Advanced Chronic Liver Disease Patients Research Articles

Erratum: Comparing serial and current liver stiffness measurements to predict decompensation in compensated advanced chronic liver disease patients.

Erratum: Comparing serial and current liver stiffness measurements to predict decompensation in compensated advanced chronic liver disease patients.

Non-invasive fibrosis markers are useful in predicting the presence of varices in compensated cirrhosis and variceal bleeding in decompensated cirrhosis.

This study aims to investigate the effectiveness of non-invasive fibrosis markers in predicting varices in compensated advanced chronic liver disease patients and variceal bleeding in decompensated cirrhotic patients. Between 1 July 2020-2021, 137 newly diagnosed cirrhosis patients (67 females/70 males; mean age: 53.35) were included in the study. The diagnosis of cirrhosis was made based on clinical, laboratory, imaging, and, if available, biopsy findings. Laboratory and clinical parameters, including lysyl oxidase-like protein 2 (LOXL2), were recorded for all patients. Commonly used noninvasive fibrosis scores were calculated, and endoscopies were performed to assess varices. All patients were followed up for 12 months, and variceal bleeding events were recorded. Parameters that could predict the presence of varices and variceal bleeding were identified using appropriate statistical methods. Out of the 137 cirrhotic patients, 55 were in the compensated stage and 82 were in the decompensated stage. Varices were detected in 36 (65%) of the compensated cirrhotic patients. It was found that a variceal score derived from spleen size and the ELF score could be used to predict varices (AUC: 0.83). Variceal bleeding developed in 26 (31%) of the patients with decompensated cirrhosis. It was determined that a scoring system derived from albumin, spleen size, LOXL2 level, and the Lok index could be used to predict variceal bleeding in this patient group (AUC: 0.845). This study demonstrates that, besides device-dependent examinations, non-invasive fibrosis scores and various serum parameters can predict varices and variceal bleeding in cirrhotic patients.

Nutritional risk assessment using the Nutritional Prognostic Index predicts mortality in Advanced Chronic Liver Disease patients.

IntroductionEarly clinical prognosis and mortality reduction remains a challenge in Chronic Liver Disease (CLD). The full potential of the Nutritional Prognostic Index (NPI) for nutritional assessment and management in CLD patients remains unexplored. AimTo establish an NPI cutoff point for identification of nutritional risk in advanced CLD (ACLD) patients, and to assess the NPI's ability to predict ACLD-associated mortality. MethodThis ethically approved prospective cohort study investigated malnutrition risk using both the NPI and the Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT) in patients hospitalized for ACLD. NPI reference values were determined using Receiver Operating Characteristic curve. Associations between nutritional risk identified by RFH-NPT and by NPI were assessed using Fisher's exact test, and agreement between tools assessed using the Kappa index. Association between NPI-defined nutritional risk and 12-month mortality was examined using Pearson Chi-square test. ResultsThe sample population consisted of 120 adults, 84 (70%) male and 57 (50.9%) of alcoholic aetiology, presenting Child-Pugh A, B or C at admission. The identified cutoff point for NPI was <41, identifying nutritional risk in 82.5% of patients. NPI presented a statistically significant association with RFH-NPT, with substantial agreement coefficient of 0.34. Association between NPI <41 cutoff and mortality were observed, with 82.1% of the sample below cutoff experiencing mortality within 12 months. ConclusionNPI is a valuable nutritional marker for identification of nutritional risk in ACLD. The NPI is a simple and effective assessment tool which can aid in CLD early diagnosis. Validation however remains necessary in other CLD populations of different aetiologies.

Palliative care in terminally ill advanced chronic liver disease patients.

While mortality rates from advanced chronic liver disease (ACLD) are rapidly increasing, patients with an advanced disease stage have acomparable or even higher symptom burden than those with other life-limiting diseases. Although evidence is limited there is increasing recognition of the need to improve care for patients with ACLD; however, there are many limiting factors to providing good palliative care for these patients, including unpredictable disease progression, the misconception of palliative care and end of life care as being equivalent, alack of confidence in prescribing medication and alack of time and resources. Health professionals working with these patients need to develop the skills to ensure effective palliative care, while referral to specialized palliative care centers should be reserved for patients with complex needs. Basic palliative care, along with active disease management, is best delivered by the treating hepatologists. This includes discussions about disease progression and advance care planning, alongside the active management of disease complications. Liver disease is closely associated with significant social, psychological, and financial burdens for patients and their caregivers. Strategies to engage the discussion in multidisciplinary teams early in disease progression help to ensure addressing these issues proactively. This review summarizes the evidence on palliative care for patients with ACLD, provides examples of current best practice and offers suggestions on how disease-modifying and palliative care can coexist, to ensure that patients do not miss opportunities for quality of life improving interventions.

High histamine levels are associated with acute-on-chronic liver failure and liver-related death in patients with advanced chronic liver disease.

The role of histamine in advanced chronic liver disease (ACLD) is poorly understood. We investigated plasma histamine levels across ACLD stages and their prognostic value. We included patients with evidence of ACLD, defined by portal hypertension (hepatic venous pressure gradient [HVPG] ≥6 mmHg) and/or a liver stiffness measurement by transient elastography ≥10 kPa, who underwent HVPG measurement between 2017 and 2020. Acute-on-chronic liver failure (ACLF) and/or liver-related death were defined as composite endpoint. Of 251 patients, 82.5% had clinically significant portal hypertension (median HVPG: 17 mmHg [interquartile range (IQR) 12-21]) and 135 patients (53.8%) were decompensated at baseline. Median plasma histamine was 8.5 nmol/L (IQR: 6.4-11.5), 37.1% of patients showed elevated values (>9.9 nmol/L). Histamine levels did not differ significantly across Child-Turcotte-Pugh (CTP) stages nor strata of model for end-stage liver disease (MELD) or HVPG. Histamine levels correlated with markers of circulatory dysfunction (i.e. sodium, renin and aldosterone). During a median follow-up of 29.2 months, 68 patients developed ACLF or liver-related death. In univariate as well as in multivariate analysis (adjusting for age, sex, HVPG as well as either MELD, clinical stage, and serum albumin or CTP and serum sodium), elevated histamine levels remained associated with the composite endpoint. CTP-based multivariate model adjusted sub-distribution hazard ratio (asHR): 1.010 (95% CI: 1.004-1.021), p < .001; MELD-based multivariate model asHR: 1.030 (95% CI: 1.017-1.040), p < .001. High levels of histamine were linked to circulatory dysfunction in ACLD patients and independently associated with increased risks of ACLF or liver-related death. Further mechanistic studies on the link between histamine signalling and development of hyperdynamic circulation and ACLF are warranted.

Prevalence and prognostic value of zinc and selenium deficiency in advanced chronic liver disease.

Zinc and selenium are essential trace elements involved in important (patho)physiological processes. The prevalence and prognostic implications of zinc and selenium deficiency in patients with advanced chronic liver disease (ACLD) remain unknown. We determined serum zinc and selenium concentrations in 309 patients with ACLD undergoing hepatic venous pressure gradient (HVPG) measurement between 2019 and 2022. We evaluated the prevalence of zinc/selenium deficiency and assessed its association with severity of ACLD and liver-related events (LRE, i.e. first/further hepatic decompensation/liver-related death). Among 309 ACLD patients (median: age: 57 [IQR: 50-64], MELD: 11 [IQR: 9-16], HVPG: 17 [IQR: 11-20]), 73% (227) and 63% (195) were deficient in zinc and selenium, respectively. Decompensated (dACLD) patients showed significantly lower serum zinc (median: 48 [IQR: 38-59] vs. compensated, cACLD: 65 [IQR: 54-78], p < 0.001) and selenium levels (median: 4.9 [IQR 4.0-6.2] vs. cACLD: 6.1 [IQR 5.1-7.3], p < 0.001). Significant correlations of zinc/selenium levels were found with MELD (zinc: ρ = -0.498, p < 0.001; selenium: ρ = -0.295, p < 0.001), HVPG (zinc: ρ = -0.400, p < 0.001; selenium: ρ = -0.157, p = 0.006) and liver disease-driving mechanisms (IL6, bile-acid homeostasis). On multivariable analysis, low zinc/selenium levels, age and MELD remained independently associated with LRE. Zinc and selenium deficiencies are common in ACLD patients especially with higher MELD and HVPG. Low zinc and selenium levels independently predicted hepatic decompensation and liver-related death. The effect of zinc/selenium supplementation in ACLD should be investigated in future trials.

Higher frequency of gastric neoplasia in advanced chronic liver disease patients: Impact of screening endoscopy in an intermediate-high risk country

BackgroundThe Baveno VII guidelines were proposed to identify which patients could safely avoid screening esophagogastroduodenoscopy (EGD) for gastroesophageal varices. We aimed to evaluate the frequency of gastric neoplasia in compensated advanced chronic liver disease (cACLD) patients who underwent EGD for screening of gastroesophageal varices (GOEV) compared to a healthy population. MethodsRetrospective study that enrolled all cACLD patients who underwent EGD for GOEV screening (January 2008-June 2018) in a tertiary reference center. cACLD patients were compared with asymptomatic healthy individuals who underwent EGD in a private hospital setting (April 2017-March 2018). ResultsWe evaluated 1845 patients (481 cACLD patients, 1364 healthy individuals). A significantly higher frequency of gastric neoplasia was observed in patients with cACLD compared to healthy individuals (4.0% vs. 1.0 %; p < 0.001). Rare histopathological subtypes (WHO Classification) accounted for 28.7 % of gastric carcinoma cases in the cACLD cohort. Seven cases of gastric neoplasia (36.8 % of gastric neoplasia cases in the cACLD patients) were diagnosed in patients who, according to the Baveno VII criteria, would have not been submitted to EGD. ConclusionWe found an increased frequency of gastric neoplasia in patients with cACLD in comparison with healthy individuals. In countries with intermediate-high risk for GC, continuing to perform EGD could be beneficial.

Comparing serial and current liver stiffness measurements to predict decompensation in compensated advanced chronic liver disease patients.

The utility of serial liver stiffness measurements (LSM) to predict decompensation in patients with compensated advanced chronic liver disease (cACLD) remains unclear. We aimed to validate whether comparing serial LSM is superior to using the current LSM to predict liver-related events (LRE) in patients with cACLD. In this retrospective analysis of an international registry, patients with cACLD and serial LSM were followed up until index LRE. We compared the performance of both the dynamic LSM changes and the current LSM in predicting LRE using Cox regression analysis, considering time zero of follow-up as the date of latest liver stiffness measurement. In all, 480 patients with cACLD with serial LSM were included from 5 countries. The commonest etiology of cACLD was viral (53%) and MASLD (34%). Over a median follow-up of 68 (IQR: 45 -92) months, 32% experienced a LSM decrease to levels below 10kPa (resolved cACLD) and 5.8% experienced LRE. Resolved cACLD were more likely to be nondiabetic and had better liver function. While a higher value of the current LSM was associated with higher LREs, LSM changes over time (LSM slope) were not associated with LRE. In multivariable Cox regression, neither the prior LSM nor the LSM slope added predictive value to latest liver stiffness measurement. Once the current LSM is known, previous LSM values do not add to the prediction of LREs in patients with cACLD.

Von Willebrand factor for outcome prediction within different clinical stages of advanced chronic liver disease.

The prognostic performance of von Willebrand factor (VWF) may vary across clinical stages of advanced chronic liver disease (ACLD). Therefore, we investigated the evolution of VWF and other biomarkers throughout the full ACLD spectrum and evaluated their stage-specific prognostic utility. We retrospectively included Viennese ACLD patients with available information on hepatic venous pressure gradient (HVPG), C-reactive protein (CRP)/VWF levels and outcomes. ACLD stages were defined according to D'Amico etal. We included an external validation cohort from Padua. We observed gradual increases in VWF throughout ACLD stages. In contrast, HVPG levelled off in decompensated ACLD (dACLD), whereas MELD showed only minor changes in the early stages and CRP did not increase until stage 3. VWF was associated with hepatic decompensation/liver-related death in compensated ACLD (cACLD) in a fully adjusted model, while it was not independently predictive of ACLF/liver-related death in dACLD. After backward selection, HVPG/CRP/VWF remained the main predictors of hepatic decompensation/liver-related death in cACLD. Notably, the performance of the non-invasive CRP/VWF-based model was comparable to invasive HVPG-based models (C-index:0.765 ± 0.034 vs. 0.756 ± 0.040). The discriminative ability of the CRP/VWF-based model was confirmed in an external validation cohort using another VWF assay which yielded systematically lower values. VWF is the only biomarker that gradually increases across all ACLD stages. It is of particular prognostic value in cACLD, where a CRP/VWF-based model is equivalent to an invasive HVPG-based model. Systematic differences in VWF underline the importance of interlaboratory surveys. Moreover, our findings reinforce the notion that, already in cACLD, inflammation is a key disease-driving mechanism.

Quality of death in patients in advanced chronic liver disease and cancer patients managed by gastroenterologists in Portugal: are we doing it right?

The incidence of chronic progressive diseases is rising and investment on quality of death and dying is of utmost importance to minimize physical and emotional suffering. There is still a gap in palliative care (PC) between patients with cancer and those with advanced chronic liver disease (ACLD). Our objectives were to characterize clinical attitudes and therapeutic interventions and to evaluate the differences in end-of-life care between inpatients with cancer and ACLD under gastroenterology care. Retrospective cohort study, including patients with cancer or ACLD who died in a Gastroenterology department between 2012 and 2021. Demographic characteristics, clinical and endoscopic procedures and symptom control were compared between the groups. From 150 patients, 118 (78.7%) died with cancer and 32 (21.3%) died from ACLD without concomitant hepatocellular carcinoma. ACLD patients were more frequently male ( P = 0.001) and younger ( P = 0.001) than patients with cancer. Median time of hospitalization in the last month of life was 16 days for both groups. Discussion of prognosis with the patient was more frequent for cancer patients (35.6% versus 3.2%, P < 0.001). Referral to PC occurred in 18.8% and 61% of the patients with ACLD and cancer respectively ( P < 0.001). Endoscopic procedures were performed in half of the patients and were more likely to be unsuccessful in those with cancer. Clinical decisions were different between groups in terms of PC access and discussion of prognostic with the patient. It is urgent to define and implement metrics of quality of death and dying to prevent potentially inappropriate treatment.

Use of Branched-Chain Amino Acids as a Potential Treatment for Improving Nutrition-Related Outcomes in Advanced Chronic Liver Disease.

Advanced chronic liver disease (ACLD) represents a complex and multifactorial clinical entity characterized by liver dysfunction and associated complications. In recent years, the significance of nutritional status in ACLD prognosis has gained considerable attention. This review article delves into the multifactorial pathogenesis of malnutrition in ACLD and its profound consequences for health outcomes. We explore the clinical implications of secondary sarcopenia in ACLD and highlight the critical relevance of frailty in both decompensated and compensated ACLD. A specific focus of this review revolves around branched-chain amino acids (BCAAs) and their pivotal role in managing liver disease. We dissect the intricate relationship between low Fischer's ratio and BCAA metabolism in ACLD, shedding light on the molecular mechanisms involved. Furthermore, we critically evaluate the existing evidence regarding the effects of BCAA supplementation on outcomes in ACLD patients, examining their potential to ameliorate the nutritional deficiencies and associated complications in this population.

WED-370 - Acute kidney injury related to metamizole in advanced chronic liver disease patients undergoing major orthopedic surgery

WED-370 - Acute kidney injury related to metamizole in advanced chronic liver disease patients undergoing major orthopedic surgery

High correlation of hepatic shear wave velocity with esophageal varices complication rate in patients with chronic liver diseases

BackgroundHistological evaluation by liver biopsy is considered the gold standard for assessing liver disease; however, it is highly invasive. Non-invasive liver stiffness measurement by shear wave elastography (SWE) is effective for evaluating the hepatic fibrosis stage and related diseases. In this study, we investigated the correlations of liver stiffness with hepatic inflammation/fibrosis, functional hepatic reserve, and related diseases in patients with chronic liver disease (CLD).MethodsShear wave velocity (Vs) values were measured using point SWE in 71 patients with liver disease from 2017 to 2019. Liver biopsy specimens and serum biomarkers were collected at the same time, and splenic volume was measured using computed tomography images with the software Ziostation2. Esophageal varices (EV) were evaluated by upper gastrointestinal endoscopy.ResultsAmong CLD-related function and complications, Vs values were highly correlated with liver fibrosis and EV complication rates. The median Vs values for liver fibrosis grades F0, F1, F2, F3, and F4 were 1.18, 1.34, 1.39, 1.80, and 2.12 m/s, respectively. Comparison of receiver operating characteristic (ROC) curves to predict cirrhosis showed that area under the ROC (AUROC) curve for Vs values was 0.902, which was not significantly different from the AUROCs for the FIB-4 index, platelet count, hyaluronic acid, or type IV collagen 7S, while it was significantly different from the AUROC for mac-2 binding protein glycosylation isomer (M2BPGi) (P < 0.01). Comparison of ROC curves to predict EV showed that the AUROC for Vs values was 0.901, which was significantly higher than the AUROCs for FIB-4 index (P < 0.05), platelet count (P < 0.05), M2BPGi (P < 0.01), hyaluronic acid (P < 0.05), and splenic volume (P < 0.05). In patients with advanced liver fibrosis (F3 + F4), there was no difference in blood markers and splenic volume, while Vs value was significantly higher in patients with EV (P < 0.01).ConclusionsHepatic shear wave velocity was highly correlated with EV complication rates in chronic liver diseases as compared to blood markers and splenic volume. In advanced CLD patients, Vs values of SWE are suggested to be effective in predicting the appearance of EV noninvasively.

The interplay between sarcopenia and portal hypertension predicts ascites and mortality in cirrhosis.

The role of sarcopenia in predicting decompensation other than hepatic encephalopathy is unclear. We aimed to evaluate the prognostic role of sarcopenia, assessed by computed tomography (CT), in the development of ascites and mortality in patients with advanced chronic liver disease (ACLD) outside the liver transplantation (LT) setting. We retrospectively evaluated ACLD patients with liver stiffness measurement (LSM) >10kPa and an available CT scan within 6 months. Sarcopenia was defined as skeletal muscle index (SMI) <50 and <39 cm2/m2, respectively, in men and women. Competing risk regression models were used to assess the variables associated with the main outcomes. 209 patients were included in the final analysis and sarcopenia was present in 134 (64.1%). During a median follow-up of 37 (20-63) months, 52 patients developed ascites, 24 underwent LT, and 30 died. Sarcopenia was found a predictive factor of decompensation with ascites (SHR 2.083, 95%-CI: 1.091-3.978), independently from the features of clinically significant portal hypertension (LSM≥21kPa or portosystemic shunts). Sarcopenia (SHR: 2.744, 95%-CI: 1.105-6.816) and LSM≥21kPa (SHR: 3.973, 95%-CI: 1.548-10.197) were independent risk factors for increased mortality. Sarcopenia and portal hypertension are two major and independent risk factors for decompensation with ascites and mortality in cirrhotic patients outside the LT context.

The systemic and hepatic alternative renin–angiotensin system is activated in liver cirrhosis, linked to endothelial dysfunction and inflammation

We aimed to assess the systemic and hepatic renin-angiotensin-system (RAS) fingerprint in advanced chronic liver disease (ACLD). This prospective study included 13 compensated (cACLD) and 12 decompensated ACLD (dACLD) patients undergoing hepatic venous pressure gradient (HVPG) measurement. Plasma components (all patients) and liver-local enzymes (n = 5) of the RAS were analyzed using liquid chromatography–tandem mass spectrometry. Patients with dACLD had significantly higher angiotensin (Ang) I, Ang II and aldosterone plasma levels. Ang 1–7, a major mediator of the alternative RAS, was almost exclusively detectable in dACLD (n = 12/13; vs. n = 1/13 in cACLD). Also, dACLD patients had higher Ang 1–5 (33.5 pmol/L versus cACLD: 6.6 pmol/L, p < 0.001) and numerically higher Ang III and Ang IV levels. Ang 1–7 correlated with HVPG (ρ = 0.655; p < 0.001), von Willebrand Factor (ρ = 0.681; p < 0.001), MELD (ρ = 0.593; p = 0.002) and interleukin-6 (ρ = 0.418; p = 0.047). Considerable activity of ACE, chymase, ACE2, and neprilysin was detectable in all liver biopsies, with highest chymase and ACE2 activity in cACLD patients. While liver-local classical and alternative RAS activity was already observed in cACLD, systemic activation of alternative RAS components occurred only in dACLD. Increased Ang 1–7 was linked to severe liver disease, portal hypertension, endothelial dysfunction and inflammation.

Characterization of a prothrombotic phenotype using thrombin generation and thrombin activity in cirrhosis and portal hypertension

BackgroundPatients with advanced chronic liver disease (ACLD) may develop a prothrombotic phenotype that seems to be more pronounced with more severe liver dysfunction. An imbalance of endogenous pro- and anticoagulants is not fully captured by routine coagulation assays. MethodsIn a cohort of ACLD patients undergoing hepatic venous pressure gradient (HVPG) measurement, we assessed thrombin generation (TGA) using two commercially available assays (Technothrombin and Thrombinoscope) with and without addition of soluble thrombomodulin (TM), as well as thrombin activity, alongside a panel of coagulation parameters. ResultsThe cohort encompassed 37 patients (median age 55.3 years, mean HVPG 16 ± 5 mm Hg). In the TM-modified Thrombinoscope TGA, the endogenous thrombin generation potential (ETP) was significantly increased in Child-Pugh-Score (CPS) B/C patients (N = 23, 62 %) compared to CPS A patients (N = 14, 38 %) (ETP: 546 nM∗min (443–696) vs. 404 nM∗min (289–573), p = 0.028). Using the Technothrombin TGA without TM, patients with CPS B/C had decreased ETP compared to CPS A patients (ETP: 2792 ± 1336 nM∗min vs. 5040 ± 816 nM∗min, p < 0.001) and with addition of TM (final concentration: 5 nM; ETP: 2545 ± 1327 nM∗min vs. 4824 ± 929 nM∗min, p < 0.001). Thrombin activity levels were 0.6pM in median (0.2–1.6pM) and above the level of detectability (0.10pM) in 94.6 % of patients but were not correlated to severity of cirrhosis (CPS A 0.7pM vs CPS B/C 0.4pM, p = 0.377) nor to parameters of TGA. ConclusionThrombin plasma levels are elevated in liver disease patients without apparent correlation to TGA or severity of cirrhosis. TGAs can be modified with TM to enable protein C-dependent anticoagulation, but result in differences with regard to severity of liver disease.

Systematic review and meta-analysis: impact of anti-viral therapy on portal hypertensive complications in HBV patients with advanced chronic liver disease.

The efficacy of nucleos(t)ide analogs (NAs) in non-cirrhotic chronic hepatitis B (CHB) patients is well-established. However, their impact on complications of portal hypertension in advanced chronic liver disease (ACLD) is less well characterized. MEDLINE/PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, and abstracts of major international hepatology meetings were searched for publications from Jan 1, 1995 to Nov 30, 2021. Randomized control trials and observational studies reporting the efficacy of NAs in ACLD patients were eligible. Pooled risk ratios (RRs) for outcomes of interest were calculated with a random-effect or fixed-effect model, as appropriate. Thirty-nine studies including 14,212 ACLD patients were included. NA treatment was associated with reduced risks of overall hepatic decompensation events (RR, 0.51; 95% confidence interval [CI]: 0.37-0.71), such as variceal bleeding (RR, 0.44; 95% CI: 0.26-0.74) and ascites (RR, 0.10; 95% CI: 0.01-1.59), on a trend-wise level. Moreover, the risks of hepatocellular carcinoma (HCC) (RR, 0.48; 95% CI: 0.30-0.75) and liver transplantation/death (RR, 0.36; 95% CI: 0.25-0.53) were also reduced by NA treatment and the first-line NAs were superior to non-first-line NAs in improving these outcomes (RR, 0.85; 95% CI: 0.75-0.97 and RR, 0.85; 95% CI: 0.73-0.99, respectively). NA therapy lowers the risk of portal hypertension-related complications, including variceal bleeding, HCC, and liver transplantation/death.

Baveno-VII criteria to predict decompensation and initiate non-selective beta-blocker in compensated advanced chronic liver disease patients.

The utility of Baveno-VII criteria of clinically significant portal hypertension (CSPH) to predict decompensation in compensated advanced chronic liver disease (cACLD) patient needs validation. We aim to validate the performance of CSPH criteria to predict the risk of decompensation in an international real-world cohort of cACLD patients. cACLD patients were stratified into three categories (CSPH excluded, grey zone, and CSPH). The risks of decompensation across different CSPH categories were estimated using competing risk regression for clustered data, with death and hepatocellular carcinoma as competing events. The performance of "treating definite CSPH" strategy to prevent decompensation using non-selective beta-blocker (NSBB) was compared against other strategies in decision curve analysis. One thousand one hundred fifty-nine cACLD patients (36.8% had CSPH) were included; 7.2% experienced decompensation over a median follow-up of 40 months. Non-invasive assessment of CSPH predicts a 5-fold higher risk of liver decompensation in cACLD patients (subdistribution hazard ratio, 5.5; 95% confidence interval, 4.0-7.4). "Probable CSPH" is suboptimal to predict decompensation risk in cACLD patients. CSPH exclusion criteria reliably exclude cACLD patients at risk of decompensation, regardless of etiology. Among the grey zone, the decompensation risk was negligible among viral-related cACLD, but was substantially higher among the non-viral cACLD group. Decision curve analysis showed that "treating definite CSPH" strategy is superior to "treating all varices" or "treating probable CSPH" strategy to prevent decompensation using NSBB. Non-invasive assessment of CSPH may stratify decompensation risk and the need for NSBB in cACLD patients.

Comparing Predictability of Non-invasive Tools for Hepatocellular Carcinoma in Treated Chronic Hepatitis C Patients.

Non-invasive tools including liver stiffness measurement (LSM) or FIB-4, assessed before or after direct acting antivirals (DAA), have been suggested to predict hepatocellular carcinoma (HCC). This study aims to compare predictability of HCC by these methods at different time points, to validate the HCC surveillance suggestion by guidelines, and to propose personalized strategy. Chronic hepatitis C whose LSM and FIB-4 were available at pretherapy and after sustained virological response (SVR) were enrolled. Advanced chronic liver disease (ACLD) was defined as pretherapy LSM ≥ 10kPa or FIB-4 index ≥ 3.25 or ultrasound signs of cirrhosis plus platelet count < 150,000/μL. The predictabilities were compared by area under ROC. The cumulative HCC incidences were calculated by Kaplan-Meier analysis. Among 466 ACLD patients, 40 patients developed HCC during a follow-up duration of 26.8months. Comparable predictive performances for HCC between LSM and FIB-4 at pretherapy and SVR were noted. By guidelines suggestion using pretherapy LSM = 10kPa (advanced fibrosis) and 13kPa (cirrhosis) for risk stratification, the annual HCC incidences of those with LSM of < 10, 10-12.9 and ≥ 13kPa were 1.1, 3.6, and 5.0%, respectively. Combination of baseline LSM < 12kPa and SVR FIB-4 < 3.7 could further stratify relatively low risk of HCC in ACLD patients of annal incidence of 1.2%. ACLD patients who met advanced fibrosis but not cirrhosis by guidelines' cut-offs still posed high risk of HCC. Baseline LSM with SVR FIB-4 can be applied to stratify low, intermediate, and high risk of HCC for personalizing surveillance strategies after SVR.

CHESS-ALARM score to stratify decompensation risk in compensated advanced chronic liver disease patients: An international multicenter study.

A combination of platelet and elastography (PE criteria) was proposed to identify compensated advanced chronic liver disease (cACLD) patients at risk of liver decompensation. We aim to validate and refine PE criteria by developing a new predictive score to predict decompensation in Asian cACLD patients. An international cohort of 633 cACLD patients with liver stiffness measurement (LSM) and esophagogastroduodenoscopy performed were included. We validated PE criteria to predict first liver decompensation using competing risk analysis, with death and hepatocellular carcinoma as competing events. We developed a predictive model using proportional subdistribution hazard regression. Prognostic accuracy was compared with the model of end-stage liver disease (MELD), albumin-bilirubin (ALBI), and ALBI-FIB-4 score using time-dependent area under operative characteristic curve (tAUC). Sixty patients developed decompensation over the median follow-up of 39months. Favorable Baveno VI status ruled out cACLD patients at risk of liver decompensation. LSM>25kPa was suboptimal to predict cACLD patients who will develop liver decompensation. We developed CHESS-ALARM score by incorporating age, platelet, and gender into LSM. CHESS-ALARM score (tAUC=0.86, 95% confidence interval [CI]: 0.79-0.94) has significantly higher accuracy than MELD (tAUC: 0.61), ALBI (tAUC: 0.62), ALBI-FIB-4 (tAUC: 0.70), and LSM>25kPa (tAUC: 0.54) to predict liver decompensation at 5years (P<0.05 for all). Patients with CHESS-ALARM score≥-0.37 had an 11-fold higher risk of decompensation (subdistribution hazard ratio=11.2, 95% CI: 5.1-24.5). CHESS-ALARM score can be readily incorporated into clinical practice of cACLD patients to estimate individual risk of liver decompensation; however, more data are required in morbidly obese cACLD patients of nonviral etiology.