Aims
This multicentre cohort study evaluated the role of ageing on clinical characteristics, treatment allocation and outcome of new hepatocellular carcinomas (HCCs), in clinical practice.
Material & ...Methods
From September 2008, 541 patients >70 years old (elderly group), and 527 ≤70 years old (non‐elderly group) with newly diagnosed HCC were consecutively enrolled in 30 Italian centres. Differences in clinical characteristics and treatment allocation between groups were described by a multivariable logistic regression model measuring the inverse probability weight to meet the elderly group. Survival differences were measured by unadjusted and adjusted (by inverse probability weight) survival analysis.
Results
Elderly patients were mainly females, hepatitis C virus infected and with better conserved liver function (P<.001). At presentation, HCC median size was similar in both groups while, in youngers, HCC was more frequently multinodular (P=.001), and associated with neoplastic thrombosis (P=.009). Adjusted survival analysis showed that age did not predict short–mid‐term survival (within 24 months), while it was a significant independent predictor of long‐term survival. Moreover, age had a significant long‐term survival impact mainly on early HCC stages (Barcelona Clinic for Liver Cancer BCLC 0‐A), its impact on BCLC B stage was lower, while it was negligible for advanced‐terminal stages.
Conclusions
Age per se does not impact on short–mid‐term prognosis (≤24 months) of HCC patients, and should not represent a limitation to its management.
Background/Aims Some evidence suggests that the systemic inflammatory response syndrome (SIRS) contributes to the poor outcome of cirrhotic patients. We studied 141 cirrhotic patients consecutively ...admitted to a tertiary referral centre assessing prevalence of SIRS and its relationship with in-hospital outcome. Methods Presence of SIRS was assessed on admission and during hospital stay. Main clinical outcomes were death and development of portal hypertension-related complications. Results Thirty-nine patients met SIRS criteria. SIRS was present on admission in 20 of 141 patients (14.1%), whereas it occurred during hospital stay in 19 of 121 (15.7%). SIRS was correlated with bacterial infection at admission ( p = 0.02), jaundice ( p = 0.011), high serum creatinine levels ( p = 0.04), high serum bilirubin levels ( p = 0.002), high international normalized ratio ( p = 0.046), high model of end-stage liver disease (MELD) score ( p = 0.001), and high SOFA score ( p = 0.003). During a follow-up of 14 ± 8 days, 16 patients died (11%), 7 developed portal hypertension-related bleeding (5%), 16 hepatic encephalopathy (11%), and 5 hepatorenal syndrome type-1 (3.5%). SIRS was correlated both to death ( p < 0.001) and to portal hypertension-related complications ( p < 0.001). On multivariate analysis, SIRS and MELD were independently associated with death. Conclusions SIRS frequently occurs in patients with advanced cirrhosis and is associated with a poor outcome.
We assessed the prognostic significance of infections in relation to current prognostic scores and explored if infection could be considered per se a distinct clinical stage in the natural history of ...cirrhosis.
We included consecutive patients with cirrhosis admitted to a tertiary referral liver unit for at least 48 h over a 2-year period. Diagnosis of infection was based on positive cultures or strict established criteria. We used competing risk analysis and propensity score matching for data analysis.
501 patients (63% male, 48% alcoholic liver disease, median Model of End-stage Liver Disease (MELD)=17) underwent 781 admissions over the study period. Portal hypertensive bleeding and complicated ascites were the commonest reasons of admission. The incidence of proven bacterial infection was 25.6% (60% community acquired and 40% nosocomial). Survival rates at 3, 6, 12, and 30 months were 83%, 77%, 71%, and 62% in patients without diagnosis of infection, vs. 50%, 46%, 41%, and 34% in patients with diagnosis of infection. Overall survival was independently associated with MELD score (hazards ratio (HR) 1.099), intensive care (ITU) stay (HR 1.967) and bacterial infection (HR 2.226). Bacterial infection was an independent predictor of survival even when patients who died within the first 30 days were excluded from the analysis in Cox regression (HR 2.013) and competing risk Cox models in all patients (HR 1.46) and propensity risk score-matched infected and non-infected patients (HR 1.67).
Infection most likely represents a distinct prognostic stage of cirrhosis, which affects survival irrespective of disease severity, even after recovery from the infective episode.
Several staging systems for hepatocellular carcinoma (HCC) have been developed. The Barcelona Clinic Liver Cancer staging system is considered the best in predicting survival, although limitations ...have emerged. Recently, the Italian Liver Cancer (ITA.LI.CA) prognostic system, integrating ITA.LI.CA tumor staging (stages 0, A, B1‐3, C) with the Child‐Turcotte‐Pugh score, Eastern Cooperative Oncology Group performance status, and alpha‐fetoprotein with a strong ability to predict survival, was proposed. The aim of our study was to provide an external validation of the ITA.LI.CA system in an independent real‐life occidental cohort of HCCs. From September 2008 to April 2016, 1,508 patients with cirrhosis and incident HCC were consecutively enrolled in 27 Italian institutions. Clinical, tumor, and treatment‐related variables were collected, and patients were stratified according to scores of the Barcelona Clinic Liver Cancer system, ITA.LI.CA prognostic system, Hong Kong Liver Cancer system, Cancer of the Liver Italian Program, Japanese Integrated System, and model to estimate survival in ambulatory patients with hepatocellular carcinoma. Harrell's C‐index, Akaike information criterion, and likelihood‐ratio test were used to compare the predictive ability of the different systems. A subgroup analysis for treatment category (curative versus palliative) was performed. Median follow‐up was 44 months (interquartile range, 23‐63 months), and median overall survival was 34 months (interquartile range, 13‐82 months). Median age was 71 years, and patients were mainly male individuals and hepatitis C virus carriers. According to ITA.LI.CA tumor staging, 246 patients were in stage 0, 472 were in stage A, 657 were in stages B1/3, and 133 were in stage C. The ITA.LI.CA prognostic system showed the best discriminatory ability (C‐index = 0.77) and monotonicity of gradients compared to other systems, and its superiority was also confirmed after stratification for treatment strategy. Conclusion: This is the first study that independently validated the ITA.LI.CA prognostic system in a large cohort of Western patients with incident HCCs. The ITA.LI.CA system performed better than other multidimensional prognostic systems, even after stratification by curative or palliative treatment. This new system appears to be particularly useful for predicting individual HCC prognosis in clinical practice. (Hepatology 2018;67:2215‐2225)
Background: Transjugular intrahepatic portosystemic shunt (TIPS) is a treatment for portal hypertension-related complications. Accurate prediction of the outcome of patients treated with TIPS is ...important, because some patients have very short survival. Diastolic dysfunction is frequently observed in patients with cirrhosis. Aim: To investigate whether or not diastolic dysfunction can predict the outcome after TIPS. Methods: Echocardiography with Doppler exploration was performed before and 28 days after TIPS insertion in 32 patients with cirrhosis. Several echocardiographic measures, including the early maximal ventricular filling velocity/late filling velocity (E/A) ratio as indicative of diastolic function, as well as laboratory, clinical and demographic variables were evaluated as predictors of survival. Results: Univariate analysis revealed that the presence of diastolic dysfunction observed 28 days after TIPS (E/A ratio ⩽1) and baseline model of end-stage liver disease score were related to survival. Multivariate analysis identified diastolic dysfunction as an independent predictor of death (RR 8.9, 95% CI 1.9 to 41.5, p = 0.005). During the first year of follow–up, six out of 10 patients with an E/A ratio ⩽1 died, whereas all 22 patients with E/A ratio >1 survived. Conclusions: Diastolic dysfunction estimated using E/A ratio is a promising predictor of death in patients with cirrhosis who are treated with TIPS.
Mean age of hepatocellular carcinoma （HCC） patients hasbeen progressively increasing over the last decades andageing of these patients is becoming a real challenge inevery day clinical practice. ...Unfortunately, internationalguidelines on HCC management do not address thisproblem exhaustively and do not provide any specific recommendation. We carried out a literature search inMEDLINE database for studies reporting on epidemiology,clinical characteristics and treatment outcome of HCCin elderly patients. Available data seem to indicatethat in elderly patients the outcome of HCC is mostlyinfluenced by liver function and tumor stage rather thanby age and the latter should not influence treatmentallocation. Age is not a risk for resection and olderpatients with resectable HCC and good liver functioncould gain benefit from surgery. Mild comorbiditiesdo not seem a contraindication for surgery in agedpatients. Conversely, major resection in elderly, evenwhen performed in experienced high-volume centres,should be avoided. Both percutaneous ablation andtransarterial chemoembolization are not contraindicatedin aged patients and safety profile of these proceduresis acceptable. Sorafenib is a viable option for advancedHCC in elderly provided that a careful evaluation ofconcomitant comorbidities, particularly cardiovascularones, is taken into account. Available data seem tosuggest that in either elderly and younger, treatment isa main predictor of outcome. Consequently, a nihilisticattitude of physicians towards under- or no-treatment ofaged patients should not be longer justified.
Background & Aims
Bacterial strains resistant to antibiotics are a serious clinical challenge. We assessed the antibiotic susceptibility of bacteria isolated from infections in patients with ...cirrhosis by a multicentre investigation.
Results
Three hundred and thirteen culture‐positive infections (173 community acquired CA and 140 hospital acquired HA) were identified in 308 patients. Urinary tract infections, spontaneous bacterial peritonitis and bacteremias were the most frequent. Quinolone‐resistant Gram‐negative isolates were 48%, 44% were extended‐spectrum beta‐lactamase producers and 9% carbapenem resistant. In 83/313 culture‐positive infections (27%), multidrug‐resistant agents (MDRA) were isolated. This prevalence did not differ between CA and HA infections. MDRA were identified in 17 of 37 patients on quinolone prophylaxis, and in 46 of 166 not on prophylaxis (45% vs 27%; P<.03). In 287 cases an empiric antibiotic therapy was undertaken, in 37 (12.9%) this therapy failed. The in‐hospital mortality rate of this subset of patients was significantly higher compared to patients who received an effective broad(er)‐spectrum therapy (P=.038). During a 3‐month follow‐up, 56/203 culture‐positive patients (27.6%) died, 24/63 who have had MDRA‐related infections (38%) and 32/140 who have had antibiotic‐susceptible infections (22.8%) (P=.025). Multivariate analysis disclosed MDRA infection, age, hepatocellular carcinoma, bilirubin, international normalized ratio and the occurrence of portal hypertension‐related complications independent predictors of death.
Conclusions
Infection by MDRA is frequent in patients with cirrhosis and the prognosis is severe, especially in patients unresponsive to empiric antibiotic therapy.
Background & Aims
In the direct‐acting antiviral era, treatment of genotype‐3 HCV (HCV‐GT3) is still challenging. Real‐life comparisons between recommended regimens, sofosbuvir (SOF)+daclatasvir ...(DAC), SOF/velpatasvir (VEL), glecaprevir/pibrentasvir (GLE/PIB), are scarce. We aimed at filling this data gap.
Methods
Sustained virological response 12 weeks after treatment completion (SVR12) was assessed for all HCV‐GT3 patients consecutively treated within the Lombardia web‐based Navigatore HCV‐Network; differences in SVR12 across regimens were evaluated by logistic regression.
Results
Of the 2082 subjects with HCV‐GT3, 1544 were evaluable for comparisons between regimens: SOF + DAC (1023, 66.2%), SOF/VEL (369, 23.9%), GLE/PIB (152, 9.8%). Patients treated with former regimens were more frequently male, cirrhotic, HIV‐positive, pretreated, used ribavirin in their regimen, and had lower baseline HCV‐RNA. SVR12 was similar across groups: 94.8% in SOF + DAC, 97.6% in SOF/VEL, 96.7% in GLE/PIB (P = .065). At univariate analysis, SVR12 was associated with female gender (97.9% vs 94.8%, P = .007) and lower median pretreatment Log10HCV‐RNA (5.87 vs 6.20, P = .001). At multivariate logistic regression analysis, treatment with SOF/VEL was associated with a higher likelihood of SVR12 than SOF + DAC, but only in the absence of ribavirin (98% vs 90.3%). Female gender and lower pretreatment HCV‐RNA were independently associated with SVR12.
Conclusions
In a large real‐life setting of HCV‐GT3‐infected patients with a high proportion of cirrhosis, the success rate was remarkable. The slight advantage of SOF/VEL on SOF + DAC was significant only without ribavirin. The current prescription shift towards novel regimens (ie SOF/VEL and GLE/PIB) in easier‐to‐treat patients allows ribavirin‐free and shorter schedules without mining SVR12 in this <<difficult‐to‐treat>> genotype.
Sofosbuvir (SOF)-based regimens have been associated with renal function worsening in HCV patients with estimated glomerular filtration rate (eGFR) ≤ 45 ml/min, but further investigations are ...lacking.
To assess renal safety in a large cohort of DAA-treated HCV patients with any chronic kidney disease (CKD).
All HCV patients treated with DAA in Lombardy (December 2014–November 2017) with available kidney function tests during and off-treatment were included.
Among 3264 patients 65% males, 67% cirrhotics, eGFR 88 (9–264) ml/min, CKD stage was 3 in 9.5% and 4/5 in 0.7%. 79% and 73% patients received SOF and RBV, respectively. During DAA, eGFR declined in CKD-1 (p < 0.0001) and CKD-2 (p = 0.0002) patients, with corresponding rates of CKD stage reduction of 25% and 8%. Conversely, eGFR improved in lower CKD stages (p < 0.0001 in CKD-3a, p = 0.0007 in CKD-3b, p = 0.024 in CKD-4/5), with 33–45% rates of CKD improvement. Changes in eGFR and CKD distribution persisted at SVR. Baseline independent predictors of CKD worsening at EOT and SVR were age (p < 0.0001), higher baseline CKD stages (p < 0.0001) and AH (p = 0.010 and p < 0.0001, respectively).
During DAA, eGFR significantly declined in patients with preserved renal function and improved in those with lower CKD stages, without reverting upon drug discontinuation.
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