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.     

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.     

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).     

Sofosbuvir plus velpatasvir treatment for hepatitis C virus in patients with decompensated cirrhosis: a Japanese real-world multicenter study

Background

Real-world data on the efficacy and safety of sofosbuvir plus velpatasvir (SOF/VEL) treatment for patients with hepatitis C virus (HCV)-related decompensated cirrhosis are limited in Japan.

Methods

A total of 190 patients with compensated (108) or decompensated (82) cirrhosis who initiated direct-acting antiviral (DAA) treatment between February 2019 and August 2019 were enrolled. Sustained virologic response (SVR) was defined as undetectable serum HCV-RNA at 12 weeks after the end of treatment (EOT).

Results

The SVR12 rates were 92.6% in patients with compensated cirrhosis and 90.2% in patients with decompensated cirrhosis (p = 0.564), and the treatment completion rates were 98.1% and 96.3%, respectively (p = 0.372). In patients with decompensated cirrhosis, 3 patients discontinued treatment and 2 patients died because of liver-related events. In patients with decompensated cirrhosis with SVR12, 50% of patients with Child–Pugh class B at baseline showed improvement to class A at SVR12, and 27% and 9% of patients with Child–Pugh class C at baseline showed improvement to class B and class A at SVR12, respectively. Patients who achieved SVR12 showed elevated serum albumin levels at the EOT, which were further elevated at SVR12, but no elevated serum albumin levels after the EOT were observed in patients with baseline serum albumin levels less than 2.8 g/dl.

Conclusions

Real-world efficacy of SOF/VEL treatment for patients with decompensated cirrhosis was similar to Japanese phase 3 study, although treatment discontinuation and death related to liver disease occurred. In patients with poor hepatic reserve, whether it improves continuously after viral clearance requires further evaluation.

     

Inadequate social support decreases survival in decompensated liver cirrhosis patients

IntroductionInadequate social support is associated with higher mortality both in the general population and in patients with chronic diseases. There are no studies that have described social support in liver cirrhosis and its impact on prognosis.ObjectivesTo analyze the impact social support has in the survival of patients with decompensated cirrhosis.MethodsProspective multicentric cohort study (2016–2019). Patients with decompensated liver cirrhosis were included. Epidemiological, clinical and social variables were collected, using the validated Medical Outcomes Study Social Support Survey, with a 12-month follow-up.ResultsA total of 127 patients were included, of which 79.5% were men. The most common etiology of cirrhosis was alcohol (74.8%), mean age was 60 years (SD 10.29), mean MELD was 15.6 (SD 6.3) and most of the patients had a Child–Pugh B (53.5%) or C (35.4%). In the assessment of social support, we observed that most of the patients (92.2%) had adequate global support. At the end of the follow-up (median 314 days), 70.1% of the patients survived. The 1-year survival rate in patients with inadequate global social support was 30%, compared to 73.5% in the presence of social support. In multivariate Cox regression analysis, inadequate social support predicted survival with an adjusted HR of 5.5 (95% CI 2,3-13,4) independently of MELD (HR 1.1, 95% CI 1–1.2), age (HR 1, 95% CI 1–1.1) and hepatocarcinoma (HR 10.6, 95% CI 4.1–27.4).ConclusionAdequate social support improves survival in liver cirrhosis, independently of clinical variables. Social intervention strategies should be considered for their management.     

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.     

Long-term clinical outcome and survival predictors in patients with cirrhosis after 10-mm-covered transjugular intrahepatic portosystemic shunt

Background and aimsTransjugular intrahepatic portosystemic shunts (TIPS) are successfully used in the management of portal hypertension (PH)-related complications. Debate surrounds the diameter of the dilation. The aim was to analyse the outcomes of and complications deriving from TIPS in patients with cirrhosis and identify predictors of survival.MethodsThis was a retrospective single-centre study, which included patients with cirrhosis who had a TIPS procedure for PH from 2009 to October 2018. Demographic, clinical and radiological data were collected. The Kaplan–Meier method was used to measure survival and predictors of survival were identified with the Cox regression model.ResultsA total of 98 patients were included (78.6% male), mean age was 58.5 (SD±/−9.9) and the median MELD was 13.3 (IQR 9.5–16). The indications were refractory ascites (RA), variceal bleeding (VB) and hepatic hydrothorax (HH). Median survival was 72 months (RA 46.4, VB 68.5 and HH 64.7) and transplant-free survival was 26 months. Clinical and technical success rates were 70.5% and 92.9% respectively. Age (HR 1.05), clinical success (HR 0.33), sodium (HR 0.92), renal failure (HR 2.46) and albumin (HR 0.35) were predictors of survival. Hepatic encephalopathy occurred in 28.6% of patients and TIPS dysfunction occurred in 16.3%.ConclusionsTIPS with 10-mm PTFE-covered stent is an effective and safe treatment for PH-related complications in patients with cirrhosis. Age, renal failure, sodium, albumin and clinical success are independent predictors of long-term survival.     

MELD Score Kinetics in Decompensated HIV+/HCV+ Patients: A Useful Prognostic Tool (ANRS HC EP 25 PRETHEVIC Cohort Study)

To assess prognostic factors for survival and describe Model for End-Stage liver disease (MELD) dynamics in human immunodeficiency virus+/hepatitis C virus+ (HIV+/HCV+) patients after an initial episode of hepatic decompensation.An HIV+/HCV+ cohort of patients experiencing an initial decompensation episode within the year preceding enrollment were followed prospectively. Clinical and biological data were collected every 3 months. Predictors for survival were identified using Kaplan–Meier curves and Cox models. A 2-slope-mixed linear model was used to estimate MELD score changes as a function of survival.Sixty seven patients were included in 32 centers between 2009 and 2012 (72% male; median age: 48 years [interquartile ratio (IQR):45–52], median follow-up: 22.4 months [range: 0.5–65.3]). Overall survival rates were 86%, 78%, and 59% at 6, 12, and 24 months, respectively. Under multivariate analysis, the MELD score at initial decompensation was predictive of survival, adjusted for age, type of decompensation, baseline CD4 counts, and further decompensation during follow-up as a time-dependent variable. The adjusted hazard ratio of death was 1.32 for a score 3 points higher (95% CI: [1.06–1.63], P = 0.012). MELD score kinetics within the 6 months after initial decompensation differed significantly between non-deceased and deceased patients, with a decreased (−0.49/month; P = 0.016), versus a flat (+0.06/month, P = 0.753) mean change in score.MELD is an effective tool to predict survival in HIV+/HCV+ patients with decompensated cirrhosis. A non-decreasing MELD score within 6 months following this initial decompensation episode may benefit from privileged access to liver transplantation in this poor prognosis population.     

Comparison of the model for end-stage liver disease (MELD), MELD-Na and MELDNa for outcome prediction in patients with acute decompensated hepatitis

Background and aimThe model for end-stage liver disease (MELD) is used to predict the outcome of patients with cirrhosis. Incorporation of serum sodium (Na) into MELD may further increase its prognostic ability. Two Na-containing MELD models, MELD-Na and MELDNa, were proposed to enhance the prognostic ability. This study compared the predictive accuracy of these models for acute decompensated hepatitis.MethodsWe investigated the outcome of 182 patients with acute decompensated hepatitis.ResultsTwenty (11%) patients died at 3 months. The MELD-Na and MELDNa both had significantly higher area under the receiver operating characteristic curve (AUC) in comparison to MELD (MELD-Na: 0.908, MELDNa: 0.895, MELD: 0.823, p = 0.004 and 0.001, respectively). Among 96 patients without specific antiviral treatment, the MELD-Na and MELDNa consistently had significantly higher AUC than the MELD (MELD-Na: 0.901, MELDNa: 0.882, MELD: 0.810, p = 0.008 and 0.004, respectively). Three independent indicators, pre-existing cirrhosis (odds ratio [OR]: 5.67, 95% confidence interval [CI]: 1.72–18.7), serum albumin <3.7 g/dL (OR: 5.68, 95% CI: 1.18–27.03) and serum sodium (Na) < 138 mequiv./L (OR: 10.0, 95% CI: 2.08–47.62), were associated with 3-month mortality.ConclusionMELD-Na and MELDNa provide better prognostic accuracy than the MELD for patients with acute decompensated hepatitis. The adequacy of liver reserve determines the outcome of these patients.     

HCV clearance after direct-acting antivirals in patients with cirrhosis by stages of liver impairment: The ITAL-C network study

BackgroundSustained virological response (SVR12) rates at 12 weeks after treatment for HCV-infected patients with decompensated cirrhosis are used when referring to those with moderate functional impairment, while few data are available for those with more severe impairment. The use of the cirrhosis staging system proposed by D’Amico might provide new insights on timing for antiviral therapy.MethodsWe investigated efficacy (SVR12), safety, and post-treatment variations in clinical and laboratory parameters in 2612 patients with advanced fibrosis (n = 575) or cirrhosis (n = 2037). Cirrhosis was in the compensated phase (without/with varices) or had previously been in the decompensated stage. Different direct-acting antiviral (DAA) regimens were administered in accordance with scientific guidelines.ResultsThe SVR12 rate was 97.6% in patients with advanced fibrosis. For patients with cirrhosis, the rate was 96.5% in stage 1, 95.1% in stage 2, 100% in stage 3, 95.7% in stage 4, and 93.6% in stage 5. These rates were independent of gender, age, HCV genotype, and treatment schedule. Positive changes in biochemical parameters and CPT classes following therapy were evident in compensated and previously decompensated patients.ConclusionOur findings support the use of DAAs in patients with advanced cirrhosis (stages 3–5) who are at greatest risk and have the most to gain from therapy.     

肝硬化门静脉高压并发症对预后的影响

目的 了解门静脉高压各并发症在失代偿肝硬化患者的发生情况和各并发症对患者预后的影响.方法 选择失代偿期肝硬化患者的病历资料进行登记和随访,根据随访结果,分析患者门静脉高压并发症的发生情况;利用终末期肝病模型(MELD)公式,计算出MELD值并进行分级,同时计算Child-Turcotte-Pugh(CTP)分级,分别分析CTP分级和MELD分级中门静脉高压并发症发生情况和患者生存状况.利用Kaplan-Meier生存分析方法分析门静脉高压并发症对肝硬化患者生存率的影响.利用x2检验和时序性检验比较生存率差别,Cox比例风险回归分析各个并发症对患者生存影响作用的大小.结果 在符合条件的322例失代偿期肝硬化患者中,发生食管胃底静脉曲张破裂出血、肝性脑病、大量腹水、自发性腹膜炎、肝肾综合征Ⅰ型和Ⅱ型的患者病死率分别是45.9%、79.4%、66.7%、100%、100%和84.6%.各并发症的发生基本按CTP分级和MELD值的增加而逐渐升高.经过Kaplan-Meier生存分析,除少量和中量腹水外,各并发症对患者生存率的影响,P值均<0.01,差异均有统计学意义.由Cox回归过程分析出肝性脑病、自发性腹膜炎、肝肾综合征Ⅰ型和Ⅱ型,食管胃底静脉曲张破裂出血和腹水的回归系数分别为0.973、0.928、0.935、0.866、0.464和0.369. 结论 门静脉高压并发症均能对失代偿期肝硬化患者的预后造成明显影响,其中影响程度最大的是肝性脑病.     

Impact of sustained viral response in the evolution of minimal hepatic encephalopathy: A prospective pilot study

Introduction and aimsTo determine the prevalence of minimal hepatic encephalopathy(MHE) in patients with liver cirrhosis (LC) due to hepatitis C virus (HCV) infection and to evaluate the impact of sustained viral response (SVR) on MHE.Materials and methodsWe performed a prospective study using MHE screening and follow-up on patients with HCV and LC. The patients were evaluated at the beginning of treatment and 24 weeks after treatment.Results64 patients were included. 51.6% were male, the median age was 62 years, Child-Pugh classification A/B/C 93.8%/4.7%/1.6% and median MELD was 8.3. Prior hydropic decompensation was present in 11 patients. Median values of liver stiffness, as measured by transient elastography (TE) were 22.8 kPa. Indirect signs of portal hypertension (PH) were present in 53.1% of patients, with a mean of 11.9 mmHg among the ones with a measurement of the hepatic venous pressure gradient. The prevalence of MHE before treatment was 26.6%. After treatment, 98.4% of patients achieved SVR. The presence of MHE at 24 weeks post-treatment had an statistically significant association with the presence of pre-treatment MHE (80% vs. 21.6%; p < 0.01), higher MELD scores at 24-weeks post-treatment (9.8 vs. 8; p = 0.02), higher Child-Pugh scores at 24-weeks post-treatment (p = 0.04), higher baseline INR levels (1.4 vs. 1.1; p < 0.001) and with the presence of indirect signs of PH (100% vs. 47.1%; p = 0.02). During follow-up, those patients without MHE at 24 weeks post-treatment had a higher probability of experiencing an improvement in post-treatment TE (80.9% vs. 40%, p = 0.04).ConclusionWe found that SVR may lead to MHE resolution in a considerable proportion of patients, which has potential implications for disease prognosis.     

Hemodynamic Studies in Acute-on-Chronic Liver Failure

Background Patients with decompensated cirrhosis and acute liver failure have circulatory dysfunctions leading to high portal pressure and cardiac output (CO) and low systemic vascular resistance (SVR). Circulatory changes in acute-on-chronic liver failure (ACLF) patients have not been studied. We studied the portal, systemic, and pulmonary hemodynamics in patients with ACLF and compared them with compensated and decompensated cirrhotics. Patients and Methods Clinical features and hemodynamic profile were studied in patients with ACLF and compared with age- and sex-matched compensated and decompensated cirrhotics with portal hypertension. Results The study cohort comprised 144 patients categorized into one of three groups (ACLF, compensated cirrhosis, and decompensated cirrhosis), with 48 (33%) patients in each group. All values are given as the mean ± standard deviation, except for frequencies (%). The mean arterial pressure (MAP) and SVR were lower in the ACLF than the compensated group and were similar to those of the decompensated group (MAP 90 ± 16 vs. 99 ± 15 vs. 96 ± 16 mmHg; SVR 912 ± 435 vs. 1350 ± 449 vs. 891 ± 333 dyn s/cm⁵). The mean CO of the ACLF patients was higher than that of the compensated group and similar to that of the decompensated group (CO 8.9 ± 3.5 vs. 6.1 ± 1.7 vs. 9.0 ± 3.0 l/min). The pulmonary vascular resistance (PVR) and pulmonary capillary wedge pressures (PCWP) were similar in all the three groups (PVR 78 ± 48 vs. 109 ± 70 vs. 61 ± 47 dyn s/cm⁵; PCWP 8 ± 4 vs. 8 ± 4 vs. 10 ± 5 mmHg). The mean hepatic venous pressure gradient (HVPG) in the ACLF group was 15.1 ± 6.3 mmHg, which was significantly higher than that of the compensated group (11.7 ± 6.3 mmHg), but lower than that of the decompensated cirrhosis group (20.2 ± 6.0 mmHg). When patients of ACLF were categorized on the basis of their variceal size, the mean HVPG in ACLF patients with small varices was similar to that of compensated cirrhotics (13.7 ± 5.7 vs. 11.7 ± 6.3 mmHg; P = 0.146), while in the ACLF patients with large varices, the HVPG was comparable to that of the decompensated cirrhotics (18.7 ± 6.6 vs. 20.2 ± 6.0 mmHg; P = 0.442). Conclusions The systemic hemodynamics in patients with ACLF is similar to that in decompensated cirrhotics. The portal pressure in these patients is higher than that in the compensated cirrhotics, and in the subgroup with large varices, it becomes similar to that of decompensated cirrhotics.     

肝硬化患者血清钠特点及含钠终末期肝病模型对预后的判断价值

目的 分析终末期肝硬化患者的血清钠特点与患者生存状况和门静脉高压并发症之间的关系,比较终末期肝病模型(MELD)及其含钠模型对预后的判断价值.方法 选取我院2005年6月至2010年10月失代偿期肝硬化患者的住院资料进行登记和随访.将血清钠水平按≤125 mmol/L、＞ 125 ～＜135 mmol/L和≥135 mmol/L进行分级,分析不同血清钠水平肝硬化患者的生存情况及与肝硬化门静脉高压相关并发症的关系,并分析Child-Pugh分级与血清钠水平的相互关系.利用Kaplan-Meier方法分析不同血清钠水平患者的生存率变化,利用接受者工作特征(ROC)曲线下面积比较MELD与MELD-Na和iMELD判断患者生存不同时间的准确性.组间均数的比较用t检验或方差分析,率的比较用x2检验,ROC曲线下面积的比较采用正态性Z检验.结果 至随访期截止,共有467例患者被纳入本研究.总体低钠血症(血清钠＜ 135 mmol/L)发生率为50.54％ (236/467),其中死亡患者低钠血症发生率为66.81％ (155/232),生存患者为34.47％ (81/235),差异有统计学意义(x2=9.73,P＜0.01).血清钠≤125 mmol/L、＞125 ～＜135 mmol/L和≥135 mmol/L患者的病死率分别为86.00％ (43/50)、60.10％ (110/183)和33.76％ (79/234),差异有统计学意义(P＜ 0.01).Child-Pugh A、B、C级患者的血清钠水平分别为(138.80±4.42)mmol/L、(135.30±6.66) mmol/L和(131.18±7.53) mmol/L,各组间差异均有统计学意义(P值均＜0.05).肝性脑病、肝肾综合征和自发性腹膜炎的发病率因血清钠水平的下降而升高(r值分别为-0.213、-0.342和- 0.142,P值均＜0.05),腹水量也随血清钠水平的降低而增加(P＜0.01),而消化道出血的发生则与血清钠水平无明显关系(r=0.40,P＞0.05).MELD、MELD-Na和iMELD模型在判断患者3个月预后方面无明显差异(P＞ 0.05),而在判断患者6个月和1年预后方面,MELD-Na和iMELD优于MELD(P值均＜0.05).结论 低钠血症与终末期肝病患者的预后及相关并发症发生有一定的关系.MELD与钠相结合后,可以提高MELD判断患者预后的能力.     

Vasodilatory State of Decompensated Cirrhosis: Relation to Hepatic Dysfunction, Ascites, and Vasoactive Substances

The objective of this study was to determine the relations between the hallmark circulatory finding of decompensated cirrhosis, a reduced systemic vascular resistance (SVR), and the indices of hepatic decompensation, the accumulation of ascites, and the concentrations of various vasoactive substances. At a university-affiliated teaching hospital, eighteen hospitalized patients with cirrhosis and 18 age- and sex-matched healthy subjects were used. This was a case-control study. Measurements included cardiac dimensions and indices derived from echocardiograms and Doppler studies, abdominal ultrasound estimates of ascites, indices of hepatic function, and various serum (S) and urinary (U) substances. Results showed that cirrhotics had increased left atrial and left ventricular dimensions, left ventricular mass, heart rate, cardiac output (CO), transvalvular velocities, and a decreased SVR. SVR was related to hepatic dysfunction, as reflected by an abnormal prothrombin time ratio (r= -0.64, p= 0.006), and also related to overall severity of liver disease as estimated by the Child-Pugh score (r= -0.53, p = 0.044). Although cirrhotics with ascites generally had a reduced SVR, estimates of ascites were directly related to SVR (r = 0.57, p = 0.03) and inversely related to CO (r= -0.53, p= 0.04). Concentrations of S and U digoxin-like immunoreactive substance (DLIS) were also increased, but the concentrations of S glucagon and estradiol were not elevated. The accumulations of S and U DLIS, S glucagon, and S estradiol were all related to hepatic dysfunction. S estradiol was also related to SVR (r = -0.55, p= 0.04), but this was only evident with S estradiol expressed as a logarithm and did not emerge as significant on a multivariate analysis. The reduced SVR observed in decompensated cirrhosis is related to various indices of hepatic dysfunction. Certain substances that accumulate in cirrhosis (such as DLIS, glucagon, and estradiol) do not explain the vasodilatation observed. Although ascites in decompensated cirrhosis generally signifies a vasodilated state, a reduced SVR may be found even before ascites is clinically evident, and tense ascites may actually obscure this finding.     

Muscle psoas indices measured by ultrasound in cirrhosis — Preliminary evaluation of sarcopenia assessment and prediction of liver decompensation and mortality

BackgroundNo data on the European population exists regarding the use of an ultrasoundbased measurement of psoas diameter for sarcopenia assessment in cirrhosis.AimsTo determine the applicability of an ultrasound measurement of the psoas muscle diameter in patients with decompensated liver cirrhosis and to assess whether this surrogate is associated with hospitalization due to decompensation and mortality.MethodsIn 75 consecutive patients with decompensated liver cirrhosis and in 20 control subjects (January 2016 to November 2017), psoas muscle diameter was prospectively measured. The reliable measurements were used for the further analysis. Relevant clinical and laboratory data was collected.ResultsUltrasound measurement was applicable in 100% of control and in 72% of study subjects. Psoas to height ratio was significantly related to hospitalization and mortality (p < 0.0001, HR 0.717, 95% CI: 0.622–0.828 and p = 0.022; HR = 0.825, 95% CI: 0.701–0.973) as was psoas muscle index (p < 0.0001, HR = 0.881, 95% CI: 0.836–0.929 and p = 0.017; HR = 0.930, 95% CI: 0.876–0.987).ConclusionsUltrasound measurement of psoas muscle diameter and its derived indices is applicable and associated with hospitalization and mortality in patients with decompensated liver cirrhosis.     

Natural history of decompensated hepatitis C virus-related cirrhosis. A study of 200 patients

BACKGROUND/AIMS: Since few data are available concerning the clinical course of decompensated hepatitis C virus (HCV)-related cirrhosis, the aim of the present study was to define the natural long-term course after the first hepatic decompensation. METHODS: Cohort of 200 consecutive patients with HCV-related cirrhosis, and without known hepatocellular carcinoma (HCC), hospitalized for the first hepatic decompensation. RESULTS: Ascites was the most frequent first decompensation (48%), followed by portal hypertensive gastrointestinal bleeding (PHGB) (32.5%), severe bacterial infection (BI) (14.5%) and hepatic encephalopathy (HE) (5%). During follow-up (34+/-2 months) there were 519 readmissions, HCC developed in 33 (16.5%) patients, and death occurred in 85 patients (42.5%). The probability of survival after diagnosis of decompensated cirrhosis was 81.8 and 50.8% at 1 and 5 years, respectively. HE and/or ascites as the first hepatic decompensation, baseline Child-Pugh score, age, and presence of more than one decompensation during follow-up were independently correlated with survival. CONCLUSIONS: Once decompensated HCV-related cirrhosis was established, patients showed not only a very high frequency of readmissions, but also developed decompensations different from the initial one. These results contribute to defining the natural course and prognosis of decompensated HCV-related cirrhosis.     

Determining the extent of quality health care for hospitalized patients with cirrhosis

BACKGROUND/AIMS: Since few data are available concerning the clinical course of decompensated hepatitis C virus (HCV)-related cirrhosis, the aim of the present study was to define the natural long-term course after the first hepatic decompensation. METHODS: Cohort of 200 consecutive patients with HCV-related cirrhosis, and without known hepatocellular carcinoma (HCC), hospitalized for the first hepatic decompensation. RESULTS: Ascites was the most frequent first decompensation (48%), followed by portal hypertensive gastrointestinal bleeding (PHGB) (32.5%), severe bacterial infection (BI) (14.5%) and hepatic encephalopathy (HE) (5%). During follow-up (34+/-2 months) there were 519 readmissions, HCC developed in 33 (16.5%) patients, and death occurred in 85 patients (42.5%). The probability of survival after diagnosis of decompensated cirrhosis was 81.8 and 50.8% at 1 and 5 years, respectively. HE and/or ascites as the first hepatic decompensation, baseline Child-Pugh score, age, and presence of more than one decompensation during follow-up were independently correlated with survival. CONCLUSIONS: Once decompensated HCV-related cirrhosis was established, patients showed not only a very high frequency of readmissions, but also developed decompensations different from the initial one. These results contribute to defining the natural course and prognosis of decompensated HCV-related cirrhosis.     

Carvedilol as the new non-selective beta-blocker of choice in patients with cirrhosis and portal hypertension

Portal hypertension (PH) is the most common complication ofcirrhosis and represents the main driver of hepatic decompensation. The overarching goal of PH treatments in patients with compensated cirrhosis is to reduce the risk of hepatic decompensation (i.e development of ascites, variceal bleeding and/or hepatic encephalopathy). In decompensated patients, PH-directed therapies aim at avoiding further decompensation (i.e. recurrent/refractory ascites, variceal rebleeding, recurrent encephalopathy, spontaneous bacterial peritonitis or hepatorenal syndrome) and at improving survival. Carvedilol is a non-selective beta-blocker (NSBB) acting on hyperdynamic circulation/splanchnic vasodilation and on intrahepatic resistance. It has shown superior efficacy than traditional NSBBs in lowering PH in patients with cirrhosis and may be, therefore, the NSBB of choice for the treatment of clinically significant portal hypertension. In primary prophylaxis of variceal bleeding, carvedilol has been demonstrated to be more effective than endoscopic variceal ligation (EVL). In patients with compensated cirrhosis carvedilol achieves higher rate of hemodynamic response than propranolol, resulting in a decreased risk of hepatic decompensation. In secondary prophylaxis, the combination of EVL with carvedilol may prevent rebleeding and non-bleeding further decompensation better than that with propranolol. In patients with ascites and gastroesophageal varices, carvedilol is safe and may improve survival, as long as no impairment of the systemic hemodynamic or renal dysfunction occurs, with maintained arterial blood pressure as suitable safety surrogate. The target dose of carvedilol to treat PH should be 12.5 mg/day. This review summarizes the evidence behind Baveno-VII recommendations on the use of carvedilol in patients with cirrhosis.     

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).