled are still in the compensated stage but are at a higher risk of decompensation than those without varices. Variceal hemorrhage constitutes a decompensating event, but its mortality differs whether it presents as an isolated complication of cirrhosis (20% 5-year mortality) or whether it presents in association with other complications (more than 80% 5-year mortality). While in the past, emphasis had been placed on managing the direct complications of PH, varices and variceal hemorrhage, it is now clear that these complications cannot be considered in an isolated manner. Rather, they should be considered in the context of advances in the staging of cirrhosis and other complications of cirrhosis that might occur concomitant or subsequent to the development of varices and variceal hemorrhage.     

Correlation and comparison of the model for end-stage liver disease, portal pressure, and serum sodium for outcome prediction in patients with liver cirrhosis

BACKGROUND: The model for end-stage liver disease (MELD), hepatic venous pressure gradient (HVPG), and serum sodium (SNa) are important prognostic markers for patients with liver cirrhosis. The correlation among these markers and their predictive accuracy for survival are unclear. METHODS: A total of 213 cirrhotic patients undergoing hemodynamic measurement were analyzed. The correlations between MELD score, SNa, and hemodynamic parameters were investigated. RESULTS: There was a significant correlation between MELD and HVPG (r=0.255, P<0.001), between SNa and MELD (r=-0.483, P<0.001), and between HVPG and SNa (r=-0.213, P=0.002). Using mortality as the end-point, the area under receiver operating characteristic curve (AUC) for MELD was 0.789, compared with 0.659 for HVPG (P=0.165) and 0.860 for SNa (P=0.34) at 3 months; the difference between HVPG and SNa was significant (P=0.015). The AUC at 6 months was significantly higher for SNa and MELD compared with that of HVPG. Among 134 patients with low (<14) MELD scores, a high (>16 mm Hg) HVPG, and low SNa (<135 mEq/L) predicted early mortality. In the Cox multivariate model, MELD, HVPG, and Child-Turcotte-Pugh scores were consistently identified as independent poor prognostic predictors when they were treated either as dichotomous or continuous variables in the model. CONCLUSIONS: MELD score is closely associated with HVPG and SNa in cirrhotic patients. HVPG is not superior to MELD score or SNa for short-term outcome prediction. High HVPG and low SNa may identify high-risk patients with low MELD scores. High MELD, HVPG, and Child-Turcotte-Pugh scores are independent predictors of poor long-term survival.     

Hepatic recompensation according to Baveno VII criteria is linked to a significant survival benefit in decompensated alcohol-related cirrhosis

Background & Aims

Removing the primary aetiological factor in decompensated cirrhosis may lead to a restoration of hepatic function. In this study, we investigated the clinical implications of recompensation and the subsequent survival in patients with decompensated alcohol-related cirrhosis.

Methods

The rate of recompensation was evaluated in patients with decompensated alcohol-related cirrhosis and persistent alcohol abstinence undergoing a hepatic venous pressure gradient (HVPG) measurement. Recompensation was defined according to Baveno VII criteria as resolution of ascites and hepatic encephalopathy, absence of variceal bleeding and improvement in liver function.

Results

Two hundred and four abstinent patients with decompensated alcohol-related cirrhosis (age: 57.2 [IQR:50.1–63.7] years; 75.0% male; median MELD: 15 [IQR:11–19]) and a median HVPG of 20 (IQR:18–24) mmHg were included. During a median follow-up of 24.4 (IQR:10.9–50.4) months, 37 patients (18.1%) achieved abstinence-induced recompensation. Lower baseline HVPG, lower Child-Pugh score, lower BMI, higher albumin and higher mean arterial pressure were linked to a higher probability of recompensation. After adjusting for age, disease severity, portal hypertension and systemic inflammation, achieving recompensation resulted in a significant and considerable reduction in liver-related mortality (adjusted HR: 0.091 [95% CI: 0.012–0.677]; p = .019). Only 13 patients (6.4%) developed hepatocellular carcinoma, with a tendency towards a lower risk upon recompensation (HR: 0.398 [95% CI: 0.084–1.878]; p = .245), yet this finding did not reach statistical significance and requires further investigation.

Conclusions

Alcohol abstinence led to recompensation in 18.1% of our cohort of HVPG-characterised patients with decompensated alcohol-related cirrhosis. Achieving hepatic recompensation resulted in a >90% risk reduction in liver-related mortality.     

Editorial: Beta-blockers and the prevention of decompensation in cirrhosis: worth the trouble

Non-selective beta-blockers have been a cornerstone of therapy for prevention of esophageal variceal bleeding in cirrhosis patients for more than two decades. When lowering the hepatic vein portal pressure gradient (HVPG) below 12?mm?Hg or decreasing the pressure by 20% from baseline, these drugs are of proven benefit in reducing variceal bleeding and improving survival in this patient population. The recent work by Hendández-Gea et al., suggests that initiation of the beta-blocker nadolol in cirrhosis patients with high-risk varices can delay or prevent the first occurrence of clinically evident ascites. This finding comes with some caveats, however. The beneficial effect was only seen in patients who had an improvement by 10% or more from baseline HVPG pressure (only 51% of the treated patients in this study). This class of medications has some risk and tolerance issues, and many patients do not respond, even when the heart rate is optimally decreased. Despite this, the use of beta-blockers may be beneficial in the primary prevention of the formation of ascites and further decompensation of cirrhosis.     

Hepatic vein pressure gradient reduction and prevention of variceal bleeding in cirrhosis: a systematic review

BACKGROUND & AIMS: A reduction of the hepatic venous pressure gradient (HVPG) to /=20% of baseline prevents variceal bleeding in cirrhosis. Because some inconsistent data have argued against the clinical application of these hemodynamic targets, we performed a systematic review of available studies from the Cochrane Library and MEDLINE. METHODS: Hemodynamic targets were HVPG reduction (1) to /=20% with final value >12 mm Hg; (3) by >/=20% or to /=20% or to /=20% significantly reduces the risk of bleeding, and a reduction of >/=20% significantly reduces mortality. These hemodynamic targets should be considered for clinical practice and for randomized controlled trials.     

Patients with liver cirrhosis show worse survival if decompensation occurs later during course of disease than at diagnosis

Objectives: Liver cirrhosis is characterized by a silent phase until decompensation, which is defined by onset of ascites, variceal bleeding, or encephalopathy. Although it is presumed that the survival of decompensated patients is the same regardless of when decompensation occurs, data to support this are scarce. We aimed to study the impact of time of decompensation on the clinical course and survival of patients with cirrhosis in a large population-based cohort.

Materials and methods: We used medical registries to define a 10-year cohort of 1317 patients with incident liver cirrhosis in the Scania region of Sweden. Medical records were reviewed. Patients were followed until December 2011, and for death or transplantation until December 2014.

Results: In the cohort, 629 patients were decompensated at diagnosis, of which 505 had ascites and 44 variceal bleeding only. During follow-up, 228 patients developed ascites and 39 variceal bleeding as first complication. Patients with ascites as first complication showed worse survival than patients who had ascites at diagnosis. (5-year survival 33% vs. 15%, HR 1.60 (95% CI 1.34–1.90)). This difference persisted after adjustment for confounders, including hepatocellular cancer (HR 1.38 (95% CI 1.15–1.67)). Worse survival was also seen when bleeding from varices occurred during follow-up rather than at diagnosis.

Conclusions: Our results provide evidence for an association between transplantation-free survival after decompensation and the time of decompensation in liver cirrhosis, with worse survival when decompensation occurs during follow-up, thus challenging the generally held, view that the survival after decompensation is independent of when decompensation occurs.     

Relationship between the degree of portal hypertension and the onset of spontaneous bacterial peritonitis in patients with cirrhosis

BACKGROUND/AIM: Spontaneous bacterial peritonitis (SBP) is a severe complication of cirrhosis but its exact pathogenesis has not yet been elucidated and the role of portal hypertension in the development of SBP has been suggested. The aim of this study was to test the hypothesis that an association exists between the degree of portal hypertension and the occurrence of SBP. METHODS: 292 patients with cirrhosis who underwent a measurement of the hepatic venous pressure gradient (HVPG) were retrospectively studied. Following their ascites profile, patients were classified in three groups: patients with ascites who suffered from SBP, patients with sterile ascites, and patients who had no ascites. RESULTS: Among the 137 patients with ascites, 24 patients suffered from SBP (17.5%). The mean HVPG was significantly different: 20.7 +/- 6.2 mm Hg in the SBP group, 17.5 +/- 5.1 mm Hg in the sterile ascites group and 14.7 +/- 5.6 mm Hg in the group without ascites (p < 0.05). Patients with the most severe portal hypertension (HVPG > or =30 mm Hg) had the highest risk to suffer from SBP (50%). Using the multivariate analysis, only the serum albumin level (p = 0.004) and the HVPG (p = 0.02) were independently correlated with the occurrence of ascites infection. CONCLUSIONS: This study suggests that in patients with SBP the degree of portal hypertension is greater than in the non infected patients. Ascites infection is independently associated with a low serum albumin level and a high HVPG.     

急性食管胃底静脉曲张破裂出血行急诊经颈静脉肝内门体分流术后发生肝性脑病的危险因素分析

目的 通过临床结果分析了解急性食管胃底静脉曲张破裂出血行急诊经颈静脉肝内门体分流术(TIPS)术后肝性脑病(HE)的危险因素。方法 回顾性分析2013年1月-2018年12月因失代偿期肝硬化伴急性食管胃底静脉曲张破裂出血在苏州大学附属第一医院接受内镜或者药物治疗失败,72 h内行覆膜支架TIPS治疗的93例患者的临床资料。根据术后发生HE情况分为HE组(n=36)和非HE组(n=57)。收集患者术前临床资料,包括性别、年龄、病因、合并症,血生化指标包括WBC、PLT、红细胞比积、TBil、AST、Alb、血清肌酐、PT等,根据实测值分别计算每位患者MELD评分,记录TIPS支架植入前测得的肝静脉锲压与游离压,肝静脉压力梯度(HVPG)为两者的差值。计量资料两组间比较采用t检验或Mann-Whitney U检验;计数资料两组间比较采用χ^2检验。二分类变量logistic回归分析TIPS术后患者的预后危险因素。结果 术后HE发病率为38.710%,两组间术前MELD评分[(13.000±3.189)分vs(11.684±2.068)分,t=2.068,P=0.043]、HVPG[(24.908±5.317) mm Hg vs (22.597±4.928) mm Hg,t=2.100,P=0.039]差异均有统计学意义。进一步HE分级显示0~1级17例(47.222%),2级9例(25.000%),3级6例(16.667%),4级4例(11.111%)。逐步logistic回归分析发现,MELD评分[比值比(OR)=0.803,95%可信区间(95%CI): 0.679~0.948,P=0.010)和HVPG(OR=0.896,95%CI: 0.816~0.984,P=0.022)是TIPS术后HE发病的独立危险因素。结论 急性食管胃底静脉曲张破裂出血行急诊TIPS术后HE发生率高,术前MELD评分和HVPG可预测TIPS术后HE发生风险。     

Clinical features and predictors of outcome in acute hepatitis A and hepatitis E virus hepatitis on cirrhosis

Background and Objectives: Acute hepatitis A and E are recognized triggers of hepatic decompensation in patients with cirrhosis, particularly from the Indian subcontinent. However, the resulting acute‐on‐chronic liver failure (ACLF) has not been well characterized and no large studies are available. Our study aimed to evaluate the clinical profile and predictors of 3‐month mortality in patients with this distinctive form of liver failure. Methods: ACLF was diagnosed in patients with acute hepatitis A or E [abrupt rise in serum bilirubin and/or alanine aminotransferase with positive immunoglobulin M anti‐hepatitis A virus (HAV)/anti‐hepatitis E virus (HEV)] presenting with clinical evidence of liver failure (significant ascites and/or hepatic encephalopathy) and clinical, biochemical, endoscopic (oesophageal varices at least grade II in size), ultrasonographical (presence of nodular irregular liver with porto‐systemic collaterals) or histological evidence of cirrhosis. Clinical and laboratory profile were evaluated, predictors of 3‐month mortality were determined using univariate and multivariate logistic regression and a prognostic model was constructed. Receiver‐operating curves were plotted to measure performance of the present prognostic model, model for end‐stage liver disease (MELD) score and Child–Turcotte–Pugh (CTP) score. Results: ACLF occurred in 121 (3.75%) of 3220 patients (mean age 36.3±18.0 years; M:F 85:36) with liver cirrhosis admitted from January 2000 to June 2006. It was due to HEV in 80 (61.1%), HAV in 33 (27.2%) and both in 8 (6.1%). The underlying liver cirrhosis was due to HBV (37), alcohol (17), Wilson's disease (8), HCV (5), autoimmune (6), Budd‐Chiari syndrome (2), haemochromatosis (2) and was cryptogenic in the rest (42). Common presentations were jaundice (100%), ascites (78%) and hepatic encephalopathy (55%). Mean (SD) CTP score was 11.4±1.6 and mean MELD score was 28.6±9.06. Three‐month mortality was 54 (44.6%). Complications seen were sepsis in 42 (31.8%), renal failure in 45 (34%), spontaneous bacterial peritonitis in 27 (20.5%), UGI bleeding in 15(11%) and hyponatraemia in 50 (41.3%). On univariate analysis, ascites, hepatic encephalopathy, renal failure, GI bleeding, total bilirubin, hyponatraemia and coagulopathy were significant predictors of mortality. Multivariate analysis revealed grades 3 and 4 HE [odds ratio (OR 32.1)], hyponatraemia (OR 9.2) and renal failure (OR 16.8) as significant predictors of 3‐month mortality and a prognostic model using these predictors was constructed. Areas under the curve for the present predicted prognostic model, MELD, and CTP were 0.952, 0.941 and 0.636 respectively. Conclusions: ACLF due to hepatitis A or E super infection results in significant short‐term mortality. The predictors of ominous outcome include grades 3 and 4 encephalopathy, hyponatraemia and renal failure. Present prognostic model and MELD scoring system were better predictors of 3‐month outcome than CTP score in these patients. Early recognition of those with dismal prognosis may permit timely use of liver replacement/supportive therapies.     

Small Esophageal Varices in Patients with Cirrhosis—Should We Treat Them?

Purpose of Review

The natural history and classification systems of small varices (≤?5 mm in diameter) in cirrhotic patients with portal hypertension are summarized. Studies that assessed the course of and therapeutic intervention for small varices are discussed.

Recent Findings

Current non-invasive methods show suboptimal sensitivity to detect small varices in patients with cirrhosis. Next to etiological therapy, hepatic venous pressure gradient (HVPG)-guided non-selective betablocker or carvedilol treatment has shown to impact on natural history of small varices.

Summary

The main therapeutic focus in cirrhotic patients with small varices is the cure of the underlying etiology. The optimal management of small varices should include measurement of HVPG. A pharmacological decrease in HVPG by non-selective betablocker therapy of ≥?10% reduces the risk of progression to large varices, first variceal bleeding, and hepatic decompensation. If HVPG is not available, we would recommend carvedilol 12.5 mg q.d. for treatment of small varices in compensated patients without severe ascites. Only if small esophageal varices (EV) are not treated or in hemodynamic non-responders, follow-up endoscopies should be performed in 1–2 years of intervals considering the activity of liver disease or if hepatic decompensation occurs.

     

Liver stiffness predicts clinical outcome in human immunodeficiency virus/hepatitis C virus-coinfected patients with compensated liver cirrhosis

Our aim was to assess the predictive value of liver stiffness (LS), measured by transient elastography (TE), for clinical outcome in human immunodeficiency virus / hepatitis C virus (HIV/HCV)-coinfected patients with compensated liver cirrhosis. This was a prospective cohort study of 239 consecutive HIV/HCV-coinfected patients with a new diagnosis of cirrhosis, done by TE, and no previous decompensation of liver disease. The time from diagnosis to the first liver decompensation and death from liver disease, as well as the predictors of these outcomes, were evaluated. After a median (Q1-Q3) follow-up of 20 (9-34) months, 31 (13%, 95% confidence interval [CI]: 9%-17%) patients developed a decompensation. The incidence of decompensation was 6.7 cases per 100 person-years (95% CI, 4.7-9-6). Fourteen (8%) out of 181 patients with a baseline LS < 40 kPa developed a decompensation versus 17 (29%) out of 58 with LS ≥ 40 kPa (P = 0.001). Factors independently associated with decompensation were Child-Turcotte-Pugh (CTP) class B versus A (hazard ratio [HR] 7.7; 95% CI 3.3-18.5; P < 0.0001), log-plasma HCV RNA load (HR 2.1; 95% CI 1.2-3.6; P = 0.01), hepatitis B virus coinfection (HR, 10.3; 95% CI, 2.1-50.4; P = 0.004) and baseline LS (HR 1.03; 95% CI 1.01-1.05; P = 0.02). Fifteen (6%, 95% CI: 3.5%-9.9%) patients died, 10 of them due to liver disease, and one underwent liver transplantation. CTP class B (HR 16.5; 95% CI 3.4-68.2; P < 0.0001) and previous exposure to HCV therapy (HR 7.4; 95% CI 1.7-32.4, P = 0.007) were independently associated with liver-related death; baseline LS (HR 1.03; 95% CI 0.98-1.07; P = 0.08) was of borderline significance. CONCLUSION: LS predicts the development of hepatic decompensations and liver-related mortality in HIV/HCV-coinfection with compensated cirrhosis and provides additional prognostic information to that provided by the CTP score.