While ascites is the most frequent first decompensating event in cirrhosis, the clinical course after ascites as the single index decompensation is not well defined. The aim of this multicentre study ...was thus, to systematically investigate the incidence and type of further decompensation after ascites as the first decompensating event and to assess risk factors for mortality.
622 cirrhotic patients presenting with grade-2/-3 ascites as the single index decompensating event at two university hospitals (Padova/Vienna) between 2003-2021 were included. Events of further decompensation, liver transplantation and death were recorded.
Mean age was 57±11years, most patients were male (n=423,68%) with alcohol-related (n=366,59%) and viral (n=200,32%) liver disease as the main etiologies. 323(52%) patients presented with grade-2 and 299(48%) with grade-3 ascites. Median Child-Pugh score at presentation was 8(IQR:7-10) and mean MELD was 15±6.
During a median follow-up period of 49 months, 350(56%) patients experienced further decompensation: refractory ascites (n=130,21%), hepatic encephalopathy (n=112,18%), SBP (n=32,5%), HRS-AKI (n=29,5%). Variceal bleeding as an isolated further decompensation event was rare (n=18,3%), while non-bleeding further decompensation (n=161,26%) and ≥2 concomitant further decompensation events (n=171,27%) were frequent. TIPS was used in only 81(13%) patients.
In patients presenting with grade-2 ascites, MELD≥15 indicated a considerable risk for further decompensation (SHR:2.18;p<0.001; 1-year-incidences:<10:10%vs.10-14:13%vs.≥15:28%) and of mortality (SHR:1.89;p=0.004; 1-year-incidences:<10:3%vs.10-14:6%vs.≥15:14%). Importantly, mortality was similarly high throughout MELD-strata in grade-3 ascites (p=n.s. for different MELD-strata; 1-year-incidences:<10:14%vs.10-14:15%vs.≥15:20%).
Further decompensation is frequent in patients with ascites as a single index decompensation event and only rarely due to bleeding. While patients with grade-2 ascites and MELD<15 seem to have a favourable prognosis, grade-3 ascites indicates high risk for mortality across all MELD-strata.
Studies on the clinical course of cirrhotic patients with first single ascites decompensation are scarce. However, many studies have shown the clinical implications of ascites graduation for risk prediction/stratification. Since the treatment paradigm in decompensated advanced chronic liver disease shifted towards prevention of further decompensation and mortality next to treating/controlling ascites, studies on first/further decompensation in patients with fist single ascites decompensation are needed. Our study demonstrates, on the one hand, that further decompensation/mortality is common in patients with presenting with single grade-3 ascites as index decompensation, yet on the other hand, unrelated to MELD stratification. In patients with single grade-2 ascites index decompensation MELD score can discriminate patients with favourable/poor outcome.
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•Course of patients with first single ascites decompensation has so far not been described yet.•MELD score is important for risk prediction/stratification in patients with grade-2 ascites but has no implications in patients with grade-3 ascites and first single ascites decompensation.•A threshold of MELD 15 points discriminates patients with favourable/poor outcome in patients with grade-2 ascites.•In patients with grade-3 ascites, regardless of MELD, treatment strategies should be intensified.
Bacterial infections are frequent in patients with cirrhosis and increase the risk of death and drop-out from liver transplant (LT) waiting list. In patients with bacterial infections, LT is ...frequently delayed because of the fear of poor outcomes. We evaluated the impact of pre-LT infections on post-LT complications and survival.
From 2012 to 2018, consecutive patients transplanted at the Hospital of Padua were identified and classified in two groups: patients surviving an episode of bacterial infection within 3 months before LT (study group) and patients without infections before LT (control group). Post-LT outcomes (complications, new infections, survival) were collected.
A total of 466 LT recipients were identified (study group n = 108; control group n = 358). After LT, the study group had a higher incidence of new bacterial (57% vs. 20%, p <0.001) and fungal infections (14% vs. 5%, p = 0.001) and of septic shock (8% vs. 2%, p = 0.004) than the control group. Along with the model for end-stage liver disease (MELD) score and alcohol-related cirrhosis, bacterial infection pre-LT was an independent predictor of post-LT infections (odds ratio = 3.92; p <0.001). Nevertheless, no significant difference was found in 1-year (88% vs. 89%, p = 0.579) and 5-year survival rates (76% vs. 75%, p = 0.829) between the study group and control group. Within the study group, no association was found between the time elapsed from infection improvement/resolution to LT and post-LT outcomes.
Patients with pre-LT infections have a higher risk of new bacterial and fungal infections and of septic shock after LT. However, post-LT survival is excellent. Therefore, as soon as the bacterial infection is improving/resolving, transplant should not be delayed, but patients with pre-transplant bacterial infections require active surveillance for infections after LT.
Bacterial infections increase mortality and delay transplant in patients with cirrhosis awaiting liver transplantation (LT). Little is known about the impact of adequately treated infections before LT on post-transplant complications and outcomes. The study highlights that pre-LT infections increase the risk of post-LT infections, but post-LT survival rates are excellent despite the risk. These findings suggest that physicians should not delay LT because of concerns about pre-LT infections, but instead should actively monitor these patients for infections after surgery.
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•In patients with cirrhosis, the prognostic impact of pre-LT infections is not completely understood.•Pre-LT infections increase the risk of post-LT infections but do not affect patients’ survival.•Time from infection resolution to LT does not affect incidence of post-LT complication and survival rates.•As soon as infections are resolving, it is safe to proceed with LT without any delay.•Patients with pre-LT infection require active surveillance for infections after LT.
Background: The risk of hepatocarcinoma in HCV cirrhotic patient responders after treatment with DAAs decrease, but HCC still occurs. A correlation between specific miRNAs and the development of ...hepatocarcinoma have been highlighted. Aim: To investigate miRNA expression in HCV-infected cirrhotic patients treated with DAAs, regarding whether or not they developed HCC at follow-up. Methods: A total of 73 outpatients with HCV-related cirrhosis treated with DAAs were enrolled, 28 of which had HCC. Samples were collected at the start and at the end of treatment. In the screening phase, 172 miRNAs were analyzed at baseline. Differentially expressed miRNAs were validated in the entire cohort. Results: In the validation phase, at baseline and in patients treated for 12 weeks, miR-28-5p was confirmed to be more highly expressed in the HCC group compared to the non-HCC group. In all of the patients treated for 12 weeks, at end of the treatment we found a significant downregulation in miR-132-3p, miR-133b-3p, miR-221-3p and miR-324-3p. In the HCC group, miR-28-5p was significantly downregulated after DAA therapy as well as in HCC patients treated for 24 weeks. Conclusion: In the HCC group, miR28-5p was differently expressed both at baseline and at the end of therapy with DAAs. This difference in expression should suggest its involvement in HCC development.
Background and Aims
Although terlipressin and albumin are effective at treating acute kidney injury‐hepatorenal syndrome (AKI‐HRS), liver transplantation (LT) is the best treatment. However, it is ...unclear if an effective treatment with terlipressin and albumin improves post‐LT outcomes in these patients. The aim of this study was to evaluate the impact of response to treatment with terlipressin and albumin on posttransplant outcomes in patients with AKI‐HRS.
Approach and Results
We analyzed two cohorts of patients with cirrhosis listed for LT between 2012 and 2016: 82 patients who developed AKI‐HRS before LT and were treated with terlipressin and albumin and 259 patients without AKI‐HRS who received transplants during the study period (control group). After LT, patients were followed up until discharge, every month for the first 3 months, and every 3 months thereafter. Of the patients, 43 (52%) responded to terlipressin and albumin. Responders had a better 30‐day transplant‐free survival (60% vs. 33%, P = 0.006), longer LT waiting list time (37 vs. 17 days, P = 0.041), and lower Model for End‐Stage Liver Disease score at the time of LT (23 vs. 29, P = 0.007). Among patients with AKI‐HRS receiving transplant, nonresponders required renal replacement therapy (RRT) more frequently than responders (20% vs. 0%, P = 0.024). Nonresponders had a significantly higher incidence of chronic kidney disease (CKD) at 1 year after LT than responders (65% vs. 31%, P = 0.019). In multivariate analysis, nonresponse to terlipressin and albumin was found to be an independent predictor for CKD at 1 year after LT (subdistribution hazard ratio SHR = 2.76, P = 0.001), whereas responders did not have an increased risk (SHR = 1.53, P = 0.210).
Conclusions
In patients with AKI‐HRS, response to terlipressin and albumin reduces the need for RRT after LT and reduces the risk of CKD at 1 year after LT.
In 2012, the KDIGO group proposed new definitions for acute kidney injury (AKI), acute kidney disease (AKD) and chronic kidney disease (CKD). According to the definition adapted by the International ...Club of Ascites, AKI has been extensively investigated in patients with cirrhosis. On the contrary, there are currently no data on the epidemiology and clinical outcomes associated with AKD. The aim of the study was to assess the prevalence and the impact of AKD on the clinical course and survival of patients with cirrhosis.
A total of 272 consecutive patients with cirrhosis attending our outpatient clinic were included in the study. Clinical and laboratory data were collected at inclusion. Patients were followed-up until death, liver transplant or the end of follow-up.
During follow-up, 80 patients developed AKD (29.4%). Forty-two (52.5%) recovered from the first episode of AKD and 26 maintained a normal renal function up to the end of follow-up. Sixteen patients developed a second episode of AKD. Globally, 36 patients (45.0%) died with AKD. Finally, AKD progressed to CKD in 11 patients (13.8%). The 5-year survival rate was significantly lower in patients who developed AKD than in those who did not (34.8% vs. 88.8%, p <0.001). The 5-year rates of complications of cirrhosis and of hospitalizations were also higher in patients with AKD than in those without AKD.
AKD is frequent in patients with cirrhosis. It can be reversible, but it may recur and progress to CKD. AKD has a very negative impact on morbidity and mortality in patients with cirrhosis.
Renal impairment has a very negative impact on patients with cirrhosis. Renal impairment seems to be characterized by a very dynamic course, which is defined according to renal function and length of the impairment as acute kidney injury, acute kidney disease and chronic kidney disease. The role of acute kidney disease is currently unknown. Our study shows for the first time that acute kidney disease is frequent in patients with cirrhosis and has a very negative impact on survival.
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•An AKI-AKD-CKD continuum has been hypothesized, whereby initial kidney injury can lead to persistent injury and eventually CKD.•AKD is a condition that is not yet well characterized in patients with cirrhosis.•According to this concept, AKD may occur as an AKI-AKD or without a previous episode of AKI (NAKI-AKD) in patients with cirrhosis.•According to our data, AKD has a very negative impact on survival and other complications of cirrhosis.•AKD is a potentially reversible condition that can recur mostly as a consequence of repeated AKI.
Acute kidney injury (AKI) commonly occurs in patients with decompensated cirrhosis. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) could help discriminate between different etiologies of ...AKI. The aim of this study was to investigate the use of uNGAL in (1) the differential diagnosis of AKI, (2) predicting the response to terlipressin and albumin in patients with hepatorenal syndrome-AKI (HRS-AKI), and (3) predicting in-hospital mortality in patients with AKI.
One hundred sixty-two consecutive patients with cirrhosis and AKI were included from 2015 to 2020 and followed until transplant, death, or 90 days. Standard urinary markers and uNGAL were measured. Data on treatment, type, and resolution of AKI were collected. Thirty-five patients (21.6%) had prerenal AKI, 64 (39.5%) HRS-AKI, 27 (16.7%) acute tubular necrosis-AKI (ATN-AKI), and 36 (22.2%) a mixed form of AKI. Mean values of uNGAL were significantly higher in ATN-AKI than in other types of AKI (1162 ng/ml 95% CI 423-2105 ng/ml vs. 109 ng/ml 95% CI 52-192 ng/ml; p < 0.001). uNGAL showed a high discrimination ability in predicting ATN-AKI (area under the receiver operating characteristic curve, 0.854; 95% CI 0.767-0.941; p < 0.001). The best-performing threshold was found to be 220 ng/ml (sensitivity, 89%; specificity, 78%). The same threshold was independently associated with a higher risk of nonresponse (adjusted OR aOR, 6.17; 95% CI 1.41-27.03; p = 0.016). In multivariable analysis (adjusted for age, Model for End-Stage Liver Disease, acute-on-chronic liver failure, leukocytes, and type of AKI), uNGAL was an independent predictor of in-hospital mortality (aOR, 1.74; 95% CI 1.26-2.38; p = 0.001).
uNGAL is an adequate biomarker for making a differential diagnosis of AKI in cirrhosis and predicting the response to terlipressin and albumin in patients with HRS-AKI. In addition, it is an independent predictor of in-hospital mortality.
The prognostic impact of acute decompensation (AD), i.e. the development of complications that require hospitalization, has recently been assessed. However, complications of cirrhosis do not ...necessarily require hospitalization and can develop progressively, as in the recently defined non-acute decompensation (NAD). Nevertheless, there is no data regarding the incidence and prognostic impact of NAD. The aim of the study was to evaluate the incidence and the prognostic impact of NAD and AD in outpatients with cirrhosis.
A total of 617 outpatients with cirrhosis from two Italian tertiary centers (Padua and Milan) were enrolled from January 2003 to June 2021 and followed prospectively until the end of the study, death or liver transplantation. The complications registered during follow-up were considered as AD if they required hospitalization, or NAD if managed at the outpatient clinic.
During follow-up, 154 patients (25.0% of total patients) developed complications, 69 patients (44.8%) developed NAD and 85 (55.2%) developed AD, while 29 patients with NAD (42.0%) developed a further episode of AD during follow-up. Sixty-month survival was significantly higher in patients with no decompensation than in patients with NAD or AD. On multivariable analysis, AD (hazard ratio HR 21.07, p <0.001), NAD (HR 7.13, p <0.001), the etiological cure of cirrhosis (HR 0.38, p <0.001) and model for end-stage liver disease score (HR 1.12, p = 0.003) were found to be independent predictors of mortality.
The first decompensation is non-acute in almost 50% of outpatients, though such events are still associated with decreased survival compared to no decompensation. Patients who develop NAD must be treated with extreme care and monitored closely to prevent the development of AD.
This multicenter study is the first to investigate the role of non-acute decompensation (NAD) in patients with cirrhosis. In fact, while the unfavorable impact of acute decompensation is well known, there is currently a dearth of evidence on NAD, despite it being a common occurrence in clinical practice. Our data show that almost half of decompensations in patients with cirrhosis can be considered NAD and that such events are associated with a higher risk of mortality than no decompensation. This study has important clinical implications because it highlights the need to carefully consider patients who develop NAD, in order to prevent further decompensation and reduce mortality.
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•In clinical practice, patients can develop complications progressively (NAD) rather than acutely (AD).•The unfavorable impact of AD in patients with cirrhosis is well known, while the role of NAD is still to be proven.•NAD accounted for 45% of decompensations and 42% of patients with NAD developed AD during follow-up.•Mortality in patients with NAD is higher than in compensated patients.•Patients with NAD should be monitored closely to prevent the development of AD.
