Sarcopenia, characterized by the loss of skeletal muscle mass and function, is a significant complication in patients with cirrhosis. This condition not only exacerbates the overall morbidity and mortality associated with liver disease but also complicates patient management, increasing the risk of hospitalization, infections, and hepatic encephalopathy. Despite its clinical significance, sarcopenia in cirrhotic patients remains underdiagnosed and undertreated. This review aims to summarize current knowledge on the pathophysiology of sarcopenia in cirrhosis, including mechanisms such as altered metabolism, hormonal imbalances, and inflammation. Additionally, we explore diagnostic challenges and discuss emerging therapeutic strategies, including nutritional support, exercise, and pharmacological interventions. By highlighting the gaps in existing research and proposing directions for future studies, this review seeks to improve the management and outcomes of cirrhotic patients affected by sarcopenia.

According to the report from the Chinese Center for Disease Control and Prevention, the prevalence of human immunodeficiency virus (HIV) infection exceeded 1.2 million individuals by the year 2022, with an annual increase of about 80000 cases. The overall prevalence of hepatitis B surface antigen among individuals co-infected with HIV reached 13.7%, almost twice the rate of the general population in China. In addition to the well-documented susceptibility to opportunistic infections and new malignancies, HIV infected patients frequently experience liver-related organ damage, with the liver and kidneys being the most commonly affected. This often leads to the development of end-stage liver and kidney diseases. Therefore, organ transplantation has emerged as an important part of active treatment for HIV infected patients. However, the curative effect is not satisfactory. HIV infection has been considered a contraindication for organ transplantation. Until the emergence of highly active anti-retroviral therapy in 1996, the once intractable replication of retrovirus was effectively inhibited. With prolonged survival, the failure of important organs has become the main cause of death among HIV patients. Therefore, transplant centers worldwide have resumed exploration of organ transplantation for HIV-infected individuals and reached a positive conclusion. This study provides an overview of the current landscape of HIV-positive patients receiving liver transplantation (LT) in mainland China. To date, our transplant center has conducted LT for eight end-stage liver disease patients co-infected with HIV, and all but one, who died two months postoperatively due to sepsis and progressive multi-organ failure, have survived. Comparative analysis with hepatitis B virus-infected patients during the same period revealed no statistically significant differences in acute rejection reactions, cytomegalovirus infection, bacteremia, pulmonary infections, acute kidney injury, new-onset cancers, or vascular and biliary complications.

BACKGROUND: Highly active antiretroviral therapy (HAART) has been able to improve the immune system function and survival of human immunodeficiency virus (HIV) patients. However, Patients coinfected with HIV and hepatitis B virus (HBV) are more likely to develop end-stage liver disease (ESLD) than those infected with HBV alone. Consequently, liver transplantation is often required for these patients. This study evaluates the outcomes of orthotopic liver transplantation (OLT) of HIV-HBV coinfected patients in China.
METHODS: We conducted a retrospective analysis on all HIV-HBV coinfected patients that underwent OLT from April 1, 2019 to December 31, 2021 and their outcomes were compared to all HBV monoinfected patients undergoing OLT during the same period. Patient outcomes were determined, including cumulative survival, viral load, CD4 T-cell count and postoperative complications.
RESULTS: The median follow-up of HIV recipients was 36 months after OLT (interquartile range 12-39 months). Almost all patients had stable CD4 T-cell count (> 200 copies/ul), undetectable HBV DNA levels, and undetectable HIV RNA load during follow-up. The 1-, 2-, and 3-year posttransplant survival rates were 85.7% for the HIV group (unchanged from 1 to 3 years) versus 82.2%, 81.2%, and 78.8% for the non-HIV group. Cumulative survival among HIV-HBV coinfected recipients was not significantly different from the HBV monoinfected recipients (log-rank test P = 0.692). The percentage of deaths attributed to infection was comparable between the HIV and non-HIV groups (14.3% vs. 9.32%, P = 0.665). Post OLT, there was no significant difference in acute rejection, cytomegalovirus infection, bacteremia, pulmonary infection, acute kidney injury, de novo tumor and vascular and biliary complications.
CONCLUSIONS: Liver transplantation in patients with HIV-HBV coinfection yields excellent outcomes in terms of intermediate- or long-term survival rate and low incidence of postoperative complications in China. These findings suggest that OLT is safe and feasible for HIV-HBV coinfected patients with ESLD.
BACKGROUND: Chinese Clinical Trial Registry (ChiCTR2300067631), registered 11 January 2023.

OBJECTIVE: Patients with end-stage liver disease (ESLD) are susceptible to invasive pulmonary aspergillosis (IPA). This study aimed to investigate the risk factors affecting the occurrence and short-term prognosis of ESLD complicated by IPA.
METHODS: This retrospective case-control study included 110 patients with ESLD. Of them, 27 ESLD-IPA received antifungal therapy with amphotericin B (AmB); 27 AmB-free-treated ESLD-IPA patients were enrolled through 1:1 propensity score matching. Fifty-six ESLD patients with other comorbid pulmonary infections were enrolled as controls. The basic features of groups were compared, while the possible risk factors affecting the occurrence and short-term outcomes of IPA were analyzed.
RESULTS: Data analysis revealed invasive procedures, glucocorticoid exposure, and broad-spectrum antibiotic use were independent risk factors for IPA. The 54 patients with ESLD-IPA exhibited an overall treatment effectiveness and 28-d mortality rate of 50.00% and 20.37%, respectively, in whom patients treated with AmB-containing showed higher treatment efficacy than patients treated with AmB-free antifungal regimens (66.7% vs. 33.3%, respectively, χ2 = 6.000, P = 0.014). Multivariate logistic regression analysis revealed that the treatment regimen was the only predictor affecting patient outcomes, with AmB-containing regimens were 4.893 times more effective than AmB-free regimens (95% CI, 1.367-17.515; P = 0.015). The only independent predictors affecting the 28-d mortality rate were neutrophil-to-lymphocyte ratio and IPA diagnosis (OR = 1.140 and 10.037, P = 0.046 and 0.025, respectively).
CONCLUSIONS: Glucocorticoid exposure, invasive procedures, and broad-spectrum antibiotic exposure increased the risk of IPA in ESLD patients. AmB alone or combined with other antifungals may serve as an economical, safe, and effective treatment option for ESLD-IPA.

OBJECTIVE: Chronic liver injury that results in cirrhosis and end-stage liver disease (ESLD) causes more than 1 million deaths annually worldwide. Although the impact of genetic factors on the severity of metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-related liver disease (ALD) has been previously studied, their contribution to the development of ESLD remains largely unexplored.
METHODS: We genotyped 6 MASLD-associated polymorphisms in healthy (n = 123), metabolic dysfunction-associated steatohepatitis (MASH) (n = 145), MASLD-associated ESLD (n = 72), and ALD-associated ESLD (n = 57) cohorts and performed multinomial logistic regression to determine the combined contribution of genetic, demographic, and clinical factors to the progression of ESLD.
RESULTS: Distinct sets of factors are associated with the progression to ESLD. The PNPLA3 rs738409:G and TM6SF2 rs58542926:T alleles, body mass index (BMI), age, and female sex were positively associated with progression from a healthy state to MASH. The PNPLA3 rs738409:G allele, age, male sex, and having type 2 diabetes mellitus were positively associated, while BMI was negatively associated with progression from MASH to MASLD-associated ESLD. The PNPLA3 rs738409:G and GCKR rs780094:T alleles, age, and male sex were positively associated, while BMI was negatively associated with progression from a healthy state to ALD-associated ESLD. The findings indicate that the PNPLA3 rs738409:G allele increases susceptibility to ESLD regardless of etiology, the TM6SF2 rs58542926:T allele increases susceptibility to MASH, and the GCKR rs780094:T allele increases susceptibility to ALD-associated ESLD.
CONCLUSIONS: The PNPLA3, TM6SF2, and GCKR minor alleles influence the progression of MASLD-associated or ALD-associated ESLD. Genotyping for these variants in MASLD and ALD patients can enhance risk assessment, prompting early interventions to prevent ESLD.

BACKGROUND: This study aimed to investigate the association between the intake of different dietary carbohydrate components and the long-term outcomes of non-alcoholic fatty liver disease (NAFLD).
METHODS: We used prospective data from 26,729 NAFLD participants from the UK Biobank cohort study. Dietary information was recorded by online 24-hour questionnaires (Oxford WebQ). Consumption of different carbohydrate components was calculated by the UK Nutrient Databank Food Composition Table. Cox proportional hazards models were used to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI). A substitution model was used to estimate the associations of hypothetical substitution for free sugars.
RESULTS: During a median of 10.5 (IQR: 10.2-11.2) years and a total of 280,135 person-years of follow-up, 310 incident end-stage liver disease (ESLD) and 1750 deaths were recorded. Compared with the lowest quartile, the multi-adjusted HRs (95% CI) of incident ESLD in the highest quartile were 1.65 (1.14-2.39) for free sugars, 0.51 (0.35-0.74) for non-free sugars, and 0.55 (0.36-0.83) for fiber. For overall mortality, the multi-adjusted HRs (95% CI) in the highest quartile were 1.21 (1.04-1.39) for free sugars, 0.79 (0.68-0.92) for non-free sugars, and 0.79 (0.67-0.94) for fiber. Substituting free sugars with equal amounts of non-free sugars, starch or fiber was associated with a lower risk of incident ESLD and overall mortality.
CONCLUSIONS: A lower intake of free sugars and a higher intake of fiber are associated with a lower incidence of ESLD and overall mortality in NAFLD patients. These findings support the important role of the quality of dietary carbohydrates in preventing ESLD and overall mortality in NAFLD patients.

OBJECTIVE: To designed a new model using pre-transplant data to predict post-transplant mortality for Chinese population and compared its performance to that of existing models.
METHODS: In this multicenter study, 544 recipients of liver transplants for non-tumor indications were enrolled in the training group and 276 patients in the validation group. The new Simplified Mortality Prediction Scores (SMOPS) model was compared to the MELD and four existing models using the C-statistic.
RESULTS: SMOPS model used 6 independent pre-transplantation risk factors screened from the training group (chronic liver failure/organ failure scores, fever > 37.6 ℃, ABO blood-type compatibility, arterial lactate level, leukocyte count and re-transplantation). The SMOPS accurately predicted patients\' 30-day, 90-day and 365-day mortality following liver transplantation, and its\' scores were more accurate than those of the other models. The SMOPS generated four levels of risk: low risk (<10 points), moderate risk (11-20 points), high risk (21-25 points) and futile risk (≥26 points). The survival within all risk levels was not different between MELD=40 and MELD<40. The survival within moderate-, high- or extreme-risk ALF was not different between ALF and non-ALF.
CONCLUSIONS: The SMOPS model uses pre-transplant risk factors to stratify post-transplant survival and is superior to current models for Chinese population, and has the potential to contribute to improvements in organ-allocation policies.

Background: Conventional methods are low in positive rates and time-consuming for ascites pathogen detection in patients with end-stage liver disease (ESLD). With many advantages, metagenomic next-generation sequencing (mNGS) may be a good alternative method. However, the related studies are still lacking. Methods: Ascites from 50 ESLD patients were sampled for pathogen detection using mNGS and conventional methods (culture and polymorphonuclear neutrophils detection) in this prospective observational study. Results: Forty-two samples were detected positive using mNGS. 29 strains of bacteria, 11 strains of fungi, and 9 strains of viruses were detected. 46% of patients were detected to be co-infected with 2 or more pathogens by mNGS. Moreover, mNGS showed similar and high positive rates in ESLD patients with different clinical characteristics. Compared to conventional methods, mNGS had higher positivity rates (84% vs. 20%, P<0.001), sensitivity (45.2% vs. 23.8%, P=0.039), broader pathogen spectrum, shorter detection time (24 hours vs. 3-7 days), but lower specificity (25% vs 100%, P = 0.010). Furthermore, compared to conventional methods, mNGS showed similar consistence with final diagnosis (42% vs. 36%, P=0.539). Conclusions: mNGS may be a good supplement for conventional methods and helpful to early etiological diagnosis of peritonitis, and thus improve ESLD patients\' survival.

UNASSIGNED: Liver cancer and cirrhosis represent the most prevalent forms of end-stage liver diseases (ESLDs). Notably, in China, deaths attributed to ESLDs contribute significantly to the global mortality rate of these disorders. Enhanced comprehension of the mortality profile associated with ESLDs in China could provide crucial insights into intervention prioritization, which could in turn help reduce the overall global burden of these diseases.
UNASSIGNED: Data were obtained from China\'s Disease Surveillance Points system. The presentation includes both crude and age-standardized mortality rates, stratified by sex, residential location, and region. Using Joinpoint Regression, trends in annual mortality rates were estimated from the period of 2008 to 2020 and expressed as the average annual percentage change (AAPC).
UNASSIGNED: In 2020, the gross mortality rate of ESLD stood at 30.08 cases per 100,000 individuals. A higher age-standardized ESLD mortality rate was observed in males and rural populations in comparison to their female and urban counterparts, respectively. Noticeably, the highest mortality rates associated with liver cancer and cirrhosis were reported in South and Southwest China, respectively. A positive correlation was noticed between age-specific ESLD mortality rates and advancing age. Interestingly, an annual decrease in the ESLD mortality rate was observed from 2008 to 2020. In urban contexts, the AAPC of cirrhosis was noted to be higher than that of liver cancer.
UNASSIGNED: The mortality rate associated with ESLDs in China decreased between 2008 and 2020. Nevertheless, the death burden attributable to ESLD continues to be alarmingly high. Future initiatives should prioritize the reduction of ESLD mortality in particular populations: males, elderly individuals, and those residing in rural regions of South and Southwest China. The emphasis of future interventions should be placed on antiviral therapy for adults diagnosed with viral hepatitis, and on the prevention of hepatitis B virus (HBV) infection across all demographics.

Liver disease is prevalent worldwide. When it reaches the end stage, mortality rises to 50% or more. Although liver transplantation has emerged as the most efficient treatment for end-stage liver disease, its application has been limited by the scarcity of donor livers. The lack of acceptable donor organs implies that patients are at high risk while waiting for suitable livers. In this scenario, cell therapy has emerged as a promising treatment approach. Most of the time, transplanted cells can replace host hepatocytes and remodel the hepatic microenvironment. For instance, hepatocytes derived from donor livers or stem cells colonize and proliferate in the liver, can replace host hepatocytes, and restore liver function. Other cellular therapy candidates, such as macrophages and mesenchymal stem cells, can remodel the hepatic microenvironment, thereby repairing the damaged liver. In recent years, cell therapy has transitioned from animal research to early human studies. In this review, we will discuss cell therapy in end-stage liver disease treatment, especially focusing on various cell types utilized for cell transplantation, and elucidate the processes involved. Furthermore, we will also summarize the practical obstacles of cell therapy and offer potential solutions.