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Medicina (Kaunas, Lithuania) Feb 2024Liver transplantation (LT) has significantly transformed the prognosis of patients with end-stage liver disease and hepatocellular carcinoma (HCC). The traditional... (Review)
Review
Liver transplantation (LT) has significantly transformed the prognosis of patients with end-stage liver disease and hepatocellular carcinoma (HCC). The traditional epidemiology of liver diseases has undergone a remarkable shift in indications for LT, marked by a decline in viral hepatitis and an increase in metabolic dysfunction-associated steatotic liver disease (MASLD), along with expanded indications for HCC. Recent advancements in surgical techniques, organ preservation and post-transplant patients' management have opened new possibilities for LT. Conditions that were historically considered absolute contraindications have emerged as potential new indications, demonstrating promising results in terms of patient survival. While these expanding indications provide newfound hope, the ethical dilemma of organ scarcity persists. Addressing this requires careful consideration and international collaboration to ensure equitable access to LT. Multidisciplinary approaches and ongoing research efforts are crucial to navigate the evolving landscape of LT. This review aims to offer a current overview of the primary emerging indications for LT, focusing on acute-on-chronic liver failure (ACLF), acute alcoholic hepatitis (AH), intrahepatic and perihilar cholangiocarcinoma (i- and p-CCA), colorectal liver metastasis (CRLM), and neuroendocrine tumor (NET) liver metastases.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Liver Transplantation; Cholangiocarcinoma; Bile Ducts, Intrahepatic; Bile Duct Neoplasms
PubMed: 38541138
DOI: 10.3390/medicina60030412 -
Biomedicines Feb 2024Hepatobiliary diseases have a high prevalence worldwide, with a wide range of diseases involved in the liver and biliary system. Modifications in gut microbiota have... (Review)
Review
Hepatobiliary diseases have a high prevalence worldwide, with a wide range of diseases involved in the liver and biliary system. Modifications in gut microbiota have been proven to have an association with unbalanced intestinal homeostasis and the dysfunction of host metabolism and the immune system, which can be the risk factors for many hepatobiliary diseases, such as nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), nonalcoholic fatty steatohepatitis (NASH), hepatitis, cirrhosis, hepatocellular carcinoma (HCC) and cholestasis, as well as infection due to liver transplantation. Probiotics are commonly used gut microbiota-targeted strategies to treat dysbiosis and intestinal dysfunction, as well as the gut-liver axis, which can enhance the effectiveness of probiotics in the management of liver diseases. Recent studies have explored more potential single or mixed strains of probiotics, and bioinformatics methods can be used to investigate the potential mechanisms of probiotics on liver diseases. In this review, we summarize the preclinical and clinical studies on the role of probiotics in hepatobiliary diseases from 2018 to 2023, revealing the possible mechanism of probiotics in the treatment of hepatobiliary diseases and discussing the limitations of probiotics in treating hepatobiliary diseases. This review provides updated evidence for the development of probiotic products, exploration of new probiotic strains, and support for clinical studies. Further studies should focus on the safety, viability, and stability of probiotics, as well as medication dosage and duration in clinical practice.
PubMed: 38540128
DOI: 10.3390/biomedicines12030515 -
Revista Da Associacao Medica Brasileira... 2024There are limited data on non-alcoholic fatty liver disease in chronic hepatitis B virus infection. We aimed to determine the predictors for non-alcoholic fatty liver...
OBJECTIVE
There are limited data on non-alcoholic fatty liver disease in chronic hepatitis B virus infection. We aimed to determine the predictors for non-alcoholic fatty liver disease in patients with treatment-naïve chronic hepatitis B virus infection.
METHODS
All consecutive treatment-naïve patients with chronic hepatitis B virus infection at the Haseki Training and Research Hospital between October 1, 2021, and September 31, 2022, were retrospectively enrolled. Chronic hepatitis B virus infection is defined by positive serum hepatitis B surface antigen for 6 months or more. Patients with significant alcohol consumption, prolonged steatogenic drug use, malignancy, monogenic hereditary disorders, patients co-infected with hepatitis D virus, hepatitis C virus infection, or human immunodeficiency virus were excluded. Demographic characteristics, anthropometric determinants, laboratory findings, and virological parameters were retrospectively collected from patients' charts and electronic medical records.
RESULTS
A total of 457 patients with treatment-naïve chronic hepatitis B virus infection were included in the study. The three multivariate regression models revealed that age (p<0.028), body mass index (p=0.046), diabetes mellitus (p=0.030), hemoglobin (p=0.008), platelet (p=0.012), and triglyceride (p=0.002) in Model 1; body mass index (p=0.033), diabetes mellitus (p<0.001), hemoglobin (p=0.008), platelet (p=0.004), LDL (p=0.023), and HDL (p=0.020) in Model 2; and age (p<0.001), body mass index (p=0.033), hemoglobin (p=0.004), platelet (p=0.004), and HDL (p=0.007) in Model 3 were independent predictors.
CONCLUSION
Non-alcoholic fatty liver disease was observed in about one-third of patients with chronic hepatitis B virus infection and was positively associated with older age, higher body mass index, presence of comorbid conditions including diabetes mellitus, increased levels of metabolic laboratory parameters, especially serum triglyceride and LDL, and decreased HDL.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Hepatitis B, Chronic; Retrospective Studies; Diabetes Mellitus; Triglycerides; Hemoglobins; Hepatitis B; Liver
PubMed: 38537007
DOI: 10.1590/1806-9282.20231036 -
Diagnostics (Basel, Switzerland) Mar 2024Liver stiffness measurement (LSM) by Fibroscan is the most used non-invasive method to assess liver fibrosis. Recently, point-shear wave elastography (pSWE) has been...
Liver stiffness measurement (LSM) by Fibroscan is the most used non-invasive method to assess liver fibrosis. Recently, point-shear wave elastography (pSWE) has been introduced as a simple alternative non-invasive test. Therefore, we aimed to compare the results of these two techniques. One hundred and eighty-four consecutive patients attending our outpatient ultrasound clinic were recruited. LSM was performed by both Fibroscan and pSWE. Statistical analysis was conducted by Spearman's test for correlation and linear regression. Bland-Altman graphs and ROC curves were drawn with area under the curve (AUC). Overall, the correlation of LS between Fibroscan and pSWE was substantial (r = 0.68, < 0.001). Linear regression showed a coefficient b= 0.94 ± 0.02. The Bland-Altman plot found a bias of -0.10, with only 11 values exceeding the 95% confidence interval. When only considering patients with a LSM of > 10 kPa ( = 31), we found an excellent r = 0.79 (0.60-0.90, < 0.001). A cutoff of 12.15 kPa for pSWE had sensitivity = 74.2% and specificity = 99.3% to detect relevant fibrosis, with an AUC = 0.98. The highest correlation was observed for hepatitis C (r = 0.91) and alcoholic liver disease (ALD)(r = 0.99). In conclusion, pSWE shows LSM estimation in agreement with Fibroscan in most cases, and the best concordance was observed for hepatitis C and ALD, and for higher ranges of LS.
PubMed: 38535025
DOI: 10.3390/diagnostics14060604 -
Cell Division Mar 2024Mechanisms and consequences of Gasdermin D (GSDMD) activation in alcoholic hepatitis (AH) are unclear. In the present study, we investigated whether GSDMD induces...
BACKGROUND
Mechanisms and consequences of Gasdermin D (GSDMD) activation in alcoholic hepatitis (AH) are unclear. In the present study, we investigated whether GSDMD induces hepatocyte pyroptosis by regulating mitochondrial dysfunction in AH.
RESULTS
Liver damage in AH mice was assessed by HE staining, serum levels of AST, ALT, TC, and TG. The levels of IL-1β, IL-18, LDH, inflammasome-associated proteins and hepatocyte death were assessed to determine pyroptosis. Mitochondrial dysfunction was assessed through various parameters including mitochondrial DNA (mtDNA) levels, ROS generation, mitochondrial membrane potential, ATP contents, levels of mitochondrial function-related proteins and morphological changes of mitochondria. AH induced gasdermin D (GSDMD) activation, leading to increased protein expression of N-terminal GSDMD (GSDMD-N), NLRP3, and Caspase 11 in liver tissues. Downregulation of GSDMD alleviated alcohol-induced hepatocyte pyroptosis. Alcohol also causes mitochondrial dysfunction in hepatocytes in AH, which was improved by inhibiting GSDMD. Furthermore, enhancing mitochondrial function suppressed alcohol-induced hepatocyte pyroptosis. Further, knockdown of GSDMD or dynamin-related protein 1 (Drp1) improved AH-induced liver injury, accompanied by a decrease in hepatocyte pyroptosis.
CONCLUSION
GSDMD induces hepatocyte pyroptosis by modulating mitochondrial dysfunction during AH-induced inflammation and liver injury. These findings may pave the way to develop new therapeutic treatments for AH.
PubMed: 38532477
DOI: 10.1186/s13008-024-00114-0 -
Biochemical Pharmacology Mar 2024The liver plays a pivotal role in drug disposition owing to the expression of transporters accounting for the uptake at the sinusoidal membrane and the efflux across the... (Review)
Review
The liver plays a pivotal role in drug disposition owing to the expression of transporters accounting for the uptake at the sinusoidal membrane and the efflux across the basolateral and canalicular membranes of hepatocytes of many different compounds. Moreover, intracellular mechanisms of phases I and II biotransformation generate, in general, inactive compounds that are more polar and easier to eliminate into bile or refluxed back toward the blood for their elimination by the kidneys, which becomes crucial when the biliary route is hampered. The set of transporters expressed at a given time, i.e., the so-called transportome, is encoded by genes belonging to two gene superfamilies named Solute Carriers (SLC) and ATP-Binding Cassette (ABC), which account mainly, but not exclusively, for the uptake and efflux of endogenous substances and xenobiotics, which include many different drugs. Besides the existence of genetic variants, which determines a marked interindividual heterogeneity regarding liver drug disposition among patients, prevalent diseases, such as cirrhosis, non-alcoholic steatohepatitis, primary sclerosing cholangitis, primary biliary cirrhosis, viral hepatitis, hepatocellular carcinoma, cholangiocarcinoma, and several cholestatic liver diseases, can alter the transportome and hence affect the pharmacokinetics of drugs used to treat these patients. Moreover, hepatic drug transporters are involved in many drug-drug interactions (DDI) that challenge the safety of using a combination of agents handled by these proteins. Updated information on these questions has been organized in this article by superfamilies and families of members of the transportome involved in hepatic drug disposition.
PubMed: 38527556
DOI: 10.1016/j.bcp.2024.116166 -
Journal of Liver Cancer Mar 2024Approximately 80% of hepatocellular carcinoma (HCC) cases arise in sub-Saharan Africa and Eastern Asia, following a similarly high prevalence of chronic hepatitis B...
Approximately 80% of hepatocellular carcinoma (HCC) cases arise in sub-Saharan Africa and Eastern Asia, following a similarly high prevalence of chronic hepatitis B virus (HBV) carriers in these regions. The etiology and epidemiology of HCC have recently changed worldwide. Although HBV infection is the main contributor to HCC development, a slow but continuous decline in HBV infection rates has been reported since 1990. Owing to the widespread use of direct-acting antivirals, the incidence of hepatitis C virus-related HCC has remarkably decreased in Japan and European countries. In Korea, Taiwan, and Singapore, the incidence of HBV-related HCC has significantly decreased owing to vaccination against HBV. Globally, while HBV accounted for more than half of HCCs in 1990, this had decreased to 42% in 2019. In contrast, the proportion of patients with alcoholic- and nonalcoholic steatohepatitis (NASH) increased from 13% to 18% and from 5% to 6%, respectively. NASH-related HCC has characteristics that differ from those of virus-associated HCC. Compared with other etiologies, patients with NASHassociated HCC are older, have a higher body mass index, and have higher rates of type 2 diabetes mellitus, hypertension, hyperlipidemia, and cardiovascular disease. Nonalcoholic fatty liver disease (NAFLD)-associated HCC is also known to develop in the absence of cirrhosis, unlike alcohol-related and autoimmune liver diseases. Because patients with NAFLD usually have diabetes or obesity, surveying this population is challenging. Optimal selection of the target population and surveillance tools among patients with NAFLD needs to be determined.
PubMed: 38523466
DOI: 10.17998/jlc.2024.03.13 -
Ecotoxicology and Environmental Safety Apr 2024Information on the relation of air pollution with non-alcoholic fatty liver disease (NAFLD) is scarce. We thus conducted a large cross-sectional study in Asia to...
BACKGROUND
Information on the relation of air pollution with non-alcoholic fatty liver disease (NAFLD) is scarce. We thus conducted a large cross-sectional study in Asia to investigate the role of air pollution in NAFLD.
METHODS
We recruited 329,048 adults (mean age: 41.0 years) without other liver disease (hepatitis and cirrhosis) or excessive alcohol consumption in Taiwan and Hong Kong from 2001 to 2018. The concentrations of nitrogen dioxide (NO) and ozone (O) were estimated using a space-time regression model, and the concentrations of fine particulate matter (PM) was evaluated using a satellite-based spatio-temporal model. NAFLD was determined using either the fatty liver index (FLI) or the hepatic steatosis index (HSI). The NAFLD-related advanced fibrosis was defined according to BARD score or the fibrosis-4 (FIB-4). A logistic regression model was adopted to explore the relationships of ambient air pollution with the odds of NAFLD and NAFLD-related advanced fibrosis.
RESULTS
We found positive relationships between PM and the odds of NAFLD and advanced fibrosis, with every standard deviation (SD, 7.5 µg/m) increases in PM exposure being associated with a 10% (95% confidence interval [CI]: 9%-11%) increment in the prevalence of NAFLD and an 8% (95% CI: 7%-9%) increment in the prevalence of advanced fibrosis. Similarly, the prevalence of NAFLD and advanced fibrosis increased by 8% (95% CI: 7%-9%) and 7% (95% CI: 6%-8%) with per SD (18.9 µg/m) increasement in NO concentration, respectively. Additionally, for every SD (9.9 µg/m) increasement in O concentration, the prevalence of NAFLD and advanced fibrosis decreased by 12% (95% CI: 11%-13%) and 11% (95% CI: 9%-12%), respectively.
CONCLUSION
Higher ambient PM and NO are linked with higher odds of NAFLD and advanced fibrosis. Our findings indicate that reducing PM and NO concentrations may be an effective way for preventing NAFLD. Further studies on O are warranted.
Topics: Adult; Humans; Non-alcoholic Fatty Liver Disease; Cross-Sectional Studies; Hong Kong; Taiwan; Nitrogen Dioxide; Air Pollution; Liver Cirrhosis; Particulate Matter; Air Pollutants; Environmental Exposure
PubMed: 38520807
DOI: 10.1016/j.ecoenv.2024.116245 -
Frontiers in Pediatrics 2024This investigation aimed to examine the epidemiological characteristics of children with liver disease hospitalized for the first time between June 2012 and May 2022 in...
BACKGROUND
This investigation aimed to examine the epidemiological characteristics of children with liver disease hospitalized for the first time between June 2012 and May 2022 in a tertiary hospital.
METHODS
The study retrospectively recruited children aged between 29 days and 18 years who had been hospitalized for liver disease. Clinical characteristics were categorized by age and etiology, and time trends were assessed using linear regression analysis.
RESULTS
A total of 4,313 children were recruited, with a median age of 0.7 (0.2-4.5) years, and 54.5% of the cases were in the 0-1 years age group. Infection was the primary cause of liver disease (30.0%), followed by undiagnosed cases (25.8%), biliary obstructive disease (15.9%), inherited metabolic liver disease (13.9%), and non-alcoholic fatty liver disease (NAFLD) (3.2%). Genetic diagnoses were established in 43.9% (478/1,088) of patients. The percentage of NAFLD demonstrated an upward trend from 1.2% in 2012 to 12.6% in 2022 (= 0.006). In contrast, the percentage of cytomegalovirus hepatitis decreased from 13.3% in 2012 to 3.4% in 2022 (= 0.002).
CONCLUSIONS
Liver disease in infancy makes up the largest group in pediatric liver disease. Infection remains the leading cause of pediatric liver disease. Hospital admissions for NAFLD in children have increased rapidly over the past decade, while cytomegalovirus hepatitis has declined markedly.
PubMed: 38510075
DOI: 10.3389/fped.2024.1344714 -
Environmental Health : a Global Access... Mar 2024Chlordecone is a persistent organochlorinated insecticide, extensively used in the French West Indies and has been contaminating the population for more than thirty...
BACKGROUND AND AIMS
Chlordecone is a persistent organochlorinated insecticide, extensively used in the French West Indies and has been contaminating the population for more than thirty years. Its potentiation effect on hepatotoxic agents has been demonstrated in animal models. We investigated the relationship between environmental exposure to chlordecone and the progression of liver fibrosis.
METHODS
This study included 182 consecutive patients with chronic alcoholic hepatitis whose liver fibrosis was assessed using non-invasive methods. Measured plasma chlordecone concentrations at inclusion were used as surrogate of long-term exposure under steady-state conditions. As the pharmacokinetic processing of chlordecone is largely determined by the liver, we used a human physiologically based pharmacokinetic model to predict plausible changes in the steady-state blood chlordecone concentrations induced by liver fibrosis.
RESULTS
With a median follow-up of 27.1 years after the onset of alcohol consumption, we found a significant decrease in the risk of advanced liver fibrosis with increasing plasma chlordecone concentration (adjusted hazard ratio = 0.56; 95% confidence interval: 0.34-0.95 for the highest vs. lowest tertile, p = 0.04). Changes induced by liver fibrosis influenced the pharmacokinetic processing of chlordecone, resulting in substantial modifications in its steady-state blood concentrations.
CONCLUSION
According to this human model of coexposure to alcohol, reverse causality is the most plausible explanation of this inverse association between plasma chlordecone concentrations and progression of liver fibrosis. This study underlines the importance of considering the pharmacokinetic of environmental contaminants in epidemiological studies when biomarkers of exposure are used to investigate their own impact on the liver.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03373396.
Topics: Animals; Humans; Chlordecone; Insecticides; Environmental Exposure; Liver Cirrhosis
PubMed: 38504260
DOI: 10.1186/s12940-024-01054-6