End-stage Liver Disease Research Articles

Validation of MELD3.0 in 2 centers from different continents.

MELD3.0 has been proposed to stratify patients on the liver transplant waiting list (WL) to reduce the historical disadvantage of women in accessing liver transplant. Our aim was to validate MELD3.0 in 2 unique populations. This study is a 2-center retrospective cohort study from Toronto, Canada, and Valencia, Spain, of all adults added to the liver transplant WL between 2015 and 2019. Listing indications whose short-term survival outcome is not adequately captured by the MELD score were excluded. All patients analyzed had a minimum follow-up of 3 months after inclusion in the WL. Six hundred nineteen patients were included; 61% were male, with a mean age of 56 years. Mean MELD at inclusion was 18.00 ± 6.88, Model for End-Stage Liver Disease Sodium (MELDNa) 19.78 ± 7.00, and MELD3.0 20.25 ± 7.22. AUC to predict 90-day mortality on the WL was 0.879 (95% CI: 0.820, 0.939) for MELD, 0.921 (95% CI: 0.876, 0.967) for MELDNa, and 0.930 (95% CI: 0.888, 0.973) for MELD3.0. MELDNa and MELD3.0 were better predictors than MELD (p = 0.055 and p = 0.024, respectively), but MELD3.0 was not statistically superior to MELDNa (p = 0.144). The same was true when stratified by sex, although the difference between MELD3.0 and MELD was only significant for women (p = 0.032), while no statistical significance was found in either sex when compared with MELDNa. In women, AUC was 0.835 (95% CI: 0.744, 0.926) for MELD, 0.873 (95% CI: 0.785, 0.961) for MELDNa, and 0.886 (95% CI: 0.803, 0.970) for MELD3.0; differences for the comparison between AUC in women versus men for all 3 scores were nonsignificant. Compared to MELD, MELD3.0 was able to reclassify 146 patients (24%), the majority of whom belonged to the MELD 10-19 interval. Compared to MELDNa, it reclassified 68 patients (11%), most of them in the MELDNa 20-29 category. MELD3.0 has been validated in centers with significant heterogeneity and offers the highest mortality prediction for women on the WL without disadvantaging men. However, in these cohorts, it was not superior to MELDNa.

Cognitive impairment in patients awaiting kidney and liver transplantation-A clinically relevant problem?

Cognitive impairment (CI) is common in both end-stage kidney disease (ESKD) and alcohol-related liver cirrhosis. The aim of this study was to assess the prevalence and patterns of CI in patients awaiting kidney and liver transplantation, and to identify its determinants. In this cross-sectional, prospective study, 31 consecutive patients with ESKD and 31 consecutive patients with alcohol-related liver cirrhosis, all currently on transplant waiting lists, were screened for cognitive decline using the Addenbrooke's Cognitive Examination. Medical history, demographics, and laboratory test results were also collected. The prevalence of CI among patients with ESKD and alcohol-related liver cirrhosis was 26% and 90%, respectively. In both groups, memory was the most affected cognitive domain, along with verbal fluency in patients with ESKD, and visuospatial abilities in patients with alcoholic cirrhosis. The most statistically significant increase in the prevalence of CI was found in patients with lower educational attainment, in both alcohol-related liver cirrhosis and ESKD populations as well as in older patients with alcoholic cirrhosis. Furthermore, better cognitive functioning in ESKD patients was associated with higher levels of total lymphocyte count and alanine transaminase (ALT), and in alcohol-related liver cirrhosis patients with higher levels of ALT and aspartate transaminase. A nonsignificant trend toward lower memory domain scores was also observed with increasing ammonia levels and increasing severity of liver disease (higher Child-Pugh scores). Finally, suboptimal performance on the screening test was correlated with the severity of liver disease as assessed by the Model for End-Stage Liver Disease Sodium (MELD-Na), but not at the statistically significant level. The prevalence of CI, especially in patients with alcohol-related liver cirrhosis, is high and can be a significant clinical problem, negatively affecting the transplantation process. Routine screening tests in this group would contribute to the implementation of appropriate management, such as rehabilitation program or psychosocial treatments and facilitate the provision of specialized health care.

Mesenchymal Stem Cells in Liver Diseases: Present Status and Future Perspectives.

Liver disease is a major worldwide health and economic problem. Allograft liver transplant is the only effective therapy for end-stage liver disease. The shortage of donors, the high costs, postoperative complications, and lifelong immunosuppression are rate-limiting factors for this established line of treatment. Hence, searching for therapeutic alternatives is mandatory. Stem cells are attractive candidates for cell-based therapy for their potential to support liver regeneration with few complications. They can differentiate into specialized cells, including hepatocytes to restore liver structure and function. Stem cells originating from different sources have been investigated for the treatment of liver diseases. In this review, we highlight the role of stem cells as an appropriate source for liver cell replacement in different liver diseases.

A novel peptide encoded by circ-SLC9A6 promotes lipid dyshomeostasis through the regulation of H4K16ac-mediated CD36 transcription in NAFLD.

As the leading cause of end-stage liver disease, nonalcoholic fatty liver disease (NAFLD) is mainly induced by lipid dyshomeostasis. The translation of endogenous circular RNAs (circRNAs) is closely related to the progression of various diseases, but the involvement of circRNAs in NAFLD has not been determined. Combined high-throughput circRNA profiles were used to identify circRNAs with translational potential. The underlying molecular mechanisms were investigated by RNA sequencing, pull-down/MS and site-specific mutagenesis. In this study, we focused on circ-SLC9A6, an abnormally highly expressed circRNA in human and mouse liver tissue during NAFLD development that exacerbates metabolic dyshomeostasis in hepatocytes by encoding a novel peptide called SLC9A6-126aa in vivo and in vitro. YTHDF2-mediated degradation of m6A-modified circ-SLC9A6 was found to be essential for the regulation of SLC9A6-126aa expression. We further found that the phosphorylation of SLC9A6-126aa by AKT was crucial for its cytoplasmic localization and the maintenance of physiological homeostasis, whereas high-fat stress induced substantial translocation of unphosphorylated SLC9A6-126aa to the nucleus, resulting in a vicious cycle of lipid metabolic dysfunction. Nuclear SLC9A6-126aa promotes transcriptional activation of the target gene CD36 and enhances its occupancy of the CD36 promoter locus by regulating MOF-mediated histone H4K16 acetylation. Hepatic CD36 depletion significantly ameliorated hyperactivated MAPK signalling and lipid disturbance in SLC9A6-126aa transgenic mice. Clinically, increasing levels of SLC9A6-126aa were observed during NAFLD progression and were found to be positively correlated with the CD36 and MAPK cascades. This study revealed the role of circ-SLC9A6-derived SLC9A6-126aa in the epigenetic modification-mediated regulation of lipid metabolism. Our findings may provide promising therapeutic targets for NAFLD and new insights into the pathological mechanisms of metabolic diseases. Under normal circumstances, driven by m6A modification, YTHDF2 directly recognizes and degrades circ-SLC9A6, thereby inhibiting the translation of SLC9A6-126aa. Additionally, AKT1 phosphorylates and inhibits the nuclear translocation of SLC9A6-126aa. In NAFLD, lipid overload leads to YTHDF2 and AKT1 deficiency, ultimately increasing the expression and nuclear import of SLC9A6-126aa. Nuclear SLC9A6-126aa binds directly to the CD36 promoter and initiates CD36 transcription, which induces lipid dyshomeostasis.

A plasma peptidomic signature reveals extracellular matrix remodeling and predicts prognosis in alcohol-associated hepatitis.

Alcohol-associated hepatitis (AH) is plagued with high mortality and difficulty in identifying at-risk patients. The extracellular matrix undergoes significant remodeling during inflammatory liver injury and could potentially be used for mortality prediction. EDTA plasma samples were collected from patients with AH (n = 62); Model for End-Stage Liver Disease score defined AH severity as moderate (12-20; n = 28) and severe (>20; n = 34). The peptidome data were collected by high resolution, high mass accuracy UPLC-MS. Univariate and multivariate analyses identified differentially abundant peptides, which were used for Gene Ontology, parent protein matrisomal composition, and protease involvement. Machine-learning methods were used to develop mortality predictors. Analysis of plasma peptides from patients with AH and healthy controls identified over 1600 significant peptide features corresponding to 130 proteins. These were enriched for extracellular matrix fragments in AH samples, likely related to the turnover of hepatic-derived proteins. Analysis of moderate versus severe AH peptidomes was dominated by changes in peptides from collagen 1A1 and fibrinogen A proteins. The dominant proteases for the AH peptidome spectrum appear to be CAPN1 and MMP12. Causal graphical modeling identified 3 peptides directly linked to 90-day mortality in >90% of the learned graphs. These peptides improved the accuracy of mortality prediction over the Model for End-Stage Liver Disease score and were used to create a clinically applicable mortality prediction assay. A signature based on plasma peptidome is a novel, noninvasive method for prognosis stratification in patients with AH. Our results could also lead to new mechanistic and/or surrogate biomarkers to identify new AH mechanisms.

Long-Term Continuous Terlipressin Infusion Improves Cardiac Reserve in Patients With Decompensated Cirrhosis

Cardiac dysfunction is a key factor in the pathogenesis of hepatorenal syndrome, for which terlipressin is the recommended first-line treatment. This study investigates whether long-term terlipressin can ameliorate the subclinical cardiac dysfunction observed in decompensated cirrhosis. Twenty-two patients with decompensated cirrhosis and ascites enrolled in a prospective study of home continuous terlipressin infusion were included. Cardiac function was assessed using dobutamine stress echocardiogram before and after 12 weeks of terlipressin. The primary outcome was the impact of terlipressin on cardiac reserve; the change in cardiac output (CO) in response to stress. Median age was 61 years (IQR 56-64), median MELD score was 15 (IQR 12.3-17.0) and 72.7% were male. The increase in CO in response to low-dose dobutamine was significantly higher following terlipressin (↑4.0L/min [↑57.8%]) as compared to baseline (↑1.8L/min [21.3%], p=0.0001). The proportion of patients with impaired cardiac reserve (defined by ΔCO <25% after low-dose dobutamine) reduced from 81.8% at baseline to 40.9% after terlipressin, (p=0.02), driven primarily by improvement in inotropic function. Resting cardiac output (CO) decreased significantly after terlipressin from 8.9±2.2L/min to 7.2±1.8 L/min (p<0.001, normal range 5-6L/min), due to a decrease in stroke volume from 108 to 86mL/beat (p=0.006). Long-term continuous terlipressin infusion resulted in a significant increase in cardiac reserve and attenuation of the hyperdynamic state usually observed in decompensated cirrhosis. These data provide important mechanistic insight into the pathogenesis and reversibility of cardiac dysfunction in cirrhosis. Future studies are required to evaluate whether long-term terlipressin can prevent hepatic decompensating events such as hepatorenal syndrome in high-risk individuals. ANZCTR NUMBER: (http://www.anzctr.org.au/): ACTRN12619000891123.

Gamma-glutamyltransferase (GGT) is a predictor of NAFLD activity score for diagnosing non- alcoholic steatohepatitis (NASH)

Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of conditions ranging from simple steatosis to steatohepatitis, advanced fibrosis and end stage liver disease. Despite the high prevalence and severity of hepatic illness, NAFLD remains underdiagnosed, because of few symptoms, lack of accurate laboratory markers. The study was aimed at to evaluate a bio-chemical score for diagnosing non-alcoholic steatohepatitis. A hospital based cross-sectional observational study was carried out for a period of two years from July 2013 to June 2015 in the Department of Hepatology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. The study was conducted among 50 patients of NAFLD attending at department of Hepatology and underwent for biochemical investigations and liver biopsy with NAFLD Activity Score (NAS). All data were presented as mean ± SD and analyzed by SPSS (version 16). Qualitative data were analyzed by Chi-square test and quantitative data were analyzed by student’s t-test. Performance of the test were assessed by sensitivity and specificity test. Statistically significant result were considered when p value &lt; 0.05. Total patients were divided into two groups 25 were NASH and 25 were non- NASH. Mean GGT was found 73.6±48.6 U/L in NASH group and 49.9±25.4 U/L in non-NASH group. There was significant difference in the NAFLD activity score for diagnosing NASH between elevated and normal GGT (P value 0.035). Higher GGT values correlated with higher specificity. The Gamma-lutamyltransferase (GGT) has been proposed as a noninvasive and available marker for assessment of NASH. Bangladesh Med J. 2023 May; 52(2): 6-10

Factors Associated with Survival Rate in Biliary Atresia Patients Following Kasai Surgery

Introduction: Biliary atresia is the most frequent cause of obstructive jaundice leading to liver fibrosis, end-stage liver disease, and death. Kasai surgery offers a bridge to attenuate liver fibrosis progression through reconstruction of the biliary system. The success of the Kasai procedure depends on the presence of jaundice, age at the time of surgery, clay-colored stool, and bilirubin counts. Aim: This study aimed to investigate and predict the death incidence of Biliary atresia patients following Kasai Surgery in our institution. Method: We conducted a case-control study from March 2020 to January 2022 at Kariadi General Hospital, Semarang, Indonesia. We collected data related to gender, age at surgery, albumin level pre and post-surgery, total and direct bilirubin before and after surgery, and the presence of ascites. Bivariate analysis using the Chi-Square test with OR (95% CI) was performed to analyze the risk factors in BA patients following the Kasai procedure. Results: 19 patients with biliary atresia underwent the Kasai procedure with a survival rate of 68.4%. Bilirubin levels ≥10 mg/dL before (p=0.033, OR 11.25) and after (p=0.025, OR 11.00) the Kasai procedure, and the presence of ascites (p=0.005) were significant factors associated with mortality cases. However, a combined multivariate analysis of these factors did not show any significant relationship with outcomes. Conclusion: Bilirubin exceeding 10 mg/dL before and after the Kasai procedure and the presence of Ascites was a marker for poor outcomes for biliary atresia patients following the Kasai procedure

HYPERAMMONEMIA IS ASSOCIATED WITH INCREASING SEVERITY OF BOTH LIVER CIRRHOSIS AND HEPATIC ENCEPHALOPATHY

Hyperammonemia is a critical condition frequently observed in patients with liver cirrhosis and hepatic encephalopathy. Objectives: The study's main aim is to find that hyperammonemia is associated with increasing severity of both liver cirrhosis and hepatic encephalopathy. Methods: This retrospective cohort study was conducted at DHQ Hospital Nowshera Khyber Pakhtunkhwa from January 2023 to June 2023. A total of 175 patients diagnosed with liver cirrhosis were included in the study. Data collection was performed using the hospital's electronic medical records system. The variables collected included demographic data like patients’ age and sex and clinical data concerning the etiology of cirrhosis, Child-Pugh score, and MELD score. Results: The study included 175 patients with liver cirrhosis, with a mean age of 54.3 ± 12.7 years, of whom 64% were male and 36% female. The etiologies of cirrhosis were predominantly hepatitis C virus (45%), hepatitis B virus (30%), alcoholic liver disease (15%), and non-alcoholic steatohepatitis (10%). The mean Child-Pugh score was 8.7 ± 2.1, indicating moderate to severe liver disease, and the mean MELD score was 14.3 ± 4.5. The study found a strong positive correlation between ammonia levels and encephalopathy severity (r = 0.72, p &lt; 0.001). Conclusion: It is concluded that hyperammonemia is significantly associated with the severity of liver cirrhosis and hepatic encephalopathy.

Single and combined strategies for mesenchymal stem cell exosomes alleviate liver fibrosis: a systematic review and meta-analysis of preclinical animal models.

Background: The efficacy of mesenchymal stem cells (MSCs) in treating liver fibrosis has been supported by various clinical studies. However, stem cell transplantation is limited in clinical application due to its low survival rate, low liver implantation rate, and possible carcinogenicity. Recently, there has been increasing interest in the use of MSC-exos due to their widespread availability, low immunogenicity, and non-carcinogenic properties. Numerous studies have demonstrated the potential of MSC-exos in treating liver fibrosis and preventing progression to end-stage liver disease. Objective: This study aimed to systematically investigate the efficacy of MSC-exos single administration in the treatment of hepatic fibrosis and the combined advantages of MSC-exos in combination with drug therapy (MSC-exos-drugs). Methods: Data sources included PubMed, Web of Science, Embase, and the Cochrane Library, which were built up to January 2024. The population, intervention, comparison, outcomes, and study design (PICOS) principle was used to screen the literature, and the quality of the literature was evaluated to assess the risk of bias. Finally, the data from each study's outcome indicators were extracted for a combined analysis. Results: After screening, a total of 18 papers (19 studies) were included, of which 12 involved MSC-exos single administration for the treatment of liver fibrosis and 6 involved MSC-exos-drugs for the treatment of liver fibrosis. Pooled analysis revealed that MSC-exos significantly improved liver function, promoted the repair of damaged liver tissue, and slowed the progression of hepatic fibrosis and that MSC-exos-drugs were more efficacious than MSC-exos single administration. Subgroup analyses revealed that the use of AD-MSC-exos resulted in more consistent and significant efficacy when MSC-exos was used to treat hepatic fibrosis. For MSC-exos-drugs, a more stable end result is obtained by kit extraction. Similarly, infusion through the abdominal cavity is more effective. Conclusion: The results suggest that MSC-exos can effectively treat liver fibrosis and that MSC-exos-drugs are more effective than MSC-exos single administration. Although the results of the subgroup analyses provide recommendations for clinical treatment, a large number of high-quality experimental validations are still needed. Systematic Review Registration: CRD42024516199.

A Minimal Invasive Approach in Living Donor Liver Transplantation – A Systematic Review

Living donor liver transplantation (LDLT) is probably the most high-profile of all surgical enterprises. At the same time, it is an amazing act of altruism. As the demand for LT continues to increase, LDLT provides life-saving therapy for many patients who would otherwise die awaiting a cadaveric organ. As long as the donor shortage continues to increase, LDLT will play an important role in the future of LT. Today, liver transplantation (LT) represents the treatment of choice for end-stage liver disease and represents the culmination of a long history of innovations made by liver surgeons based on hemorrhage control, appreciating the occurrence of regeneration and understanding the liver anatomy. In the past few years, a number of centers with significant laparoscopic and living donor experience have reported fully minimally invasive approach to hemi-hepatectomies. It has invaluable potential to alleviate the vast gap between supply and demand of hepatic allografts, even though its advantages such as shorter hospital stay and faster return to normal life could attract additional living donors, safety for donors is still being questioned and investigated due to its relatively recent development.

Generation of an induced pluripotent stem cell (iPSC) line (EXSURGi001-A) from a patient homozygous for the p.Ala165Thr mutation in the MTARC1 gene

Metabolic dysfunction-associated fatty liver disease (MAFLD), the leading cause of end-stage liver disease in developed countries, is expected to increase over the next decade. Characterized by hepatic steatosis, MAFLD is commonly studied in animal models. Here, we generated a human induced pluripotent stem cell (iPSC) line from a patient homozygous of the protective MTARC1 gene variant rs2642438:A. This line displays a normal karyotype and typical pluripotent stem cell morphology and can differentiate into all three germ layers in vitro.

Alcohol-associated liver disease increases the risk of muscle loss and mortality in patients with cirrhosis

BackgroundRapid skeletal muscle loss adversely affects the clinical outcomes of liver cirrhosis. However, the relationships between the annual changes in skeletal muscle area (ΔSMA/year) and the etiology of cirrhosis, factors associated with muscle loss, and risk of mortality remains unclear.MethodsA total of 384 patients who underwent multiple computed tomography (CT) scans between March 2004 and June 2021 were enrolled in this study (median age, 67 years; 64% men; median model for end-stage liver disease score, 9). Body composition and ΔSMA/year were estimated using a 3D image analysis system and data from at least two distinct CT scans. Differences in ΔSMA/year among different etiologies of cirrhosis, factors associated with rapid muscle loss (defined as ΔSMA/year ≤ − 3.1%), and the association between ΔSMA/year and mortality were examined.ResultsPatients with alcohol-associated liver disease (ALD) cirrhosis experienced more rapid muscle loss (ΔSMA/year, − 5.7%) than those with hepatitis B (ΔSMA/year, − 2.8%) and hepatitis C cirrhosis (ΔSMA/year, − 3.1%). ALD cirrhosis was independently associated with ΔSMA/year ≤ − 3.1% after adjusting for age, sex, and liver functional reserve. Over a median follow-up period of 3.8 years, ALD cirrhosis, ΔSMA/year ≤ − 3.1%, and low subcutaneous adipose tissue level were found to be significantly associated with reduced survival. ALD cirrhosis (hazard ratio [HR], 2.43; 95% confidence interval [CI] 1.12–5.28) and ΔSMA/year ≤ − 3.1% (HR, 3.68; 95% CI 2.46–5.52) were also predictive of mortality.ConclusionsThese results suggest that ALD cirrhosis increases the risk of rapid muscle loss and mortality in affected patients.

Hip replacement in a heart transplant patient: a case report

Solid organ transplantation is considered the most effective treatment for endstage heart, lung, pancreatic, liver, and kidney diseases. The increasing number of transplants performed, and long-term survival of recipients have contributed to an increase in the diagnostic rate of non-transplant-related diseases.Heart transplant patients are at increased risk of complications when undergoing elective or emergency surgery. We report a case of hip replacement in a young man after orthotopic heart transplantation.

Interaction between the albumin-bilirubin score and nutritional risk index in the prediction of post-hepatectomy liver failure.

Post-hepatectomy liver failure (PHLF) is the most common postoperative complication and the leading cause of death after hepatectomy. The albumin-bilirubin (ALBI) score and nutritional risk index (NRI) have been shown to assess end-stage liver disease and predict PHLF and patient survival. We hypothesized that the ALBI score and NRI interact in the prediction of PHLF. To analyze the interaction between the ALBI score and NRI in PHLF in patients with hepatocellular carcinoma. This retrospective study included 186 patients who underwent hepatectomy for hepatocellular carcinoma at the Affiliated Hospital of Youjiang Medical University for Nationalities between January 2020 and July 2023. Data on patient characteristics and laboratory indices were collected from their medical records. Univariate and multivariate logistic regression were performed to determine the interaction effect between the ALBI score and NRI in PHLF. Of the 186 patients included in the study, PHLF occurred in 44 (23.66%). After adjusting for confounders, multivariate logistic regression identified ALBI grade 2/3 [odds ratio (OR) = 73.713, 95% confidence interval (CI): 9.175-592.199] and NRI > 97.5 (OR = 58.990, 95%CI: 7.337-474.297) as risk factors for PHLF. No multiplicative interaction was observed between the ALBI score and NRI (OR = 0.357, 95%CI: 0.022-5.889). However, the risk of PHLF in patients with ALBI grade 2/3 and NRI < 97.5 was 101 times greater than that in patients with ALBI grade 1 and NRI ≥ 97.5 (95%CI: 56.445-523.839), indicating a significant additive interaction between the ALBI score and NRI in PHLF. Both the ALBI score and NRI were risk factors for PHLF, and there was an additive interaction between the ALBI score and NRI in PHLF.

Expanding the Donor Pool to the Ultimate Level: Introducing the Revolutionary Hybrid Dual Graft Liver Transplant Using Domino and Living Donors.

Innovative solutions are crucial as the demand for liver transplants continues to outpace available grafts. Dual graft liver transplantation offers a promising avenue to address graft volume challenges while minimizing donor risks. This report introduces a groundbreaking approach, combining a full organ domino donor graft with a living donor graft for a hybrid dual graft liver transplant. A 2-y-old child with Maple syrup urine disease and a 40-y-old adult with end-stage liver disease became the focus of this unique case. A hybrid dual graft liver transplant was executed, uniting the domino donor's full organ graft with a living donor's left lateral segment. Precise vascular and biliary reconstructions facilitated a successful transplant. The hybrid dual graft liver transplant, merging domino donor and living donor grafts, presents a viable strategy to combat graft shortages, particularly in regions predominantly reliant on living donor transplants. Despite challenges, this pioneering approach should be embraced by established liver transplant centers because it enables concurrent living donor liver transplantation while prioritizing donor safety and recipient outcomes.

Serum Phosphatidylcholine Species 32:0 as a Biomarker for Liver Cirrhosis Pre- and Post-Hepatitis C Virus Clearance.

Phosphatidylcholine (PC) is an essential lipid for liver health and lipoprotein metabolism, but its circulating levels have rarely been studied in patients with cirrhosis. Chronic hepatitis C virus (HCV) infection causes lipid abnormalities and is a major cause of cirrhosis. Effective HCV elimination with direct-acting antivirals (DAAs) is associated with the normalization of serum low-density lipoprotein cholesterol levels. Since PC is abundant in all lipoprotein particles, this study analyzed the association between serum PC species levels and liver cirrhosis before and after HCV eradication. Therefore, 27 PC species were measured by Fourier Transform Mass Spectrometry in the serum of 178 patients with chronic HCV infection at baseline and in 176 of these patients at the end of therapy. The PC species did not correlate with viral load, and the levels of 13 PC species were reduced in patients infected with genotype 3a compared to those affected with genotype 1. Four PC species were slightly elevated 12 weeks after DAA initiation, and genotype-related changes were largely normalized. Patients with HCV and cirrhosis had higher serum levels of PC 30:0 and 32:0 before and at the end of therapy. PC species containing polyunsaturated fatty acids were mostly decreased in cirrhosis. The levels of polyunsaturated, but not saturated, PC species were inversely correlated with the model of the end-stage liver disease score. A receiver operating characteristic curve analysis showed area under the curve values of 0.814 and 0.826 for PC 32:0 and 0.917 and 0.914 for % PC 32:0 (relative to the total PC levels) for the classification of cirrhosis at baseline and at the end of therapy, respectively. In conclusion, the specific upregulation of PC 32:0 in cirrhosis before and after therapy may be of diagnostic value in HCV-related cirrhosis.

Delivery of Outpatient Cirrhosis Care Through Tele-Visit Is Not Associated With Increased Mortality as Compared With Traditional In-Person Visits.

Providers and patients have expressed concern that care provided through telehealth results in poorer outcomes than traditional in-person care. On the contrary, we hypothesized that patients with cirrhosis engaging in video/phone-based outpatient gastroenterology/hepatology tele-visits do not differ in mortality from those receiving in-person outpatient clinic visits. This was a retrospective, case-control study using Veterans Health Administration administrative data of veterans with a cirrhosis diagnosis. Cases were patients who died between April 2021 and July 2022 and had a cirrhosis diagnosis for ≥1 year before death. For each case, a control was randomly selected from the pool of patients alive on the date of death of the case (index date) and matched on age, average Model for End-Stage Liver Disease, and number of gastroenterology/hepatology clinic visits in the prior year. Primary exposure variable was % tele-visits (video/phone) out of total visits in the year before the index date, scaled in 10% increments. Conditional logistic regression was used to assess the association between mortality and % tele-visits. A secondary analysis matched on electronic Child-Turcotte-Pugh score rather than Model for End-Stage Liver Disease. Two thousand nine hundred thirty-three cases were identified and matched with 2,933 controls. After adjusting for covariates, tele-visit-based outpatient care was associated with a small reduction in mortality (odds ratio TH = 0.95, 95% confidence interval = 0.94-0.97). Matching on electronic Child-Turcotte-Pugh score did not change the results. Our findings suggest that outpatient cirrhosis care by tele-visit is associated with outcomes no worse than traditional in-person visits. This should reassure providers who hesitate to provide virtual care to patients with cirrhosis due to concerns for poorer outcomes.

Mesenchymal Stem Cell Therapy for Hepatic Encephalopathy Due to Advance Liver Cirrhosis: Case Study

Mesenchymal stem cell (MSC) transplantation may be an alternative to liver transplantation for patients with end-stage liver disease. A 24-year-old patient with Hepatic Encephalopathy due to alcoholic liver cirrhosis underwent UCMSC transplantation because there were no donors available for liver transplants involving adult deceased and living individuals. The patient was given allogeneic Umbilical cord-derived MSCs, which were then cultured following accepted practices. Subsequently, the UCMSCs were infused through the intravenous route 3 times at the interval of 30 days. Serum bilirubin, globulin, and ammonia levels were improved after the infusion and the morphology of the liver and spleen had also improved.

Clinical characteristics and prognosis of liver injury induced by immune checkpoint inhibitors in patients with malignancies: A real-world retrospective study.

Programmed cell death receptor (ligand)-1 inhibitors (PD-(L)1), as the preferred immunotherapy, have been widely used in the Chinese mainland and drug-induced liver injury (DILI) has been reported. The study aimed to investigate the clinical features or risk factors for immunotherapy-related DILI. Patients who received PD-(L)1 inhibitors from January 2020 to July 2021 were retrospectively reviewed. The likelihood of DILI was adjudicated by the Roussel-Uclaf causality assessment. A total of 1175 patients were included in the study and 89 patients (7.6%) developed DILI, of which 12 (13.5%) progressed to acute liver failure (ALF) and three (3.4%) died. Among the DILI population, 56 (62.9%) had a cholestatic pattern and exhibited a prolonged treatment course and duration for resolution compared to the hepatocellular and mixed patterns. Hepatocellular carcinoma (HCC), hepatitis B virus (HBV) and abnormal baseline of alkaline phosphatase (ALP) had increased risks of DILI by 2.1-fold (95% confidence interval [CI], 1.231-3.621), 1.9-fold [95% CI, 1.123-3.325] and 2.1-fold [95% CI, 1.317-3.508], respectively. The model for end-stage liver disease (MELD) score had a c-statistic of 0.894 (95% CI, 0.778-1.000) with a sensitivity of 67% and a specificity of 95% for poor outcomes. COX analysis showed that the MELD ≥ 18 was predictive of immunotherapy-related ALF or death. PD-(L)1 inhibitor-related liver injury manifests primarily as a cholestatic pattern, on which corticosteroid treatment has minimal effect compared to hepatocellular and mixed patterns. MELD score ≥ 18 at the time of liver injury performed best in the prediction of ALF or death in immune checkpoint inhibitor (ICI)-related DILI.