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Journal of Gastroenterology and... May 2024The Model for End-Stage Liver Disease (MELD) is a reliable prognostic tool for short-term outcome prediction in patients with end-stage liver disease. MELD 3.0 was...
BACKGROUND AND AIM
The Model for End-Stage Liver Disease (MELD) is a reliable prognostic tool for short-term outcome prediction in patients with end-stage liver disease. MELD 3.0 was introduced to enhance the predictive accuracy. This study assessed the performance of MELD 3.0, in comparison to MELD and MELD-Na, in patients with alcoholic liver cirrhosis.
METHODS
This multicenter prospective cohort study comprised patients with alcoholic cirrhosis admitted for acute deterioration of liver function in the Republic of Korea between 2015 and 2019. This study compared the predictive abilities of MELD, MELD-Na, and MELD 3.0, for 30-day and 90-day outcomes, specifically death or liver transplantation, and explored the factors influencing these outcomes.
RESULTS
A total of 1096 patients were included in the study, with a mean age of 53.3 ± 10.4 years, and 82.0% were male. The mean scores for MELD, MELD-Na, and MELD 3.0 at the time of admission were 18.7 ± 7.2, 20.6 ± 7.7, and 21.0 ± 7.8, respectively. At 30 and 90 days, 7.2% and 14.1% of patients experienced mortality or liver transplantation. The areas under the receiver operating characteristic curves for MELD, MELD-Na, and MELD 3.0 at 30 days were 0.823, 0.820, and 0.828; and at 90 days were 0.765, 0.772, and 0.776, respectively. Factors associated with the 90-day outcome included concomitant chronic viral hepatitis, prolonged prothrombin time, elevated levels of aspartate transaminase, bilirubin, and creatinine, and low albumin levels.
CONCLUSION
MELD 3.0 demonstrated improved performance compared to previous models, although the differences were not statistically significant.
PubMed: 38720448
DOI: 10.1111/jgh.16591 -
Journal of Pharmacy Practice May 2024Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) help manage type 2 diabetes (T2DM) and may have efficacy in steatotic liver disease. To determine the prevalence...
Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) help manage type 2 diabetes (T2DM) and may have efficacy in steatotic liver disease. To determine the prevalence and clinical impact of GLP-1 RA use in patients with T2DM and liver disease. This was a retrospective study of adult patients with T2DM and nonalcoholic fatty liver disease (NAFLD), nonalcoholic fatty liver (NAFL), or nonalcoholic steatohepatitis (NASH) between 1/1/21-12/31/21. Patients with hepatitis B or C, or on pioglitazone were excluded. Eligible patients treated with a GLP-1 RA were compared to controls. The primary outcome was change in Fibrosis-4 (FIB-4) score, with NAFLD Fibrosis Score (NFS) as a secondary outcome. Follow-up scores were calculated from labs within 3 to 15 months after baseline. Of 242 eligible patients, 79 patients (32.6%) were treated with a GLP-1 RA. At baseline, FIB-4 score was lower and NFS was higher in the GLP-1 RA group vs controls (1.80 vs 2.33; P = .101, .36 vs -.47, P < .001; respectively). At follow up, FIB-4 score decreased to 1.77 in the GLP-1 RA group and increased to 2.71 in controls (P = .045). Follow up NFS was stable in the GLP-1 RA group and increased in the control group (.36 vs -.43; P = .308). Patients treated with GLP-1 RAs had less evidence of liver fibrosis progression compared to no treatment, although the differences were small. These results suggest that treatment with GLP-1 RAs may have clinical impact on slowing liver fibrosis, however results should be confirmed in a larger, more diverse sample.
PubMed: 38720191
DOI: 10.1177/08971900241253661 -
Transplantation Proceedings May 2024There is continuous growth of combined liver-kidney transplantation (CLKTx) numbers with remarkable outcomes, especially among patient with liver cirrhosis and end-stage...
BACKGROUND
There is continuous growth of combined liver-kidney transplantation (CLKTx) numbers with remarkable outcomes, especially among patient with liver cirrhosis and end-stage renal disease. The aim was to present a single center experience.
METHODS
Twenty patients (9 males) with a mean age of 48 (range: 20-62) years underwent CLKTx from 2005 to 2022. Indications were polycystic liver and kidney diseases (ADPKD) in 12 cases, cirrhosis due to hepatitis (4 patients), and 1 case of amyloidosis, alcoholic liver disease, nonalcoholic steatosis, and congenital hepatic fibrosis with concomitant glomerulonephritis. After hepatectomy, half of the patients had orthotopic liver transplantation with piggy-back technique, and the other had conventional technique. All but 1 recipient had biliary end-to-end anastomosis. 3 patients had preemptive kidney graft transplantation. 4 underwent simultaneous right-side nephrectomy due to volume of the right kidney. Kidney was transplanted from the separate incision after abdominal closure with typical anastomoses. Tacrolimus, mycophenolate mofetile, basiliximab, and steroids were applied for all recipients.
RESULTS
Mean follow-up was 57.7 ± 54 months. No primary non-function of the grafts occurred. Delayed kidney graft function (DGF) occurred in 8 patients. Three-month, 1-year, and 5-year cumulative survival rates were: 90%, 80%, and 72% respectively. None of the patients required retransplantation, and 1 recipient returned to hemodialysis 19 months after transplantation. Preemptive kidney transplantation and simultaneous right-side nephrectomy were not significant for DGF and recipient survival. No deaths within the first year occurred in piggy-back technique.
CONCLUSIONS
CLKTx is safe and effective in the treatment of both liver and kidney failure.
Topics: Humans; Kidney Transplantation; Male; Adult; Liver Transplantation; Female; Middle Aged; Treatment Outcome; Young Adult; Kidney Failure, Chronic; Retrospective Studies; Graft Survival
PubMed: 38719623
DOI: 10.1016/j.transproceed.2024.03.014 -
Journal of Biological Engineering May 2024Alcohol consumption, a pervasive societal issue, poses considerable health risks and socioeconomic consequences. Alcohol-induced hepatic disorders, such as fatty liver...
Alcohol consumption, a pervasive societal issue, poses considerable health risks and socioeconomic consequences. Alcohol-induced hepatic disorders, such as fatty liver disease, alcoholic hepatitis, chronic hepatitis, liver fibrosis, and cirrhosis, underscore the need for comprehensive research. Existing challenges in mimicking chronic alcohol exposure in cellular systems, attributed to ethanol evaporation, necessitate innovative approaches. In this study, we developed a simple, reusable, and controllable device for examining the physiological reactions of hepatocytes to long-term alcohol exposure. Our approach involved a novel device designed to continuously release ethanol into the culture medium, maintaining a consistent ethanol concentration over several days. We evaluated device performance by examining gene expression patterns and cytokine secretion alterations during long-term exposure to ethanol. These patterns were correlated with those observed in patients with alcoholic hepatitis. Our results suggest that our ethanol-releasing device can be used as a valuable tool to study the mechanisms of chronic alcohol-mediated hepatic diseases at the cellular level. Our device offers a practical solution for studying chronic alcohol exposure, providing a reliable platform for cellular research. This innovative tool holds promise for advancing our understanding of the molecular processes involved in chronic alcohol-mediated hepatic diseases. Future research avenues should explore broader applications and potential implications for predicting and treating alcohol-related illnesses.
PubMed: 38715085
DOI: 10.1186/s13036-024-00428-1 -
European Review For Medical and... Apr 2024Liver cirrhosis is the end-stage entity for a wide variety of chronic liver pathologies. These include viral hepatitis B and C, alcoholic liver disease, non-alcoholic...
BACKGROUND
Liver cirrhosis is the end-stage entity for a wide variety of chronic liver pathologies. These include viral hepatitis B and C, alcoholic liver disease, non-alcoholic fatty liver disease, hemochromatosis, Wilson disease, autoimmune hepatitis, primary sclerosing cholangitis, and primary biliary cirrhosis. In the majority of cases, liver cirrhosis remains completely asymptomatic until acute decompensation occurs. Patients may present complications of portal hypertension such as gastro-esophageal varices and upper digestive hemorrhage, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, or hepato-renal syndrome. Establishing the right etiology of cirrhosis is of paramount importance as it helps the treating physician plan the best suitable treatment options and also improves overall outcome.
CASE REPORT
We present a case of a chronic alcohol consumer, which, over time, resulted in alcoholic cirrhosis. Initial diagnosis comprised of alcoholic liver disease. However, a further look into the medical history of the patients indicated the presence of underlying autoimmune liver disease, such as autoimmune hepatitis, which might have also contributed to the chronic liver injury.
CONCLUSIONS
Multiple factors can lead to liver cirrhosis. Although the most commonly found entity is alcoholism, it cannot be taken as a thumb rule for the only possible etiology. In-depth analysis and proper differential diagnosis should be carefully conducted in order not to miss out on other possible causes. As seen in our case, where an underlying autoimmune hepatitis was found to be the culprit, but due to a long history of alcohol consumption, it was masked at first instance.
Topics: Humans; Alcoholism; Hepatitis, Autoimmune; Liver Cirrhosis; Liver Cirrhosis, Alcoholic
PubMed: 38708468
DOI: 10.26355/eurrev_202404_36025 -
Journal of Cell Science May 2024Hepatocyte organoids (HOs) generated in vitro are powerful tools for liver regeneration. However, previously reported HOs have mostly been fetal in nature with low...
Hepatocyte organoids (HOs) generated in vitro are powerful tools for liver regeneration. However, previously reported HOs have mostly been fetal in nature with low expression levels of metabolic genes characteristic of adult liver functions, hampering their application in studies of metabolic regulation and therapeutic testing for liver disorders. Here, we report development of novel culture conditions that combine optimized levels of triiodothyronine (T3) with the removal of growth factors to enable successful generation of mature hepatocyte organoids (MHOs) of both mouse and human origin with metabolic functions characteristic of adult livers. We show that the MHOs can be used to study various metabolic functions including bile and urea production, zonal metabolic gene expression, and metabolic alterations in both alcoholic liver disease and non-alcoholic fatty liver disease, as well as hepatocyte proliferation, injury and cell fate changes. Notably, MHOs derived from human fetal hepatocytes also show improved hepatitis B virus infection. Therefore, these MHOs provide a powerful in vitro model for studies of human liver physiology and diseases. The human MHOs are potentially also a robust research tool for therapeutic development.
Topics: Hepatocytes; Organoids; Humans; Animals; Mice; Liver; Mice, Inbred C57BL; Cell Differentiation
PubMed: 38700490
DOI: 10.1242/jcs.261961 -
Hepatology (Baltimore, Md.) Apr 2024Liver macrophages are heterogeneous and play an important role in alcohol-associated liver disease (ALD) but there is limited understanding of the functions of specific...
BACKGROUND AND AIMS
Liver macrophages are heterogeneous and play an important role in alcohol-associated liver disease (ALD) but there is limited understanding of the functions of specific macrophage subsets in the disease. We used a Western diet alcohol (WDA) mouse model of ALD to examine the hepatic myeloid cell compartment by single cell RNAseq and targeted KC ablation to understand the diversity and function of liver macrophages in ALD.
APPROACH AND RESULTS
In the WDA liver, KCs and infiltrating monocytes/macrophages each represented about 50% of the myeloid pool. Five major KC clusters all expressed genes associated with receptor-mediated endocytosis and lipid metabolism, but most were predicted to be noninflammatory and antifibrotic with 1 minor KC cluster having a proinflammatory and extracellular matrix degradation gene signature. Infiltrating monocyte/macrophage clusters, in contrast, were predicted to be proinflammatory and profibrotic. In vivo, diphtheria toxin-based selective KC ablation during alcohol exposure resulted in a liver failure phenotype with increases in PT/INR and bilirubin, loss of differentiated hepatocyte gene expression, and an increase in expression of hepatocyte progenitor markers such as EpCAM, CK7, and Igf2bp3. Gene set enrichment analysis of whole-liver RNAseq from the KC-ablated WDA mice showed a similar pattern as seen in human alcoholic hepatitis.
CONCLUSIONS
In this ALD model, KCs are anti-inflammatory and are critical for the maintenance of hepatocyte differentiation. Infiltrating monocytes/macrophages are largely proinflammatory and contribute more to liver fibrosis. Future targeting of specific macrophage subsets may provide new approaches to the treatment of liver failure and fibrosis in ALD.
PubMed: 38687563
DOI: 10.1097/HEP.0000000000000918 -
Journal of Cellular and Molecular... May 2024Liver diseases include all types of viral hepatitis, alcoholic liver disease (ALD), nonalcoholic fatty liver disease (NAFLD), cirrhosis, liver failure (LF) and... (Review)
Review
Liver diseases include all types of viral hepatitis, alcoholic liver disease (ALD), nonalcoholic fatty liver disease (NAFLD), cirrhosis, liver failure (LF) and hepatocellular carcinoma (HCC). Liver disease is now one of the leading causes of disease and death worldwide, which compels us to better understand the mechanisms involved in the development of liver diseases. Anoctamin 1 (ANO1), a calcium-activated chloride channel (CaCC), plays an important role in epithelial cell secretion, proliferation and migration. ANO1 plays a key role in transcriptional regulation as well as in many signalling pathways. It is involved in the genesis, development, progression and/or metastasis of several tumours and other diseases including liver diseases. This paper reviews the role and molecular mechanisms of ANO1 in the development of various liver diseases, aiming to provide a reference for further research on the role of ANO1 in liver diseases and to contribute to the improvement of therapeutic strategies for liver diseases by regulating ANO1.
Topics: Humans; Anoctamin-1; Liver Diseases; Animals; Signal Transduction; Neoplasm Proteins; Liver Neoplasms; Carcinoma, Hepatocellular; Gene Expression Regulation
PubMed: 38685684
DOI: 10.1111/jcmm.18320 -
Scientific Reports Apr 2024This study evaluated the effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on cancer development, particularly in hepatocellular carcinoma (HCC), in...
This study evaluated the effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on cancer development, particularly in hepatocellular carcinoma (HCC), in individuals with concomitant fatty liver disease (FLD) and type 2 diabetes mellitus (T2DM). Using data from Korea's Health Insurance Review and Assessment Service, we performed Kaplan-Meier and Cox regression analyses in patients with non-alcoholic fatty liver disease (NAFLD) and T2DM (NAFLD-T2DM cohort) and those with chronic viral hepatitis (CVH) alongside FLD and T2DM (FLD-T2DM-CVH cohort). In the propensity score (PS) matched NAFLD-T2DM cohort (N = 107,972), SGLT2i use was not associated with the occurrence of overall cancer, including HCC. However, old age, male sex, liver cirrhosis, and hypothyroidism were identified as independent risk factors for HCC occurrence, whereas statin and fibrate usage were associated with reduced HCC risk in this cohort in multivariate Cox analysis. In the PS-matched FLD-T2DM-CVH cohort (N = 2798), a significant decrease in HCC occurrence was observed among SGLT2i users (P = 0.03). This finding remained consistent in the multivariate Cox regression analysis (Hazard ratio = 2.21, 95% confidence interval = 1.01-4.85, P = 0.048). In conclusion, SGLT2i may be a beneficial option for diabetes management in patients with concomitant T2DM, FLD, and CVH while affirming the overall safety of SGLT2i in other types of cancer.
Topics: Humans; Male; Female; Republic of Korea; Liver Neoplasms; Middle Aged; Diabetes Mellitus, Type 2; Carcinoma, Hepatocellular; Sodium-Glucose Transporter 2 Inhibitors; Incidence; Non-alcoholic Fatty Liver Disease; Aged; Risk Factors; Cohort Studies; Adult; Proportional Hazards Models; Propensity Score
PubMed: 38684838
DOI: 10.1038/s41598-024-60133-3