Recent papers report significant survival gain after liver resection in BCLC-B and -C HCC patients. The results of minimally invasive liver surgery (MILS) in such patients have not been widely investigated so far.

Data regarding patients undergoing MILS or open liver resection (OLR) for HCC staged BCLC -B and -C were extracted from the HERCOLES database. An inverse probability of treatment weighting (IPTW) method was adopted to balance the confounders. The primary outcome was a composite endpoint including post-hepatectomy liver failure, severe postoperative complications and in-hospital mortality.

627 patients were included (459 undergoing OLR and 168 receiving MILS). After IPTW, no difference was found in the composite endpoint between MILS and OLR (OR 0.86 [95%CI 0.46-1-60]; p = 0.62). MILS reduced the risk of receiving intra-operative transfusions (OR 0.28 [95%CI 0.13-0.58]; p < 0.001) and of developing postoperative ascites (OR 0.56 [95%CI 0,32-0,98]; p = 0.039), with reduced length of stay (OR 0.82 [95%CI 0.66-1.01]; p = 0.045). The survival analysis showed no differences between MILS and OLR for both OS (p = 0.13) and DFS (p = 0.491).

MILS was shown to be safe and feasible for selected non-metastatic HCC patients staged BCLC B and C, reducing the risk of perioperative transfusions and postoperative ascites, and shortening the length of stay.

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that can lead to cirrhosis in up to 30% of patients. Cirrhotic patients are at risk of high morbidity and mortality due to cirrhosis decompensation and hepatocellular carcinoma (HCC). This retrospective study assessed the rates of decompensated cirrhosis and HCC in patients with AIH-related cirrhosis. A total of 774 AIH patients were included, with 40% developing cirrhosis. Over a median follow-up of 8.2 years (IQR 2.9-12.3), the annual incidence of decompensated cirrhosis was 4.25%, with a mean time of 8.2 years from cirrhosis diagnosis to decompensation. Nineteen cirrhotic patients (6.2%) developed HCC, with a yearly incidence rate of 0.63%. Most HCC cases occurred within the first years of cirrhosis diagnosis. The rate of decompensated cirrhosis in AIH patients was lower than in other cirrhotic liver diseases, suggesting AIH may follow a different clinical course. The annual incidence of HCC was also significantly lower than the threshold for HCC surveillance. This indicates the need to reassess current surveillance guidelines, particularly in the late years following a cirrhosis diagnosis.

Ascites can develop in the setting of a variety of pathologies. The approach to treatment depends on accurate determination of the underlying cause, for which fluid analysis plays a central role. In particular, the serum-ascites-albumin gradient serves as a primary diagnostic test for differentiating among causes, with certain additional fluid tests performed based on clinical suspicion. Treatment options range from nonspecific fluid removal, including large-volume paracentesis and tunneled peritoneal catheters, to targeted therapies (e.g., diuretics, transjugular intrahepatic portosystemic shunt, and lymphangiography). Societal guidelines exist for the approach to cirrhotic ascites, but the management of other less common causes remains less well defined. The goal of this AJR Expert Panel Narrative Review is to provide guidance for the diagnosis and management of ascites, based on available evidence and the authors' clinical experience.

The heterogenous presentation patterns in decompensated cirrhosis confer variable outcomes. While acute decompensation (AD) is well-characterized, the presentation patterns and outcomes of non-acute decompensation (NAD) remain unclear. The aim of this study was to characterize clinical and pathophysiological features of NAD and identify predictors of progression in NAD.

In this prospective study, patients across the cirrhosis spectrum were enrolled from two centers in India between 2020-2023: compensated cirrhosis (CC; n = 29), NAD (n = 311), AD (n = 201), and healthy controls (n = 10). Clinical and laboratory parameters, cytokine levels (IL-6, TNF, IL-10, MCP-1) and cell death markers (M30, M65, Gasdermin-D, RIPK3, MLKL) were assessed at baseline. Twelve-month overall survival was assessed in all patients. The predictors of progression to AD and mortality were evaluated in patients with NAD.

Survival was lower in patients with NAD (81.7%) than in those with CC (100%), but higher than in those with AD (31.2%) (p <0.001). Despite no significant systemic inflammation, patients with NAD exhibited elevated levels of cell death markers, particularly Gasdermin-D and RIPK3, compared to healthy controls and patients with CC. Both inflammatory and cell death markers were most pronounced in AD. Over 12 months, the cumulative incidence of progression to AD among those with NAD was 55.1%, significantly reducing their survival (68.2% vs. 95.3%, p <0.001). Predictors of such progression to AD included severe ascites, lower IGF-1, albumin, BMI, and higher bilirubin, Gasdermin-D, and RIPK3 levels, as well as higher CTP and MELD scores.

NAD represents a clinically, prognostically and pathophysiologically distinct entity in cirrhosis. Patients with NAD express elevated cell death markers and remain at risk of progression to AD and mortality. Identifying such high-risk patients should prompt interventions to prevent progression. Modulation of cell death is a potentially disease-modifying target in cirrhosis.

This study highlights non-acute decompensation as a clinically, prognostically and pathophysiologically distinct subset of cirrhosis, underscoring the importance of understanding its progression dynamics. Identifying key predictors of acute decompensation, including ascites severity, low IGF-1 levels, and elevated cell death markers, such as Gasdermin-D and RIPK3, potentially uncovers new therapeutic avenues. These findings are crucial for helping hepatologists and researchers to risk stratify patients and optimize transplant candidacy. Interventions targeting necroptosis and pyroptosis pathways may improve outcomes, providing a significant shift towards precision medicine in cirrhosis care.

A consensus has not yet been reached regarding the optimal timing for the combination of transjugular intrahepatic portosystemic shunt (TIPS) and partial splenic embolization (PSE) in patients with cirrhosis-related variceal bleeding and hypersplenism. This study aimed to compare the clinical outcomes of patients who underwent either an early or late combination of TIPS and PSE.

A total of 84 consecutive patients with cirrhosis-related variceal bleeding and hypersplenism who underwent TIPS and PSE between September 2016 and April 2023 were included in this retrospective multicenter study. These patients were subsequently divided into early combination (n = 36) and late combination (n = 48) groups based on the timing of the combination therapy.

Kaplan-Meier curves revealed a significant increase in cumulative survival in the late combination group, compared with that in the early combination group (log-rank P = 0.018). Additionally, the late combination group exhibited a lower cumulative incidence of overt hepatic encephalopathy (OHE), compared with the early combination group (log-rank P = 0.002). In Cox regression models, noninfarcted splenic volume (hazard ratio [HR] = 0.995, 95% confidence interval [CI] = 0.991-0.999, P = 0.044) and grouping (HR = 0.101, 95% CI = 0.011-0.921, P = 0.034) were identified as independent risk factors for mortality. Furthermore, the independent risk factors for OHE were serum albumin (ALB) level (P = 0.032) and grouping (P = 0.028).

The early combination of TIPS and PSE was associated with higher risks of death and OHE than the late combination.

The impact of bulevirtide in patients awaiting liver transplantation (LT) for decompensated liver disease and/or hepatocellular carcinoma (HCC) is unclear. We assessed clinical, virological, and biochemical responses to bulevirtide in patients with chronic hepatitis delta virus (HDV) awaiting LT and compared outcomes with a cohort of similar untreated patients.

Consecutive HDV-infected patients waiting for LT since bulevirtide approval were included. Patients receiving 2 mg of bulevirtide daily had clinical, biological, and virological data collected at baseline, Week 24, Week 48, at LT, and post-LT. Patients not receiving bulevirtide had data collected at baseline, LT, and post-LT for comparison.

Forty-one patients from nine LT centers were included. In the bulevirtide group (20 patients; mean age 52.8 ± 9.98 years; 75% male), 65%, 10% and 25% were Child-Pugh A, B and C, respectively. Fifteen completed 48 weeks of therapy. At 48 weeks, median HDV RNA decreased by 2.56 log IU/mL (p = 0.004). Virological and biochemical responses were obtained in 73.3% and 66.6% of patients. Twelve patients (60%) underwent LT. No serious adverse events occurred. Bulevirtide improved liver function, enabling one (7.1%) HCC patient to undergo chemoembolization while on the WL and leading to delisting of three (15%) other patients. In untreated patients (mean age 42.9 ± 7.9 years; 76.2% Child-Pugh C), none were delisted. Three-month transplant-free survival was 76.9% in the bulevirtide group versus 36.7% (p = 0.007) in the control group.

Bulevirtide demonstrates safety and efficacy in HDV-infected patients listed on the LT waiting list and may potentially improve pre-transplant outcomes.

Unlike other malignancies, hepatic functional reserve competes with tumor progression in determining the risk of mortality from hepatocellular carcinoma (HCC). However, the relative contribution of hepatic decompensation over tumor progression in influencing overall survival (OS) has not been assessed in combination immunotherapy recipients.

From the AB-real observational study (n = 898), we accrued 571 patients with advanced/unresectable hepatocellular carcinoma, Child-Pugh A class treated with frontline atezolizumab + bevacizumab (AB). Hepatic decompensation and tumor progression during follow-up were studied in relationship to patients' OS using a time-dependent Cox model. Baseline characteristics were evaluated as predictors of decompensation in competing risks analysis. During a median follow-up of 11.0 months (95% CI: 5.1-19.7), 293 patients (51.3%) developed tumor progression without decompensation, and 94 (16.5%) developed decompensation. In multivariable time-dependent analysis, decompensation (HR: 19.04, 95% CI: 9.75-37.19), hepatocellular carcinoma progression (HR: 9.91, 95% CI: 5.85-16.78), albumin-bilirubin (ALBI) grade 2/3 (HR: 2.16, 95% CI: 1.69-2.77), and number of nodules >3(HR: 1.63, 95% CI: 1.28-2.08) were independently associated with OS. Pretreatment ALBI grade 2/3 (subdistribution hazard ratio [sHR]: 3.35, 95% CI: 1.98-5.67) was independently associated with decompensation, whereas viral etiology was protective (sHR: 0.55, 95% CI: 0.34-0.87). Among patients with viral etiology, effective antiviral treatment was significantly associated with a lower risk of decompensation (sHR: 0.48, 95% CI: 0.25-0.93).

Hepatic decompensation identifies patients with the worst prognosis following AB and is more common in patients with baseline ALBI >1 and nonviral etiology. Effective antiviral treatment may protect from decompensation, highlighting the prognostic disadvantage of patients with nonviral etiologies and the importance of multidisciplinary management to maximize OS.

Ascites is the most common complication from cirrhosis related to portal hypertension and depicts the onset of hepatic decompensation. Ranging from uncomplicated to refractory ascites, the progression carries prognostic value by reflecting the deterioration of underlying cirrhosis and portal hypertension. Diuretics have been the mainstay of treatment to control ascites, but the side effects heighten when the dosage is escalated. Non-selective beta-blockers (NSBBs) are widely used nowadays to prevent hepatic decompensation and variceal hemorrhage. However, with worsening systemic vasodilation and inflammation when ascites progresses, patients on NSBBs are at risk of hemodynamic collapse leading to renal hypoperfusion and thus hepatorenal syndrome. Long-term albumin infusion was studied to prevent the progression of ascites. However, the results were conflicting. Sodium-glucose cotransporter-2 inhibitors are under investigation to control refractory ascites. With that, patients with refractory ascites may require regular large-volume paracentesis. With an aging population, more patients are put on anti-thrombotic agents and their risks in decompensated cirrhosis and invasive procedures have to be considered. In general, decompensated cirrhosis with ascites poses multiple issues to pharmacological treatment. In the present review, we discuss the challenges and controversies in the pharmacological treatment of ascites.

This study aimed to reveal the independent risk factors for overt hepatic encephalopathy (OHE) after transjugular intrahepatic portosystemic shunt (TIPS) in patients with decompensated cirrhosis complicated with diabetes.

This study retrospectively analyzed 126 consecutive patients with cirrhosis combined with diabetes who underwent TIPS in our department from January 2016 to June 2022. The patients were divided into two groups according to the presence or absence of OHE after TIPS. Data were analyzed using the χ 2 -tests, unpaired t -tests, logistic regression, receiver operating characteristic curves, and Kaplan-Meier curves.

Age and ascites were independent risk factors for OHE after TIPS in patients with cirrhosis and diabetes. Elder patients had a higher risk of postoperative OHE than younger patients [odds ratio (OR): 1.040; 95% confidence interval (CI): 1.003-1.079]. Compared with patients without ascites, patients with ascites were significantly more likely to develop OHE (OR: 3.757; 95% CI: 1.274-11.080; OR: 4.338; 95% CI: 1.069-17.603).

Age and ascites are independent risk factors of post-TIPS OHE in cirrhotic patients with diabetes.

Sarcopenia is an acknowledged risk factor for individuals with chronic liver disease, however, the influence on outcomes in patients receiving transjugular intrahepatic portosystemic shunt (TIPS) remains underexplored.

This study aimed to investigate the association between sarcopenia and incidence of complications and mortality post-TIPS.

A retrospective analysis was performed on 175 patients who underwent TIPS between 2011-2021 at a Belgian tertiary care center. Transverse psoas muscle thickness (TPMT) was measured at baseline, with a subset of 85 patients having a second TPMT after 1-2 years for assessment of evolution.

Over a median follow-up of 453 days (IQR 76-1179), sarcopenic patients exhibited a higher prevalence of complications (74.1% vs. 57.9%, p = 0.04) and one-year mortality (53.4% vs. 22.3%, p < 0.001) post-TIPS. Notably, 58.8% of patients showed an increase >10% from baseline TPMT/length post-TIPS, with the greatest improvement observed in severely sarcopenic patients (4.00 ± 4.55 mm/m vs. -0.82 ± 2.68 mm/m, p < 0.001) and in those patients free from TIPS-related complications (3.18 ± 4.09 mm/m vs. 1.31 ± 3.21 mm/m, p = 0.022).

Sarcopenia increases the risk of complications and mortality post-TIPS. Importantly, sarcopenia improves in patients receiving TIPS, particularly in those with severe sarcopenia at baseline and free of TIPS-related complications.

Reduced abdominal perfusion pressure (APP) is an underdiagnosed potential pathophysiological mechanism for acute kidney injury (AKI) in the patient with liver cirrhosis and ascites. This study aimed to analyze the prevalence of abdominal hypoperfusion (AhP) (APP <60 mm Hg) and the impact of APP on AKI in critically ill patients with liver cirrhosis.

This was a post hoc analysis from a prospective cohort study set in a general ICU at a tertiary university hospital. Patients were recruited between October 2016 and December 2021. Acute renal failure (ARF) was defined by stage 3 AKI according to the International Club of Ascites.

Fifty-eight patients where included, with a mean age of 57 (±8.4) years, 79% were male, and 93% had acute-on-chronic liver failure at admission. The prevalence of AhP reached 75%, and 29% of cases had persisting AhP during the first week of ICU stay. Patients with baseline AhP had a higher 28-day mortality compared to those without AhP (respectively, 76% vs. 49%, p = 0.03). Acute renal failure developed in 48% of patients. Higher serum urea (aOR: 1.01, 95% CI: 1.00-1.02, p = 0.04) and white blood cell count (aOR: 1.1, 95% CI: 1.01-1.2, p = 0.02) at ICU admission, as well as low persisting APP (aOR: 0.9, 95% CI: 0.86-0.98, p = 0.02) were independent risk factors for ARF.

Critically ill patients with liver cirrhosis presented a high prevalence of ARF, independently associated with higher baseline serum urea and WBC, and lower persisting APP. A structured clinical approach to optimize APP may reduce renal dysfunction in high-risk patients with cirrhosis.

Background/Objectives: Sarcopenia is an important clinical feature of patients with chronic liver disease (CLD). However, special devices are required to determine skeletal muscle mass. We evaluated the usefulness of body surface area (BSA) for estimating muscle mass and diagnosing sarcopenia in patients with CLD. Methods: We retrospectively studied 1889 Japanese patients with CLD who underwent bioimpedance analysis (BIA) (training cohort, n = 983; validation cohort, n = 906). The optimal cutoff values for predicting low skeletal muscle mass index (SMI) were determined using ROC analysis. We also assessed 1229 patients whose BSA and grip strength (GS) data were obtained on the same day and evaluated the diagnostic performance of the determined cutoff values of BSA for the diagnosis of sarcopenia. Results: In the training cohort, a strong correlation was observed between the SMI and BSA (r = 0.883, p < 0.0001). The cutoff values of BSA for predicting low SMI were 1.68 m2 for men and 1.48 m2 for women. Regarding the presence of low SMI, 776 (78.9%) and 730 (80.5%) patients were correctly diagnosed in the training and validation cohorts, respectively. The sensitivity and specificity of the combination of BSA and GS for sarcopenia were 82.7% and 97.1%, respectively, and 1175 patients (95.6%) were correctly diagnosed. Conclusions: BSA was highly correlated with SMI, suggesting that BSA could facilitate noninvasive estimation of low skeletal muscle mass in patients with CLD.

Portal vein tumor thrombus (PVTT)-related severe symptomatic portal hypertension (SPH) leads to a poor prognosis in patients with advanced hepatocellular carcinoma (HCC). Traditional transjugular intrahepatic portosystemic shunt (TIPS) using covered plus bare stent can effectively relieve SPH, however, the bare segment is susceptible to obstruction due to PVTT invasion. This study aimed to evaluate the safety and efficacy of fully covered stent-TIPS (FCS-TIPS) for treatment of PVTT-related SPH in advanced HCC patients.

This retrospective study enrolled 25 patients with advanced HCC who underwent FCS-TIPS for PVTT-related severe SPH from June 2018 to January 2024. The evaluated outcomes included overall survival (OS), technical success rate, reduction in portal venous pressure gradient (PPG), stent patency rate, SPH control rate, liver function and complications.

The technical success rate was 100% without perioperative deaths or severe procedure-related adverse events. The average PPG decreased by 13.4±4.6 mmHg. The overall symptom control rate of SPH was 96.0%. Variceal bleeding, ascites/hydrothorax, and enteropathy control rates were 100%, 95.0%, and 100%, respectively. Liver function showed mild improvement one month after TIPS. One patient (4.0%) experienced overt hepatic encephalopathy (OHE) and three (12.0%) patients developed shunt dysfunction during the follow-up period. None of the patients experienced shunt-induced extrahepatic metastasis. The median OS was 6.0 months and the cumulative survival rates at 3, 6, 12 months were 80.0%, 52.0% and 21.3%.

FCS-TIPS is safe and effective for treating PVTT-related severe SPH and can serve as a bridging therapy for advanced HCC.

Cirrhotic patients with refractory ascites exhibit severe portal hypertension and hemodynamic disturbances. The risks associated modest-volume paracentesis (<5 L) for refractory ascites remains unclear. We aimed to explore the impact of modest-volume paracentesis in refractory ascites.

Cirrhotic patients with refractory ascites undergoing paracentesis <5 L with albumin infusion were retrospectively enrolled. Patients were categorized into two groups based on the volume of paracentesis: ≥3 L and <3 L. Logistic regression analyses were used to determine risk factors for post-paracentesis complications, while Kaplan-Meier analysis was used to assess 28-day survival rates.

Among 116 patients, 40 (34.5%) experienced post-paracentesis complications within one week, predominantly acute kidney injury (AKI) (19.8%). Twenty patients had paracentesis ≥3 L and 96 patients had <3 L. Overall complications were comparable between two groups (50% vs. 31.3%, p = 0.109), but ≥3 L group had more AKI (40% vs. 15.6%, p = 0.013). Additionally, paracentesis ≥3 L is an independent risk factor for AKI [Odds ratio (OR) = 4.15, p = 0.012], while higher MELD scores (OR = 1.14, p = 0.001) and older age (OR = 1.03, p = 0.047) are risk factors for overall complications. Furthermore, patients with post-paracentesis complications had significantly poorer 28-day survival.

Cirrhotic patients with refractory ascites face a high risk of complications from modest-volume paracentesis, even with albumin infusion. Paracentesis ≥3 L increases AKI risks, while higher MELD scores are linked to greater overall complications, leading to poor short-term survival.

Liver cirrhosis is a major health burden, resulting in over 1 million deaths per year worldwide. Nutritional imbalance often complicates the course of liver diseases, particularly of cirrhosis and has been linked to increased mortality. Despite the high disease burden, there is paucity of literature regarding the magnitude of under-nutrition in patients with cirrhosis and its associated factors in Ethiopia and sub-Saharan Africa. The study aimed to assess the prevalence of under-nutrition and its associated factors among adult out-patients with liver cirrhosis. A hospital-based cross-sectional study was conducted among 136 adult out-patients with cirrhosis who visited the hepatology clinic of St. Paul's Hospital Millennium Medical College. Data were obtained through patient interviews, medical record reviews, anthropometric and handgrip strength measurements and collected using a structured checklist and analyzed using Statistical Package for the Social Sciences (SPSS) version 26.0. Body mass index with cutoff points adjusted for the degree of ascites were used to diagnose under-nutrition. Descriptive statistical tools and binary and multivariable logistic regression analyses were employed, and statistical significance was set at <0.05. The mean age of study participants was 39.5 years (standard deviation: ±11.2) and 62.5% were males. Chronic hepatitis B virus infection (57.4%) was the most common cause of liver cirrhosis, followed by alcohol-associated liver cirrhosis (12.5%). The majority (70.6%) of the study participants were undernourished. The factors found to have statistically significant association with under-nutrition were, rural area of residence (adjusted odds ratios [AOR]: 5.65, 95% confidence interval [CI]: 1.98-16.1), presence of ascites (AOR: 2.43, 95% CI: 1.03-5.7) and the disease severity, as measured by the child-pugh class (AOR, 1.11; 95% CI: 0.45-2.7). Under-nutrition was found to be a common problem among out-patients with liver cirrhosis and patients from rural areas and those with advanced disease were disproportionately affected. It is imperative to implement routine nutritional screening and plan on appropriate interventions for patients with liver cirrhosis.

Global Leadership Initiative on Malnutrition (GLIM) criteria have gradually accounted for the mainstay evaluating nutritional status. We sought to establish GLIM-dictated nomograms with other prognostic factors influencing long-term mortality and externally validate their predictive performance in decompensated cirrhosis.

The derivation cohort comprised 301 patients presenting with cirrhosis-associated acute insults, while the validation cohort encompassed 101 subjects from another tertiary hospital. Two nomograms were constructed to predict the 1-year all-cause mortality by integrating the GLIM criteria. The study population was stratified into low-, moderate- and high-risk mortality groups according to aforesaid proposed models.

Adjusting Child-Turcotte-Pugh classification (Nomo#1) or Model for End-stage Liver Disease-Sodium score (Nomo#2) separately, the GLIM criteria were independently associated with 1-year mortality in the multivariate Cox regression analysis (Nomo#1 hazard ratio (HR) = 3.139, p < 0.001; Nomo#2 HR = 3.456, p < 0.001). The C-index and time AUC for Nomo#1 and Nomo#2 performed significantly better than those of the GLIM criteria or conventional scoring systems alone. The survival rate of the low-risk group was significantly higher than those of the moderate- or high-risk groups (Nomo#1: 95% vs 65.8% vs 33.3%, p < 0.001; Nomo#2: 94.3% vs 64.5% vs 25%, p < 0.001). Furthermore, our proposed models exhibited moderate prediction accuracy and may identify malnourished patients with poor survival conditions in the external validation cohort.

GLIM criteria-defined malnutrition negatively impacted long-term mortality in the context of decompensated cirrhosis. Our established nomograms may predict survival status with sufficient discriminatory ability, alongside good consistency and clinical benefits, supporting their effectiveness in daily practice.

To evaluate the potential of interpretable machine learning (ML) models to predict ascites improvement in patients undergoing transjugular intrahepatic portosystemic shunt (TIPS) placement for refractory ascites.

In this retrospective study, 218 patients with refractory ascites who underwent TIPS placement were analyzed. Data on 29 demographic, clinical, and procedural features were collected. Ascites improvement was defined as reduction in the need of paracentesis by 50% or more at the 1-month follow-up. Univariate statistical analysis was performed. Data were split into train and test sets. Feature selection was performed using a wrapper-based sequential feature selection algorithm. Two ML models were built using support vector machine (SVM) and CatBoost algorithms. Shapley additive explanations values were calculated to assess interpretability of ML models. Performance metrics were calculated using the test set.

Refractory ascites improved in 168 (77%) patients. Higher sodium (Na; 136 mEq/L vs 134 mEq/L; P = .001) and albumin (2.91 g/dL vs 2.68 g/dL; P = .03) levels, lower creatinine levels (1.01 mg/dL vs 1.17 mg/dL; P = .04), and lower Model for End-stage Liver Disease (MELD) (13 vs 15; P = .01) and MELD-Na (15 vs 17.5, P = .002) scores were associated with significant improvement, whereas main portal vein puncture was associated with a lower improvement rate (P = .02). SVM and CatBoost models had accuracy ratios of 83% and 87%, with area under the curve values of 0.83 and 0.87, respectively. No statistically significant difference was found between performances of the models in DeLong test (P = .3).

ML models may have potential in patient selection for TIPS placement by predicting the improvement in refractory ascites.

Background   Ultrasound (US) surveillance for transjugular intrahepatic portosystemic shunt (TIPS) dysfunction has yet to be standardized, as clear-cut criteria have not been conventionally defined. This study evaluated the role of US-based parameters in detecting hemodynamic TIPS dysfunction (HD). Methods   We included consecutive patients treated with TIPS. All patients were scheduled within the first six weeks after the procedure for TIPS revision, comprised of a Doppler US exam and invasive hemodynamic reassessment. Clinical TIPS dysfunction (CD) was defined as symptom recurrence, while HD was defined by a portal pressure gradient (PPG)≥12 mmHg. The predictive capabilities of Doppler US for predicting TIPS dysfunction were tested against the hemodynamic gold standard. Results   86 patients were included. Secondary prophylaxis of variceal bleeding was the main indication for TIPS in 72 patients (83.7%), while 27 (31.4%) had refractory ascites. HD occurred in 37 cases (43%), of which 25 patients (67.5%) had no CD. Patients with HD had a significantly lower portal vein velocity (PVV): 35 (20-45) cm/s vs. 40.5 (35-50) cm/s, p=0.02. Compared to the immediate post-TIPS assessment, the patients without HD had a ΔPVV of 6.08±19.8 cm/s vs. a decrease of - 8.2±20.2 cm/s in HD (p=0.04). Using a cut-off value of 40.5 cm/s, PVV had an AUROC of 0.705 for predicting HD, while the addition of ΔPVV (cut-off 9.5 cm/s) improved the AUROC to 0.78. Conclusion   Despite adequate symptom control, a considerable percentage of patients have a post-TIPS PPG≥12 mmHg. The dynamic assessment of PVV and its temporal dynamics can reliably predict TIPS dysfunction.

Long-term albumin (LTA) is currently standard of care for patients with decompensated cirrhosis in many Italian hepatology centres. In this real-life study, we aimed to describe patient, logistical and treatment-related characteristics in daily clinical practice and to identify predictors of response.

We performed a multicentre, retrospective, observational study in patients with cirrhosis and ascites receiving LTA between 01/2016 and 02/2022 and followed until death, TIPS (transjugular intrahepatic portosystemic shunt) placement, transplantation or 02/2023.

A total of 312 patients, the majority with alcohol-related cirrhosis, were included. At baseline, median Child-Pugh, MELD, and MELD-Na were 8, 15, and 18, respectively. Ascites was grade 2 in 55% of patients, grade 3 in 35% and refractory in 27%, while 47% had received large volume paracentesis in the previous 6 months. Median LTA was 10 months with a median dose of 40 g/week. Ascites resolved to grade 0-1 in 34% of patients within the first 3 months and 56% by the end of treatment. Predictors of ascites resolution were age (p = 0.007), baseline grade of ascites (p = 0.007), no paracentesis in the previous 6 months (p = 0.001), aetiological treatment in the past 12 months or during LTA (p = 0.005), weekly albumin dose (p = 0.014) and serum albumin concentration of 40 g/L after 1 month of treatment (p = 0.017). Of the 83 patients with refractory ascites at inclusion, 26% had grade 0/1 ascites at the last observation. No severe albumin-related side-effects were reported and only 1% discontinued for logistical reasons.

LTA is feasible as an outpatient treatment for the management of ascites. In the current study, ascites resolved in more than half of patients receiving LTA on top of diuretics, including in some with refractory ascites. Predictors of response to LTA provide useful information for tailoring treatment.

The ANSWER randomised-controlled trial has shown that long-term albumin treatment (LTA) is an effective approach for the management of patients with cirrhosis and ascites. This observational study provides novel information on target patients, modalities and length of treatment, predictors of ascites resolution, stopping criteria, and clinical trajectories of patients on treatment. LTA is a feasible option in the daily clinical practice for the management of ascites when given on top of diuretics. Rather than an alternative therapy, LTA should be integrated with the other treatment options already available for patients with difficult-to-treat ascites. The predictive factors of response identified in the present study can help physicians to individualise LTA and optimise the decision-making process.

There is still poor evidence about the safety and feasibility of laparoscopic liver resection (LLR) for huge (> 10 cm) hepatocellular carcinomas (HCC). The aim of this study was to assess the short- and long-term outcomes of LLR versus open liver resection (OLR) for patients with huge HCC from real-life data from consecutive patients.

Data regarding all consecutive patients undergoing liver resection for huge HCC were retrospectively collected from a Korean referral HPB center. Primary outcomes were the postoperative results, while secondary outcomes were the oncologic survivals.

Sixty-three patients were included in the study: 46 undergoing OLR and 17 LLR. Regarding postoperative outcomes, there were no statistically significant differences in estimated blood loss, operation time, transfusions, postoperative bile leak, ascites, severe complications, and R1 resection rates. After a median follow-up of 48.4 (95% CI 8.9-86.8) months, there were no statistically significant differences in 3 years OS (59.3 ± 8.7 months vs. 85.2 ± 9.8 months) and 5 years OS (31.1 ± 9 months vs. 73.1 ± 14.1 months), after OLR and LLR, respectively (p = 0.10). Similarly, there was not a statistically significant difference in both 3 years DFS (23.5% ± 8.1 months vs. 51.6 ± months) and 5 years DFS (15.7 ± 7.1 months vs. 38.7 ± 15.3 months), respectively (p = 0.13), despite a potential clinically significant difference.

LLR for huge HCC may be safe and effective in selected cases. Further studies with larger sample size and more appropriate design are needed to confirm these results.

Malnutrition coexisting with abdominal adipose tissue accumulation bring a double burden on prognosis. More recently, the Global Leadership Initiative on Malnutrition (GLIM) has reached a novel consensus concerning the diagnostic criteria, that is, a two-step modality combining nutritional risk screening and subsequent phenotypic/etiologic parameters for comprehensive evaluation in hopes of harmonizing the malnutrition diagnosis. We aimed to elucidate their synergistic impact among inpatients with decompensated cirrhosis concerning long-term mortality.

Malnutrition, visceral obesity, and visceral adiposity were defined by the Global Leadership Initiative on Malnutrition (GLIM), visceral fat area (VFA), and visceral to subcutaneous adipose tissue area ratio (VSR) on computed tomography, respectively. Accordingly, the patients were categorized into different groups given their nutritional status and visceral obesity/adiposity. Multivariate Cox regression was performed to identify independent risk factors associated with 1-year all-cause mortality. Kaplan-Meier curves with log-rank tests were compared among distinct groups.

Totally, 295 patients were recruited. GLIM, VFA, and VSR identified 131 (44.4%), 158 (53.6%), and 59 (20%) patients with malnutrition, visceral obesity and visceral adiposity, respectively. Malnutrition coexisted with visceral obesity in 55 (MO group) relative to visceral adiposity in 40 patients (MA group). Multivariate Cox analysis showed that MA (hazard ratio: 2.48; 95% confidence interval: 1.06, 5.79; P = 0.036) was independently associated with dire outcome rather than MO. Moreover, patients with cirrhosis in the MA group had the worst survival status when compared with other groups (log-rank test: P < 0.001).

The current study indicated that coexisting GLIM-defined malnutrition and VSR-defined visceral adiposity were in relation to worse long-term mortality among inpatients. It is imperative to delicately manage nutritional status and provide personalized treatment in this vulnerable subgroup for achieving better prognosis.

Rifaximin, derived from rifamycin, is a broad-spectrum antibiotic by inhibiting bacterial RNA synthesis. Rifaximin has a very low intestinal absorption and exerts its antimicrobial activity primarily in the intestinal tract. It regulates the gut microbiota with limited side effects systemically. Rifaximin has been recommended for the treatment of hepatic encephalopathy but some studies shed light on its medicinal effects in many other diseases. For instance, rifaximin may suppress the progression of liver fibrosis and its related complications, and ameliorate metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease, etc. Rifaximin can also mediate anti-inflammation, antiproliferation, and proapoptotic events by activating pregnane X receptor, which is efficious in cancers such as colon cancer. In addition, some investigations have shown rifaximin may play a therapeutic role in various autoimmune and neurological disorders. However, these findings still need more real-world practices and in-depth investigations to obtain more precise indications and fully elucidate the multifaceted potentials of rifaximin.

Abdominal paracentesis is a common procedure performed for both diagnostic and therapeutic purposes in patients with chronic liver disease and ascites. This review aims to provide an overview of the current evidence on the risk of bleeding associated with abdominal paracentesis. Electronic search was performed using PubMed, MEDLINE, and Ovid EMBASE from inception to 29 October 2023. Studies were included if they examined the risk of bleeding post-abdominal paracentesis or the efficacy of interventions to reduce bleeding in patients with chronic liver disease. Random-effects model was used to calculate the pooled proportions of bleeding events following abdominal paracentesis. Heterogeneity was determined by I 2, τ2 statistics, and P-value. Eight studies were included for review. Six studies reported incident events of post-abdominal paracentesis bleeding. Pooled proportion of bleeding events following abdominal paracentesis was 0.32% (95% CI: 0.15-0.69%). The mean values for pre-procedural INR and platelet count of patients in these studies ranged between 1.4 and 2.0, and 50 and 153 × 109/L, respectively. The highest recorded INR was 8.7, and the lowest platelet count was 19 × 109/L. Major bleeding after abdominal paracentesis occurred in 0-0.97% of the study cohorts. Two studies demonstrated that the use of thromboelastography (TEG) before paracentesis in patients with chronic liver disease identified those at risk of procedure-related bleeding and reduced transfusion requirements. The overall risk of major bleeding after abdominal paracentesis is low in patients with chronic liver disease and coagulopathy. TEG may be used to predict bleeding risk and guide transfusion requirements.

Palliative care is often suboptimal for patients with end-stage liver disease (ESLD). Ascites remains the most common complication in ESLD. Though long-term abdominal drains (LTAD) are commonly used in refractory malignant ascites, the standard care for ESLD is hospital drainage (large volume paracentesis (LVP)). There is an ongoing National Institute for Health and Care Research (NIHR) funded trial (REDUCe 2 Study) (ISRCTN269936824) comparing palliative LTAD to LVP in ESLD. This 35-site trial is being conducted in England, Scotland and Wales.

To understand the views and experience of healthcare professionals (HCP) on the use of palliative LTAD in ESLD.

An electronic survey comprised of seven questions with fixed quantitative options and three exploratory questions was used between August-December 2019. The survey was distributed electronically via the British Association for Study of Liver newsletter and to relevant hospital departments in Southeast England and Northeast London. An email reminder was sent at 4 and 8 weeks after the initial invitation to the survey.

There were 211 respondents (hepatologists (36.5%), specialist nurses (24.6%), gastroenterologists (16.6%), trainees (17%) and others (5.2%)). All respondents had access to LVP, 86% to a transjugular intrahepatic portosystemic shunt procedure for patients, 67% to LTADs and 10% to other options, such as the automated low-flow ascites (ALFA) pump. The majority of respondents to the survey (68%) reported their experience of using LTAD. Almost all respondents (91%) were willing to consider LTAD in ESLD. However, the main deterrents of this were the perceived risk of infection (90%), followed by LTAD management in community (57%). Some 51% of those with prior experience of using LTAD reported clinical complications for patients (including bleeding, infection and renal impairment), 41% reported technical issues and 35% inadequate community support.

Almost all HCPs are willing to consider palliative LTAD in refractory ascites due to ESLD, but the main deterrents are the perceived infection risk and lack of published data to guide community management. The REDUCe 2 trial will clarify if these concerns are real and provide conclusive evidence on role, if any, of palliative LTADs in this vulnerable and under researched cohort with ESLD.

Inadequate food intake contributes to malnutrition in patients with cirrhosis on the waiting list for liver transplantation (LTx).

To evaluate food intake during 12 weeks of nutritional follow-up and assess factors independently associated with the difference between energy and protein intake in LTx patients.

A secondary analysis of data from a randomized controlled trial that evaluated the effects of Beta-Hydroxy-Beta-Methylbutyrate (HMB) supplementation and nutritional intervention in patients on a liver transplant waiting list. Dietary guidelines for patients with cirrhosis were used to prescribe the nutritional plan (35 kcal/kg; 1.5 g/kg dry weight for protein) and to evaluate the nutritional goals (30 kcal/kg; 1.2 g/kg dry weight for protein; late evening snack) and nutritional counseling dietary follow-ups were performed in each evaluation. Food intake was assessed in six moments: Baseline, week 0 (W0), week 2 (W2), week 4 (W4), week 8 (W8), and week 12 (W12).

Forty-seven patients (55.0 ± 10.6y; 72.3% male) were evaluated. Only 25.5% (n = 12) of patients achieved nutritional goals at the end of the study. The mean energy intake at Baseline was 1782 ± 784 kcal (27.6 ± 13.2 kcal/kg) without difference between moments. The protein intake increased between W0 [63.4 ± 29.8g; 0.8(0.2-2.2 g/kg)] and W8 [72.0 ± 28.0g; 1.0(0.4-2.6 g/kg); p = 0.03; p = 0.03, respectively]. The consumption of cholesterol, calcium, phosphorus, magnesium, iron, and niacin increased (p < 0.05), as well as the consumption of legumes; roots and tubers; dairy; and meat, poultry and fish groups through time (p < 0.05). The percentage of patients that consumed a late evening snack rised from 40.4% (Baseline) to 76.6% (W8) (p < 0.001). The presence of ascites, nourished patients, frailty index classification, short physical performance battery score, systemic symptoms, and emotional function in the Quality of Life Test were independently associated with the energy intake difference between W12 and Baseline (p < 0.05). Diabetes mellitus, patients with moderately malnourishment, poor performance, fatigue, systemic symptoms, and emotional function in the Quality of Life Test were independently associated with the difference in protein intake between W12 and Baseline (p < 0.05).

Patients on the liver transplant waiting list showed slight food intake improvement during the follow-up, but few met nutritional guidelines. Various clinical and nutritional factors independently affected energy and protein intake from W12 to Baseline.

Minimally Invasive thermal ablation (MITA) of liver tumors is a commonly performed procedure, alone or in combination with liver resection. Despite being a first-option strategy for small lesions, it is technically demanding, and many concerns still exist about local disease control.

Consecutive patients undergoing MITA from 1-2019 to 12-2022 were retrospectively enrolled. Risk factors of local recurrence were investigated through univariate and multivariable cox regression analysis.

At the multivariable analysis of the 207 nodules undergoing MITA, RFA was associated with worse local Recurrence Free Survival (lRFS) than MWA (HR 2.87 [95 % CI 0.96-8.66], p = 0.05), as well as a concomitant surgical resection (HR 3.89 [95 % CI 1.06-9.77], p = 0.02). A concomitant surgical resection showed worse lRFS in the subgroup analysis of both HCC (HR 3.98 [95 % CI 1.16-13.62], p = 0.02) and CRLM patients (HR 2.68 [95 % CI 0.66-5.92], p = 0.04). Interestingly, a tumor size between 30 and 40 mm was not associated to worse lRFS.

MWA may reduce the risk of local recurrence in comparison to RFA, while MITA associated to liver resection may face an increased risk of local recurrence. Further prospective studies are needed to confirm such results.

The prognostic impact of acute decompensation (AD), i.e. the development of complications that require hospitalization, has recently been assessed. However, complications of cirrhosis do not necessarily require hospitalization and can develop progressively, as in the recently defined non-acute decompensation (NAD). Nevertheless, there is no data regarding the incidence and prognostic impact of NAD. The aim of the study was to evaluate the incidence and the prognostic impact of NAD and AD in outpatients with cirrhosis.

A total of 617 outpatients with cirrhosis from two Italian tertiary centers (Padua and Milan) were enrolled from January 2003 to June 2021 and followed prospectively until the end of the study, death or liver transplantation. The complications registered during follow-up were considered as AD if they required hospitalization, or NAD if managed at the outpatient clinic.

During follow-up, 154 patients (25.0% of total patients) developed complications, 69 patients (44.8%) developed NAD and 85 (55.2%) developed AD, while 29 patients with NAD (42.0%) developed a further episode of AD during follow-up. Sixty-month survival was significantly higher in patients with no decompensation than in patients with NAD or AD. On multivariable analysis, AD (hazard ratio [HR] 21.07, p <0.001), NAD (HR 7.13, p <0.001), the etiological cure of cirrhosis (HR 0.38, p <0.001) and model for end-stage liver disease score (HR 1.12, p = 0.003) were found to be independent predictors of mortality.

The first decompensation is non-acute in almost 50% of outpatients, though such events are still associated with decreased survival compared to no decompensation. Patients who develop NAD must be treated with extreme care and monitored closely to prevent the development of AD.

This multicenter study is the first to investigate the role of non-acute decompensation (NAD) in patients with cirrhosis. In fact, while the unfavorable impact of acute decompensation is well known, there is currently a dearth of evidence on NAD, despite it being a common occurrence in clinical practice. Our data show that almost half of decompensations in patients with cirrhosis can be considered NAD and that such events are associated with a higher risk of mortality than no decompensation. This study has important clinical implications because it highlights the need to carefully consider patients who develop NAD, in order to prevent further decompensation and reduce mortality.

This work aims to explore the long-term prognosis of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). In this prospective study, eligible inpatients with HBV-ACLF are enrolled and followed up from December 2012 to February 2023, for clinical events, laboratory tests at least every 6 months. Overall, the survival rates at 28 days, 90 days, 1 year, 5 years, and 8 years are 64.7%, 48.8%, 46.1%, 43.8%, and 42.2%, respectively. Among the 8-year mortality and liver transplant cases, ACLF survivors (who survived over 90 days) accounted for 7.8% (9/115). Among 101 patients who survived for more than 90 days, 97.9% of patients achieve virologic response at 1 year. For HBeAg-positive patients, the HBeAg seroconversion are 25.5%, 63.6%, and 76.9% at 1, 5, and 8 years, respectively. Alanine aminotransferase, aspartate aminotransferase, total bilirubin, INR, white blood cell count, and albumin levels gradually improve within the first year. Fibrosis biomarkers APRI, FIB-4 and Chitinase-3-like protein 1 (CHI3L1) levels decreases within the first 5 years. The Cox proportional hazards regression reveal that high total bilirubin (HR = 1.008, p = 0.021) is the independent risk factor for 8-year survival of ALCF survivors. The 90-day period following of HBV-ACLF represented a critical juncture for long-term prognosis, revealing favorable outcomes beyond this timeframe.