Accurate prediction of disease severity and prognosis are challenging in patients with cirrhosis. We evaluated whether the deep learning-based AI-Cirrhosis-ECG (ACE) score could detect hepatic decompensation and predict clinical outcomes in cirrhosis.

We analyzed 2,166 ECGs from 472 patients in a retrospective Mayo Clinic cohort, 420 patients in a prospective Mayo transplant cohort, and 341 patients in an external validation cohort from Hospital Clínic de Barcelona. The ACE score's performance was assessed using receiver-operating characteristic analysis for decompensation detection and competing risks Cox regression for outcome prediction.

The ACE score showed high accuracy in detecting hepatic decompensation (area under the curve 0.933, 95% CI: 0.923-0.942) with 88.0% sensitivity and 84.3% specificity at an optimal threshold of 0.25. In multivariable analysis, each 0.1-point increase in ACE score was independently associated with increased risk of liver-related death (hazard ratio [HR] 1.44, 95% CI 1.32-1.58, p <0.001). Adding ACE to model for end-stage liver disease-sodium significantly improved prediction of adverse outcomes across all cohorts (c-statistics: retrospective cohort 0.903 vs. 0.844; prospective cohort 0.779 vs. 0.735; external validation 0.744 vs. 0.732; all p <0.001).

The ACE score accurately identifies hepatic decompensation and independently predicts liver-related outcomes in cirrhosis. This non-invasive tool enhances current prognostic models and may improve risk stratification in cirrhosis management.

This study demonstrates the potential of artificial intelligence to enhance prognostication in liver disease, addressing the critical need for improved risk stratification in cirrhosis management. The AI-Cirrhosis-ECG (ACE) score, derived from widely available ECGs, shows promise as a non-invasive tool for detecting hepatic decompensation and predicting liver-related outcomes, which could significantly impact clinical decision-making and resource allocation in hepatology. These findings are particularly important for hepatologists, transplant surgeons, and patients with cirrhosis, as they offer a novel approach to complement existing prognostic models such as model for end-stage liver disease-sodium. In practical terms, the ACE score could be integrated into routine clinical assessments to provide more accurate risk predictions, potentially improving the timing of interventions, optimizing transplant listing decisions, and ultimately enhancing patient outcomes. However, further validation in diverse populations and integration with other established predictors is necessary before widespread clinical implementation.

Cirrhosis is a dynamic disease process leading to liver-related death, which has increased by over 65% over the last decade. Unpredictable hepatic decompensation complications are a major source of morbidity and mortality. Thus, accurately characterizing disease progression through discrete stages of cirrhosis is critical towards implementing timely intervention and liver transplant (LT) waitlisting.

A retrospective, longitudinal, population-cohort study of adult patients with cirrhosis from a US metropolitan area (2006-2012) was conducted. Clinical diagnoses were defined by ICD-9 and CPT codes. Cirrhosis stages were defined as: compensated without portal hypertension (Stage 1), compensated with portal hypertension (Stage 2), variceal bleeding (Stage 3), hepatic encephalopathy (Stage 4a), ascites (Stage 4b), and ≥2 different decompensating complications (Stage 5). Multivariate Fine-Gray competing risk survival analysis adjusted for clinicodemographic covariates.

Among 12,196 patients with cirrhosis, the mean (±SD) age was 56.8 (±11.7) years with a follow-up time of 2.35 (±1.81) years. A novel 5-stage disease progression framework was used. The 1-year mortality rates for each stage were 7.3% for Stage 1, 5.4% for Stage 2, 11.4% for Stage 3, 10.0% for Stage 4a, 20.2% for Stage 4b, and 43.8% for Stage 5. Compared to those in Stage 1, Stage 3 (sHR:1.83, 95% CI:1.36-2.48, P<0.001), Stage 4b (sHR:1.45, 95% CI:1.23-1.70, P<0.001), and Stage 5 (sHR:1.95, 95% CI:1.71-2.23, P<0.001) patients had higher risks of mortality. Additional disease progression rates were identified.

Even among patients with compensated cirrhosis, the 1-year mortality rate was as high as 7.3% and subsequently increases with each decompensation complication. This one-year mortality rate is higher than 5-years mortality rate reported in previously known non-US studies. The highest associated risk of death was observed among patients with ≥2 different decompensating complications (95.2%), variceal bleeding (83.2%) and ascites (44.9%). Overall, patients in advanced stages of cirrhosis were more likely to die than they were to receive a LT, suggesting that patients should be referred and waitlisted for LT earlier in the disease process.

The role of diet in reducing the burden of liver disease and mortality attributed to cirrhosis is very imperative. The present study scrutinized the relationship between dietary advanced glycation end products (AGEs) and mortality in patients with cirrhosis. This research was a prospective cohort study on 166 ambulatory cirrhotic patients who had been diagnosed with cirrhosis for a maximum of six months. Follow-up of patients continued for 5 years until May 2024. To determine the incidence of mortality in the quartiles of dietary AGEs, cox regression models were used with the adjustment of potential confounding variables. Although the first model of the analysis by adjusting the results for age and sex failed to show a significant increase in the risk of mortality in patients (HRQ4 vs. Q1 = 2.64; 95% CI = 0.9-7.5, P trend = 0.075), after adjusting the results for further confounders in the second (HRQ4 vs. Q1 = 3.56; 95% CI = 1.1-11.6, P trend = 0.040) and third (HRQ4 vs. Q1 = 3.3; 95% CI = 1.79-13.7, P trend = 0.048) models, the P trend for the risk of mortality during the quartiles of AGEs became significant. In addition, along with increasing trend of dietary AGEs, the number of deaths increased significantly (P = 0.024). Higher mortality risk was generally attributed to higher dietary AGEs in patients with cirrhosis.

Immunosuppressive therapy in decompensated cirrhotic patients with an indication for liver transplantation (LT) is controversial. This study aims to evaluate transplant-free survival rates in patients diagnosed with decompensated autoimmune hepatitis (AIH) with and without immunosuppressants (IS) treatment, and to identify predictors of mortality or LT. We retrospectively analyzed LT-evaluated consecutive patients with decompensated AIH at a single center, between 2013 and 2021. Patients were categorized into IS (IS Group) and non-IS (No IS Group). Survival curves for the 2 groups were evaluated using the Kaplan-Meier method, and differences were compared using the Log-rank test. Multiple regression analysis was conducted using Cox test. A total of 125 consecutive patients (mean age: 36.4 years; 81.6% female) were evaluated. The median transplant-free survival in the IS Group (72/125) were 22.6 months vs 6.57 months in the No IS Group (53/125) (P = .002). Cox-regression analysis revealed associations between moderate/severe ascites (hazard ratio [HR] = 2.37, 95% CI = 1.48-3.80, P = <.001) and MELD-Na (HR = 1.12, 95% CI = 1.08-1.16, P = <.001) with transplantation or death, while immunosuppression treatment acted protectively (HR = 0.55, 95% CI = 0.86-0.85, P = .008). Analyzing patients with MELD >22 (27/125) showed a loss of IS protective effect (OR = 0.45, 95% CI = 0.17-1.20, P = .11), and the presence of moderate/severe ascites increased the risk of death/LT (HR = 5.86, 95% CI = 1.26-27.2, P = .02). Autoimmune decompensated cirrhosis is associated with high overall mortality, and IS improves the transplant-free survival rate. In patients with MELD-Na >22, treatment ceases to be beneficial, especially if they have moderate/severe ascites. These patients, if receiving immunosuppression, may be disadvantaged in the possibility of accessing LT.

The objective of this study was to identify the association between tooth extraction and occurrence of spontaneous bacterial peritonitis (SBP) and to assess delayed soft tissue healing of extraction sockets in patients with cirrhosis.

One hundred nineteen participants awaiting liver transplantation who required tooth extraction were included. Seven days before the surgery, the patients underwent panoramic radiography and laboratory examinations. Soft tissue healing was evaluated 7 days after the tooth extraction and medical records were checked after 21 days for development of SBP. The relationship between predictive factors and outcomes was assessed by using multiple binomial logistic regression.

One hundred ninety-five teeth were extracted, resulting in 146 alveolar wounds, in which the majority (47%) consisted of alveolar sockets of multirooted teeth. One participant was diagnosed with SBP (Escherichia coli [E. coli]) and another diagnosed with bacterascites (Streptococcus viridans [S. viridans] group), occurring 11 and 6 days after tooth extraction. Poor soft tissue healing was observed in 20 (13.7%) patients, which was correlated to 2 risk factors, that is, jaundice (P = .007, adjusted odds ratio [OR] = 4.91, 95% confidence interval [CI] = 1.56-15.47) and moderate neutropenia (P = .048, adjusted OR = 13.99, 95% CI = 1.02-192.07).

No association was found between tooth extraction and SBP in patients with cirrhosis. The delayed soft tissue healing was related to jaundice (hyperbilirubinemia) and moderate neutropenia.

In response to direct-acting antivirals (DAAs) therapy, patients who experience a decrease in hepatic venous pressure gradient (HVPG) considerably reduce liver complications and have increased survival. This study aimed to assess the metabolomic changes associated with the changes in HVPG from the start of DAA therapy until 48 weeks after effective DAA therapy in patients with advanced HCV-related cirrhosis.

We carried out a multicenter longitudinal study in 31 patients with advanced hepatitis C virus (HCV)-related cirrhosis. We performed a non-targeted metabolomic analysis using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry, as well as analysis of inflammation-related biomarkers using Luminex technology. The statistical analysis was performed by Generalised Linear Mixed-effects Models (GLMM), correcting for multiple testing.

We found that increases of 2,3-butanediol (AMR = 1.15; q-value = 0.023) and taurocholic acid (AMR = 1.06; q-value < 0.001) were significantly associated with increases in HVPG and inflammatory biomarker levels from before DAA therapy to one year after completion of successful HCV treatment.

These metabolites have a potential role as indicators of portal hypertension evolution.

Despite the slow, progressive nature of NAFLD, the number of patients with NAFLD-related cirrhosis has significantly increased. Although the management of patients with cirrhosis is constantly evolving, improving the prognosis of patients with NAFLD-related cirrhosis is a challenge because it is situated at the crossroads between the liver, the metabolic, and the cardiovascular diseases. Therefore, the therapeutic interventions should not only target the liver but also the associated cardiometabolic conditions and should be adapted accordingly. The objective of the current review is to critically discuss the particularities in the management of patients with NAFLD-related cirrhosis. We relied on the recommendations of scientific societies and discussed them in the specific context of NAFLD cirrhosis and the surrounding cardiometabolic milieu. Herein, we covered the following aspects: (1) the weight loss strategies through lifestyle interventions to avoid sarcopenia and improve portal hypertension; (2) the optimal control of metabolic comorbidities in particular type 2 diabetes aimed not only to improve cardiovascular morbidity/mortality but also to lower the incidence of cirrhosis-related complications (we discussed various aspects related to the safety of oral antidiabetic drugs in cirrhosis); (3) the challenges in performing bariatric surgery in patients with cirrhosis related to the portal hypertension and the risk of cirrhosis decompensation; (4) the particularities in the diagnosis and management of the portal hypertension and the difficulties in managing patients awaiting for liver transplantation; and (5) the difficulties in developing drugs and conducting clinical trials in patients with NAFLD-related cirrhosis. Moreover, we discussed the emerging options to overcome these obstacles.

Agile scores, including liver stiffness measurements (LSM) and routine clinical/laboratory biomarkers, have been developed for advanced fibrosis (F≥3) and cirrhosis (F4), respectively, in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). We independently validated the diagnostic accuracy of these scores in MASLD, alcohol-related liver disease (ALD) and chronic hepatitis B or C (CHB/C) and assessed them in clinical algorithms with FIB-4 and LSM.

We included 4,243 patients (MASLD: 912, ALD: 386, CHB: 597, CHC: 2,348) with LSM, liver biopsy and laboratory tests within 6 months. FIB-4, Agile 3+ and Agile 4 scores were calculated.

For F≥3, the diagnostic accuracy of Agile 3+ and LSM were similar in MASLD (AUC: 0.86 vs. 0.86, p = 0.831) and ALD (0.92 vs. 0.94, p = 0.123). For cirrhosis, Agile 4 was similar to LSM in MASLD (0.89 vs. 0.90, p = 0.412) and ALD (0.94 vs. 0.95, p = 0.513). Agile 3+/4 performed worse than LSM in CHB/C. Using predefined dual thresholds of 90% sensitivity/specificity, correct classification rates in MASLD were 66% vs. 61% using Agile 3+ vs. LS dual cut-offs and 71% vs. 67% in ALD, respectively. When using Agile 3+ or LSM as a second step after FIB-4 >1.3, correct classification rates were higher with Agile 3+ than LSM, both for MASLD (75% vs. 71%) and ALD (76% vs. 72%), with fewer indeterminate results. Positive agreement of LSM and Agile 3+/4 significantly increased the specificity of a diagnosis of advanced fibrosis/cirrhosis.

Agile 3+ and Agile 4 have equal diagnostic accuracy with LSM in both MASLD and ALD but result in fewer indeterminate results. Sequential use of FIB-4 and Agile 3+/4 or concurrent Agile 3+/4 and LSM can be used to further optimize F≥3 diagnosis.

As of today, it is accepted that there will be no single non-invasive test or an isolated cut-off for identifying patients with advanced chronic liver disease. Here, we confirmed that Agile 3+ and Agile 4 scores are useful alternatives to simple liver stiffness measurement in diagnosing advanced fibrosis/cirrhosis in steatotic liver disease, but they do not perform as well in chronic viral hepatitis. Agile scores can help optimize the diagnosis of advanced fibrosis/cirrhosis in a dual cut-off strategy by reducing the number of indeterminate results either alone or in a sequential strategy after FIB-4. The combination of Agile scores and liver stiffness measurement can further increase our confidence in a positive diagnosis of advanced fibrosis/cirrhosis. These novel combination strategies can be useful tools to predict the likelihood of advanced stages of liver disease with the highest possible accuracy in a secondary/tertiary healthcare setting.

Hepatorenal syndrome (HRS) is the most prevalent form of acute kidney injury in cirrhotic patients. It is characterized by reduced renal blood flow and represents the most severe complication in cirrhotic patients with advanced disease. Previous research has indicated that antioxidants can delay the onset of a hyperdynamic circulatory state in cirrhosis and improve renal function in HRS patients. Regular omega-3 supplementation has significantly reduced the risk of liver disease. This supplementation could represent an additional therapy for individuals with HRS.

To evaluated the antioxidant effect of omega-3 polyunsaturated fatty acid supplementation on the kidneys of cirrhotic rats.

Secondary biliary cirrhosis was induced in rats by biliary duct ligation (BDL) for 28 d. We used 24 male Wistar rats divided into the following groups: I (control); II (treated with omega-3, 1 g/kg of body weight); III (BDL treated with omega-3, 1 g/kg of body weight); and IV (BDL without treatment). The animals were killed by overdose of anesthetic; the kidneys were dissected, removed, frozen in liquid nitrogen, and stored in a freezer at -80℃ for later analysis. We evaluated oxidative stress, nitric oxide (NO) metabolites, DNA damage by the comet assay, cell viability test, and apoptosis in the kidneys. Data were analyzed by one-way analysis of variance, and means were compared using the Tukey test, with P ≤ 0.05.

Omega-3 significantly decreased the production of reactive oxygen species (P < 0.001) and lipoperoxidation in the kidneys of cirrhotic rats treated with omega-3 (P < 0.001). The activity of the antioxidant enzymes superoxide dismutase and catalase increased in the BDL+omega-3 group compared to the BDL group (P < 0.01). NO production, DNA damage, and caspase-9 cleavage decreased significantly in the omega-3-treated BDL group. There was an increase in mitochondrial electrochemical potential (P < 0.001) in BDL treated with omega-3 compared to BDL. No changes in the cell survival index in HRS with omega-3 compared to the control group (P > 0.05) were observed.

The study demonstrates that omega-3 can protect cellular integrity and function by increasing antioxidant enzymes, inhibiting the formation of free radicals, and reducing apoptosis.

The objective of this study was to identify the presence of human herpesvirus (HHV) in the plasma and saliva of hepatic-cirrhosis patients and correlate it with clinical data and laboratory tests. This is a pilot, observational, and cross-sectional study.

Specimens of plasma and saliva from 72 cirrhotic individuals were analyzed by means of polymerase chain reaction. The patient population had a mean age of 54.84 years old (SD ± 10) and was 70% males (51/72). Approximately 47% (n = 34) of the patients had leukopenia and HHV was not identified in the plasma specimens. The main species of HHV identified in the saliva were HHV-7 (n = 42, 62%) and Epstein-Barr virus (EBV) (n = 30, 41%). Moreover, there was a significant decrease in the total number of leukocytes and lymphocytes in saliva containing EBV (P = .038 and P = .047, respectively).

The results show that the presence of EBV in the saliva of cirrhotic patients was correlated with their circulating immune status. It may be possible that the immune dysfunction displayed by the cirrhotic patients plays a role in the shedding of EBV into saliva.

Ultrasonography is a noninvasive and widely accessible modality in clinical practice. Recently, ultrasonography has been used to evaluate tissue stiffness; the two representative techniques are transient elastography (FibroScan®) and shear wave elastography. These modalities are now generally used for the assessment of liver fibrosis, the prediction of hepatocarcinogenesis, and determining prognosis. In addition, shear wave elastography is available, not only for the liver but also for various other organs, including the breast and brain. In the breast and brain, shear wave elastography distinguishes malignant lesions from benign ones. Moreover, shear wave elastography can be useful for differentiating between ischemic and hemorrhagic strokes. This review summarizes the recent progress in transient elastography and shear wave elastography of the liver and introduces the advantages of ultrasonographic assessment of tissue stiffness in various organs, including the breast, brain, kidney, heart, thyroid, pancreas, muscle, and bone.

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.

Patients with chronic liver disease (CLD) often develop thrombocytopenia (TCP) as a complication. Severe TCP (platelet count<50×109/L) can increase morbidity and complicate CLD management, increasing bleeding risk during invasive procedures.

To describe the real-world scenario of CLD-associated severe TCP patients' clinical characteristics. To evaluate the association between invasive procedures, prophylactic treatments, and bleeding events in this group of patients. To describe their need of medical resource use in Spain.

This is a retrospective, multicenter study including patients who had confirmed diagnosis of CLD and severe TCP in four hospitals within the Spanish National Healthcare Network from January 2014 to December 2018. We analyzed the free-text information from Electronic Health Records (EHRs) of patients using Natural Language Processing (NLP), machine learning techniques, and SNOMED-CT terminology. Demographics, comorbidities, analytical parameters and characteristics of CLD were extracted at baseline and need for invasive procedures, prophylactic treatments, bleeding events and medical resources used in the follow up period. Frequency tables were generated for categorical variables, whereas continuous variables were described in summary tables as mean (SD) and median (Q1-Q3).

Out of 1,765,675 patients, 1787 had CLD and severe TCP; 65.2% were male with a mean age of 54.7 years old. Cirrhosis was detected in 46% (n=820) of patients and 9.1% (n=163) had hepatocellular carcinoma. Invasive procedures were needed in 85.6% of patients during the follow up period. Patients undergoing procedures compared to those patients without invasive procedures presented higher rates of bleeding events (33% vs 8%, p<0.0001) and higher number of bleedings. While prophylactic platelet transfusions were given to 25.6% of patients undergoing procedures, TPO receptor agonist use was only detected in 3.1% of them. Most patients (60.9%) required at least one hospital admission during the follow up and 14.4% of admissions were due to bleeding events with a hospital length of stay of 6 (3, 9) days.

NLP and machine learning are useful tools to describe real-world data in patients with CLD and severe TCP in Spain. Bleeding events are frequent in those patients who need invasive procedures, even receiving platelet transfusions as a prophylactic treatment, increasing the further use of medical resources. Because that, new prophylactic treatments that are not yet generalized, are needed.

To evaluate the diagnostic performance of dual elastography (dual-elasto) in continuous differentiation of liver fibrosis and inflammation in a large prospective cohort of patients with chronic HBV.

Adults with positive HBsAg for at least 6 months were recruited from 12 medical centers. Participants underwent dual-elasto evaluations. Biopsy was performed 3 days after dual-elasto examination. Four logistic regression models were trained and strung together into series models. Decision trees based on the series models were performed to achieve continuous differentiation of liver fibrosis and inflammation. The influence of inflammation on the fibrosis stage was also evaluated. A total of 560 patients were included in the training set and 240 in the validation set. Areas under the receiver operating characteristic curve of the series model were 0.82, 0.86, 0.93, and 0.96 to predict ≥F1, ≥F2, ≥F3, and F4 in the validation set, which were significantly higher than those of serum markers and shear wave elastography (all p < 0.05), except for the ≥ F1 levels ( p = 0.09). The AUCs of the series model were 0.93, 0.86, 0.95, and 0.84 to predict inflammation stages ≥G1, ≥G2, ≥G3, and G4, respectively. Decision trees realized 5 continuous classifications of fibrosis and inflammation. Inflammation could enhance the mild fibrosis stage classification while showing limited influences on severe fibrosis or cirrhosis diagnosis.

Dual-elasto demonstrated high performance in the continuous discrimination of fibrosis and inflammation in patients with HBV and could be used to diagnose mild fibrosis without the influence of inflammation.

The value of magnetic resonance elastography (MRE) in portal hypertension (PH) has yet to be determined in the context of chronic liver disease (CLD). This study examined the value of MRE for the prediction of hepatic venous pressure gradient (HVPG) and high-risk esophageal varices (EVs) in a CLD cohort with a generally high HVPG.

Patients with CLD who underwent both HVPG measurement and two-dimensional MRE examination at Beijing Friendship Hospital between April 2018 and March 2022 were prospectively included. Two-dimensional MRE was performed within the liver and spleen. Endoscopy results and laboratory parameters were collected. Some selected published serum markers were calculated, including fibrosis 4, aspartate aminotransferase-to-platelet ratio index, and King's score. The efficacy of the parameters for assessing PH was analyzed by using the Pearson correlation coefficient, linear and logistic regression, and receiver operating characteristic curve analyses.

A total of 48 patients were included. The mean HVPG was 16.8±5.8 mmHg. Among these patients, 47 patients had PH (HVPG >5 mmHg), and 43 patients had clinically significant PH (HVPG ≥10 mmHg). Among the parameters associated with HVPG, the strongest correlation was found for spleen stiffness (SS) (R=0.638; P<0.001). In multiple regression analyses, SS was independently associated with an elevated HVPG and high-risk EVs. The areas under the receiver operating characteristic curve of SS for identifying patients with an HVPG ≥16 mmHg, HVPG ≥20 mmHg, and high-risk EVs were 0.790, 0.822, and 0.886, respectively, which were higher than those of liver stiffness (LS) and serum markers but slightly inferior to that of fibrosis 4 (area under the receiver operating characteristic curve =0.844) in identifying an HVPG ≥16 mmHg. SS cutoff values of 9.5, 10.05, and 9.9 kPa were selected to rule out the presence of an HVPG ≥16 mmHg, HVPG ≥20 mmHg, and high-risk EVs (sensitivity: 100%, 100%, and 100%, respectively; specificity: 45.5%, 50%, and 60%, respectively).

In patients with generally high HVPG, SS measured by two-dimensional MRE may be a better predictor of HVPG values and high-risk EVs than LS and serum markers.

Background: This study estimated utility values for non-alcoholic steatohepatitis (NASH). Previous studies have assumed that health-related quality of life does not vary between the early stages of NASH. Materials & Methods: Discrete choice experiment (DCE) surveys estimated the value of avoiding fibrosis progression. Patients also completed the EQ-5D-5L. Marginal rates of substitution estimated utility change associated with fibrosis progression. Results: DCE surveys were completed by the UK general public (n = 520) and patients with NASH (n = 154). The utility decline between fibrosis stages F1 and F4 decompensated was between -0.521 to -0.646 (depending on method). Conclusion: Three methods were used to estimate utilities for NASH, each one showed sensitivity to advancing fibrosis, including in the early stages, which is often considered asymptomatic.

Decompensated liver cirrhosis (DC) has high mortality, but liver transplantation is limited due to organ scarcity and contraindications for transplantation. Granulocyte-colony stimulating factor (GCSF) shows potential for liver disease treatment with its regenerative and immunomodulatory properties. To assess the controversial use of GCSF in DC, a meta-analysis of randomized controlled trials (RCTs) compared survival benefits in patients receiving GCSF plus standard medical therapy (SMT) versus SMT alone.

A literature search was performed in four databases from data inception up to December 2022, and all registered randomized controlled (RCTs) evaluating GCSF-based therapies for cirrhotic patients were included.

A study combining four RCTs assessed the impact of GCSF with SMT in 595 patients with decompensated cirrhosis. The results indicated that GCSF + SMT led to higher odds of survival compared to SMT alone [risk ratio 1.28, 95% CI (1.08-1.5)]. Heterogeneity existed among the studies, but overall, GCSF showed potential in improving survival. The intervention group exhibited improved Child-Pugh-Turcotte scores [-2.51, CI (-4.33 to -0.70)], and increased CD34 levels, but no significant improvement in MELD scores. These findings suggest GCSF may benefit patients with decompensated cirrhosis in terms of survival and liver function.

These results suggest that the combination of GCSF and SMT may have a positive impact on the survival rate and improvement in CPT score in patients with DC. Further RCTs are needed to shed more light on this promising modality in end-stage liver disease.

Chronic liver diseases, especially cirrhosis, are associated with significant morbidity and mortality. Besides predisposing to chronic liver disease per se, diabetes, hypertension, and dyslipidemia worsen the prognosis of patients with cirrhosis induced by other causes. There is no standard of care in the management of these factors in patients with cirrhosis. Also, in particular, it is not known whether nutritional interventions in the modification of cardiometabolic factors can improve the course of cirrhosis or not. This narrative review aimed to investigate the clinical significance of diabetes, hypertension, and dyslipidemia and appropriate nutritional interventions in cirrhotic patients. A comprehensive literature search of the published data was performed in regard to the association of cirrhosis with cardiometabolic factors and the management of cirrhosis and its complications. There is limited evidence on the association of cirrhosis with cardiometabolic risk factors. Cirrhotic cardiometabolic abnormalities are associated with an increased risk of complications, such that the coexistence of diabetes, hypertension, and dyslipidemia increases the risk of clinical decompensation in cirrhosis. Dietary management of cirrhotic patients with risk factors such as diabetes, hypertension, or dyslipidemia does not seem to be considerably different from non-cirrhotic patients.

The extracellular matrix of cirrhotic liver tissue is highly crosslinked. Here we show that advanced glycation end-products (AGEs) mediate crosslinking in liver extracellular matrix and that high levels of crosslinking are a hallmark of cirrhosis. We used liquid chromatography-tandem mass spectrometry to quantify the degree of crosslinking of the matrix of decellularized cirrhotic liver samples from patients and from two mouse models of liver fibrosis and show that the structure, biomechanics and degree of AGE-mediated crosslinking of the matrices can be recapitulated in collagen matrix crosslinked by AGEs in vitro. Analyses via cryo-electron microscopy and optical tweezers revealed that crosslinked collagen fibrils form thick bundles with reduced stress relaxation rates; moreover, they resist remodelling by macrophages, leading to reductions in their levels of adhesion-associated proteins, altering HDAC3 expression and the organization of their cytoskeleton, and promoting a type II immune response of macrophages. We also show that rosmarinic acid inhibited AGE-mediated crosslinking and alleviated the progression of fibrosis in mice. Our findings support the development of therapeutics targeting crosslinked extracellular matrix in scarred liver tissue.

The purpose of this article is to review fibrosis staging systems, reversibility of fibrosis, histologic pattern of fibrosis regression, and recently proposed fibrosis staging systems that address the more nuanced fibrosis information needed clinically for management purposes. In most chronic liver diseases, the extent of liver fibrosis often drives patient outcomes. The evolving knowledge of the reversibility of fibrosis and the observed patterns of fibrosis seen in the setting of remodeling/regression can create staging difficulties, and problems in applying the existing "conventional" staging systems. The heterogeneity of liver fibrosis in congestive liver disease is an emerging problem in biopsies from patients with congestive heart failure. The fibrosis staging in these biopsies is of significant import as it is used to determine suitability of some congestive heart disease patients for heart transplantation alone, dual heart and liver transplantation, or be denied transplantation. Pathologist should be aware of these newly recognized concepts, the recently proposed staging systems that attempt to incorporate these new fibrosis patterns and be able to apply the knowledge in daily practice.

Portal hypertension (PH) constitutes a pivotal factor in the progression of cirrhosis, giving rise to severe complications and a diminished survival rate. The transjugular intrahepatic portosystemic shunt (TIPS) procedure has undergone significant evolution, with advancements in stent technology assuming a central role in managing PH-related complications. This review aims to outline the progression of TIPS and emphasizes the significant influence of stent advancement on its effectiveness. Initially, the use of bare metal stents (BMSs) was limited due to frequent dysfunction. However, the advent of expanding polytetrafluoroethylene-covered stent grafts (ePTFE-SGs) heralded a transformative era, greatly enhancing patency rates. Further innovation culminated in the creation of ePTFE-SGs with controlled expansion, enabling precise adjustment of TIPS diameters. Comparative analyses demonstrated the superiority of ePTFE-SGs over BMSs, resulting in improved patency, fewer complications, and higher survival rates. Additional technical findings highlight the importance of central stent placement and adequate stent length, as well as the use of smaller calibers to reduce the risk of shunt-related complications. However, improving TIPS through technical means alone is inadequate for optimizing patient outcomes. An extensive understanding of hemodynamic, cardiac, and systemic factors is required to predict outcomes and tailor a personalized approach. Looking forward, the ongoing progress in SG technology, paired with the control of clinical factors that can impact outcomes, holds the promise of reshaping the management of PH-related complications in cirrhosis.

Non-alcoholic fatty liver disease (NAFLD) has emerged as a global epidemic intricately linked to the rising tide of obesity and metabolic syndrome. This comprehensive review delves into the complex web of relationships between NAFLD, liver fibrosis, and subclinical atherosclerosis, shedding light on their interplay, shared risk factors, and clinical implications. NAFLD encompasses a spectrum of liver conditions, from the benign non-alcoholic fatty liver (NAFL) to the more severe non-alcoholic steatohepatitis (NASH), characterized by inflammation and hepatocellular injury. Central to the discussion is the insidious development of liver fibrosis, the ominous harbinger of progressive liver damage, cirrhosis, and hepatocellular carcinoma. The increasing prevalence of NAFLD, now affecting a quarter of the global population, poses a significant public health challenge. Its association with obesity, insulin resistance, and metabolic syndrome highlights the multifactorial nature of this disease. However, NAFLD's repercussions extend beyond the liver. This review unveils a potent connection between NAFLD and subclinical atherosclerosis, the early precursor to cardiovascular disease. Individuals with NAFLD face an elevated risk of atherosclerosis, even without traditional cardiovascular risk factors. The intricate link between these two conditions is illuminated through shared pathophysiological pathways, including systemic inflammation, insulin resistance, and dyslipidemia. Understanding the interplay between liver fibrosis and subclinical atherosclerosis has profound clinical implications. Patients with advanced fibrosis or cirrhosis are not only at risk of liver-related complications but also of cardiovascular events. This necessitates a holistic approach to patient care, with lifestyle modifications and pharmacological interventions simultaneously managing both conditions. Physicians must prioritize early detection and collaborate across disciplines to provide comprehensive care. Looking ahead, the future holds promising avenues of research. Emerging areas include genetics and precision medicine, microbiome research, and epigenetics, which may unveil new therapeutic targets. Innovations in diagnostics and therapeutics, such as non-invasive biomarkers and combination therapies, offer hope for more effective management. Long-term outcomes and survivorship research will provide insights into the lasting impact of interventions. In conclusion, this review underscores the imperative of addressing liver fibrosis and atherosclerosis in the context of NAFLD. It is a call to action for healthcare professionals, researchers, and policymakers to work collaboratively, promote early detection, and advance our understanding of these interconnected conditions. By doing so, we can enhance patient outcomes and chart a course toward a healthier future for those grappling with NAFLD and its intricate web of consequences.

The most common cause of portal hypertension is liver cirrhosis. Portal hypertension causes many complications in cirrhotic patients; a significant complication is the formation of varices and the subsequent life-threatening variceal bleeding due to elevated portal venous pressures. Hepatic venous pressure gradient (HVPG) is the gold standard for measuring portal hypertension and guides management. Pharmacological treatments lower the HVPG, preventing the progression of varices and subsequent variceal bleeding. The pharmacological treatments frequently used in primary and secondary prophylaxis of a variceal bleed are nonselective beta (β)-adrenergic blockers. Propranolol was the first nonselective β-adrenergic blocker used for lowering HVPG and has been well studied. However, in the past decade, clinical trials have shown that carvedilol has been more effective. This study aims to establish whether carvedilol is more effective than propranolol in reducing the hepatic venous pressure gradient and decreasing the risk of variceal bleeding in adult cirrhotic patients. A systematic review has been conducted to gather relevant clinical trials comparing drugs and their effects on HVPG. Four databases: PubMed (Medical Literature Analysis and Retrieval System Online (MEDLINE)), Google Scholar, the Cochrane Library, and ScienceDirect, were analyzed, and records from January 1, 1999, to January 1, 2023, were chosen. There were a total of 1,235 potentially eligible records across the four databases. Using the eligibility criteria for this systematic review, seven studies of 533 patients were included. Across all seven clinical trials, it was found that carvedilol reduced HVPG more than propranolol and decreased the risk of variceal bleeding in adult cirrhotic patients.

Liver cirrhosis is a worldwide burden and is associated with poor clinical outcomes, including increased mortality. The beneficial effects of dietary modifications in reducing morbidity and mortality are inevitable.

The current study aimed to evaluate the potential association of dietary protein intake with the cirrhosis-related mortality.

In this cohort study, 121 ambulatory cirrhotic patients with at least 6 months of cirrhosis diagnosis were followed-up for 48 months. A 168-item validated food frequency questionnaire was used for dietary intake assessment. Total dietary protein was classified as dairy, vegetable and animal protein. We estimated crude and multivariable-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs), applying Cox proportional hazard analyses.

After full adjustment for confounders, analyses showed that total (HR = 0.38, 95% CI = 0.2-1.1, p trend = 0.045) and dairy (HR = 0.38, 95% CI = 0.13-1.1, p trend = 0.046) protein intake was associated with a 62% lower risk of cirrhosis-related mortality. While a higher intake of animal protein was associated with a 3.8-fold increase in the risk of mortality in patients (HR = 3.8, 95% CI = 1.7-8.2, p trend = 0.035). Higher intake of vegetable protein was inversely but not significantly associated with mortality risk.

A comprehensive evaluation of the associations of dietary protein intake with cirrhosis-related mortality indicated that a higher intakes of total and dairy protein and a lower intakes of animal protein are associated with a reduced risk of mortality in cirrhotic patients.

Cirrhosis has traditionally been considered an irreversible process of end-stage liver disease. With new treatments for chronic liver disease, there is regression of fibrosis and cirrhosis, improvement in clinical parameters (i.e. liver function and hemodynamic markers, hepatic venous pressure gradient), and survival rates, demonstrating that fibrosis and fibrolysis are a dynamic process moving in two directions. Microscopically, hepatocytes push into thinning fibrous septa with eventual perforation leaving behind delicate periportal spikes in the portal tracts and loss of portal veins. Obliterated portal veins during progressive fibrosis and cirrhosis due to parenchymal extinction, vascular remodeling and thrombosis often leave behind a bile duct and hepatic artery within the portal tract. Traditional staging classification systems focused on a linear, progressive process; however, the Beijing classification system incorporates both the bidirectional nature for the progression and regression of fibrosis. However, even with regression, vascular lesions/remodeling, parenchymal extinction and a cumulative mutational burden place patients at an increased risk for developing hepatocellular carcinoma and should continue to undergo active clinical surveillance. It is more appropriate to consider cirrhosis as another stage in the evolution of chronic liver disease as a bidirectional process rather than an end-stage, irreversible state.

Advanced chronic liver disease is characterised by a long compensated phase followed by a rapidly progressive 'decompensated' phase, which is marked by the development of complications of portal hypertension and liver dysfunction. Advanced chronic liver disease is considered responsible for more than one million deaths annually worldwide. No treatment is available to specifically target fibrosis and cirrhosis; liver transplantation remains the only curative option. Researchers are investigating strategies to restore liver functionality to avoid or slow progression towards end-stage liver disease. Cytokine mobilisation of stem cells from the bone marrow to the liver could improve liver function. Granulocyte colony-stimulating factor (G-CSF) is a 175-amino-acid protein currently available for mobilisation of haematopoietic stem cells from the bone marrow. Multiple courses of G-CSF, with or without stem or progenitor cell or growth factors (erythropoietin or growth hormone) infusion, might be associated with accelerated hepatic regeneration, improved liver function, and survival.

To evaluate the benefits and harms of G-CSF with or without stem or progenitor cell or growth factors (erythropoietin or growth hormone) infusion, compared with no intervention or placebo in people with compensated or decompensated advanced chronic liver disease.

We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, three other databases, and two trial registers (October 2022) together with reference-checking and web-searching to identify additional studies. We applied no restrictions on language and document type.

We only included randomised clinical trials comparing G-CSF, independent of the schedule of administration, as a single treatment or combined with stem or progenitor cell infusion, or with other medical co-interventions, with no intervention or placebo, in adults with chronic compensated or decompensated advanced chronic liver disease or acute-on-chronic liver failure. We included trials irrespective of publication type, publication status, outcomes reported, or language.

We followed standard Cochrane procedures. All-cause mortality, serious adverse events, and health-related quality of life were our primary outcomes, and liver disease-related morbidity, non-serious adverse events, and no improvement of liver function scores were our secondary outcomes. We undertook meta-analyses, based on intention-to-treat, and presented results using risk ratios (RR) for dichotomous outcomes and the mean difference (MD) for continuous outcomes, with 95% confidence intervals (CI) and I2 statistic values as a marker of heterogeneity. We assessed all outcomes at maximum follow-up. We determined the certainty of evidence using GRADE, evaluated the risk of small-study effects in regression analyses, and conducted subgroup and sensitivity analyses.

We included 20 trials (1419 participants; sample size ranged from 28 to 259), which lasted between 11 and 57 months. Nineteen trials included only participants with decompensated cirrhosis; in one trial, 30% had compensated cirrhosis. The included trials were conducted in Asia (15), Europe (four), and the USA (one). Not all trials provided data for our outcomes. All trials reported data allowing intention-to-treat analyses. The experimental intervention consisted of G-CSF alone or G-CSF plus any of the following: growth hormone, erythropoietin, N-acetyl cysteine, infusion of CD133-positive haemopoietic stem cells, or infusion of autologous bone marrow mononuclear cells. The control group consisted of no intervention in 15 trials and placebo (normal saline) in five trials. Standard medical therapy (antivirals, alcohol abstinence, nutrition, diuretics, β-blockers, selective intestinal decontamination, pentoxifylline, prednisolone, and other supportive measures depending on the clinical status and requirement) was administered equally to the trial groups. Very low-certainty evidence suggested a decrease in mortality with G-CSF, administered alone or in combination with any of the above, versus placebo (RR 0.53, 95% CI 0.38 to 0.72; I2 = 75%; 1419 participants; 20 trials). Very low-certainty evidence suggested no difference in serious adverse events (G-CSF alone or in combination versus placebo: RR 1.03, 95% CI 0.66 to 1.61; I2 = 66%; 315 participants; three trials). Eight trials, with 518 participants, reported no serious adverse events. Two trials, with 165 participants, used two components of the quality of life score for assessment, with ranges from 0 to 100, where higher scores indicate better quality of life, with a mean increase from baseline of the physical component summary of 20.7 (95% CI 17.4 to 24.0; very low-certainty evidence) and a mean increase from baseline of the mental component summary of 27.8 (95% CI 12.3 to 43.3; very low-certainty evidence). G-CSF, alone or in combination, suggested a beneficial effect on the proportion of participants who developed one or more liver disease-related complications (RR 0.40, 95% CI 0.17 to 0.92; I2 = 62%; 195 participants; four trials; very low-certainty evidence). When we analysed the occurrences of single complications, there was no suggestion of a difference between G-CSF, alone or in combination, versus control, in participants in need of liver transplantation (RR 0.85, 95% CI 0.39 to 1.85; 692 participants; five trials), in the development of hepatorenal syndrome (RR 0.65, 95% CI 0.33 to 1.30; 520 participants; six trials), in the occurrence of variceal bleeding (RR 0.68, 95% CI 0.37 to 1.23; 614 participants; eight trials), and in the development of encephalopathy (RR 0.56, 95% CI 0.31 to 1.01; 605 participants; seven trials) (very low-certainty evidence). The same comparison suggested that G-CSF reduces the development of infections (including sepsis) (RR 0.50, 95% CI 0.29 to 0.84; 583 participants; eight trials) and does not improve liver function scores (RR 0.67, 95% CI 0.53 to 0.86; 319 participants; two trials) (very low-certainty evidence).

G-CSF, alone or in combination, seems to decrease mortality in people with decompensated advanced chronic liver disease of whatever aetiology and with or without acute-on-chronic liver failure, but the certainty of evidence is very low because of high risk of bias, inconsistency, and imprecision. The results of trials conducted in Asia and Europe were discrepant; this could not be explained by differences in participant selection, intervention, and outcome measurement. Data on serious adverse events and health-related quality of life were few and inconsistently reported. The evidence is also very uncertain regarding the occurrence of one or more liver disease-related complications. We lack high-quality, global randomised clinical trials assessing the effect of G-CSF on clinically relevant outcomes.

Portal hypertension (PH) is the most common complication ofcirrhosis and represents the main driver of hepatic decompensation. The overarching goal of PH treatments in patients with compensated cirrhosis is to reduce the risk of hepatic decompensation (i.e development of ascites, variceal bleeding and/or hepatic encephalopathy). In decompensated patients, PH-directed therapies aim at avoiding further decompensation (i.e. recurrent/refractory ascites, variceal rebleeding, recurrent encephalopathy, spontaneous bacterial peritonitis or hepatorenal syndrome) and at improving survival. Carvedilol is a non-selective beta-blocker (NSBB) acting on hyperdynamic circulation/splanchnic vasodilation and on intrahepatic resistance. It has shown superior efficacy than traditional NSBBs in lowering PH in patients with cirrhosis and may be, therefore, the NSBB of choice for the treatment of clinically significant portal hypertension. In primary prophylaxis of variceal bleeding, carvedilol has been demonstrated to be more effective than endoscopic variceal ligation (EVL). In patients with compensated cirrhosis carvedilol achieves higher rate of hemodynamic response than propranolol, resulting in a decreased risk of hepatic decompensation. In secondary prophylaxis, the combination of EVL with carvedilol may prevent rebleeding and non-bleeding further decompensation better than that with propranolol. In patients with ascites and gastroesophageal varices, carvedilol is safe and may improve survival, as long as no impairment of the systemic hemodynamic or renal dysfunction occurs, with maintained arterial blood pressure as suitable safety surrogate. The target dose of carvedilol to treat PH should be 12.5 mg/day. This review summarizes the evidence behind Baveno-VII recommendations on the use of carvedilol in patients with cirrhosis.

Liver cirrhosis affects the structures and physiological functions of the intestine. Our previous study revealed that liver injury inhibited 25-hydroxylation of vitamin D (25(OH)-VD). The aim of this study was to investigate the roles and mechanisms of vitamin D in liver cirrhosis-induced intestinal injury. The rat liver cirrhosis model was established through the administration of carbon tetrachloride (CCl₄) for 8 weeks. Hematoxylin-eosin staining was performed to unveil the intestinal injury induced by liver cirrhosis. Enzyme-linked immunosorbent and reverse transcription PCR (RT-PCR) analysis were used to determine the levels of 25(OH)-VD, vitamin D receptor, Cytochrome P450 24A1 (CYP24A1), and α-defensin 5 (DEFA5) in rat and human serum of liver cirrhosis. Furthermore, liver cirrhosis rats were treated with low-dose (500 IU/kg) and high-dose (2,000 IU/kg) vitamin D intraperitoneally. The expression levels of TLR4/MyD88/NF-κB signaling pathway were evaluated by RT-PCR and Western blot. In conclusion, we determined the deficiency of vitamin D and down-regulation of DEFA5 and intestinal damage induced by liver cirrhosis. Moreover, vitamin D effectively inhibited liver cirrhosis-induced intestinal inflammation and oxidative stress through the TLR4/MyD88/NF-κB pathway. Vitamin D might be a promising therapeutic strategy for future treatment of liver-induced intestinal injury.

Simvastatin administration to decompensated cirrhosis patients improved Child-Pugh (CP) at the end of a safety trial (EST).

To evaluate whether simvastatin reduces cirrhosis severity through a secondary analysis of the safety trial.

Thirty patients CP class (CPc) CPc A (n = 6), CPc B (n = 22), and CPc C (n = 2) received simvastatin for one year.

cirrhosis severity. Secondary endpoints: health-related quality of life (HRQoL) and hospitalizations for cirrhosis complications.

Cirrhosis severity decreased baseline versus EST only across CP score (7.3 ± 1.3 versus 6.7 ± 1.7, P = 0.041), and CPc: 12 patients lessened from CPc B to CPc A, and three patients increased from CPc A to CPc B (P = 0.029). Due to cirrhosis severity changes and differences in clinical outcomes, 15 patients completed the trial as CPc A_EST and another 15 as CPc B/C. At baseline, CPc A_EST showed greater albumin and high-density lipoprotein cholesterol concentrations than CPc B/C (P = 0.036 and P = 0.028, respectively). Comparing EST versus baseline, only in CPc A_EST, there was a reduction in white-cell blood (P = 0.012), neutrophils (P = 0.029), monocytes (P = 0.035), and C-reactive protein (P = 0.046); an increase in albumin (P = 0.011); and a recovery in HRQoL (P < 0.030). Finally, admissions for cirrhosis complications decreased in CPc A_EST versus CPc B/C (P = 0.017).

Simvastatin would reduce cirrhosis severity only in CPc B at baseline in a suitable protein and lipid milieu, possibly due to its anti-inflammatory effects. Furthermore, only in CPc A_EST would improve HRQoL and reduce admissions by cirrhosis complications. However, as these outcomes were not primary endpoints, they require validation.

To investigate the value of contrast-enhanced portal vein imaging at the hepatobiliary phase obtained with gadobenate dimeglumine for predicting clinical outcomes in patients with chronic liver disease (CLD).

Three hundred and fourteen CLD patients who underwent gadobenate dimeglumine-enhanced hepatic magnetic resonance imaging were stratified into three groups: nonadvanced CLD (n = 116), compensated advanced CLD (n = 120), and decompensated advanced CLD (n = 78) groups. The liver-to-portal vein contrast ratio (LPC) and liver-spleen contrast ratio (LSC) at the hepatobiliary phase were measured. The value of LPC for predicting hepatic decompensation and transplant-free survival was assessed using Cox regression analysis and Kaplan-Meier analysis.

The diagnostic performance of LPC was significantly better than LSC in evaluating the severity of CLD. During a median follow-up period of 53.0 months, the LPC was a significant predictor for hepatic decompensation (p < 0.001) in patients with compensated advanced CLD. The predictive performance of LPC was higher than that of the model for end-stage liver disease score (p = 0.006). With the optimal cut-off value, patients with LPC ≤ 0.98 had a higher cumulative incidence of hepatic decompensation than patients with LPC > 0.98 (p < 0.001). The LPC was also a significant predictive factor for transplant-free survival in patients with compensated advanced CLD (p = 0.007) and those with decompensated advanced CLD (p = 0.002).

Contrast-enhanced portal vein imaging at the hepatobiliary phase obtained with gadobenate dimeglumine is a valuable imaging biomarker for predicting hepatic decompensation and transplant-free survival in CLD patients.

• The liver-to-portal vein contrast ratio (LPC) significantly outperformed liver-spleen contrast ratio in evaluating the severity of chronic liver disease. • The LPC was a significant predictor for hepatic decompensation in patients with compensated advanced chronic liver disease. • The LPC was a significant predictor for transplant-free survival in patients with compensated and those with decompensated advanced chronic liver disease.

In this systematic review and meta-analysis, we examined the evidence on transjugular intrahepatic portosystemic shunt (TIPS) as a bridge to elective and emergency surgery in cirrhotic patients. We aimed to assess the perioperative characteristics, management approaches, and outcomes of this intervention, which is used to achieve portal decompression and enable the safe performance of elective and emergent surgery.

MEDLINE and Scopus were searched for studies reporting the outcomes of cirrhotic patients undergoing elective and emergency surgery with preoperative TIPS. The risk of bias was evaluated using the methodological index for non-randomized studies of interventions, and the JBI critical appraisal tool for case reports. The outcomes of interest were: 1. Surgery after TIPS; 2. Mortality; 3. Perioperative transfusions; and 4. Postoperative liver-related events. A DerSimonian and Laird (random-effects) model was used to perform the meta-analyses in which the overall (combined) effect estimate was presented in the form of an odds ratio (summary statistic).

Of 426 patients (from 27 articles), 256 (60.1%) underwent preoperative TIPS. Random effects MA showed significantly lower odds of postoperative ascites with preoperative TIPS (OR = 0.40, 95% CI 0.22-0.72; I2 = 0%). There were no significant differences in 90-day mortality (3 studies: OR = 0.76, 95% CI 0.33-1.77; I2 = 18.2%), perioperative transfusion requirement (3 studies: OR = 0.89, 95% CI 0.28-2,84; I2 = 70.1%), postoperative hepatic encephalopathy (2 studies: OR = 0.97, 95% CI 0.35-2.69; I2 = 0%), and postoperative ACLF (3 studies: OR = 1.02, 95% CI 0.15-6.8, I2 = 78.9%).

Preoperative TIPS appears safe in cirrhotic patients who undergo elective and emergency surgery and may have a potential role in postoperative ascites control. Future randomized clinical trials should test these preliminary results.

To demonstrate that patients with pre-cirrhotic bridging fibrosis (Meta-analysis of Histological Data in Viral Hepatitis, METAVIR stage F3) and clinically significant portal hypertension (CSPH, Hepatic Venous Pressure Gradient ≥10 mmHg) experience a higher rate of clinical decompensation than patients without CSPH.

128 consecutive patients with pathology proven bridging fibrosis without cirrhosis between 2012 and 2019 were reviewed. Inclusion criteria were patients with HVPG measurement obtained during the same outpatient transjugular liver biopsy and clinical follow up of at least two years. Primary endpoint included rate of overall complication related to portal hypertension including evidence of either ascites, presence of varices on imaging or endoscopy, or evidence of hepatic encephalopathy.

Among 128 patients with bridging fibrosis (67 females and 61 males; average age 56 years), 42 (33%) and 86 (67%) were with and without CSPH (HVPG ≥10 mmHg). Median follow-up time was 4 years. Rate of overall complication (either ascites, varices or hepatic encephalopathy) in patients with and without CSPH was 36/42 (86%) and 39/86 (45%) (p < .001) respectively. Rate of developing ascites, varices and hepatic encephalopathy in patients with and without CSPH was 21/42 (50%) vs 26/86 (30%) (p = .034), 32/42 (76%) vs 26/86 (30%) (p ≤ .001) and 18/42 (43%) vs 12/86 (14%) (p = .001) respectively.

Patients with pre-cirrhotic bridging fibrosis and CSPH were associated with higher rates of developing ascites, varices and hepatic encephalopathy. Measuring HVPG during transjugular liver biopsy provides additional prognostic value in anticipating clinical decompensation in patients with pre-cirrhotic bridging fibrosis.

The liver is a vital organ that plays a crucial role in the physiological operation of the human body. The liver controls the body's detoxification processes as well as the storage and breakdown of red blood cells, plasma protein and hormone production, and red blood cell destruction; therefore, it is vulnerable to their harmful effects, making it more prone to illness. The most frequent complications of chronic liver conditions include cirrhosis, fatty liver, liver fibrosis, hepatitis, and illnesses brought on by alcohol and drugs. Hepatic fibrosis involves the activation of hepatic stellate cells to cause persistent liver damage through the accumulation of cytosolic matrix proteins. The purpose of this review is to educate a concise discussion of the epidemiology of chronic liver disease, the pathogenesis and pathophysiology of liver fibrosis, the symptoms of liver fibrosis progression and regression, the clinical evaluation of liver fibrosis and the research into nanotechnology-based synthetic and herbal treatments for the liver fibrosis is summarized in this article. The herbal remedies summarized in this review article include epigallocathechin-3-gallate, silymarin, oxymatrine, curcumin, tetrandrine, glycyrrhetinic acid, salvianolic acid, plumbagin, Scutellaria baicalnsis Georgi, astragalosides, hawthorn extract, and andrographolides.

Alcoholic liver disease (ALD) is a clinical-pathologic entity caused by the chronic excessive consumption of alcohol. The disease includes a broad spectrum of anomalies at the cellular and tissual level that can cause acute-on-chronic (alcoholic hepatitis) or chronic (fibrosis, cirrhosis, hepatocellular cancer) injury, having a great impact on morbidity and mortality worldwide. Alcohol is metabolized mainly in the liver. During alcohol metabolism, toxic metabolites, such as acetaldehyde and oxygen reactive species, are produced. At the intestinal level, alcohol consumption can cause dysbiosis and alter intestinal permeability, promoting the translocation of bacterial products and causing the production of inflammatory cytokines in the liver, perpetuating local inflammation during the progression of ALD. Different study groups have reported systemic inflammatory response disturbances, but reports containing a compendium of the cytokines and cells involved in the pathophysiology of the disease, from the early stages, are difficult to find. In the present review article, the role of the inflammatory mediators involved in ALD progression are described, from risky patterns of alcohol consumption to advanced stages of the disease, with the aim of understanding the involvement of immune dysregulation in the pathophysiology of ALD.

Complications of cirrhotic portal hypertension (PHTN) in children are broad and include clinical manifestations ranging from variceal hemorrhage, hepatic encephalopathy (HE), ascites, spontaneous bacterial peritonitis (SBP), and hepatorenal syndrome (HRS) to less common conditions such as hepatopulmonary syndrome, portopulmonary hypertension, and cirrhotic cardiomyopathy. The approaches to the diagnosis and management of these complications have become standard of practice in adults with cirrhosis with many guidance statements available. However, there is limited literature on the diagnosis and management of these complications of PHTN in children with much of the current guidance available focused on variceal hemorrhage. The aim of this review is to summarize the current literature in adults who experience these complications of cirrhotic PHTN beyond variceal hemorrhage and present the available literature in children, with a focus on diagnosis, management, and liver transplant decision making in children with cirrhosis who develop ascites, SBP, HRS, HE, and cardiopulmonary complications.

In cirrhotic nonalcoholic steatohepatitis (NASH) clinical trials, primary efficacy endpoints have been hepatic venous pressure gradient (HVPG), liver histology and clinical liver outcomes. Important histologic features, such as septa thickness, nodules features and fibrosis area have not been included in the histologic assessment and may have important clinical relevance. We assessed these features with a machine learning (ML) model.

NASH patients with compensated cirrhosis and HVPG ≥6 mm Hg (n = 143) from the Belapectin phase 2b trial were studied. Liver biopsies, HVPG measurements and upper endoscopies were performed at baseline and at end of treatment (EOT). A second harmonic generation/two-photon excitation fluorescence provided an automated quantitative assessment of septa, nodules and fibrosis (SNOF). We created ML scores and tested their association with HVPG, clinically significant HVPG (≥10 mm Hg) and the presence of varices (SNOF-V).

We derived 448 histologic variables (243 related to septa, 21 related to nodules and 184 related to fibrosis). The SNOF score (≥11.78) reliably distinguished CSPH at baseline and in the validation cohort (baseline + EOT) [AUC = 0.85 and 0.74, respectively]. The SNOF-V score (≥0.57) distinguished the presence of varices at baseline and in the same validation cohort [AUC = 0.86 and 0.73, respectively]. Finally, the SNOF-C score differentiated those who had >20% change in HVPG against those who did not, with an AUROC of 0.89.

The ML algorithm accurately predicted HVPG, CSPH, the development of varices and HVPG changes in patients with NASH cirrhosis. The use of ML histology model in NASH cirrhosis trials may improve the assessment of key outcome changes.

Cirrhosis is a progressive chronic liver disease caused by one or more causes and characterized by diffuse fibrosis, pseudolobules, and regenerated nodules. Once progression to hepatic decompensation, the function of the liver and other organs is impaired and almost impossible to reverse and recover, which often results in hospitalization, impaired quality of life, and high mortality. However, in the early stage of cirrhosis, there seems to be a possibility of cirrhosis reversal. The development of cirrhosis is related to the intestinal microbiota and activation of toll-like receptors (TLRs) pathways, which could regulate cell proliferation, apoptosis, expression of the hepatomitogen epiregulin, and liver inflammation. Targeting regulation of intestinal microbiota and TLRs pathways could affect the occurrence and development of cirrhosis and its complications. In this paper, we first reviewed the dynamic change of intestinal microbiota and TLRs during cirrhosis progression. And further discussed the interaction between them and potential therapeutic targets to reverse early staged cirrhosis.