In hepatitis C patients with sustained virologic response (SVR) achieved after direct-acting antivirals (DAAs), the incidence of adverse clinical outcomes can be reduced but not completely eliminated. This meta-analysis aims at estimating the incidence of clinical outcomes in hepatitis C patients after achieving SVR with DAAs.

Literature search was carried out in PubMed, Cochrane Library database, Web of Science, and Embase. The primary endpoint was the incidence of hepatocellular carcinoma (HCC) occurrence, HCC recurrence, decompensated cirrhosis, and liver-related mortality, following DAA-induced elimination of hepatitis C virus (HCV). Subgroup analyses were performed according to age, gender, comorbidities, region, fibrosis stage, presence of decompensation, duration of follow-up, start point of follow-up, and HCC treatment modality. Furthermore, meta-regression was performed to explore sources of high heterogeneity.

Finally, 132 articles were included in our study. The pooled HCC occurrence rate was 1.50/100 person-years (95% CI, 1.35-1.65), HCC recurrence rate was 17.00/100 person-years (95% CI, 13.83-20.42), decompensation rate was 0.30/100 person-years (95% CI, 0.16-0.48), and liver-related mortality was 0.32/100 person-years (95% CI, 0.14-0.56). Meta-regression showed that duration of follow-up and fibrosis grade were important contributors to HCC occurrence. Age, start point of follow-up, and duration of follow-up were important contributors to HCC recurrence rate.

Patients with DAA-induced HCV elimination remain at risk for adverse outcomes, particularly those with cirrhosis and HCC history. The exposure to adverse outcomes tended to decrease over time, and the frequency and intensity of follow-up might be reduced in the future, which will require new scoring models to identify these individuals.

Over the past several years, there has been a wealth of new data pertaining to the management of complications of cirrhosis, resulting in several important updates to best practices and consensus guidelines. Despite these advancements and numerous recent targeted quality initiatives, hospitalizations resulting from complications of cirrhosis remain frequent, costly and associated with poor patient outcomes. An emphasis on evidence-based management of hospitalized patients with decompensated cirrhosis has the potential to decrease readmission rates and length of stay while improving overall patient outcomes. Herein, we provide an updated, evidence-based overview of the optimal inpatient management of the most frequently encountered complications associated with cirrhosis.

Globally, Liver cirrhosis is the 14th leading cause of death and poses a significant threat to human health.

To investigate the effects of a multidisciplinary collaboration model on postoperative recovery and psychological stress in patients with liver cirrhosis undergoing esophageal variceal bleeding (EVB) surgery within an integrated healthcare system.

Between January 2022 and March 2024, a total of 180 patients with cirrhosis and EVB were admitted and randomly assigned to either a control group (standard care) or an observation group (standard care plus the multidisciplinary collaboration model), with 90 patients in each group. Postoperative recovery indicators (time to symptom improvement, time to start eating, time to bowel sound recovery, time to first flatus, and hospital stay), psychological stress responses [self-rating anxiety scale (SAS); self-rating depression scale (SDS)], subjective well-being, and incidence of complications were compared between the two groups.

Compared to the control group, the observation group showed earlier symptom improvement, earlier return to eating, bowel sound recovery, first flatus, and a shorter hospital stay. Pre-intervention SAS and SDS scores were not significantly different between the groups, but post-intervention scores were significantly lower in the observation group. Similarly, there was no significant difference in the subjective well-being scores before the intervention between the two groups. After the intervention, both groups showed improved scores, with the observation group scoring significantly higher than the control group.

The observation group also had a lower incidence of complications. Therefore, for patients with liver cirrhosis undergoing EVB surgery, a multidisciplinary collaboration model within an integrated healthcare system can promote early postoperative recovery, reduces psychological stress, improves subjective well-being, and reduces complications and rebleeding.

The recent introduction of the term metabolic-dysfunction-associated steatotic liver disease (MASLD) has highlighted the critical role of metabolism in the disease's pathophysiology. This innovative nomenclature signifies a shift from the previous designation of non-alcoholic fatty liver disease (NAFLD), emphasizing the condition's progressive nature. Simultaneously, MASLD has become one of the most prevalent liver diseases worldwide, highlighting the urgent need for research to elucidate its etiology and develop effective treatment strategies. This review examines and delineates the revised definition of MASLD, exploring its epidemiology and the pathological changes occurring at various stages of the disease. Additionally, it identifies metabolically relevant targets within MASLD and provides a summary of the latest metabolically targeted drugs under development, including those in clinical and some preclinical stages. The review finishes with a look ahead to the future of targeted therapy for MASLD, with the goal of summarizing and providing fresh ideas and insights.

Transjugular intrahepatic portosystemic shunts (TIPSs) are generally used for the management of complications of portal hypertension in patients with decompensated cirrhosis. However, hepatic encephalopathy (HE), which impairs neuropsychiatric function and motor control, remains the primary adverse effect of TIPS, limiting its utility. Prompt prevention and treatment of post-TIPS HE are critical, as they are strongly associated with readmission rates and poor quality of life. This review focuses on the main pathophysiological mechanisms underlying post-TIPS HE, explores advanced biomarkers and predictive tools, and discusses current management strategies and future directions to prevent or reverse HE following TIPS. These strategies include preoperative patient assessment, individualized shunt diameter optimization, spontaneous portosystemic shunt embolization during the TIPS procedure, postoperative preventive and therapeutic measures such as nutrition management, medical therapy, fecal microbiota transplantation, and stent reduction.

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.

Transjugular intrahepatic portosystemic shunt (TIPS) is an established procedure for managing portal hypertension in cirrhotic patients, but the impact of post-TIPS overt hepatic encephalopathy (OHE) on survival remains controversial. While its effect on short-term survival is well-documented, its long-term implications remain unclear.

This study aims to investigate the long-term impact of post-TIPS OHE on mortality in cirrhotic patients for variceal bleeding, focusing on the timing and predictive value of OHE beyond the first year post-TIPS.

A multicenter, retrospective cohort study was conducted involving 3262 cirrhotic patients who underwent TIPS for variceal bleeding at seven Chinese tertiary centers between January 2010 and June 2020. Clinical data, including demographics, procedure details, post-TIPS complications and survival outcomes, were collected. The primary endpoints were all-cause mortality and OHE, with follow-up until death, liver transplantation or 60 months. Propensity score matching minimised confounding effects, and multivariate Fine-Grey competing risk models identified independent mortality predictors.

During a median follow-up of 1077 days, 33.2% developed post-TIPS OHE, associated with higher MELD and Child-Pugh scores. Among these, 19.3% died, with a median time from OHE onset to death of 947 days. Post-TIPS OHE was not linked to early survival (within 12 months) but emerged as an independent predictor of long-term mortality beyond 24 months, consistent across various clinical scenarios.

Post-TIPS OHE does not affect short-term survival but significantly increases long-term mortality risk. These findings highlight the need for continuous monitoring and tailored interventions to improve long-term outcomes in post-TIPS patients.

Patients with decompensated liver cirrhosis suffering from esophagogastric variceal bleeding (EGVB) face high mortality.

To investigate the risk factors for EGVB in patients with liver cirrhosis and establish a diagnostic nomogram.

Patients with liver cirrhosis who met the inclusion criteria were randomly divided into training and validation cohorts in a 6:4 ratio in this retrospective research. Univariate analysis, least absolute shrinkage and selection operator regression, and multivariate analysis were employed to establish the nomogram model. Calibration curve, the area under the receiver operating characteristic curve (AUC), and decision curve analysis (DCA) were applied to assess the discrimination, accuracy, and clinical practicability of the nomogram, respectively.

A total of 1115 patients were enrolled in this study. The nomogram was established based on white blood cells (P < 0.001), hemoglobin (P < 0.001), fibrinogen (P < 0.001), total bilirubin (P = 0.007), activated partial thromboplastin time (P = 0.002), total bile acid (P = 0.012), and ascites (P = 0.006). The calibration curve indicated that the actual observation results were in good agreement with the prediction results of the model. The AUC values of the diagnostic model were 0.861 and 0.859 in the training and validation cohorts, respectively, which were higher than that of the aspartate aminotransferase-to-platelet ratio index, fibrosis index based on 4 factors, and aspartate aminotransferase-to-alanine aminotransferase ratio. Additionally, DCA indicated that the net benefit value of the model was higher than that of the other models.

This research constructed and validated a nomogram with perfect performance for predicting EGVB events in patients with liver cirrhosis, which could help clinicians with timely diagnosis, individualized treatment, and follow-up.

No therapy has been shown to reduce the risk of major adverse liver outcomes (MALO) in patients with cirrhosis due to metabolic dysfunction-associated steatohepatitis (MASH). The Surgical Procedures Eliminate Compensated Cirrhosis In Advancing Long-term (SPECCIAL) observational study compared the effects of metabolic surgery and nonsurgical treatment in patients with obesity and compensated histologically proven MASH-related cirrhosis. Using a doubly robust estimation methodology to balance key baseline characteristics between groups, the time-to-incident MALO was compared between 62 patients (68% female) who underwent metabolic surgery and 106 nonsurgical controls (71% female), with a mean follow-up of 10.0 ± 4.5 years. The 15 year cumulative incidence of MALO was 20.9% (95% confidence interval (CI), 2.5-35.9%) in the surgical group compared with 46.4% (95% CI, 25.6-61.3%) in the nonsurgical group, with an adjusted hazard ratio of 0.28 (95% CI, 0.12-0.64), P = 0.003. The 15 year cumulative incidence of decompensated cirrhosis was 15.6% (95% CI, 0-31.3%) in the surgical group compared with 30.7% (95% CI, 12.9-44.8%) in the nonsurgical group, with an adjusted hazard ratio of 0.20 (95% CI, 0.06-0.68), P = 0.01. Among patients with compensated MASH-related cirrhosis and obesity, metabolic surgery, compared with nonsurgical management, was associated with a significantly lower risk of incident MALO. In the absence of approved medical therapies for compensated MASH-related cirrhosis, metabolic surgery may represent a safe and effective therapeutic option to influence the trajectory of cirrhosis.

Hemodynamic processes from the portal vein(PV) to the inferior vena cava(IVC) were mimicked for three patients with portal hypertension(PH) and the effects of stent parameters on the outcomes of transjugular intrahepatic portosystemic shunt(TIPS) were investigated through computational fluid dynamics(CFD). The liver region was simulated with porous media model and the spatial distributions of superior mesenteric vein(SMV) and splenic vein(SV) blood were solved through the Eulerian multiphase model. The present method is able to simulate the PH flow and predict the PV pressure, the stent shunt rate and the SMV blood proportion after TIPS treatment. According to the CFD results, the stent diameter exerts dominant effects on the TIPS outcomes while the stent placement shows substantial effects on the TIPS outcomes. Energy loss of the TIPS stents and distributary effects of the PV bifurcation dominate the PV hemodynamics and the TIPS outcomes. For stents with large diameter or proper placement, the energy loss is low therefore the PV pressure reduction and stent shunt rate are high. Stents inserted on the left and right branches of the PV are able to utilize distributary effects of the PV bifurcation therefore reduce the SMV blood flowing into the IVC.

This is a narrative review in which the advances in technical aspects, the main indications, limitations and clinical results of the transjugular intrahepatic portosystemic shunt (TIPS) in portal hypertension (PH) are addressed. With the emergence of the coated prosthesis, a better shunt patency, a lower incidence of hepatic encephalopathy (HE) and better survival when compared to TIPS with the conventional prosthesis are demonstrated. The main indications for TIPS are refractory ascites, acute variceal bleeding unresponsive to pharmacological/endoscopic therapy and, lastly, patients considered at high risk for rebleeding preemptive TIPS (pTIPS). Absolute contraindications to the use of TIPS are severe uncontrolled HE, systemic infection or sepsis, congestive heart failure, severe pulmonary arterial hypertension, and biliary obstruction. The control of hemorrhage due to variceal rupture can reach up to 90%-100% of cases, and 55% in refractory ascites. Despite evidences regarding pTIPS in patients at high risk for rebleeding, less than 20% of eligible patients are treated. TIPS may also decrease the incidence of future decompensation in cirrhosis and increase survival in selected patients. In conclusion, TIPS is an essential treatment for patients with PH, but is often neglected. It is important for the hepatologist to form a multidisciplinary team, in which the role of the radiologist with experience in interventional procedures is prominent.

Background: Acute-on-chronic liver failure (ACLF) is a severe, rapidly progressing syndrome in patients with liver cirrhosis, often triggered by bacterial infections. Piperacillin/Tazobactam is a key antibiotic in this setting, and therapeutic drug monitoring (TDM) helps optimize its dosing. This study evaluates the impact of an interprofessional TDM strategy for Piperacillin/Tazobactam in ACLF patients in the ICU. Methods: This retrospective ICU study evaluated an interprofessional TDM approach for optimizing Piperacillin/Tazobactam dosing in critically ill ACLF patients. The team, consisting of physicians, clinical pharmacists, and staff nurses, engaged in shared decision making, collaboratively interpreting TDM results and adjusting the dosing accordingly. This study included 26 patients with ACLF who underwent initial TDM and 7 who received follow-up TDM. Piperacillin/Tazobactam dosing was modified based on TDM recommendations, with serum concentrations measured weekly. Adherence to and the implementation of interprofessional dosing recommendations were systematically analyzed to assess the impact of this approach. Results: The initial TDM showed that 30.8% of patients had Piperacillin/Tazobactam levels within the target range, while 53.8% were above and 15.4% below. The interprofessional team recommended dose reductions in seven patients, increases in three, and no change in eleven, with five requiring antibiotic modifications. At the first follow-up TDM, 20.0% reached target levels, while 80.0% remained above, with no subtherapeutic cases. The team recommended one further dose reduction and maintained dosing in four patients. All recommendations were fully implemented, demonstrating strong adherence to the collaborative protocol. Conclusions: The interprofessional TDM strategy optimized Piperacillin/Tazobactam dosing in ACLF patients with full adherence to the recommendations. This collaborative approach improves outcomes and supports global efforts to curb antibiotic resistance.

Subharmonic-aided pressure estimation (SHAPE) is a technique for determining changes in ambient pressure. We aimed to analyze a novel SHAPE integrated into ultrasound diagnostic equipment to predict patients with liver cirrhosis at high risk of esophagogastric varices (EV).

This prospective study included 111 patients with liver cirrhosis diagnosed between 2020 and 2023. We obtained liver stiffness measurements (LSM) and spleen stiffness measurements (SSM) using shear wave elastography and hepatic vein-portal vein (HV-PV) gradient using the SHAPE method. The EV risk was determined either as null, low, or high by esophagoscopy and Child-Pugh stage.

HV-PV gradient increased concordantly with the increase in EV risk (- 7.0 dB in null-risk, - 4.4 dB in low-risk, and - 2.0 dB in high-risk) with statistically significant difference among any two groups. The most appropriate cut-off value of the HV-PV gradient was - 3.5 dB, and sensitivity, specificity, and positive and negative predictive values were 80.0%, 89.0%, 80.0%, and 88.0%, respectively. The areas under the curve values for predicting the high-risk EV were 0.920, 0.843, and 0.824 for the HV-PV gradient, LSM, and SSM, respectively.

The novel SHAPE system demonstrated high accuracy in identifying patients with liver cirrhosis at a high risk of EV.

Trans-jugular intrahepatic portosystemic stent shunting (TIPSS) has been in use for many years with great results and many evolutions. The procedure essentially involves the insertion of a metal covert stent to create an Hepato-Hepatic portosystemic shunt. Over time, TIPSS has become the subject of many studies aimed at examining its clinical utility and evaluating the results of using TIPSS to manage complications related to portal hypertension. From the outset, this procedure has been met with hope and enthusiasm and give the chance to consider another possibility to treat the complications of portal hypertension without the use of surgery. Considering that TIPSS is an attractive alternative to shunt surgery because it does not require the use of general anesthesia or laparotomy, in fact this method is applicable to many patients with severe liver disease not suitable for it. TIPSS has been studied for the management of variceal bleeding, ascites, hepatic hydrothorax, hepatorenal syndrome, and other types of cirrhosis. However, some drawbacks of the TIPSS, such as shunt stenosis and hepatic encephalopathy, have also been reported in the literature. On the basis of the available evidence and the new epidemiological findings regarding liver disease, the following question may be posed: What is the place of TIPSS in current clinical practice?

Acute variceal bleeding (AVB) portends significant 6-week mortality in patients with cirrhosis. It remains unclear if the correlation between liver prognostic scores and 6-week mortality are similar across different etiologies of liver cirrhosis, particularly alcohol-related liver disease (ALD) vs non-alcohol-related liver disease (non-ALD). This study aims to compare the 6-week mortality following AVB in these 2 patient populations.

We assessed outcomes after AVB in 2 large multicenter cohorts from the United States and Singapore of patients with cirrhosis presenting with AVB. Using multivariable logistic regression, 6-week mortality between ALD and non-ALD cirrhosis was compared. Sensitivity analyses were performed with propensity-score matching analyses of the overall cohort.

A total of 1349 patients with AVB from the United States (n = 469) and Singapore (n = 880) cohorts were included. The aggregated cohort consisted of 379 patients (27.5%) with ALD cirrhosis. The overall 6-week mortality was 14.4%. Non-ALD cirrhosis was associated with a significantly higher 6-week mortality than ALD cirrhosis after accounting for Child-Turcotte-Pugh (CTP) score (adjusted odds ratio [aOR], 2.9; 95% confidence interval [CI], 1.5-5.3), Model of End-stage Liver Disease (MELD) score (aOR, 3.0; 95% CI, 1.6-5.6), and MELD 3.0 score (aOR, 3.3; 95% CI, 1.7-6.4). Addition of cirrhosis etiology (ALD vs non-ALD) to existing prognostic scores improved the prediction of 6-week mortality following AVB (MELD 3.0 c-statistic: 0.784 vs 0.770; P < .001). An etiology-adjusted updated MELD 3.0 model was the best prediction model for 6-week mortality after AVB.

Patients with non-ALD cirrhosis presenting with AVB had a higher risk of 6-week mortality, at each severity of liver disease by standard indices, than patients with ALD cirrhosis. Cirrhosis etiology (ALD vs non-ALD) should be incorporated into the risk stratification of patients with AVB.

Esophageal-gastric variceal bleeding (EGVB) is a serious complication in patients with liver cirrhosis, characterized by high mortality and rebleeding rates. The effect of sequential endoscopic therapy on patient mortality and rebleeding rates remains unclear.

This study aimed to evaluate the effects of sequential endoscopic therapy on mortality and rebleeding rates in patients with EGVB.

In this single-center retrospective study, 373 hospitalized cases of EGVB caused by liver cirrhosis, collected between November 2019 and November 2023, were divided into four groups according to different treatment methods: a sequential endoscopy group, emergency endoscopy group, emergency endoscopy plus transjugular intrahepatic portosystemic shunt (TIPS) group and control group.

Mortality and rebleeding rates were compared among the four groups using statistical analyses.

The mortality and rebleeding rates of the sequential endoscopy group (3.7% and 19%, respectively) were significantly lower than those of the emergency endoscopy (22% and 36%, respectively), emergency endoscopy plus TIPS (33% and 28%, respectively), and control groups (33% and 51%, respectively) (p = 0.013 and p = 0.013, respectively).

Sequential endoscopic therapy may significantly reduce the mortality and rebleeding rates of patients with EGVB compared to other conventional treatment strategies. The findings of the study could help develop approaches benefiting EGVB treatment.

This exhaustive review, explored the multifaceted symptoms and their management in patients with cirrhosis. Patients frequently endure pain, muscle cramps, sleep disturbances, psychological distress, and gastrointestinal issues, significantly impairing their quality of life. Pain is prevalent, often requiring analgesics, while muscle cramps affect up to 68% of patients, treated with supplements like zinc and taurine despite limited evidence. Sleep disturbances, including insomnia and excessive daytime sleepiness, afflict up to 80% of patients, managed through lactulose, melatonin, and cognitive behavioral therapies. Gastrointestinal symptoms, affecting 80%, include abdominal pain and bloating, necessitating lifestyle and dietary adjustments. Mental health disorders, such as depression and anxiety, are common, managed with a combination of pharmacotherapy and psychotherapy. Sexual dysfunction, often overlooked, profoundly impacts both men and women, requiring holistic treatment approaches. Pruritus, another distressing symptom, is managed with moisturizers and antihistamines, though many treatments show limited success. Hair loss and skin changes add to the psychological burden, highlighting the need for a comprehensive, multidisciplinary approach. The review underscores the imperative for tailored, compassionate care to enhance patient outcomes and quality of life in cirrhosis.

Cirrhosis represents a significant global health challenge, characterized by high morbidity and mortality rates that severely impact human health. Timely and precise prognostic assessments of liver cirrhosis are crucial for improving patient outcomes and reducing mortality rates as they enable physicians to identify high-risk patients and implement early interventions. This paper features a thorough literature review on the prognostic assessment of liver cirrhosis, aiming to summarize and delineate the present status and constraints associated with the application of traditional prognostic tools in clinical settings. Among these tools, the Child-Pugh and Model for End-Stage Liver Disease (MELD) scoring systems are predominantly utilized. However, their accuracy varies significantly. These systems are generally suitable for broad assessments but lack condition-specific applicability and fail to capture the risks associated with dynamic changes in patient conditions. Future research in this field is poised for deep exploration into the integration of artificial intelligence (AI) with routine clinical and multi-omics data in patients with cirrhosis. The goal is to transition from static, unimodal assessment models to dynamic, multimodal frameworks. Such advancements will not only improve the precision of prognostic tools but also facilitate personalized medicine approaches, potentially revolutionizing clinical outcomes.

Terlipressin has been widely used for various cirrhosis-related complications, but its safety profile remains controversial. Herein, this issue was systematically evaluated.

All studies reporting adverse events (AEs) of terlipressin in cirrhosis were screened. Incidences were pooled using a random-effects model. Subgroup analyses were performed according to the patient's characteristics and treatment regimens. Interaction among subgroups was evaluated.

Seventy-eight studies with 7257 patients with cirrhosis were included. The pooled incidences of any AEs, treatment-related AEs, any serious AEs (SAEs), treatment-related SAEs, treatment withdrawal due to AEs, and treatment withdrawal due to treatment-related AEs were 31%, 22%, 5%, 5%, 4%, and 4% in patients with cirrhosis receiving terlipressin, respectively. Patients with hepatorenal syndrome had higher incidences of any SAEs (29% vs. 0% vs. 0%, pinteraction = 0.01) and treatment-related SAEs (8% vs. 1% vs. 7%, pinteraction = 0.02) than those with variceal bleeding or ascites. Patients who received terlipressin with human albumin had higher incidences of any SAEs (18% vs. 1%, pinteraction = 0.04) and treatment-related SAEs (7% vs. 0%, pinteraction = 0.09) than those without albumin. Patients with total bilirubin level >4.3 mg/dL had higher incidences of any AEs (69% vs. 24%, pinteraction = 0.02), any SAEs (64% vs. 0%, pinteraction < 0.01), and treatment-related SAEs (8% vs. 1%, pinteraction = 0.04) than those ≤4.3 mg/dL.

AEs are common in patients with cirrhosis receiving terlipressin and influenced by clinical scenarios, combination with albumin, and bilirubin levels.

Portal hypertension represents the primary non-neoplastic complication of liver cirrhosis and has life-threatening consequences, such as oesophageal variceal bleeding, ascites, and hepatic encephalopathy. Portal hypertension occurs due to increased resistance of the cirrhotic liver vasculature to portal blood flow and is further aggravated by the hyperdynamic circulatory syndrome. Existing knowledge indicates that the profibrogenic phenotype acquired by sinusoidal cells is the initial factor leading to increased hepatic vascular tone and fibrosis, which cause increased vascular resistance and portal hypertension. Data also suggest that the phenotype of hepatic cells could be further impaired due to the altered mechanical properties of the cirrhotic liver itself, creating a deleterious cycle that worsens portal hypertension in the advanced stages of liver disease. In this Review, we discuss recent discoveries in the pathophysiology and treatment of cirrhotic portal hypertension, a condition with few pharmacological treatment options.

Transjugular intrahepatic portosystemic shunt (TIPS) placement is a procedure that can effectively treat complications of portal hypertension, such as variceal bleeding and refractory ascites. However, there have been no specific studies on predicting long-term survival after TIPS placement.

To establish a model to predict long-term survival in patients with hepatitis cirrhosis after TIPS.

A retrospective analysis was conducted on a cohort of 224 patients who underwent TIPS implantation. Through univariate and multivariate Cox regression analyses, various factors were examined for their ability to predict survival at 6 years after TIPS. Consequently, a composite score was formulated, encompassing the indication, shunt reasonability, portal venous pressure gradient (PPG) after TIPS, percentage decrease in portal venous pressure (PVP), indocyanine green retention rate at 15 min (ICGR15) and total bilirubin (Tbil) level. Furthermore, the performance of the newly developed Cox (NDC) model was evaluated in an internal validation cohort and compared with that of a series of existing models.

The indication (variceal bleeding or ascites), shunt reasonability (reasonable or unreasonable), ICGR15, postoperative PPG, percentage of PVP decrease and Tbil were found to be independent factors affecting long-term survival after TIPS placement. The NDC model incorporated these parameters and successfully identified patients at high risk, exhibiting a notably elevated mortality rate following the TIPS procedure, as observed in both the training and validation cohorts. Additionally, in terms of predicting the long-term survival rate, the performance of the NDC model was significantly better than that of the other four models [Child-Pugh, model for end-stage liver disease (MELD), MELD-sodium and the Freiburg index of post-TIPS survival].

The NDC model can accurately predict long-term survival after the TIPS procedure in patients with hepatitis cirrhosis, help identify high-risk patients and guide follow-up management after TIPS implantation.

As recommended by Baveno VII consensus, the utilization of pre-emptive transjugular intrahepatic portosystemic shunt (pTIPS) has been considered as standard therapeutic approach for the management of acute variceal bleeding (AVB) associated with cirrhosis., but the 72-h window for pTIPS is too narrow. This study aimed to compare the clinical outcomes between patients who received <72 h pTIPS and 72 h-5d pTIPS. In this study, a total of 63 cirrhotic patients with AVB who underwent pTIPS between October 2016 and December 2021 were included in this retrospective study. They were divided into <72 h group (n = 32) and 72 h-5d group (n = 31), based on the timing of the intervention. The Kaplan-Meier curves demonstrated that there were no significant differences in the cumulative incidence of death (22.3% ± 7.4% vs. 19.9% ± 7.3%, log-rank P = 0.849), variceal rebleeding (9.7% ± 5.3% vs. 17.8% ± 7.3%, log-rank P = 0.406), OHE (28.5% ± 8.0% vs. 23.9% ± 8.0%, log-rank P = 0.641) and shunt dysfunction (8.6% ± 6.0% vs. 17.4% ± 8.1%, log-rank P = 0.328) between <72 h and 72 h-5d groups. In the total cohort, sarcopenia was identified as an independent risk factor for mortality (HR = 11.268, 95% CI = 1.435-88.462, P = 0.021) and OHE(HR = 12.504, 95% CI = 1.598-97.814, P = 0.016). In conclusion, the clinical outcomes of cirrhotic patients with AVB who underwent pTIPS within the 72-h to 5-day window were found to be comparable to those treated within the 72-h window.

Cirrhosis is a major cause of morbidity and mortality in the United States and worldwide. It consists of compensated, decompensated, and further decompensated stages; median survival is more than 15 years, 2 years, and 9 months for each stage, respectively. With each stage, there is progressive worsening of portal hypertension and the vasodilatory-hyperdynamic circulatory state, resulting in a progressive decrease in effective arterial blood volume and renal perfusion. Vasoconstrictors reduce portal pressure via splanchnic vasoconstriction and are used in the management of variceal hemorrhage. Intravenous (IV) albumin increases effective arterial blood volume and is used in the prevention of acute kidney injury (AKI) and death after large-volume paracentesis and in patients with spontaneous bacterial peritonitis (SBP). The combination of vasoconstrictors and albumin is used in the reversal of hepatorenal syndrome (HRS-AKI), the most lethal complication of cirrhosis. Because a potent vasoconstrictor, terlipressin, was recently approved by the US Food and Drug Administration, and because recent trials have explored use of IV albumin in other settings, it was considered that a best practice update would be relevant regarding the use of vasoactive drugs and IV albumin in the following 3 specific scenarios: variceal hemorrhage, ascites and SBP, and HRS.

This expert review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership. It underwent internal peer review through standard procedures of Gastroenterology. These Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Some of the statements are unchanged from published guidelines because of lack of new evidence in the literature. Because systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings regarding the quality and evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Vasoactive drugs should be initiated as soon as the diagnosis of variceal hemorrhage is suspected or confirmed, preferably before diagnostic and/or therapeutic endoscopy. BEST PRACTICE ADVICE 2: After initial endoscopic hemostasis, vasoactive drugs should be continued for 2-5 days to prevent early rebleeding. BEST PRACTICE ADVICE 3: Octreotide is the vasoactive drug of choice in the management of variceal hemorrhage based on its safety profile. BEST PRACTICE ADVICE 4: IV albumin should be administered at the time of large-volume (>5 L) paracentesis. BEST PRACTICE ADVICE 5: IV albumin may be considered in patients with SBP. BEST PRACTICE ADVICE 6: Albumin should not be used in patients (hospitalized or not) with cirrhosis and uncomplicated ascites. BEST PRACTICE ADVICE 7: Vasoconstrictors should not be used in the management of uncomplicated ascites, after large-volume paracentesis or in patients with SBP. BEST PRACTICE ADVICE 8: IV albumin is the volume expander of choice in hospitalized patients with cirrhosis and ascites presenting with AKI. BEST PRACTICE ADVICE 9: Vasoactive drugs (eg, terlipressin, norepinephrine, and combination of octreotide and midodrine) should be used in the treatment of HRS-AKI, but not in other forms of AKI in cirrhosis. BEST PRACTICE ADVICE 10: Terlipressin is the vasoactive drug of choice in the treatment of HRS-AKI and use of concurrent albumin can be considered when accounting for patient's volume status. BEST PRACTICE ADVICE 11: Terlipressin treatment does not require intensive care unit monitoring and can be administered intravenously through a peripheral line. BEST PRACTICE ADVICE 12: Terlipressin use is contraindicated in patients with hypoxemia and in patients with ongoing coronary, peripheral, or mesenteric ischemia, and should be used with caution in patients with acute-on-chronic liver failure grade 3. The benefits may not outweigh the risks in patients with serum creatinine >5 mg/dL and in patients listed for transplantation with a Model for End-stage Liver Disease ≥35.

(1) Background: Acute-on-chronic liver failure (ACLF) is a severe, rapidly progressing disease in patients with liver cirrhosis. Meropenem is crucial for treating severe infections. Therapeutic drug monitoring (TDM) offers an effective means to control drug dosages, especially vital for bactericidal antibiotics like meropenem. We aimed to assess the outcomes of implementing TDM for meropenem using an innovative interprofessional approach in ACLF patients on a medical intensive care unit (ICU). (2) Methods: The retrospective study was conducted on a medical ICU. The outcomes of an interprofessional approach comprising physicians, hospital pharmacists, and staff nurses to TDM for meropenem in critically ill patients with ACLF were examined in 25 patients. Meropenem was administered continuously via an infusion pump after the application of an initial loading dose. TDM was performed weekly using high-performance liquid chromatography (HPLC). Meropenem serum levels, implementation of the recommendations of the interprofessional team, and meropenem consumption were analyzed. (3) Results: Initial TDM for meropenem showed a mean meropenem serum concentration of 20.9 ± 9.6 mg/L in the 25 analyzed patients. Of note, in the initial TDM, only 16.0% of the patients had meropenem serum concentrations within the respective target range, while 84.0% exceeded this range. Follow-up TDM showed serum concentrations of 15.2 ± 5.7 mg/L (9.0-24.6) in Week 2 and 11.9 ± 2.3 mg/L (10.2-13.5) in Week 3. In Week 2, 41.7% of the patients had meropenem serum concentrations that were within the respective target range, while 58.3% of the patients were above this range. In Week 3, 50% of the analyzed serum concentrations of meropenem were within the targeted range, and 50% were above the range. In total, 100% of the advice given by the interprofessional team regarding meropenem dosing or a change in antibiotic therapy was implemented. During the intervention period, the meropenem application density was 37.9 recommended daily doses (RDD)/100 patient days (PD), compared to 42.1 RDD/100 PD in the control period, representing a 10.0% decrease. (4) Conclusions: Our interprofessional approach to TDM significantly reduced meropenem dosing, with all the team's recommendations being implemented. This method not only improved patient safety but also considerably decreased the application density of meropenem.

Background: Hepatic encephalopathy (HE) caused by cirrhosis has severe consequences on an individual's lifespan, leading to long-term liver complications and potentially life-threatening outcomes. Despite recent interest in this condition, the effectiveness of secondary prophylaxis involving rixafimin, lactulose, or L-ornithine L-aspartate (LOLA) may be hindered by the unique microbial profiles each patient possesses. Methods: Thus, in this manuscript, we aimed to search, identify, and gather all randomized controlled trials (RCTs) published between 2000-2023 (November) in four major academic databases such as PubMed, ISI Web of Science, Scopus, and ScienceDirect by using a controlled terminology and web strings that reunite six main keywords. We complementarily retrieved data on the ongoing RCTs. Results: Regardless of the relatively high number of results displayed (n = 75), 46.66% (n = 35) were initially deemed eligible after the first evaluation phase after removing duplicates, n = 40 (53.34%). At the second assessment stage, we eliminated 11.42% (n = 4) studies, of which n = 22 finally met the eligibility criteria to be included in the main body of the manuscript. In terms of RCTs, otherwise found in distinct stages of development, n = 3 target FMT and n = 1 probiotics. Conclusions: Although we benefit from the necessary information and technology to design novel strategies for microbiota, only probiotics and synbiotics have been extensively studied in the last decade compared to FMT.

Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have garnered considerable attention as prospective modalities of treatment for liver fibrosis (LF). The inhibition of hepatic stellate cell (HSC) activation underlies the anti-fibrotic effects of hUC-MSCs. However, the precise mechanism by which hUC-MSCs impede HSC activation remains unclarified. We aimed to elucidate the intrinsic mechanisms underlying the therapeutic effects of hUC-MSCs in LF patients.

Mice with liver cirrhosis induced by carbon tetrachloride (CCl4) were used as experimental models and administered hUC-MSCs via tail-vein injection. The alterations in inflammation and fibrosis were evaluated through histopathological examinations. RNA sequencing (RNA-seq) and bioinformatics analysis were then conducted to investigate the therapeutic mechanism of hUC-MSCs. Finally, an in-vitro experiment involving the co-cultivation of hUC-MSCs or hUC-MSC-derived exosomes (MSC-Exos) with LX2 cells was performed to validate the potential mechanism underlying the hepatoprotective effects of hUC-MSCs in LF patients.

hUC-MSC therapy significantly improved liver function and alleviated LF in CCl4-induced mice. High-throughput RNA-Seq analysis identified 1142 differentially expressed genes that were potentially involved in mediating the therapeutic effects of hUC-MSCs. These genes play an important role in regulating the extracellular matrix. miRNA expression data (GSE151098) indicated that the miR-148a-5p level was downregulated in LF samples, but restored following hUC-MSC treatment. miR-148a-5p was delivered to LX2 cells by hUC-MSCs via the exosome pathway, and the upregulated expression of miR-148a-5p significantly suppressed the expression of the activated phenotype of LX2 cells. SLIT3 was identified within the pool of potential target genes regulated by miR-148a-5p. Furthermore, hUC-MSC administration upregulated the expression of miR-148a-5p, which played a crucial role in suppressing the expression of SLIT3, thereby palliating fibrosis.

hUC-MSCs inhibit the activation of HSCs through the miR-148a-5p/SLIT3 pathway and are thus capable of alleviating LF.

Hepatorenal syndrome (HRS), defined by the extreme manifestation of renal impairment in patients with cirrhosis, is characterized by reduced renal blood flow and glomerular filtration rate. It is diagnosed with reduced kidney function confirming the absence of intrinsic kidney disease, such as hematuria or proteinuria. HRS is potentially reversible with liver transplantation or vasoconstrictor drugs. The condition carries a poor prognosis with high mortality rates, particularly in patients with advanced cirrhosis. The latest management for HRS involves a combination of pharmacological and non-pharmacological interventions, aiming to improve renal function and reduce the risk of mortality. Pharmacological treatments include vasoconstrictors, such as terlipressin and midodrine, and albumin infusion, which have been shown to improve renal function and reduce mortality in HRS patients. Non-pharmacological interventions, including invasive procedures such as transjugular intrahepatic portosystemic shunt (TIPS), plasma exchange, liver transplantation, and renal replacement therapy, may also be considered. Though TIPS has been shown to be effective in improving renal function in HRS patients, liver transplantation remains at the top of the consideration for the treatment of end-stage liver disease and HRS. Recent studies have placed importance on early recognition and prompt intervention in HRS patients, as delaying treatment can result in poorer outcomes. Although there are numerous reviews that summarize various aspects of HRS, the recent advancements in the management and pathophysiology of HRS are still insufficient. Therefore, in this review, we summarized a brief pathophysiology and highlighted recent advancements in the management of HRS with a quick review of the latest articles.