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Background Accurate estimation of the hepatic functional reserve before liver resection is important to avoid post-hepatectomy liver failure (PHLF). The aim of the present study was to evaluate the association of indocyanine green retention test with portal pressure by the cause of cirrhosis (non-viral vs. viral) and assessed postoperative outcomes including incidence of PHLF in patients with viral and non-viral cirrhosis. Methods The cohort includes 50 consecutive patients with liver cirrhosis scheduled for liver resection for primary liver tumors at the Lausanne University Hospital between 2009 and 2018. Results There were 31 patients with non-viral liver cirrhosis (Non-virus group) and 19 with viral liver cirrhosis (virus group). The indocyanine green retention rate at 15 min (ICG-R15) ( p  = 0.276), Hepatic Venous Portal Gradient (HVPG; p  = 0.301), and postoperative outcomes did not differ between the non-virus group and viral group. ICG-R15 and HVPG showed a significant linear correlation in all patients (Spearman’s rank correlation coefficient, ρ  = 0.599, p  < 0.001), the non-virus group ( ρ  = 0.555, p  = 0.026), and the virus group ( ρ  = 0.534, p  = 0.007). A receiver operating characteristic curve analysis showed that ICG-R15 was a predictor for presence of portal hypertension (PH; HVPG ≥ 12 mmHg) (area under the curve [AUC] = 0.780). The cut-off value of ICG-R15 for predicting the presence of PH was 16.0% with 72.3% of sensitivity and 79.0% of specificity. Conclusions The ICG-R15 level was associated with portal pressure in both patients with non-virus cirrhosis and patients with virus cirrhosis and predicts the incidence of PH with relatively good discriminatory ability. Clinical trial number https://clinicalTrials.gov(ID:NCT00827723) Local ethics committee number CER-VD 251.08

Limited information and divergent results are available on the prevalence/incidence, survival, and risk factors for developing extrahepatic malignancies (EMs) in primary biliary cirrhosis (PBC). The aim of the study was to analyze the epidemiology and survival rates for EM in PBC patients. The study was conducted on two series of patients followed up at two European centers (361 in Padova, Italy, and 397 in Barcelona, Spain) for a mean 7.7 ± 7 and 12.2 ± 7 years, respectively. The cancer incidence was compared with the standardized incidence ratios (SIRs) calculated using the Cancer Registry of the Veneto Region (Italy) and the Cancer Registry of Tarragona (Spain). Seventy-two patients developed EM. The prevalence of cases was similar in Padova (9.7 %) and Barcelona (9.4 %). The overall cancer incidence was similar to the expected incidence for the general population in the same geographical area (SIR = 1.2), and so was the crude EM rate (855.01 vs 652.86 per 100,000 patient-years, respectively, RR = 1.3). Logistic regression analysis showed that advanced histological stage and extrahepatic autoimmune diseases were significantly associated with the onset of EM. Survival was similar for PBC patients with and without EM ( p  = n.s.), and actual survival was similar to the one predicted by the Mayo model. The incidence of EM in PBC patients was found similar in Italy and Spain and no different from that of the general population. Advanced histological stage and extrahepatic autoimmune disease were risk factors significantly associated with EM developing in PBC. The onset of cancer in PBC patients does not influence the natural history of their liver disease.

Baveno-VI guidelines recommend that patients with compensated cirrhosis with liver stiffness by transient elastography (LSM-TE) <20 kPa and platelets >150,000/mm(3) do not need an esophagogastroduodenoscopy (EGD) to screen for varices, since the risk of having varices needing treatment (VNT) is <5%. It remains uncertain if this tool can be used in patients with cholestatic liver diseases (ChLDs): primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). These patients may have a pre-sinusoidal component of portal hypertension that could affect the performance of this rule. In this study we evaluated the performance of Baveno-VI, expanded Baveno-VI (LSM-TE <25 kPa and platelets >110,000/mm(3)), and other criteria in predicting the absence of VNT. This was a multicenter cross-sectional study in four referral hospitals. We retrospectively analyzed data from 227 patients with compensated advanced chronic liver disease (cACLD) due to PBC (n = 147) and PSC (n = 80) that had paired EGD and LSM-TE. We calculated false negative rate (FNR) and number of saved endoscopies for each prediction rule. Prevalence of VNT was 13%. Baveno-VI criteria had a 0% FNR in PBC and PSC, saving 39 and 30% of EGDs, respectively. In PBC the other LSM-TE-based criteria resulted in FNRs >5%. In PSC the expanded Baveno criteria had an adequate performance. In both conditions LSM-TE-independent criteria resulted in an acceptable FNR but saved less EGDs. Baveno-VI criteria can be applied in patients with cACLD due to ChLDs, which would result in saving 30-40% of EGDs. Expanded criteria in PBC would lead to FNRs >5%.

Background The consequences of lymphadenectomy (LND) on cirrhotic patients undergoing hepatectomy for intrahepatic cholangiocarcinoma (ICC) have not been investigated. We sought to analyze the impact of LND on morbidity among patients undergoing resection for ICC. Methods A total of 1005 patients who underwent hepatectomy for ICC at one of the 14 participating institutions between 1990 and 2015 were identified. A propensity score match analysis was performed to reduce confounding biases between cirrhosis and non-cirrhosis groups. Results Cirrhosis was diagnosed in 118 (11.7%) patients. Among non-cirrhotic patients, 63% underwent major liver resection versus only 20% among patients with cirrhosis ( p  < 0.001). LND was also less common among cirrhotic versus non-cirrhotic patients (19 vs. 50%, p  < 0.001). The incidence of complications was 41 and 30% among patients who did not and did have cirrhosis, respectively ( p  = 0.022). The propensity-matched cohort included 150 patients. The incidence of complications was 71% among patients who underwent lymphadenectomy versus 23% among patients who did not undergo lymphadenectomy (OR 8.39) ( p  < 0.001). In the propensity-matched analysis, the median HLN was comparable among patients independent of cirrhosis status (median HLN: non-cirrhosis, 2.5 vs. cirrhosis, 2) ( p  = 0.95). While lymphadenectomy was associated with a higher risk of infections (non-cirrhosis, 0% vs. cirrhosis, 21%, p  < 0.001) among patients with cirrhosis, infections were not associated with lymphadenectomy among non-cirrhotic patients ( p  = 0.19). Conclusion Lymphadenectomy was associated with an increased risk of complications among patients with cirrhosis undergoing surgery for ICC. The benefit of lymphadenectomy in cirrhotic patients should be considered in light of the higher risk of postoperative complications compared with non-cirrhotic patients.

In critical patients, abdominal perfusion pressure (APP) has been shown to correlate with outcome. However, data from cirrhotic patients is scarce. We aimed to characterize APP in critically ill cirrhotic patients, analyze the prevalence and risk factors of abdominal hypoperfusion (AhP) and outcomes. A prospective cohort study in a general ICU specialized in liver disease at a tertiary hospital center recruited consecutive cirrhotic patients between October 2016 and December 2021. The study included 101 patients, with a mean age of 57.2 (± 10.4) years and a female gender proportion of 23.5%. The most frequent etiology of cirrhosis was alcohol (51.0%), and the precipitant event was infection (37.3%). ACLF grade (1–3) distribution was 8.9%, 26.7% and 52.5%, respectively. A total of 1274 measurements presented a mean APP of 63 (± 15) mmHg. Baseline AhP prevalence was 47%, independently associated with paracentesis (aOR 4.81, CI 95% 1.46–15.8, p = 0.01) and ACLF grade (aOR 2.41, CI 95% 1.20–4.85, p = 0.01). Similarly, AhP during the first week (64%) had baseline ACLF grade (aOR 2.09, CI 95% 1.29–3.39, p = 0.003) as a risk factor. Independent risk factors for 28-day mortality were bilirubin (aOR 1.10, CI 95% 1.04–1.16, p < 0.001) and SAPS II score (aOR 1.07, CI 95% 1.03–1.11, p = 0.001). There was a high prevalence of AhP in critical cirrhotic patients. Abdominal hypoperfusion was independently associated with higher ACLF grade and baseline paracentesis. Risk factors for 28-day mortality included clinical severity and total bilirubin. The prevention and treatment of AhP in the high-risk cirrhotic patient is prudential.

ObjectiveSystemic inflammation predisposes acutely decompensated (AD) cirrhosis to the development of acute-on-chronic liver failure (ACLF). Supportive treatment can improve AD patients, becoming recompensated. Little is known about the outcome of patients recompensated after AD. We hypothesise that different inflammasome activation is involved in ACLF development in compensated and recompensated patients.Design249 patients with cirrhosis, divided into compensated and recompensated (previous AD), were followed prospectively for fatal ACLF development. Two external cohorts (n=327) (recompensation, AD and ACLF) were included. Inflammasome-driving interleukins (ILs), IL-1α (caspase-4/11-dependent) and IL-1β (caspase-1-dependent), were measured. In rats, bile duct ligation-induced cirrhosis and lipopolysaccharide exposition were used to induce AD and subsequent recompensation. IL-1α and IL-1β levels and upstream/downstream gene expression were measured.ResultsPatients developing ACLF showed higher baseline levels of ILs. Recompensated patients and patients with detectable ILs had higher rates of ACLF development than compensated patients. Baseline CLIF-C (European Foundation for the study of chronic liver failure consortium) AD, albumin and IL-1α were independent predictors of ACLF development in compensated and CLIF-C AD and IL-1β in recompensated patients. Compensated rats showed higher IL-1α gene expression and recompensated rats higher IL-1β levels with higher hepatic gene expression. Higher IL-1β detection rates in recompensated patients developing ACLF and higher IL-1α and IL-1β detection rates in patients with ACLF were confirmed in the two external cohorts.ConclusionPrevious AD is an important risk factor for fatal ACLF development and possibly linked with inflammasome activation. Animal models confirmed the results showing a link between ACLF development and IL-1α in compensated cirrhosis and IL-1β in recompensated cirrhosis.

Background Surgical resection for perihilar cholangiocarcinoma (pCCA) is associated with high operative risks. Impaired liver regeneration in patients with pre-existing liver disease may contribute to posthepatectomy liver failure (PHLF) and postoperative mortality. This study aimed to determine the incidence of hepatic steatosis and fibrosis and their association with PHLF and 90-day postoperative mortality in pCCA patients. Methods Patients who underwent a major liver resection for pCCA were included in the study between 2000 and 2021 from three tertiary referral hospitals. Histopathologic assessment of hepatic steatosis and fibrosis was performed. The primary outcomes were PHLF and 90-day mortality. Results Of the 401 included patients, steatosis was absent in 334 patients (83.3%), mild in 58 patients (14.5%) and moderate to severe in 9 patients (2.2%). There was no fibrosis in 92 patients (23.1%), periportal fibrosis in 150 patients (37.6%), septal fibrosis in 123 patients (30.8%), and biliary cirrhosis in 34 patients (8.5%). Steatosis (≥ 5%) was not associated with PHLF (odds ratio [OR] 1.36; 95% confidence interval [CI] 0.69–2.68) or 90-day mortality (OR 1.22; 95% CI 0.62–2.39). Neither was fibrosis (i.e., periportal, septal, or biliary cirrhosis) associated with PHLF (OR 0.76; 95% CI 0.41–1.41) or 90-day mortality (OR 0.60; 95% CI 0.33–1.06). The independent risk factors for PHLF were preoperative cholangitis (OR 2.38; 95% CI 1. 36–4.17) and future liver remnant smaller than 40% (OR 2.40; 95% CI 1.31–4.38). The independent risk factors for 90-day mortality were age of 65 years or older (OR 2.40; 95% CI 1.36–4.23) and preoperative cholangitis (OR 2.25; 95% CI 1.30–3.87). Conclusion In this study, no association could be demonstrated between hepatic steatosis or fibrosis and postoperative outcomes after resection of pCCA.

Stigmatization is a well-documented problem of some diseases. Perceived stigma is common in alcohol-related liver disease and hepatitis C, but little information exists on stigma in patients with non-alcoholic fatty liver disease (NAFLD). Aim of the study was to investigate frequency and characteristics of perceived stigma among patients with NAFLD. One-hundred and ninety-seven patients seen at the liver clinic were included: a study group of 144 patients with NAFLD, 50 with cirrhosis (34 compensated, 16 decompensated), and a control group of 53 patients with alcohol-related cirrhosis. Demographic, clinical, and laboratory data were collected. Quality-of-life was assessed by chronic liver disease questionnaire (CLDQ). Perceived stigma was assessed using a specific questionnaire for patients with liver diseases categorized in 4 domains: stereotypes, discrimination, shame, and social isolation. Perceived stigma was common in patients with NAFLD (99 patients, 69%) and affected all 4 domains assessed. The frequency was slightly higher, yet not significant, in patients with NAFLD cirrhosis vs those without (72% vs 67%, respectively; p = 0.576). In patients without cirrhosis perceived stigma was unrelated to stage of disease, since frequency was similar in patients with no or mild fibrosis compared to those with moderate/severe fibrosis (66% vs 68%, respectively). There were no differences in perceived stigma between patients with compensated cirrhosis and these with decompensated cirrhosis. Among patients with cirrhosis, stigmatization was more common in alcohol-related vs NAFLD-cirrhosis, yet differences were only significant in two domains. In patients with NAFLD, perceived stigma correlated with poor quality-of-life, but not with demographic or clinical variables. Perceived stigmatization is common among patients with NAFLD independently of disease stage, is associated with impaired quality-of-life, and may be responsible for stereotypes, discrimination, shame, and social isolation, which may affect human and social rights of affected patients.

Both transient elastography (TE)-based and non-TE-based criteria exist for detection of varices needing treatment (VNT) in patients with asymptomatic advanced chronic liver disease (CLD). However, their performance in clinical settings at different risk thresholds of detection of VNT and in regions where elastography is not widely available is unknown. We aimed to validate existing noninvasive criteria in our patients with CLD and identify best TE- and non-TE-based criteria for VNT screening at usual risk thresholds. Patients with compensated advanced CLD (cACLD) who underwent esophagogastroduodenoscopy and TE within 3 months were included. Diagnostic performance of Baveno VI, expanded Baveno VI, platelet-model for end-stage liver disease, and platelet-albumin (Rete Sicilia Selezione Terapia-hepatitis C virus) criteria were estimated. Decision curve analysis was conducted for different predictors across range of threshold probabilities. A repeat analysis including all patients with compensated CLD (cACLD and non-cACLD) was performed to simulate absence of TE. A total of 1,657 patients (cACLD, 895; non-cACLD, 762) related to hepatitis B virus (38.2%), hepatitis C virus (33.4%), nonalcoholic steatohepatitis (14.7%), and alcohol (11.8%) were included. Baveno VI identified maximum VNT (97.3%) and had best negative predictive value (96.9%), followed by platelet-albumin criteria. Expanded Baveno VI and platelet-model for end-stage liver disease had intermediate performance. At threshold probability of 5%, Baveno VI criteria showed maximum net benefit, and platelet-albumin criteria was next best, with need for 95 additional elastographies to detect 1 additional VNT. Similar results were obtained on including all patients with compensated CLD irrespective of TE. Baveno VI criteria maximizes VNT yield at 5% threshold probability. An acceptable alternative is the platelet-albumin criteria in resource-limited settings.