Development and validation of a new prognostic model for patients with acute-on-chronic liver failure in intensive care unit.

BACKGROUND: Cirrhotic patients with acute-on-chronic liver failure (ACLF) in the intensive care unit (ICU) have a poor but variable prognoses. Accurate prognosis evaluation can guide the rational management of patients with ACLF. However, existing prognostic scores for ACLF in the ICU environment lack sufficient accuracy. AIM: To develop a new prognostic model for patients with ACLF in ICU. METHODS: Data from 938 ACLF patients in the Medical Information Mart for Intensive Care (MIMIC) database were used to develop a new prognostic model (MIMIC ACLF) for ACLF. Discrimination, calibration and clinical utility of MIMIC ACLF were assessed by area under receiver operating characteristic curve (AUROC), calibration curve and decision curve analysis (DCA), respectively. MIMIC ACLF was then externally validated in a multiple-center cohort, the Electronic Intensive Care Collaborative Research Database and a single-center cohort from the Second Hospital of Hebei Medical University in China. RESULTS: The MIMIC ACLF score was determined using nine variables: ln (age) × 2.2 + ln (white blood cell count) × 0.22 - ln (mean arterial pressure) × 2.7 + respiratory failure × 0.6 + renal failure × 0.51 + cerebral failure × 0.31 + ln (total bilirubin) × 0.44 + ln (internationalized normal ratio) × 0.59 + ln (serum potassium) × 0.59. In MIMIC cohort, the AUROC (0.81/0.79) for MIMIC ACLF for 28/90-day ACLF mortality were significantly greater than those of Chronic Liver Failure Consortium ACLF (0.76/0.74), Model for End-stage Liver Disease (MELD; 0.73/0.71) and MELD-Na (0.72/0.70) (all P < 0.001). The consistency between actual and predicted 28/90-day survival rates of patients according to MIMIC ACLF score was excellent and superior to that of existing scores. The net benefit of MIMIC ACLF was greater than that achieved using existing scores within the 50% threshold probability. The superior predictive accuracy and clinical utility of MIMIC ACLF were validated in the external cohorts. CONCLUSION: We developed and validated a new prognostic model with satisfactory accuracy for cirrhotic patients with ACLF hospitalized in the ICU. The model-based risk stratification and online calculator might facilitate the rational management of patients with ACLF.

[Analysis of clinical characteristics and risk factors for nosocomial mortality in patients with liver cirrhosis combined with atrial arrhythmia].

Objective: To analyze and explore the clinical characteristics and risk factors related to nosocomial mortality in patients with liver cirrhosis combined with atrial arrhythmia. Methods: 252 hospitalized patients with liver cirrhosis combined with atrial arrhythmia from January 2014 to December 2021 were enrolled, and their clinical characteristics were analyzed. The above-mentioned patients were divided into groups according to their nosocomial mortality rate. Among them, 45 nosocomial mortality cases were classified as the mortality group, and 207 survival cases were classified as the survival group. The differences in clinical data and laboratory data between the two groups were compared. The risk factors for nosocomial mortality in patients with liver cirrhosis combined with atrial arrhythmia were analyzed. The t-test, or rank-sum test, was used to compare measurement data. The chi-square test, or Fisher's exact probability method, was used to compare enumeration data. Multivariate analysis was performed by the logistic regression method. Results: Among the 252 cases, the male-to-female ratio was the same (male/female ratio: 126/126). The age range was 26 to 89 (66.77±10.46) years. Han ethnicity accounted for 79.5%. The main type of atrial arrhythmia was atrial fibrillation (P < 0.001). The main cause of liver cirrhosis was post-hepatitis B cirrhosis (56.3%). There were 57/72/123 cases of CTP grade A/B/C. The CTP and Model for End-Stage Liver Disease (MELD) scores were 10.30±1.77 and 18.0(11.0, 29.0), respectively. The nosocomial mortality rate was 17.9% (45/252). The overall incidence rate of complications in all patients was 89.28%, with complications occurring in the following order: 71.4% ascites, 71.0% hypersplenism, 64.7% spontaneous peritonitis, 64.3% esophageal gastric varices, 32.5% hepatorenal syndrome, 32.1% hepatic encephalopathy, and 26.2% esophageal gastric variceal bleeding. The incidence rate of new-onset atrial fibrillation in the nosocomial mortality group was 73.3%, which was much higher than the 44.0% rate in the survival group (P < 0.05). Multivariate logistic regression analysis showed that new-onset atrial fibrillation (OR=2.707, 95%CI 1.119 ~ 6.549), esophageal-gastric varices (OR=3.287, 95%CI 1.189 ~ 9.085), serum potassium (OR=3.820, 95%CI 1.532 ~ 9.526), and MELD score (OR=1.108, 95%CI 1.061~1.157) were independent risk factors for nosocomial mortality in patients with liver cirrhosis combined with atrial arrhythmia. Conclusion: Patients with cirrhosis combined with atrial arrhythmias have more severe liver function damage and are more likely to develop complications such as ascites, hypersplenism, and hepatorenal syndrome. New-onset atrial fibrillation, esophageal-gastric varices, hyperkalemia, and a high MELD score are risk factors for nosocomial mortality in patients with liver cirrhosis combined with atrial arrhythmia, so more attention should be paid to corresponding patients for timely symptomatic treatment.

Statins, metformin, and RAS inhibitors did not reduce variceal bleeding risk and mortality in a large, real-life cohort of patients with cirrhosis.

BACKGROUND: Previous experimental and clinical studies suggested a beneficial effect of statins, metformin, angiotensin-converting-enzyme inhibitors and angiotensin II receptor blockers (RASi) on portal hypertension. Still, their effects on hard cirrhosis-related clinical endpoints, such as variceal bleeding and bleeding-related mortality, remain to be investigated. METHODS: Thus, we recorded the use of statins, metformin and RASi in a large cohort of cirrhotic patients undergoing endoscopic band ligation (EBL) for primary (PP, n = 440) and secondary bleeding prophylaxis (SP, n = 480) between 01/2000 and 05/2020. Variceal (re-) bleeding and survival rates were compared between patients with vs. without these co-medications. RESULTS: A total of 920 cirrhotic patients with varices were included. At first EBL, median MELD was 13 and 515 (56%) patients showed ascites. Statins, metformin and RASi were used by 49 (5.3%), 74 (8%), and 91 (9.9%) patients, respectively. MELD and platelet counts were similar in patients with and without the co-medications of interest. Rates of first variceal bleeding and variceal rebleeding at 2 years were 5.2% and 11.7%, respectively. Neither of the co-medications were associated with decreased first bleeding rates (log-rank tests in PP: statins p = 0.813, metformin p = 0.862, RASi p = 0.919) nor rebleeding rates (log-rank tests in SP: statin p = 0.113, metformin p = 0.348, RASi p = 0.273). Similar mortality rates were documented in patients with and without co-medications for PP (log-rank tests: statins p = 0.630, metformin p = 0.591, RASi p = 0.064) and for SP (statins p = 0.720, metformin p = 0.584, RASi p = 0.118). CONCLUSION: In clinical practice, variceal bleeding and mortality rates of cirrhotic patients were not reduced by co-medication with statins, metformin or RASi. Nevertheless, we recommend the use of these co-medications by indication, as they may still exert beneficial effects on non-bleeding complications in patients with liver cirrhosis.

Acute-on-chronic liver failure: a retrospective review of cases at a transplantation center in Brazil.

PURPOSE: Acute-on-chronic liver failure (ACLF) is a leading cause of death in cirrhotic patients. This study aims to describe the outcomes of in-patients with ACLF at a liver transplantation (LT) center in Brazil. METHODS: Retrospective study analyzing patient data from 2017 to 2022. Re-transplant cases and patients without previous chronic liver disease were excluded. The ACLF diagnosis was based on the European Association for the Study of the Liver-Chronic Liver Failure criteria and assessments repeated on days 3 and 7 after the initial diagnosis. RESULTS: Among 381 patients, 10.49% (n = 40) were diagnosed with ACLF. Bacterial infection was the most common precipitating factor (45%). Kidney failure occurred in 65% of the cases. The 28-day mortality rate was 35% and varied according to ACLF severity at diagnosis, from single organ failure (ACLF-1) at 22% to three organ failures (ACLF-3) at 60%. Eighteen patients (45%) were transplanted with a 100% 28-day survival rate. For ACLF-3 cases at diagnosis (n = 15), the 28-day and 1-year survival rates with a transplant (n = 4) were 100% and 80%, respectively, and without transplant (n = 11), 10 and 0%, respectively. CONCLUSIONS: ACLF was associated with high mortality rates. LT was an effective therapeutic option, particularly for ACLF-3 cases.

Circulating bacterial peptides and linked metabolomic signatures are indicative of early mortality in pediatric cirrhosis.

BACKGROUND: Patients with pediatric cirrhosis-sepsis (PC-S) attain early mortality. Plasma bacterial composition, the cognate metabolites, and their contribution to the deterioration of patients with PC-S to early mortality are unknown. We aimed to delineate the plasma metaproteome-metabolome landscape and identify molecular indicators capable of segregating patients with PC-S predisposed to early mortality in plasma, and we further validated the selected metabolite panel in paired 1-drop blood samples using untargeted metaproteomics-metabolomics by UHPLC-HRMS followed by validation using machine-learning algorithms. METHODS: We enrolled 160 patients with liver diseases (cirrhosis-sepsis/nonsepsis [n=110] and noncirrhosis [n=50]) and performed untargeted metaproteomics-metabolomics on a training cohort of 110 patients (Cirrhosis-Sepsis/Nonsepsis, n=70 and noncirrhosis, n=40). The candidate predictors were validated on 2 test cohorts-T1 (plasma test cohort) and T2 (1-drop blood test cohort). Both T1 and T2 had 120 patients each, of which 70 were from the training cohort. RESULTS: Increased levels of tryptophan metabolites and Salmonella enterica and Escherichia coli-associated peptides segregated patients with cirrhosis. Increased levels of deoxyribose-1-phosphate, N5-citryl-d-ornithine, and Herbinix hemicellulolytic and Leifsonia xyli segregated patients with PC-S. MMCN-based integration analysis of WMCNA-WMpCNA identified key microbial-metabolic modules linked to PC-S nonsurvivors. Increased Indican, Staphylobillin, glucose-6-phosphate, 2-octenoylcarnitine, palmitic acid, and guanidoacetic acid along with L. xyli, Mycoplasma genitalium, and Hungateiclostridium thermocellum segregated PC-S nonsurvivors and superseded the liver disease severity indices with high accuracy, sensitivity, and specificity for mortality prediction using random forest machine-learning algorithm. CONCLUSIONS: Our study reveals a novel metabolite signature panel capable of segregating patients with PC-S predisposed to early mortality using as low as 1-drop blood.

Hematological ratios in patients with acute decompensation and acute-on-chronic liver failure: prognostic factors.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is the most severe form of acutely decompensated cirrhosis and is characterized by the presence of intense systemic inflammation. Leucocyte quantification can serve as an indirect indicator of systemic inflammation. In our study, we investigated the predictive value of hematological ratios (neutrophils to lymphocytes, monocyte to lymphocytes, platelets to lymphocytes, lymphocytes to C-reactive protein, and neutrophils to lymphocytes and platelets) in acute decompensation (AD) and ACLF patients and their relation to disease severity and early mortality. PATIENTS AND METHODS: We included 60 patients with ACLF and AD, and 30 cirrhotic controls. Clinical data were collected, and survival was followed for 1 and 6 months. Blood samples were analyzed at admission for differential leucocytes and assessed for liver and renal function tests. The leukocyte ratios were calculated and compared, and their correlation with liver function indicators and prognosis was assessed. RESULTS: All ratios were significantly higher in AD and ACLF patients compared to control (except for lymphocyte to C-reactive protein ratio which was significantly lower), and were positively correlated with Child-Pugh score, model for end-stage liver disease (MELD)-Na, and ACLF severity scores. Multivariate regression revealed that neutrophil to lymphocyte ratio, monocyte to lymphocyte ratio, and MELD-Na were independent prognostic factors of 1-month and 6-month mortality. A unique prognostic nomogram incorporating MELD-Na, neutrophil to lymphocyte ratio, and monocyte to lymphocyte ratio could be proposed for predicting prognosis in AD and ACLF patients. CONCLUSIONS: Cheap, easy, and noninvasive hematological ratios are introduced as a tool for early identification and risk stratification of AD and ACLF patients.

Alpha-fetoprotein and APRI as predictive markers for patients with Type C hepatitis B-related acute-on-chronic liver failure: a retrospective study.

BACKGROUND: Type C hepatitis B-related acute-on-chronic liver failure (HBV-ACLF), which is based on decompensated cirrhosis, has different laboratory tests, precipitating events, organ failure and clinical outcomes. The predictors of prognosis for type C HBV-ACLF patients are different from those for other subgroups. This study aimed to construct a novel, short-term prognostic score that applied serological indicators of hepatic regeneration and noninvasive assessment of liver fibrosis to predict outcomes in patients with type C HBV-ACLF. METHOD: Patients with type C HBV-ACLF were observed for 90 days. Demographic information, clinical examination, and laboratory test results of the enrolled patients were collected. Univariate and multivariate logistic regression were performed to identify independent prognostic factors and develop a novel prognostic scoring system. A receiver operating characteristic (ROC) curve was used to analyse the performance of the model. RESULTS: A total of 224 patients with type C HBV-ACLF were finally included. The overall survival rate within 90 days was 47.77%. Age, total bilirubin (TBil), international normalized ratio (INR), alpha-fetoprotein (AFP), white blood cell (WBC), serum sodium (Na), and aspartate aminotransferase/platelet ratio index (APRI) were found to be independent prognostic factors. According to the results of the logistic regression analysis, a new prognostic model (named the A3Twin score) was established. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) was 0.851 [95% CI (0.801-0.901)], the sensitivity was 78.8%, and the specificity was 71.8%, which were significantly higher than those of the MELD, IMELD, MELD-Na, TACIA and COSSH-ACLF II scores (all P < 0.001). Patients with lower A3Twin scores (<-9.07) survived longer. CONCLUSIONS: A new prognostic scoring system for patients with type C HBV-ACLF based on seven routine indices was established in our study and can accurately predict short-term mortality and might be used to guide clinical management.

External validation of the modified CTP score based on ammonia to predict survival in patients with cirrhosis after TIPS placement.

This study aimed to perform the first external validation of the modified Child-Turcotte-Pugh score based on plasma ammonia (aCTP) and compare it with other risk scoring systems to predict survival in patients with cirrhosis after transjugular intrahepatic portosystemic shunt (TIPS) placement. We retrospectively reviewed 473 patients from three cohorts between January 2016 and June 2022 and compared the aCTP score with the Child-Turcotte-Pugh (CTP) score, albumin-bilirubin (ALBI), model for end-stage liver disease (MELD) and sodium MELD (MELD-Na) in predicting transplant-free survival by the concordance index (C-index), area under the receiver operating characteristic curve, calibration plot, and decision curve analysis (DCA) curve. The median follow-up time was 29 months, during which a total of 62 (20.74%) patients died or underwent liver transplantation. The survival curves for the three aCTP grades differed significantly. Patients with aCTP grade C had a shorter expected lifespan than patients with aCTP grades A and B (P < 0.0001). The aCTP score showed the best discriminative performance using the C-index compared with other scores at each time point during follow-up, it also showed better calibration in the calibration plot and the lowest Brier scores, and it also showed a higher net benefit than the other scores in the DCA curve. The aCTP score outperformed the other risk scores in predicting survival after TIPS placement in patients with cirrhosis and may be useful for risk stratification and survival prediction.

Portal hypertension and its prognostic implications in patients with Wilson's disease.

BACKGROUND AND AIMS: Wilson's disease may progress to cirrhosis and clinically significant portal hypertension (CSPH). We aimed to assess the prevalence and prognostic impact of CSPH-related features on hepatic decompensation and transplant-free survival in patients with Wilson's disease. METHODS AND RESULTS: About 137 patients with Wilson's disease (Leipzig score ≥4), followed for a median observation period of 9.0 (3.9-17.7) years at the Vienna General Hospital, were included in this retrospective study. Overall, 49 (35.8%) developed features of CSPH: 14 (10.2%) varices, 40 (29.2%) splenomegaly, 20 (14.6%) ascites, 18 (13.1%) hepatic encephalopathy and 3 (2.2%) experienced acute variceal bleeding. Overall, 8 (5.8%) patients died, including three deaths caused by CSPH-related complications. Within 10 years, compensated patients with features of CSPH developed more decompensation events (8.3% vs. 1.5% in patients without CSPH, p = 0.3) and had worse transplant-free-survival (91.7% vs. 98.6%), which further declined in patients with hepatic decompensation (26.7%, log-rank: p < 0.0001). Patients with liver stiffness <15 kPa and normal platelets (≥150 G/L) were less likely to decompensate within 10 years (2.6% vs. 8.4%, p = 0.002) and had a better 10-year transplant-free-survival (97.7% vs. 83.9%, p = 0.006). CONCLUSIONS: Patients with Wilson's disease developing features of CSPH are at an increased risk for hepatic decompensation and liver-related mortality, warranting for regular screening and timely initiation of effective CSPH-directed treatments.

Development and validation of a nomogram for predicting in-hospital death in cirrhotic patients with acute kidney injury.

BACKGROUND: The purpose of this study was to develop a nomogram for predicting in-hospital mortality in cirrhotic patients with acute kidney injury (AKI) in order to identify patients with a high risk of in-hospital death early. METHODS: This study collected data on cirrhotic patients with AKI from 2008 to 2019 using the Medical Information Mart for Intensive Care IV. Multivariate logistic regression was used to identify confounding factors related to in-hospital mortality, which were then integrated into the nomogram. The concordance index (C-Index) was used to evaluate the accuracy of the model predictions. The area under the curve (AUC) and decision curve analysis (DCA) was used to assess the predictive performance and clinical utility of the nomogram. RESULTS: The final study population included 886 cirrhotic patients with AKI, and 264 (29.8%) died in the hospital. After multivariate logistic regression, age, gender, cerebrovascular disease, heart rate, respiration rate, temperature, oxygen saturation, hemoglobin, blood urea nitrogen, serum creatinine, international normalized ratio, bilirubin, urine volume, and sequential organ failure assessment score were predictive factors of in-hospital mortality. In addition, the nomogram showed good accuracy in estimating the in-hospital mortality of patients. The calibration plots showed the best agreement with the actual presence of in-hospital mortality in patients. In addition, the AUC and DCA curves showed that the nomogram has good prediction accuracy and clinical value. CONCLUSIONS: We have created a prognostic nomogram for predicting in-hospital death in cirrhotic patients with AKI, which may facilitate timely intervention to improve prognosis in these patients.

Clinical profile of adult and pediatric patients with hepatic Wilson's disease.

BACKGROUND: The clinical profile varies in patients with Wilson's disease (WD). There is paucity of data regarding adult and pediatric patients with hepatic WD. METHODS: As many as 140 consecutive patients diagnosed with hepatic WD between December 2006 and January 2021 were included in the study. Data was collected regarding the demographic parameters, clinical presentation, extrahepatic organ involvement, liver histology and laboratory investigations. Adult and children (0-14 years) with hepatic WD were compared regarding these features. RESULT: Eighty-eight adults and 52 children were included in the study. The median age of presentation was 17 years (range: 1.1-42 years). Male preponderance was seen (adult 68/88, 69%; children 40/52, 77%). Adults as compared to children presented more commonly as cirrhosis (52/88 vs. 15/52, p = 0.0005) and with hepatic decompensation (35/88 vs. 9/52, p = 0.005). Presentation with acute-on-chronic liver failure (ACLF) was more common in children (10/52 vs. 2/88, p = 0.0005). Twenty-eight-day mortality was 50% (5/10) in children and none in adults presenting with ACLF. Nazer's Prognostic Index (≥ 7) and New Wilson Index were more accurate in predicting mortality among children with ACLF with AUROC 1, while AARC (APASL ACLF Research Consortium) was less accurate with AUROC 0.45. Liver histology findings were similar in adults and children. Extrahepatic involvement was also similar. (8/88 in adults vs. 3/52 children, p value 0.48). CONCLUSION: Most patients with WD present as cirrhosis in adulthood. ACLF is more common in children. Nazer's prognostic index and new Wilson Index score are accurate in predicting mortality in children with ACLF.

Circulating fatty acids and risk of hepatocellular carcinoma and chronic liver disease mortality in the UK Biobank.

Nuclear magnetic resonance (NMR)-based plasma fatty acids are objective biomarkers of many diseases. Herein, we aim to explore the associations of NMR-based plasma fatty acids with the risk of hepatocellular carcinoma (HCC) and chronic liver disease (CLD) mortality in 252,398 UK Biobank participants. Here we show plasma levels of n-3 poly-unsaturated fatty acids (PUFA) and n-6 PUFA are negatively associated with the risk of incident HCC [HRQ4vsQ1: 0.48 (95% CI: 0.33-0.69) and 0.48 (95% CI: 0.28-0.81), respectively] and CLD mortality [HRQ4vsQ1: 0.21 (95% CI: 0.13-0.33) and 0.15 (95% CI: 0.08-0.30), respectively], whereas plasma levels of saturated fatty acids are positively associated with these outcomes [HRQ4vsQ1: 3.55 (95% CI: 2.25-5.61) for HCC and 6.34 (95% CI: 3.68-10.92) for CLD mortality]. Furthermore, fibrosis stage significantly modifies the associations between PUFA and CLD mortality. This study contributes to the limited prospective evidence on the associations between plasma-specific fatty acids and end-stage liver outcomes.

Frailty and transplant-free survival of patients with liver cirrhosis: A meta-analysis.

BACKGROUND: Frailty is a common condition among patients with liver cirrhosis. Nonetheless, its role in predicting liver transplant-free survival (TFS) remains unclear. AIM: This systematic review and meta-analysis were conducted to elucidate the relationship between frailty and TFS in patients with cirrhosis. METHODS: Cohort studies addressing the objective of this meta-analysis were extracted from PubMed, Embase, and Web of Science databases. Between-study heterogeneity was assessed with the Cochrane Q test, and the I^2 statistic was estimated. Random-effect models, considering potential heterogeneity, were employed to combine the results. RESULTS: The meta-analysis encompassed 17 cohort studies involving 6273 patients with cirrhosis, of whom 1983 (31.6%) were classified as frail at baseline. The follow-up periods in the included studies ranged from 3 to 29 months, with an average duration of 11.5 months. The analysis revealed that frailty was significantly associated with a poor TFS (risk ratio [RR]: 2.07, 95% confidence interval: 1.72 to 2.50, p<0.001; I2 = 51%). Sensitivity analyses that sequentially omitted one dataset consistently supported these findings (RR: 1.95 to 2.17, p<0.05 in all cases). Subgroup analyses based on variables such as study design, mean age of patients, baseline Model for End-Stage Liver Disease score, tool used for frailty evaluation, follow-up duration, and study quality score also yielded congruent results. CONCLUSIONS: The evidence suggests that frailty may be an independent risk factor for poor TFS in patients with liver cirrhosis, thus emphasizing the importance of early identification and management of frailty in this population.

PNPLA3 risk allele is associated with risk of hepatocellular carcinoma but not decompensation in compensated cirrhosis.

BACKGROUND: The PNPLA3-rs738409-G, TM6SF2-rs58542926-T, and HSD17B13-rs6834314-A polymorphisms have been associated with cirrhosis, hepatic decompensation, and HCC. However, whether they remain associated with HCC and decompensation in people who already have cirrhosis remains unclear, which limits the clinical utility of genetics in risk stratification as HCC is uncommon in the absence of cirrhosis. We aimed to characterize the effects of PNPLA3, TM6SF2, and HSD17B13 genotype on hepatic decompensation, HCC, and liver-related mortality or liver transplant in patients with baseline compensated cirrhosis. METHODS: We conducted a single-center retrospective study of patients in the Michigan Genomics Initiative who underwent genotyping. The primary predictors were PNPLA3, TM6SF2, and HSD17B13 genotypes. Primary outcomes were either hepatic decompensation, HCC, or liver-related mortality/transplant. We conducted competing risk Fine-Gray analyses on our cohort. RESULTS: We identified 732 patients with baseline compensated cirrhosis. During follow-up, 50% of patients developed decompensation, 13% developed HCC, 24% underwent liver transplant, and 27% died. PNPLA3-rs738409-G genotype was associated with risk of incident HCC: adjusted subhazard hazard ratio 2.42 (1.40-4.17), p=0.0015 for PNPLA3-rs738409-GG vs. PNPLA3-rs738409-CC genotype. The 5-year cumulative incidence of HCC was higher in PNPLA3-rs738409-GG carriers than PNPLA3-rs738409-CC/-CG carriers: 15.6% (9.0%-24.0%) vs. 7.4% (5.2%-10.0%), p<0.001. PNPLA3 genotype was not associated with decompensation or the combined outcome of liver-related mortality or liver transplant. TM6SF2 and HSD17B13 genotypes were not associated with decompensation or HCC. CONCLUSIONS: The PNPLA3-rs738409-G allele is associated with an increased risk of HCC among patients with baseline compensated cirrhosis. People with cirrhosis and PNPLA3-rs738409-GG genotype may warrant more intensive HCC surveillance.

The burden of significant pain in the cirrhosis population: Risk factors, analgesic use, and impact on health care utilization and clinical outcomes.

BACKGROUND: We aimed to characterize pain and analgesic use in a large contemporary cohort of patients with cirrhosis and to associate pain with unplanned health care utilization and clinical outcomes in this population. METHODS: We included all patients with cirrhosis seen in UCSF hepatology clinics from 2013 to 2020. Pain severity and location were determined using documented pain scores at the initial visit; "significant pain" was defined as moderate or severe using established cutoffs. Demographic, clinical, and medication data were abstracted from electronic medical records. Associations between significant pain and our primary outcome of 1-year unplanned health care utilization (ie, emergency department visit or hospitalization) and our secondary outcomes of mortality and liver transplantation were explored in multivariable models. RESULTS: Among 5333 patients with cirrhosis, 32% had a nonzero pain score at their initial visit and 25% had significant (ie moderate/severe) pain. Sixty percent of patients with significant pain used ≥1 analgesic; 34% used opioids. Patients with cirrhosis with significant pain had similar Model for End-Stage Liver Disease-Sodium scores (14 vs. 13), but higher rates of decompensation (65% vs. 55%). The most common pain location was the abdomen (44%). Patients with abdominal pain, compared to pain in other locations, were more likely to have decompensation (72% vs. 56%). Significant pain was independently associated with unplanned health care utilization (adjusted odds ratio: 1.3, 95% CI: 1.1-1.5) and mortality (adjusted hazard ratio: 1.4, 95% CI: 1.2-1.6). CONCLUSIONS: Pain among patients with cirrhosis is often not well-controlled despite analgesic use, and significant pain is associated with unplanned health care utilization and mortality in this population. Effectively identifying and treating pain are essential in reducing costs and improving quality of life and outcomes among patients with cirrhosis.

Impact of liver fibrosis on COVID-19 in-hospital mortality in Southern Italy.

BACKGROUND & AIMS: SARS-Cov-2 infection manifests as a wide spectrum of clinical presentation and even now, despite the global spread of the vaccine, contagiousness is still elevated. The aim of the study was the evaluation of the impact of liver fibrosis assessed by FIB-4 and liver impairment, assessed by cytolysis indices, on intrahospital mortality in COVID-19 subjects. METHODS: This is a retrospective observational cohort study, which involved 23 COVID Hospital Units in Campania Region, Italy. Exposure variables were collected during hospital admission and at discharge. According to FIB-4 values, we subdivided the overall population in three groups (FIB-4<1.45; 1.453.25), respectively group 1,2,3. RESULTS: At the end of the study, 938 individuals had complete discharged/dead data. At admission, 428 patients were in group 1 (45.6%), 387 in group 2 (41.3%) and 123 in group 3 (13.1%). Among them, 758 (81%) subjects were discharged, while the remaining 180 (19%) individuals died. Multivariable Cox's regression model showed a significant association between mortality risk and severity of FIB-4 stages (group 3 vs group 1, HR 2.12, 95%CI 1.38-3.28, p<0.001). Moreover, Kaplan-Meier analysis described a progressive and statistically significant difference (p<0.001 Log-rank test) in mortality according to FIB-4 groups. Among discharged subjects, 507 showed a FIB-4<1.45 (66.9%, group 1), 182 a value 1.453.25 (9.0%, group 3). Among dead subjects, 42 showed a FIB-4<1.45 (23.3%, group 1), 62 a value 1.453.25 (42.3%, group 3). CONCLUSIONS: FIB-4 value is significantly associated with intrahospital mortality of COVID-19 patients. During hospitalization, particularly in patients with worse outcomes, COVID-19 seems to increase the risk of acute progression of liver damage.

Updates in characteristics and survival rates of cirrhosis in a nationwide cohort of real-world U.S. patients, 2003-2021.

BACKGROUND: Adverse outcomes of cirrhosis remain a top priority. AIMS: We examined the distribution of cirrhosis causes, HCC incidence and mortality and related changes over time in a nationwide U.S. METHODS: A retrospective study of a national sample of commercially insured patients with cirrhosis from Optum's de-identified Clinformatics® Data Mart Database (CDM). RESULTS: A total of 628,743 cirrhosis cases were identified with 45% having NAFLD, 19.5% HCV, and 16.3% ALD. African Americans had the highest rate of decompensation (60.6%), while Asians had the highest rate of HCC (2.4%), both p < 0.001. African Americans more frequently had HCV (28.4%) while Hispanic/Latinos more frequently had NAFLD (49.2%, p < 0.001). Patients in the 2014-2021 cohort were significantly older (63.0 ± 12.8 vs. 57.0 ± 14.3), less frequently decompensated (54.5% vs. 58.3%) but more frequently had HCC (1.7% vs. 0.6%) and NAFLD (46.5% vs. 44.2%), all p < 0.001. The overall annual incidence of HCC was 0.76% (95% CI: 0.75-0.77) with a 5-year cumulative incidence of 4.03% (95% CI: 3.98-4.09), with significant variation by sex, race/ethnicity, and cirrhosis aetiology. The overall median years of survival were 11.4 (95% CI: 11.3-11.5) with a 5-year cumulative survival of 73.4% (95% CI: 73.3%-73.6%), also with significant disparities in similar subgroups (lowest in cryptogenic cirrhosis and worse in 2014-2021 vs. 2003-2013). The 2014-2021 period was independently associated with worse survival (aHR: 1.14, 95% CI: 1.08-1.20). CONCLUSIONS: HCC incidence and survival vary by aetiology among patients with cirrhosis, with cryptogenic cirrhosis having the lowest survival and lower survival in the more recent time period.

Development of a nomogram for predicting in-hospital mortality in patients with liver cirrhosis and sepsis.

In this study, we aimed to investigate the risk factors associated with in-hospital mortality in patients with cirrhosis and sepsis, establish and validate the nomogram. This retrospective study included patients diagnosed with liver cirrhosis and sepsis in the Medical Information Mart for Intensive Care IV (MIMIC-IV). Models were compared by the area under the curve (AUC), integrated discriminant improvement (IDI), net reclassification index (NRI) and decision curve analysis (DCA). A total of 1,696 patients with cirrhosis and sepsis were included in the final cohort. Our final model included the following 9 variables: age, heartrate, total bilirubin (TBIL), glucose, sodium, anion gap (AG), fungal infections, mechanical ventilation, and vasopressin. The nomogram were constructed based on these variables. The AUC values of the nomograms were 0.805 (95% CI 0.776-0.833), which provided significantly higher discrimination compared to that of SOFA score [0.684 (95% CI 0.647-0.720)], MELD-Na [0.672 (95% CI 0.636-0.709)] and ABIC [0.674(95% CI 0.638-0.710)]. We established the first nomogram for predicting in-hospital mortality in patients with liver cirrhosis and sepsis based on these factors. This nomogram can performs well and facilitates clinicians to identify people at high risk of in-hospital mortality.

Hepatic inflammation and fibrosis are profiles related to mid-term mortality in biopsy-proven MASLD: A multicenter study in Japan.

AIMS: A multi-stakeholder consensus has proposed MASLD (metabolic dysfunction-associated steatotic liver disease). We aimed to investigate the pathological findings related to the mid-term mortality of patients with biopsy-proven MASLD in Japan. METHODS: We enrolled 1349 patients with biopsy-proven MASLD. The observational period was 8010 person years. We evaluated independent factors associated with mortality in patients with MASLD by Cox regression analysis. We also investigated pathological profiles related to mortality in patients with MASLD using data-mining analysis. RESULTS: The prevalence of MASH and stage 3/4 fibrosis was observed in 65.6% and 17.4%, respectively. Forty-five patients with MASLD died. Of these, liver-related events were the most common cause at 40% (n = 18), followed by extrahepatic malignancies at 26.7% (n = 12). Grade 2/3 lobular inflammation and stage 3/4 fibrosis had a 1.9-fold and 1.8-fold risk of mortality, respectively. In the decision-tree analysis, the profiles with the worst prognosis were characterised by Grade 2/3 hepatic inflammation, along with advanced ballooning (grade 1/2) and fibrosis (stage 3/4). This profile showed a mortality at 8.3%. Furthermore, the random forest analysis identified that hepatic fibrosis and inflammation were the first and second responsible factors for the mid-term prognosis of patients with MASLD. CONCLUSIONS: In patients with biopsy-proven MASLD, the prevalence of MASH and advanced fibrosis was approximately 65% and 20%, respectively. The leading cause of mortality was liver-related events. Hepatic inflammation and fibrosis were significant factors influencing mid-term mortality. These findings highlight the importance of targeting inflammation and fibrosis in the management of patients with MASLD.

Bayesian network-based survival prediction model for patients having undergone post-transjugular intrahepatic portosystemic shunt for portal hypertension.

BACKGROUND: Portal hypertension (PHT), primarily induced by cirrhosis, manifests severe symptoms impacting patient survival. Although transjugular intrahepatic portosystemic shunt (TIPS) is a critical intervention for managing PHT, it carries risks like hepatic encephalopathy, thus affecting patient survival prognosis. To our knowledge, existing prognostic models for post-TIPS survival in patients with PHT fail to account for the interplay among and collective impact of various prognostic factors on outcomes. Consequently, the development of an innovative modeling approach is essential to address this limitation. AIM: To develop and validate a Bayesian network (BN)-based survival prediction model for patients with cirrhosis-induced PHT having undergone TIPS. METHODS: The clinical data of 393 patients with cirrhosis-induced PHT who underwent TIPS surgery at the Second Affiliated Hospital of Chongqing Medical University between January 2015 and May 2022 were retrospectively analyzed. Variables were selected using Cox and least absolute shrinkage and selection operator regression methods, and a BN-based model was established and evaluated to predict survival in patients having undergone TIPS surgery for PHT. RESULTS: Variable selection revealed the following as key factors impacting survival: age, ascites, hypertension, indications for TIPS, postoperative portal vein pressure (post-PVP), aspartate aminotransferase, alkaline phosphatase, total bilirubin, prealbumin, the Child-Pugh grade, and the model for end-stage liver disease (MELD) score. Based on the above-mentioned variables, a BN-based 2-year survival prognostic prediction model was constructed, which identified the following factors to be directly linked to the survival time: age, ascites, indications for TIPS, concurrent hypertension, post-PVP, the Child-Pugh grade, and the MELD score. The Bayesian information criterion was 3589.04, and 10-fold cross-validation indicated an average log-likelihood loss of 5.55 with a standard deviation of 0.16. The model's accuracy, precision, recall, and F1 score were 0.90, 0.92, 0.97, and 0.95 respectively, with the area under the receiver operating characteristic curve being 0.72. CONCLUSION: This study successfully developed a BN-based survival prediction model with good predictive capabilities. It offers valuable insights for treatment strategies and prognostic evaluations in patients having undergone TIPS surgery for PHT.