Compensated cirrhosis due to metabolic dysfunction-associated steatotic liver disease (CC-MASLD) increases morbidity and mortality risk but has no aetiology-specific treatment. We investigated the safety and efficacy signals of severe energy restriction.

In this randomised controlled trial, adults with CC-MASLD and obesity in a tertiary hepatology centre were randomised 2:1 to receive one-to-one remote dietetic support with a low-energy (880 kcal/day, 80 g protein/day) total diet replacement programme for 12 weeks and stepped food reintroduction for another 12 weeks or standard of care (SoC). Given the exploratory nature of the study, three pre-defined co-primary outcomes were used to assess safety and efficacy signals: severe increases in liver biochemistry, changes in iron-corrected T1, and changes in liver stiffness on magnetic resonance elastography. Changes in liver steatosis on magnetic resonance imaging, physical performance based on the physical performance test and liver frailty index, and changes in fat-free mass were secondary outcomes. Magnetic resonance outcomes were assessed blind.

Between February 2022 and September 2023, 17 participants (36% female, median [IQR] age 58 [7.5] years) were randomised to SoC (n = 6) or intervention (n = 11). The trial stopped earlier than planned due to slow recruitment rate. 91% and 94% of participants completed the intervention and attended the 24-week follow-up, respectively. Compared with the SoC, the between-group weight change in the intervention was -11.9 kg (95% CI: -17.2, -6.6, p < 0.001) at 24 weeks. Liver biochemistry markers (alanine transaminase, aspartate transaminase, and total bilirubin) were stable in everyone throughout the trial. Iron-corrected T1 and steatosis significantly reduced (-149.9 ms [95% CI -258.1, -41.7, p = 0.01] and -6% [95% CI -11.3, -0.6, p = 0.03], respectively). There were no between-group differences in changes in liver stiffness (0.2 kPa [95% CI -1.1, 1.6]), the physical performance test (1.5 points [95% CI -1.9 to 4.9], p = 0.70) or the liver frailty index (0 [95% CI -0.6 to 0.6], p = 0.97). Compared with SoC, absolute fat-free mass reduced (-3.2 kg [95% CI -6 to -0.3], p = 0.04) but relative fat-free mass as percentage of total body weight increased (5.4% [95% CI 0.5 to 10.3], p = 0.046). No participant met the pre-defined safety criteria for enhanced observation or intervention discontinuation. There was no between-group differences in changes in cardiovascular markers and no evidence of hepatic decompensation or serious adverse events.

Severe energy restriction appears a safe option to achieve significant weight loss and reduce liver fat without adverse effects in people with CC-MASLD. A larger study is needed to confirm these findings.

ISRCTN13053035, prospectively registered, overall study status: closed.

Steatotic liver diseases (SLD) encompasses metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic alcohol-related liver disease (MetALD), and alcohol-related liver disease (ALD). Our aim was to determine the age-standardized prevalence of fibrosis stages and cirrhosis in US adults with different subtypes of SLD.

We utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning 2017 to 2023. SLD was defined by a controlled attenuation parameter (CAP) ≥280 dB/m. MASLD, MetALD, and ALD were defined according to the new nomenclature. Fibrosis and cirrhosis were estimated by liver stiffness measurements.

The age-standardized prevalence of SLD was 37.08% (MASLD: 32.42%, MetALD: 2.20%, and ALD: 1.29%) with males having higher prevalence rates versus females [SLD (42.40% vs. 31.59%), MASLD (35.84% vs. 28.88%), MetALD (2.82% vs. 1.56%), and ALD (2.17% vs. 0.38%) (all P < 0.03)]. For MASLD, the highest burden was observed in Mexicans (43.96%), followed by Whites (31.75%), Hispanics (32.69%), Asians (32.41%), and Blacks (27.39%). MetALD was most prevalent among Whites (2.56%) and least prevalent among Asians (0.25%). Between 2017 and 2020 and 2021 and 2023, the prevalence of SLD and its subtypes with fibrosis and cirrhosis increased, coinciding with rising alcohol consumption. Among individuals with MASLD, component of metabolic syndrome (type 2 diabetes and Obesity, especially severe obesity with BMI ≥40 kg/m²) were associated with increased risk of fibrosis and cirrhosis.

The burden of SLD, its subtypes, and associated fibrosis in the US is substantial. This highlights an urgent need for targeted public health strategies to manage the rising burden of this important liver disease in the US population.

Obesity is a worldwide epidemic and is pervasive in the liver disease community. Given that liver disease is both caused and worsened by obesity, our study assesses the risks of bariatric surgery in patients with chronic liver disease.

This retrospective study using the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program 2023 database includes adult patients who underwent minimally invasive sleeve gastrectomy, Roux-en-Y gastric bypass, or gastric band placement procedures. Liver disease (LD) includes a spectrum of severity (borderline to moderate) and etiologies (including steatosis). LD and non-liver disease (non-LD) cohorts were compared using Chi-square and t-tests. Univariate and multivariate analyses were performed using logistic regression.

Our sample of 201,605 patients included 22,476 (11.2%) LD and 179,129 (88.9%) non-LD patients. Overall mean body mass index was 44.68 kg/m2 (SD 7.86). The mortality rates were no different between groups (0.07% and 0.07%, p = 0.85). While multivariate subset analyses of each procedure showed a statistically slightly elevated risk of bleeding, infection, bowel obstruction, Clavien-Dindo I-III complications, and ICU admission for the liver group patients (odds ratios ranged from 1.42-1.76), rates of complications were clinically very low (3.1% and 0.8% for Clavien-Dindo I-III and IV).

Given the low 30-day complication rate, our study shows that in the appropriate candidates with mild-to-moderate chronic liver disease, minimally invasive bariatric surgery is safe in the short-term, and the documented benefits of weight loss likely outweigh the slightly elevated risk. Bariatric surgeons can feel more comfortable and informed operating in this context.

Baveno-VII consensus recently defined recompensation in patients with decompensated cirrhosis achieving etiological cure. However, incidence, predictors and clinical significance of recompensation are poorly known. This study aimed to evaluate the incidence and prognostic impact of recompensation in patients with decompensated cirrhosis.

Outpatients with cirrhosis and curable etiologies (alcohol, HCV, HBV) were consecutively included and followed up. Recompensation was defined according to Baveno VII criteria. Additionally, expanded recompensation criteria were evaluated for patients on low dose diuretics and/or lactulose/rifaximin for ≥12 months. In 160 patients, inflammatory cytokines (IL-6,IL-1β, IL-10) were measured in serum samples. An external cohort was used to validate study findings.

298 out of 525 decompensated cirrhotic outpatients achieved an effective etiological treatment and 21 (7%) achieved recompensation (Baveno-VII criteria), while 112 patients achieved expanded recompensation criteria (37.6%). MELD score (sHR=0.89; p<0.001), BMI (sHR=0.93; p=0.020), hemoglobin (sHR=1.14; p=0.010) and further decompensation (sHR=0.50; p=0.001) were independent predictors of recompensation. In multivariable analysis, mortality risk was not significantly different between patients achieving recompensation and compensated patients (HR=0.97; p=0.947), while decompensated patients had the highest mortality risk (HR=4.96; p<0.001). Mortality risk was not significantly different between patients meeting expanded recompensation criteria and Baveno-VII criteria (HR=0.97; p=0.938). Serum IL-6, IL-1beta and IL-10 were significantly higher in decompensated patients than in compensated and recompensated patients.

Baveno-VII criteria identify cirrhotic patients with a good prognosis, but fewer than 10% of decompensated patients achieve recompensation. Expanding these criteria to include patients receiving minimal decompensation treatment identifies those with similarly low mortality risk.

In recent years, growing evidence has shown that achieving an etiological cure can significantly improve the prognosis of decompensated patients, leading to the development of the concept of recompensation. Baveno VII recently proposed a definition for recompensation; however, data on the clinical impact of this condition remain limited. In this study we evaluated Baveno VII criteria and developed and validated expanded Baveno VII criteria for recompensation. Our findings demonstrates that recompensation is associated with improved survival, reduced hyperdynamic circulation and decreased systemic inflammation in outpatients with decompensated cirrhosis. These results are valuable for hepatologists and researchers aiming to refine patient management strategies and risk stratification in cirrhosis care.

Metabolic hepatic steatosis (MetHS) is a clinically heterogeneous, multisystemic, dynamic, and complex disease, whose progression is one of the main causes of cirrhosis and hepatocarcinoma. This clinical practice guideline aims to respond to its main challenges, both in terms of disease burden and complexity. To this end, recommendations have been proposed to experts through the Delphi method. The consensus was optimal in recommendations regarding type 2 diabetes as a risk factor (1.5.1, 4.5.1), in which cases early detection of MetHS should be carried out (4.5.2). Its results also emphasize the importance of the use of non-invasive tests (FIB-4, NFS, HFS) for the exclusion of significant fibrosis in patients with suspected MetHS (2.3.1, 2.3.3). Diagnosis should be carried out through the sequential combination of non-invasive indices and transient elastography by FibroScan® for its risk stratification (2.3.3). A nearly unanimous consensus was reached regarding the role of early prevention in the impact on the quality of life and survival of patients (5.1.2), as well as on the effectiveness of the Mediterranean diet and physical exercise in relation to the improvement of steatosis, steatohepatitis and fibrosis in MetHS patients (5.2.2) and on the positive results offered by resmiterom and semaglutide in promoting fibrosis regression (5.4.1). Finally, a great consensus has been reached regarding the importance of multidisciplinary management in MetHS, for which it is essential to agree on multidisciplinary protocols for referral between levels in each health area (6.2.1), as well as ensuring that referrals to Hepatology/Digestive and Endocrinology or Internal Medicine services are effective and beneficial to prevent the risk of disease progression (6.2.3, 6.3.1).

The global prevalence of Metabolic Dysfunction-Associated Liver Disease is dramatically increasing with the diffusion of cardiometabolic risk factors (CMRFs). The aim of the present study was to assess the natural course of liver cirrhosis, in terms of decompensation, development of hepatocellular carcinoma and mortality, in relation to the presence of CMRFs (type 2 diabetes mellitus, obesity, arterial hypertension, low HDL levels, hypertriglyceridemia).

667 patients with liver cirrhosis (50 with CMRFs and without non-metabolic aetiological factors, 167 with non-metabolic aetiological factors and without CMRFs, and 450 with both non-metabolic aetiological factors and at least one CMRF) followed at the University and General Hospital of Padua, Italy, from 1998 to 2022, were included.

No difference in the occurrence of cirrhosis decompensating events and development of hepatocellular carcinoma was observed, whereas patients in the metabolic or mixed group had 4-3-fold higher all-cause mortality and significantly lower 3-years survival compared to patients in the non-metabolic group, despite a better liver function at enrolment. Hypertriglyceridemia and low HDL levels were the less prevalent CMRFs, but those associated with the highest risk of cirrhosis decompensation. Hypertriglyceridemia was also associated with an increased risk of mortality. Arterial hypertension was associated with a reduced risk of cirrhosis decompensation, but a higher risk of mortality.

Compared to patients without CMRFs, those with CMRFs had similar rates of liver cirrhosis decompensation but higher overall mortality. Hypertriglyceridemia was associated with a high risk of both liver decompensation and death.

Two main stages are differentiated in patients with advanced chronic liver disease (ACLD), one compensated (cACLD) with an excellent prognosis, and the other decompensated (dACLD), defined by the appearance of complications (ascites, variceal bleeding and hepatic encephalopathy) and associated with high mortality. Preventing the progression to dACLD might dramatically improve prognosis and reduce the burden of care associated with ACLD. Portal hypertension is a major driver of the transition from cACLD to dACLD, and a portal pressure of ≥10 mmHg defines clinically significant portal hypertension (CSPH) as the threshold from which decompensating events may occur. In recent years, innovative studies have provided evidence supporting new strategies to prevent decompensation in cACLD. These studies have yielded major advances, including the development of noninvasive tests (NITs) to identify patients with CSPH with reasonable confidence, the demonstration that aetiological therapies can prevent disease progression and even achieve regression of cirrhosis, and the finding that non-selective β-blockers can effectively prevent decompensation in patients with cACLD and CSPH, mainly by reducing the risk of ascites, the most frequent decompensating event. Here, we review the evidence supporting new strategies to manage cACLD to prevent decompensation and the caveats for their implementation, from patient selection using NITs to ancillary therapies.

Hepatic decompensation carries profound implications for patient quality of life and risk of mortality. We lack comparative data on how noninvasive tools perform in risk stratification for those with compensated cirrhosis. We performed a systematic review to assess the performance of laboratory and transient elastography-based models for predicting hepatic decompensation in patients with compensated cirrhosis.

The following databases were searched by an informationist to identify relevant studies, including adult patients with compensated cirrhosis from inception to August 2023: Medline, Embase, Scopus, Web of Science, and ClinicalTrials.gov. Title and abstract screening followed by full-text review were performed by 2 independent reviewers, and data abstraction was completed using standardized forms. Studies of patients with decompensation at baseline (defined by ascites, variceal bleeding, and HE) or any primary hepatic malignancy were excluded. The primary outcome was hepatic decompensation, as defined above. Pooled HRs were calculated using the common-effect inverse-variance model.

Forty-four full-text studies met the inclusion criteria. Across 52,589 patients, the cumulative incidence of any decompensation was 17.9% over a follow-up time of 111,401 patient years. Pooled risk estimates for all-cause decompensation demonstrated that MELD (HR: 1.08; 95% CI: 1.06-1.10), albumin-bilirubin (HR: 2.13, 95% CI: 1.92-2.36), fibrosis-4 (HR: 1.04, 95% CI: 1.03-1.06), albumin-bilirubin-fibrosis-4 (HR: 1.25, 95% CI: 1.18-1.33), and liver stiffness by transient elastography (HR: 1.04; 95% CI: 1.04-1.05) predict decompensation.

Available blood and imaging-based biomarkers can risk-stratify patients for hepatic decompensation. Changes in albumin-bilirubin appear to have the highest discrimination in predicting decompensation events.

Alcoholic hepatitis (AH) is a severe manifestation of alcoholic liver disease with high morbidity and mortality. This study used the 2016-2020 National Readmission Database to investigate how obesity influences AH outcomes.

Adult hospitalizations were categorized as those without obesity, Class 1 obesity (BMI 30-34.9), Class 2 obesity (BMI 35-39.9), or Class 3 obesity (BMI ≥ 40). We compared mortality, complications, and resource utilization across these groups using regression models.

Among 82 367 AH admissions, 4.09% had Class 1 obesity, 2.73% had Class 2 obesity, and 4.02% had Class 3 obesity. After adjusting for confounders, Class 3 obesity was associated with higher odds of mortality (Odds ratio OR = 1.74; 95% CI: 1.40-2.17; p < 0.01), septic shock (OR = 2.27; 95% CI: 1.60-3.22; p < 0.01), hepatic encephalopathy (OR = 2.53; 95% CI: 1.15-5.56; p = 0.02), and intensive care unit (ICU) admission (OR = 1.93; 95% CI: 1.57-2.36; p < 0.01). All obesity classes had increased associations with hepatorenal syndrome. No significant differences emerged for spontaneous bacterial peritonitis or variceal bleeding. Resource utilization rose with increasing obesity severity, with Class 3 obesity having a 1.84-day longer adjusted length of stay (p < 0.01) and an additional $20 174 in total hospitalization charges (p < 0.01) compared with hospitalizations without obesity.

Class 3 obesity conferred the greatest burden of mortality, complications, and healthcare costs among hospitalizations with AH. Further research is warranted to clarify the intricate interplay between obesity and AH.

Malnutrition in patients with liver cirrhosis (LC) and/or hepatocellular carcinoma (HCC) has been associated with adverse outcomes. However, there is little information on the incidence of HCC during the compensated phase of LC in relation to the nutritional status.

To evaluate the association between the incidence of HCC in compensated LC and their nutritional status.

Patients with compensated liver cirrhosis with no previous history of ascites, hepatic encephalopathy, or variceal bleeding attending the Gastroenterology outpatient service at Centro Medico Nacional Siglo XXI were included in a prospective cohort. Clinical and nutritional parameters were collected, including the Royal Free Hospital Subjective Global Assessment (RFH-SGA) as an indicator of protein-calorie malnutrition and the triceps skinfold thickness, which classified patients as having normal subcutaneous adipose tissue (SAT), above average SAT, and below average SAT. Follow-up was censored at the time of HCC diagnosis or LC decompensation.

About 31/187 (16.0%) and 22/187 (11.8%) patients were categorized as having above- or below-average SAT at baseline, respectively. 10/187 patients (5.3%) developed HCC during the compensated phase of LC at a median of 22 months (IQR: 10.0-36.75). A higher risk of HCC was observed in subjects below average SAT (HR: 4.064, CI 95%: 1.012-16.317, p = 0.048). After adjusting the Cox models for age and α-fetoprotein at baseline, the statistical significance of the association between SAT and HCC was not modified.

These results suggest that decreased SAT may precede the diagnosis of HCC in compensated LC.

Hepatic venous pressure gradient (HVPG) is a strong surrogate of severity and outcome but its relative prognostic value in metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (ALD) is yet to be clarified. We compared HVPG in MASLD with ALD and other etiologies according to cirrhosis complications.

In our cirrhosis registry RH7, we identified patients with data on HVPG and scrutinized them against the etiology of advanced chronic liver disease (ACLD) (MASLD, ALD, Other) and specific complications of ACLD such as variceal bleeding or ascites. We excluded patients with advanced malignancies and less than 6 months of follow-up.

We enrolled 220 patients with ALD, MASLD, and Other etiology in 128, 52, and 40 cases, respectively; te median age was 57, 60, and 52 years (P = 0.09); the proportion of females was 31, 67, and 55%, respectively (P < 0.01). Median MELD scores in ALD, MASLD, and Other etiologies were 16.0, 13.0, and 12.0 (P < 0.01), and the median HVPG was 18.0, 14.0, and 11.5 mmHg (P < 0.001). In 19, 30, and 25 compensated patients, the median HVPG was 10.0, 11.5, and 11.0 mmHg (P = 0.97). In 109, 22, and 15 decompensated patients, the median HVPG was 19.0, 15.5 and 14 mmHg (P = 0.01 for trend, difference ALD vs. other P < 0.01, ALD vs. MASLD, P = 0.295). Between decompensated MASLD and ALD patients, we observed no differences in the proportion of clinically significant portal hypertension (CSPH) (>10 mmHg).

In our cirrhosis registry study of hospitalized patients with ACLD, baseline HVPG measured for accepted indications differed according to the etiology of dACLD: patients with ALD had the highest values followed by MASLD and Other etiologies. Importantly, when looked at from the point of view of complications, the treshold for clinically significant portal hypertension remained fixed at the level recommended by BAVENO Consensus - 10 mm Hg irrespective of etiology.

Liver cirrhosis represents the advanced pathological stage of chronic liver disease, characterized by the progressive destruction and regeneration of the hepatic parenchyma over years, culminating in fibrosis and disruption of the vascular architecture. As a leading global cause of morbidity and mortality, it continues to affect millions worldwide, imposing a substantial burden on healthcare systems. Alcoholic/nonalcoholic fatty liver disease and chronic viral hepatitis infection, hepatitis C (HCV) in particular, remain leading causes of cirrhosis. Despite significant advances in understanding the pathogenesis of cirrhosis, its management is still complex due to the multifaceted complications, including ascites, hepatic encephalopathy, variceal bleeding, and hepatocellular carcinoma, all of which severely compromise the patient outcomes and quality of life. This review aims at filling a critical gap by providing a comprehensive summary of the latest evidence on the complications and management of liver cirrhosis. Evidence-based therapies targeting both the etiologies and complications of cirrhosis are essential for improving outcomes. While liver transplantation is considered a definitive cure, advancements in pharmacological therapies offer promising avenues for halting and potentially reversing disease progression. This review summarizes the latest management strategies for cirrhosis and its associated complications, emphasizing the importance of early intervention and novel therapeutic options for improving outcomes and quality of life in affected individuals.

In cirrhotic patients, portal hypertension increases mortality after surgery. We evaluated the impact of pre-operative transjugular intrahepatic portosystemic shunt (TIPS) on the outcomes of bariatric surgery in cirrhosis.

Multicentric retrospective cohort. The decision for TIPS placement has been made according to hepatic venous pressure gradient (HVPG) values and centers' policy. The primary outcome: 1-year decompensation-free survival; secondary outcomes: 1-year acute-on-chronic liver failure (ACLF) and survival.

Fifty-three patients were included (2010-2022): 92% Child-Pugh A, MELD score 8, age 55 years, BMI 38.3 ± 13 kg/m2, 9 (18%) had TIPS. At baseline, patients with TIPS had more esophageal varices (89% vs 10%, p < 0.001), more previous decompensations (22% vs 0%, p = 0.002), and a higher HVPG (14 vs 7 mmHg, p < 0.001). All patients in the TIPS group had clinically significant portal hypertension vs 11% of patients without TIPS, p < 0.001. One-year decompensation-free survival was 77.8% and 93.2% in patients with and without TIPS, p = 0.064. ALCF occurred in 3 patients (6.8%) without TIPS and none with TIPS. All patients were alive 1 year after surgery.

In patients with cirrhosis and clinically significant portal hypertension (CSPH) undergoing bariatric surgery, TIPS placement was safe and had similar outcomes after surgery as patients without TIPS.

Dysgeusia is a distortion of the sense of taste whose prevalence and relationship with nutritional status in Metabolic dysfunction-associated Steatotic Liver Disease (MASLD)-related advanced chronic liver disease (ACLD) have never been systematically explored.

200 MASLD patients [60 ≤ F3 fibrosis, 70 compensated ACLD (cACLD), and 70 decompensated (dACLD)] were enrolled. At baseline, the Child-Pugh (CP) score was determined. Dietary habits, body composition, and frailty were evaluated. The European Working Group (EWGSOP2) criteria defined sarcopenia. Dysgeusia was assessed by the Dysgeusia-Total-Score (DTS). A visual analog scale identified appetite impairment (VASAI). During a 6-month follow-up, liver-related decompensation events (LRDEs) were recorded.

The prevalence of dysgeusia increased with the liver disease progression, appearing significantly higher in ACLD compared with ≤ F3 (65.7% vs 5%, p:0.003), as well as in dACLD compared to cACLD patients (58.5 vs 7.1% p < 0.0001). On 41 dACLD patients presenting dysgeusia, 37 (90.2%) showed a significant impairment of appetite levels. In dACLD, the CP score was positively correlated with both DTS (R:0.742) and VASAI (R:0.704), as well as DTS was directly correlated with VASAI (R:0.765) (all p < 0.0001). Compared with dACLD patients without dysgeusia, dysgeusia-affected dACLD patients presented a lower daily protein intake (g/kg/die) (1.55 ± 0.192 vs 1.34 ± 0.15, p < 0.0001). Sarcopenia (70.7 vs 41.3%) and frailty (69.29 vs 37.9%) were significantly more prevalent in dysgeusia-affected dACLD individuals (both p < 0.0001). These patients showed a higher risk of LRDEs occurrence during the follow-up [HR:2.205; C.I. 95%:1.186-4.099; p:0.01]. Logistic regression analysis revealed dysgeusia (aOR: 3.32), appetite impairment (aOR:1.32), sarcopenia (aOR: 3.75), and frailty (aOR:3.03) significantly associated with this outcome (all p < 0.0001).

Dysgeusia appears predominant in MASLD-dACLD and, via appetite impairment, in a close relationship with malnutrition, sarcopenia, and frailty, negatively influencing patients' outcomes.

Decompensated cirrhosis has long been considered the irreversible end stage of liver disease, characterised by further decompensating events until death or liver transplantation. However, the observed clinical improvements after effective antiviral treatments for HBV and HCV and after sustained alcohol abstinence have changed this paradigm, leading to the concept of "recompensation" of cirrhosis. Recompensation of cirrhosis was recently defined by Baveno VII as (i) cure of the primary liver disease aetiology; (ii) disappearance of signs of decompensation (ascites, encephalopathy and portal hypertensive bleeding) off therapy; and (iii) stable improvement of liver function tests (bilirubin, international normalised ratio and albumin). Achieving these recompensation criteria is linked to a significant survival benefit. However, apart from aetiological therapies, no interventions/treatments that facilitate recompensation are available, the molecular mechanisms underlying recompensation remain incompletely understood, and early predictors of recompensation are lacking. Moreover, current recompensation criteria are based on expert opinion and may be refined in the future. Herein, we review the available evidence on cirrhosis recompensation, provide guidance on the clinical management of recompensated patients and discuss future challenges related to cirrhosis recompensation.

Following a plant-based diet is associated with a wide range of health benefits. The current study aimed to investigate the association between plant-based diet indices, specifically the plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI) and risk of mortality in cirrhotic patients.

This cohort study included a total of 121 patients with cirrhosis, who were followed for four years. Plant-based diet indices were calculated based on a validated semi-quantitative food frequency questionnaire consisting of 168 items. The Hazard ratio (HR) with their corresponding 95% confidence intervals (CIs) were estimated using the Cox proportional risk models.

During 414 person-year of follow-up, 43 deaths (7 women, 36 men) were documented. After adjusting all confounders, it has been found that the PDI (HR T3 vs. T1 = 0.16, 95% CI = 0.03-0.89, P trend = 0.024) and hPDI (HR T3 vs. T1 = 0.04, 95% CI = 0.02-0.61, P trend = 0.020) were inversely associated with the risk of mortality. While uPDI was directly associated with a significant increase in mortality risk (HR T3 vs. T1 = 8.74, 95% CI = 0.33-17.14, P trend = 0.018). The 4-year survival rate among patients showed a significant relationship with all three indices.

Our findings highlight that higher scores of PDI and hPDI can significantly reduce the risk of mortality in patients with cirrhosis, while a significant increase in mortality risk was found in those with higher uPDI. However, confirmation of these findings requires further studies.

Obesity is associated with increased morbidity in patients with advanced liver disease, but it is particularly challenging for these patients to preserve skeletal muscle mass during weight loss and accelerating sarcopenia is a concern. Alternate-day modified fasting (ADMF) may be particularly effective for weight loss in patients with concomitant cirrhosis and obesity due to preservation of fat-free mass (FFM).

A weight loss program featuring either ADMF or a continuous low-calorie diet (LCD) was evaluated in a 24-week randomized clinical trial in 20 adult patients with Child-Pugh Class A cirrhosis and obesity. Participants were randomized to either ADMF (n = 11) or LCD (n = 9). Both groups received a remotely delivered exercise program. Body composition, sarcopenia measures, and functional outcomes were assessed pre-post.

Thirteen participants completed the intervention (Age = 57 ± 10; BMI = 37.7 ± 5.8 kg/m2). The median body weight lost in ADMF was 13.7 ± 4.8 kg (13.9% of initial body weight), while LCD lost 9.9 ± 6.9 kg (10.7% of initial body weight). Total body fat percentage decreased in both groups (ADMF: -4.1 ± 4.0%; LCD = -2.8 ± 1.4%). Fat-free mass accounted for 34 ± 20% of total weight loss in ADMF and 38 ± 10% in LCD. Functional measures, such as timed chair stands, improved in both groups.

This pilot study demonstrates the feasibility of the ADMF and LCD interventions to produce significant weight loss while improving body composition in patients with cirrhosis and obesity. Further research is needed to validate these findings in larger cohorts and to assess changes in muscle quality and visceral fat.

ClinicalTrials.gov Identifier: NCT05367596.

Chronic hepatitis C (CHC) increases the risk of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). This nationwide cohort study assessed the effectiveness of viral eradication of CHC.

The Taiwanese chronic hepatitis C cohort and Taiwan hepatitis C virus (HCV) registry are nationwide HCV registry cohorts incorporating data from 23 and 53 hospitals in Taiwan, respectively. This study included 27,577 individuals from these cohorts that were given a diagnosis of CHC and with data linked to the Taiwan National Health Insurance Research Database. Patients received either pegylated interferon and ribavirin or direct-acting antiviral agent therapy for > 4 weeks for new-onset LC and liver-related events.

Among the 27,577 analyzed patients, 25,461 (92.3%) achieved sustained virologic response (SVR). The mean follow-up duration was 51.2 ± 48.4 months, totaling 118,567 person-years. In the multivariable Cox proportional hazard analysis, the hazard ratio (HR) for incident HCC was 1.39 (95% confidence interval [CI]: 1.00-1.95, p = 0.052) among noncirrhotic patients without SVR compared with those with SVR and 1.82 (95% CI 1.34-2.48) among cirrhotic patients without SVR. The HR for liver-related events, including HCC and decompensated LC, was 1.70 (95% CI 1.30-2.24) among cirrhotic patients without SVR. Patients with SVR had a lower 10-year cumulative incidence of new-onset HCC than those without SVR did (21.7 vs. 38.7% in patients with LC, p < 0.001; 6.0 vs. 18.4% in patients without LC, p < 0.001).

HCV eradication reduced the incidence of HCC in patients with and without LC and reduced the incidence of liver-related events in patients with LC.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), is defined as steatotic liver disease (SLD) in the presence of one or more cardiometabolic risk factor(s) and the absence of harmful alcohol intake. The spectrum of MASLD includes steatosis, metabolic dysfunction-associated steatohepatitis (MASH, previously NASH), fibrosis, cirrhosis and MASH-related hepatocellular carcinoma (HCC). This joint EASL-EASD-EASO guideline provides an update on definitions, prevention, screening, diagnosis and treatment for MASLD. Case-finding strategies for MASLD with liver fibrosis, using non-invasive tests, should be applied in individuals with cardiometabolic risk factors, abnormal liver enzymes, and/or radiological signs of hepatic steatosis, particularly in the presence of type 2 diabetes (T2D) or obesity with additional metabolic risk factor(s). A stepwise approach using blood-based scores (such as FIB-4) and, sequentially, imaging techniques (such as transient elastography) is suitable to rule-out/in advanced fibrosis, which is predictive of liver-related outcomes. In adults with MASLD, lifestyle modification - including weight loss, dietary changes, physical exercise and discouraging alcohol consumption - as well as optimal management of comorbidities - including use of incretin-based therapies (e.g. semaglutide, tirzepatide) for T2D or obesity, if indicated - is advised. Bariatric surgery is also an option in individuals with MASLD and obesity. If locally approved and dependent on the label, adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥2) should be considered for a MASH-targeted treatment with resmetirom, which demonstrated histological effectiveness on steatohepatitis and fibrosis with an acceptable safety and tolerability profile. No MASH-targeted pharmacotherapy can currently be recommended for the cirrhotic stage. Management of MASH-related cirrhosis includes adaptations of metabolic drugs, nutritional counselling, surveillance for portal hypertension and HCC, as well as liver transplantation in decompensated cirrhosis.

Intermittent fasting (IF) is an intervention that involves not only dietary modifications but also behavioral changes with the main core being a period of fasting alternating with a period of controlled feeding. The duration of fasting differs from one regimen to another. Ramadan fasting (RF) is a religious fasting for Muslims, it lasts for only one month every one lunar year. In this model of fasting, observers abstain from food and water for a period that extends from dawn to sunset. The period of daily fasting is variable (12-18 hours) as Ramadan rotates in all seasons of the year. Consequently, longer duration of daily fasting is observed during the summer. In fact, RF is a peculiar type of IF. It is a dry IF as no water is allowed during the fasting hours, also there are no calorie restrictions during feeding hours, and the mealtime is exclusively nighttime. These three variables of the RF model are believed to have a variable impact on different liver diseases. RF was evaluated by different observational and interventional studies among patients with non-alcoholic fatty liver disease and it was associated with improvements in anthropometric measures, metabolic profile, and liver biochemistry regardless of the calorie restriction among lean and obese patients. The situation is rather different for patients with liver cirrhosis. RF was associated with adverse events among patients with liver cirrhosis irrespective of the underlying etiology of cirrhosis. Cirrhotic patients developed new ascites, ascites were increased, had higher serum bilirubin levels after Ramadan, and frequently developed hepatic encephalopathy and acute upper gastrointestinal bleeding. These complications were higher among patients with Child class B and C cirrhosis, and some fatalities occurred due to fasting. Liver transplant recipients as a special group of patients, are vulnerable to dehydration, fluctuation in blood immunosuppressive levels, likelihood of deterioration and hence observing RF without special precautions could represent a real danger for them. Patients with Gilbert syndrome can safely observe RF despite the minor elevations in serum bilirubin reported during the early days of fasting.

The transition from compensated to decompensated cirrhosis is crucial, drastically reducing prognosis from a median survival of over 10 years to 2 years. There is currently an unmet need to accurately predict decompensation. We systematically reviewed and meta-analysed data regarding biomarker use to predict decompensation in individuals with compensated cirrhosis.

PubMed and EMBASE database searches were conducted for all studies from inception until February 2024. The study was carried out according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Quality of Prognosis Studies framework was used to assess the risk of bias. The meta-analysis was conducted with a random effects model using STATA software.

Of the 652 studies initially identified, 63 studies (n=31 438 patients) were included in the final review, examining 49 biomarkers. 25 studies (40%) were prospective with the majority of studies looking at all-cause decompensation (90%). The most well-studied biomarkers were platelets (n=17), Model for End-Stage Liver Disease (n=17) and albumin (n=16). A meta-analysis revealed elevated international normalised ratio was the strongest predictor of decompensation, followed by decreased albumin. However, high statistical heterogeneity was noted (l2 result of 96.3%). Furthermore, 21 studies were assessed as having a low risk of bias (34%), 26 (41%) moderate risk and 16 (25%) high risk.

This review highlights key biomarkers that should potentially be incorporated into future scoring systems to predict decompensation. However, future biomarker studies should be conducted with rigorous and standardised methodology to ensure robust and comparable data.

The study aims to determine the prognostic impact of obesity, sarcopenic obesity, and dynapenic obesity in patients with chronic liver disease.

This retrospective observational study enrolled patients with chronic hepatitis (n = 746) and liver cirrhosis (n = 434) without hepatocellular carcinoma at entry. The patients were evaluated for sarcopenia and obesity between April 2016 and April 2022. Obesity was defined as a body mass index of ≥ 25 kg/m2. Sarcopenic obesity was defined as low skeletal muscle mass (pre-sarcopenia) with obesity and dynapenic obesity was defined as low muscle strength (dynapenia) with obesity. The effects of obesity on survival were evaluated retrospectively.

The mean observation period was 2.5 years. Obesity, sarcopenic obesity, and dynapenic obesity were found in 271 (45.5%), 17 (2.9%), and 21 (3.5%) men, and 261 (44.7%), 59 (10.1%), and 53 (9.1%) women, respectively. A multivariate Cox proportional hazards model revealed that Child-Pugh class, dynapenia (hazard ratio [HR] 3.89), elderly (≥ 65 years old) (HR 2.11), and obesity (HR 0.58) were independently associated with overall survival (OS). However, neither sarcopenic nor dynapenic obesity were associated with OS. In patients with cirrhosis, the OS of the obese group was significantly higher than that of the non-obese group. The effect of obesity on OS was significant in elderly patients, but not in younger patients.

Sarcopenic and dynapenic obesity seem unrelated to the prognosis of patients with chronic liver disease. Obesity has a positive effect on the prognosis of elderly patients with cirrhosis.

Measurement of hepatic venous pressure gradient (HVPG) effectively mirrors the severity of portal hypertension (PH) and offers valuable insights into prognosis of liver disease, including the risk of decompensation and mortality. Additionally, HVPG offers crucial information about treatment response to nonselective beta-blockers and other medications, with its utility demonstrated in clinical trials in patients with PH. Despite the widespread dissemination and validation of noninvasive tests, HVPG still holds a significant role in hepatology. Physicians treating patients with liver diseases should comprehend the HVPG measurement procedure, its applications, and how to interpret the results and potential pitfalls.

Cirrhosis is a chronic liver disease with severe consequences for a patient's health and survival. Exercise is an essential therapeutic strategy for both cirrhosis prevention and treatment. On the other hand, information regarding the present status of exercise-related research in cirrhosis is limited. Therefore, this study seeks to close the information gap in the scientific literature by using bibliometric techniques to analyze the trends, focal points, and cutting-edge research areas on exercise and cirrhosis. On September 22, 2023, research articles and reviews on exercise intervention for cirrhosis were obtained and downloaded from the Web of Science Core Collection (WoSCC). Subsequently, we employed CiteSpace (version 6.1.R6) to conduct bibliometric and knowledge graph analyses. 588 papers in 301 scholarly journals were written by 673 authors from 460 institutions spread over 63 countries and regions. The most productive nation among them is the United States. Not only is Zobair M. Younossi 1 of the most prolific writers, but he also receives the most co-citations. Most articles were published by the University of Michigan in the US, with the University of Alberta in Canada coming in second. Meanwhile, the WORLD JOURNAL OF GASTROENTEROLOGY has the most published articles, whereas HEPATOLOGY has the greatest number of co-citations. Apart from the theme words, the most frequently utilized keywords were "quality of life," "insulin resistance," and "mortality." Future research may concentrate on "obesity," "sarcopenia," and "Mediterranean diet," according to the analysis of keyword emergence. CiteSpace is used in this work to visually represent the topic of exercise intervention in cirrhosis, offering valuable information to researchers regarding the field's current status and possible future direction.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), is defined as steatotic liver disease (SLD) in the presence of one or more cardiometabolic risk factor(s) and the absence of harmful alcohol intake. The spectrum of MASLD includes steatosis, metabolic dysfunction-associated steatohepatitis (MASH, previously NASH), fibrosis, cirrhosis and MASH-related hepatocellular carcinoma (HCC). This joint EASL-EASD-EASO guideline provides an update on definitions, prevention, screening, diagnosis and treatment for MASLD. Case-finding strategies for MASLD with liver fibrosis, using non-invasive tests, should be applied in individuals with cardiometabolic risk factors, abnormal liver enzymes, and/or radiological signs of hepatic steatosis, particularly in the presence of type 2 diabetes (T2D) or obesity with additional metabolic risk factor(s). A stepwise approach using blood-based scores (such as FIB-4) and, sequentially, imaging techniques (such as transient elastography) is suitable to rule-out/in advanced fibrosis, which is predictive of liver-related outcomes. In adults with MASLD, lifestyle modification - including weight loss, dietary changes, physical exercise and discouraging alcohol consumption - as well as optimal management of comorbidities - including use of incretin-based therapies (e.g. semaglutide, tirzepatide) for T2D or obesity, if indicated - is advised. Bariatric surgery is also an option in individuals with MASLD and obesity. If locally approved and dependent on the label, adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥2) should be considered for a MASH-targeted treatment with resmetirom, which demonstrated histological effectiveness on steatohepatitis and fibrosis with an acceptable safety and tolerability profile. No MASH-targeted pharmacotherapy can currently be recommended for the cirrhotic stage. Management of MASH-related cirrhosis includes adaptations of metabolic drugs, nutritional counselling, surveillance for portal hypertension and HCC, as well as liver transplantation in decompensated cirrhosis.

The obesity epidemic has led to an increase in the proportion of patients with chronic liver disease due to metabolic associated steatosic liver disease and in the prevalence of obesity in patients with cirrhosis. Metabolic and bariatric surgery (MBS) has been proven to determine weight loss, obesity-related medical problems remission, and liver steatosis, inflammation, and fibrosis improvement. However, cirrhosis and portal hypertension are well-known risk factors for increased morbidity and mortality after surgery. The aim of this study is to evaluate the safety of MBS in patients with compensated advanced chronic liver disease (cALCD) and clinically significant portal hypertension (CSPH).

This is an international, multicentric, retrospective study on 63 individuals affected by obesity with cALCD and CSPH who underwent MBS in tertiary referral centers with experts hepatobiliary surgeons between January 2010 and October 2022. The primary endpoint was postoperative mortality at 90 days. The secondary endpoints included postoperative weight loss at last follow-up and postoperative complication rate. In addition, the authors performed subgroup analyses of Child-Pugh (A vs. B) score, MELD (≤9 vs. >9) score, and type of surgery.

One patient (1.6%) experienced gastric leakage and mortality. There were three (5%) reported cases of portal vein thrombosis, two (3%) postoperative acute renal failure, and one (1.6%) postoperative encephalopathy. Child-Pugh score A resulted to be a protective factor for intraoperative bleeding requiring transfusion at univariate analysis (OR: 0.73, 95% CI: 0.55-0.97, P =0.046) but not at multivariate analysis. MELD>9 score and the type of surgery did not result to be a risk factor for any postoperative complication.

MBS is safe in patients with cALCD and CSPH performed in tertiary bariatric referral centers with hepatobiliary expert surgeons. Larger, prospective studies with longer follow-up periods are needed to confirm these results.

Individuals with cirrhosis experience higher morbidity and mortality rates than the general population, irrespective of the type or scope of surgery. This increased risk is attributed to adverse effects of liver disease, encompassing coagulation dysfunction, altered metabolism of anesthesia and sedatives, immunologic dysfunction, hemorrhage related to varices, malnutrition and frailty, impaired wound healing, as well as diminished portal blood flow, overall hepatic circulation, and hepatic oxygen supply during surgical procedures. Therefore, a frequent clinical dilemma is whether surgical interventions should be pursued in patients with cirrhosis. Several risk scores are widely used to aid in the decision-making process, each with specific advantages and limitations. This review aims to discuss the preoperative risk factors in patients with cirrhosis, describe and compare surgical risk assessment models used in everyday practice, provide insights into the surgical risk according to the type of surgery and present recommendations for optimizing those with cirrhosis for surgical procedures. As the primary focus is on currently available risk models, the review describes the predictive value of each model, highlighting its specific advantages and limitations. Furthermore, for models that do not account for the type of surgical procedure to be performed, the review suggests incorporating both patient-related and surgery-related risks into the decision-making process. Finally, we provide an algorithm for the preoperative assessment of patients with cirrhosis before elective surgery as well as guidance perioperative management.

Non-invasive tests to assess the probability of clinically significant portal hypertension (CSPH) - including the ANTICIPATE±NASH models based on liver stiffness measurement and platelet count±BMI, and the von Willebrand factor antigen to platelet count ratio (VITRO) - have fundamentally changed the management of compensated advanced chronic liver disease (cACLD). However, their prognostic utility has not been compared head-to-head to the gold standard for prognostication in cACLD, i.e. the hepatic venous pressure gradient (HVPG).

Patients with cACLD (liver stiffness measurement ≥10 kPa) who underwent advanced characterization via same-day HVPG/non-invasive test assessment from 2007-2022 were retrospectively included. Long-term follow-up data on hepatic decompensation was recorded.

Four hundred and twenty patients with cACLD of varying etiologies, with a CSPH prevalence of 67.6%, were included. The cumulative incidence of hepatic decompensation at 1 and 2 years was 4.7% and 8.0%, respectively. HVPG, VITRO, and ANTICIPATE±NASH-CSPH-probability showed similar time-dependent prognostic value (AUROCs 0.683-0.811 at 1 year and 0.699-0.801 at 2 years). In competing risk analyses adjusted for MELD score and albumin, HVPG (adjusted subdistribution hazard ratio [aSHR] 1.099 [95% CI 1.054-1.150] per mmHg; p <0.001), or VITRO (aSHR 1.134 [95% CI 1.062-1.211] per unit; p <0.001), or ANTICIPATE±NASH-CSPH-probability (aSHR 1.232 [95% CI 1.094-1.387] per 10%; p <0.001) all predicted first decompensation during follow-up. Previously proposed cut-offs (HVPG ≥10 mmHg vs. <10 mmHg, VITRO ≥2.5 vs. <2.5, and ANTICIPATE-CSPH probability ≥60% vs. <60%) all accurately discriminated between patients at negligible risk and those at substantial risk of hepatic decompensation.

The prognostic performance of ANTICIPATE±NASH-CSPH-probability and VITRO is comparable to that of HVPG, supporting their utility for identifying patients who may benefit from medical therapies to prevent first hepatic decompensation.

Non-invasive tests have revolutionized the diagnosis and management of clinically significant portal hypertension in patients with compensated advanced chronic liver disease (cACLD). However, limited data exists regarding the prognostic utility of non-invasive tests in direct comparison to the gold standard for prognostication in cACLD, i.e. the hepatic venous pressure gradient. In our study including 420 patients with cACLD, the ANTICIPATE±NASH model and VITRO yielded similar AUROCs to hepatic venous pressure gradient for hepatic decompensation within 1 to 2 years. Thus, non-invasive tests should be applied and updated in yearly intervals in clinical routine to identify patients at short-term risk, thereby identifying patients who may benefit from treatment aimed at preventing hepatic decompensation.

Obesity and liver cirrhosis represent significant health challenges, often leading to various complications.

This prospective study aimed to investigate the impact of a four-year bariatric intervention, focusing on adherence to the Mediterranean Diet, on anthropometric, hematologic, and biochemical parameters in obese patients with compensated liver cirrhosis. Additionally, the study evaluated the concurrent contribution of weight loss to these health indicators.

The study involved 62 patients with compensated liver cirrhosis (mean age 65.87 ± 6 years) and 44 healthy controls (mean age 59.11 ± 8 years), all with a BMI > 30 kg/m2. Both groups underwent a weight loss intervention based on the Mediterranean diet, with a four-year follow-up. Anthropometric, biochemical and hematologic parameters were evaluated at several time points during the study and their statistical significance was assessed.

Anthropometric parameters, including weight, BMI, waist and hip circumference, percentage of fat mass, and handgrip strength, exhibited significant improvements (p < 0.05), particularly within the first year of the intervention. Liver function tests and lipid profiles of the patients also showed significant enhancements (p < 0.05). Hematological and biochemical indices, such as hematocrit and ferritin, experienced discreet improvements in the patient cohort (p < 0.05).

This study highlights the potential of a structured bariatric intervention rooted in the Mediterranean diet to positively influence the health of obese patients with compensated liver cirrhosis. The observed improvements in anthropometric, biochemical, and hematologic parameters, particularly within the first year of the intervention, suggest the importance of dietary modifications in managing the health of this patient population.

In recent decades, following the spread of obesity, metabolic dysfunction has come to represent the leading cause of liver disease. The classical clinical presentation of the cirrhotic patient has, therefore, greatly changed, with a dramatic increase in subjects who appear overweight or obese. Due to an obesogenic lifestyle (lack of physical activity and overall malnutrition, with an excess of caloric intake together with a deficit of proteins and micronutrients), these patients frequently develop a complex clinical condition defined as sarcopenic obesity (SO). The interplay between cirrhosis and SO lies in the sharing of multiple pathogenetic mechanisms, including malnutrition/malabsorption, chronic inflammation, hyperammonemia and insulin resistance. The presence of SO worsens the outcome of cirrhotic patients, affecting overall morbidity and mortality. International nutrition and liver diseases societies strongly agree on recommending the use of food as an integral part of the healing process in the comprehensive management of these patients, including a reduction in caloric intake, protein and micronutrient supplementation and sodium restriction. Based on the pathophysiological paths shared by cirrhosis and SO, this narrative review aims to highlight the nutritional interventions currently advocated by international guidelines, as well as to provide hints on the possible role of micronutrients and nutraceuticals in the treatment of this multifaceted clinical condition.

Determining the effects of pre-liver transplant (LT) BMI independent of underlying ascites on the post-LT outcomes of patients with nonalcoholic steatohepatitis (NASH) is needed to clarify the paradoxical and protective effects of obesity on post-LT endpoints. In order to accomplish this, we used graded severities of ascites to stratify the NASH-LT population and to perform an ascites-specific strata analysis with differing pre-LT BMI levels.

2005-2019 United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research (STAR) database was queried to select patients with NASH, who were categorized into specific sets of ascites severity: no ascites (n = 1188), mild ascites (n = 4463), and moderate ascites (n = 3525). Then, BMI classification (underweight: < 18.5, normal: 18.5-25, overweight: 25-30, obese: ≥ 30 kg/m2) was used to stratify each ascites-specific group and to compare to the post-LT mortality endpoints. Those under 18 years old and those who received living/multi-organ transplants were excluded.

Among each ascites category, there were the following numbers of normal, underweight, overweight, and obese BMI patients respectively; no ascites: 161, 4, 359, 664; mild ascites: 643, 28, 1311, 2481; and moderate ascites: 529, 25, 1030, 1941. The obese BMI cohort was at a lower risk of all-cause mortality compared to recipients with normal BMI with mild ascites (aHR: 0.79, 95% Confidence Interval (CI) 0.65-0.94, p-value = 0.010; case-incidence 47.10 vs 56.81 deaths per 1000 person-years) and moderate ascites (aHR: 0.77, 95% CI 0.63-0.94, p-value = 0.009; case-incidence 53.71 vs 66.17 deaths per 1000 person-years). In addition, the overweight BMI cohort with mild ascites demonstrated a lower hazard of all-cause mortality (aHR: 0.80, 95% CI 0.66-0.97, p-value = 0.03; case-incidence 49.09 vs 56.81 deaths per 1000 person-years). There was no difference in graft failure for the three BMI groups (underweight, overweight, and obese) in comparison to normal BMI. Furthermore, the overweight BMI group with mild ascites cohort demonstrated a lower hazard of death due to general infectious causes (aHR: 0.51, 95% CI 0.32-0.83, p = 0.006; case-incidence 6.12 vs 11.91 deaths per 1000 person-years) and sepsis (aHR: 0.49, 95% CI 0.27-0.86, p = 0.01; case-incidence 4.31 vs 8.50 deaths per 1000 person-years).

The paradoxical effects of obesity in reducing the risks of all-cause death appears to be in part modulated by ascites. The current study emphasizes the need to evaluate BMI with concomitant ascites severity pre-LT to accurately prognosticate post-LT outcomes when evaluating NASH patients with advanced liver disease.

The prediction of clinical outcomes in patients with chronic hepatitis B (CHB) is paramount for effective management. This study aimed to evaluate the prognostic value of computed tomography (CT) analysis using deep learning algorithms in patients with CHB.

This retrospective study included 2,169 patients with CHB without hepatic decompensation who underwent contrast-enhanced abdominal CT for hepatocellular carcinoma (HCC) surveillance between January 2005 and June 2016. Liver and spleen volumes and body composition measurements including subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and skeletal muscle indices were acquired from CT images using deep learning-based fully automated organ segmentation algorithms. We assessed the significant predictors of HCC, hepatic decompensation, diabetes mellitus (DM), and overall survival (OS) using Cox proportional hazard analyses.

During a median follow-up period of 103.0 months, HCC (n=134, 6.2%), hepatic decompensation (n=103, 4.7%), DM (n=432, 19.9%), and death (n=120, 5.5%) occurred. According to the multivariate analysis, standardized spleen volume significantly predicted HCC development (hazard ratio [HR]=1.01, P=0.025), along with age, sex, albumin and platelet count. Standardized spleen volume (HR=1.01, P<0.001) and VAT index (HR=0.98, P=0.004) were significantly associated with hepatic decompensation along with age and albumin. Furthermore, VAT index (HR=1.01, P=0.001) and standardized spleen volume (HR=1.01, P=0.001) were significant predictors for DM, along with sex, age, and albumin. SAT index (HR=0.99, P=0.004) was significantly associated with OS, along with age, albumin, and MELD.

Deep learning-based automatically measured spleen volume, VAT, and SAT indices may provide various prognostic information in patients with CHB.

Non-selective betablockers (NSBBs) reduce the risk of hepatic decompensation in patients with compensated advanced chronic liver disease (cACLD). Metabolic co-morbidities (MetC) are increasingly observed in cACLD patients.

To investigate the impact of MetC on the haemodynamic effects of NSBB and hepatic decompensation in cACLD.

cACLD patients undergoing paired hepatic venous pressure gradient (HVPG) measurements before/under NSBB therapy were retrospectively considered for this study. We recorded baseline characteristics on MetC (obesity, dyslipidaemia and diabetes), as well as hepatic decompensation and liver-related mortality during follow-up.

We included 92 patients (Child-A n = 80, 87%; Child-B n = 12, 13%). MetC were found in 34 (37%) patients: 19 (20.7%) with obesity, 14 (15.2%) with dyslipidaemia and 23 (34.8%) with diabetes. The median baseline HVPG of 18 (IQR:15-21) mmHg decreased to 15 (IQR:9-12) mmHg under NSBB. HVPG-response (decrease ≥10% or to ≤12 mmHg) was achieved in 60 (65.2.%) patients. Patients with diabetes (OR: 0.35, p = 0.021) and higher BMI (OR: 0.89 per kg/m2 , p = 0.031) were less likely to achieve HVPG-response. During a median follow-up of 2.3 (0.5-4.2) years, 18 (19.5%) patients experienced hepatic decompensation. Child-B (adjusted subdistribution hazard ratio, aSHR: 4.3 [95% CI:1.5-12.2], p = 0.006), HVPG-response (aSHR: 0.3 [95% CI:0.1-0.9], p = 0.037) and diabetes (aSHR: 2.8 [95% CI:1.1-7.2], p = 0.036) were independently associated with hepatic decompensation.

In patients with cACLD, diabetes and a higher BMI impair the HVPG-response to NSBB. Furthermore, diabetes-independently from Child B and lack of HVPG-response-increases the risk of hepatic decompensation.