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World Journal of Virology Mar 2024Hepatitis B virus (HBV) infection poses a global health concern without a definitive cure; however, antiviral medications can effectively suppress viral replication....
Hepatitis B virus (HBV) infection poses a global health concern without a definitive cure; however, antiviral medications can effectively suppress viral replication. This study delves into the intricate interplay between lipid metabolism and HBV replication, implicating molecular mechanisms such as the stearoyl coenzyme A desaturase 1 autophagy pathway, SAC1-like phosphatidylinositol phosphatase, and galectin-9 mediated selective autophagy of viral core proteins in regulating HBV replication. Within lipid droplets, perilipin 2 (PLIN2) emerges as a pivotal guardian, with its overexpression protecting against autophagy and downregulation stimulating triglyceride catabolism through the autophagy pathway. This editorial discusses the correlation between hepatic steatosis and HBV replication, emphasizing the role of PLIN2 in this process. The study underscores the multifaceted roles of lipid metabolism, autophagy, and perilipins in HBV replication, shedding light on potential therapeutic avenues.
PubMed: 38616854
DOI: 10.5501/wjv.v13.i1.90384 -
International Journal of Molecular... Mar 2024The objective of this study was to investigate gut dysbiosis and its metabolic and inflammatory implications in pediatric metabolic dysfunction-associated fatty liver...
The objective of this study was to investigate gut dysbiosis and its metabolic and inflammatory implications in pediatric metabolic dysfunction-associated fatty liver disease (MAFLD). This study included 105 children and utilized anthropometric measurements, blood tests, the Ultrasound Fatty Liver Index, and fecal DNA sequencing to assess the relationship between gut microbiota and pediatric MAFLD. Notable decreases in spp., spp., spp., and spp. were found in the MAFLD group. spp. was particularly reduced in children with MAFLD and hepatitis compared to controls. Both MAFLD groups showed a reduction in flavone and flavonol biosynthesis sequences. spp. correlated positively with flavone and flavonol biosynthesis and negatively with insulin levels and insulin resistance. Body weight, body mass index (BMI), and total cholesterol levels were inversely correlated with flavone and flavonol biosynthesis. Reduced spp. in children with MAFLD may exacerbate insulin resistance and inflammation through reduced flavone and flavonol biosynthesis, offering potential therapeutic targets.
Topics: Humans; Child; Insulin Resistance; Clostridiales; Flavones; Hepatitis A; Non-alcoholic Fatty Liver Disease; Flavonols
PubMed: 38612453
DOI: 10.3390/ijms25073640 -
Frontiers in Medicine 2024Excessive accumulation of extracellular matrix (ECM) components within the liver leads to a pathological condition known as liver fibrosis. Alcohol abuse, non-alcoholic... (Review)
Review
Excessive accumulation of extracellular matrix (ECM) components within the liver leads to a pathological condition known as liver fibrosis. Alcohol abuse, non-alcoholic fatty liver disease (NAFLD), autoimmune issues, and viral hepatitis cause chronic liver injury. Exploring potential therapeutic targets and understanding the molecular mechanisms involved in liver fibrosis are essential for the development of effective interventions. The goal of this comprehensive review is to explain how the PI3K/AKT signaling pathway contributes to the reduction of liver fibrosis. The potential of this pathway as a therapeutic target is investigated through a summary of results from and studies. Studies focusing on PI3K/AKT activation have shown a significant decrease in fibrosis markers and a significant improvement in liver function. The review emphasizes how this pathway may prevent ECM synthesis and hepatic stellate cell (HSC) activation, ultimately reducing the fibrotic response. The specific mechanisms and downstream effectors of the PI3K/AKT pathway in liver fibrosis constitute a rapidly developing field of study. In conclusion, the PI3K/AKT signaling pathway plays a significant role in attenuating liver fibrosis. Its complex role in regulating HSC activation and ECM production, demonstrated both and , underscores its potential as a effective therapeutic approach for managing liver fibrosis and slowing disease progression. A comprehensive review of this field provides valuable insights into its future developments and implications for clinical applications.
PubMed: 38590313
DOI: 10.3389/fmed.2024.1389329 -
World Journal of Gastrointestinal... Mar 2024Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the second leading cause of cancer deaths worldwide. It is often diagnosed at an advanced...
BACKGROUND
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the second leading cause of cancer deaths worldwide. It is often diagnosed at an advanced stage and therefore its prognosis remains poor with a low 5-year survival rate. HCC patients have increasingly complex and constantly changing characteristics, thus up-to-date and comprehensive data are fundamental.
AIM
To analyze the epidemiology and main clinical characteristics of HCC patients in a referral center hospital in the northwest of Italy between 2010 and 2019.
METHODS
In this retrospective study, we analyzed the clinical data of all consecutive patients with a new diagnosis of HCC recorded at "Santa Croce e Carle" Hospital in Cuneo (Italy) between 1 January 2010 and 31 December 2019. To highlight possible changes in HCC patterns over the 10-year period, we split the population into two 5-year groups, according to the diagnosis period (2010-2014 and 2015-2019).
RESULTS
Of the 328 HCC patients who were included (M/F 255/73; mean age 68.9 ± 11.3 years), 154 in the first period, and 174 in the second. Hepatitis C virus infection was the most common HCC risk factor (41%, 135 patients). The alcoholic etiology rate was 18%, the hepatitis B virus infection etiology was 5%, and the non-viral/non-alcoholic etiology rate was 22%. The Child-Pugh score distribution of the patients was: class A 75%, class B 21% and class C 4%. The average Mayo end-stage liver disease score was 10.6 ± 3.7. A total of 55 patients (17%) were affected by portal vein thrombosis and 158 (48%) by portal hypertension. The average nodule size of the HCC was 4.6 ± 3.1 cm. A total of 204 patients (63%) had more than one nodule < 3, and 92% (305 patients) had a non-metastatic stage of the disease. The Barcelona Clinic Liver Cancer (BCLC) staging distribution of all patients was: 4% very early, 32% early, 23% intermediate, 34% advanced, and 7% terminal. Average survival rate was 1.6 ± 0.3 years. Only 20% of the patients underwent treatment. Age, presence of ascites, BCLC stage and therapy were predictors of a better prognosis ( < 0.01). A comparison of the two 5-year groups revealed a statistically significant difference only in global etiology ( < 0.05) and alpha-fetoprotein (AFP) levels ( < 0.01).
CONCLUSION
In this study analyzing patients with a new diagnosis of HCC between 2010-2019, hepatitis C virus infection was the most common etiology. Most patients presented with an advanced stage disease and a poor prognosis. When comparing the two 5-year groups, we observed a statistically significant difference only in global etiology ( < 0.05) and AFP levels ( < 0.01).
PubMed: 38577451
DOI: 10.4251/wjgo.v16.i3.761 -
JCI Insight Apr 2024Diagnostic challenges continue to impede development of effective therapies for successful management of alcohol-associated hepatitis (AH), creating an unmet need to...
Diagnostic challenges continue to impede development of effective therapies for successful management of alcohol-associated hepatitis (AH), creating an unmet need to identify noninvasive biomarkers for AH. In murine models, complement contributes to ethanol-induced liver injury. Therefore, we hypothesized that complement proteins could be rational diagnostic/prognostic biomarkers in AH. Here, we performed a comparative analysis of data derived from human hepatic and serum proteome to identify and characterize complement protein signatures in severe AH (sAH). The quantity of multiple complement proteins was perturbed in liver and serum proteome of patients with sAH. Multiple complement proteins differentiated patients with sAH from those with alcohol cirrhosis (AC) or alcohol use disorder (AUD) and healthy controls (HCs). Serum collectin 11 and C1q binding protein were strongly associated with sAH and exhibited good discriminatory performance among patients with sAH, AC, or AUD and HCs. Furthermore, complement component receptor 1-like protein was negatively associated with pro-inflammatory cytokines. Additionally, lower serum MBL associated serine protease 1 and coagulation factor II independently predicted 90-day mortality. In summary, meta-analysis of proteomic profiles from liver and circulation revealed complement protein signatures of sAH, highlighting a complex perturbation of complement and identifying potential diagnostic and prognostic biomarkers for patients with sAH.
Topics: Humans; Hepatitis, Alcoholic; Proteomics; Male; Female; Complement System Proteins; Biomarkers; Middle Aged; Adult; Liver; Alcoholism; Proteome; Prognosis; Aged
PubMed: 38573776
DOI: 10.1172/jci.insight.174127 -
ACG Case Reports Journal Apr 2024is an opportunistic fungus typically causing pulmonary infection in immunocompromised persons. We present a case of pneumonia (PJP) in a patient with alcoholic...
is an opportunistic fungus typically causing pulmonary infection in immunocompromised persons. We present a case of pneumonia (PJP) in a patient with alcoholic hepatitis and underlying cirrhosis. PJP in patients with alcoholic hepatitis or cirrhosis is sparsely reported in literature. This condition carries a poor prognosis and high mortality. Clinicians need to recognize alcohol use resulting in liver damage as a significant etiological risk factor for PJP.
PubMed: 38560014
DOI: 10.14309/crj.0000000000001316 -
Frontiers in Immunology 2024Alcohol-related liver disease (ARLD) accounts for over one third of all deaths from liver conditions, and mortality from alcohol-related liver disease has increased...
INTRODUCTION
Alcohol-related liver disease (ARLD) accounts for over one third of all deaths from liver conditions, and mortality from alcohol-related liver disease has increased nearly five-fold over the last 30 years. Severe alcohol-related hepatitis almost always occurs in patients with a background of chronic liver disease with extensive fibrosis or cirrhosis, can precipitate 'acute on chronic' liver failure and has a high short-term mortality. Patients with alcohol-related liver disease have impaired immune responses, and increased susceptibility to infections, thus prompt diagnosis of infection and careful patient management is required. The identification of early and non-invasive diagnostic and prognostic biomarkers in ARLD remains an unresolved challenge. Easily calculated predictors of infection and mortality are required for use in patients who often exhibit variable symptoms and disease severity and may not always present in a specialized gastroenterology unit.
METHODS
We have used a simple haematological analyser to rapidly measure circulating myeloid cell parameters across the ARLD spectrum.
RESULTS AND DISCUSSION
We demonstrate for the first time that immature granulocyte (IG) counts correlate with markers of disease severity, and our data suggests that elevated counts are associated with increased short-term mortality and risk of infection. Other myeloid populations such as eosinophils and basophils also show promise. Thus IG count has the potential to serve alongside established markers such as neutrophil: lymphocyte ratio as a simply calculated predictor of mortality and risk of infectious complications in patients with alcohol-related hepatitis. This would allow identification of patients who may require more intensive management.
Topics: Humans; Prognosis; Liver Diseases; Liver Cirrhosis; Hepatitis, Alcoholic; Leukocyte Count
PubMed: 38545104
DOI: 10.3389/fimmu.2024.1330536 -
International Journal of Molecular... Mar 2024This study was performed to investigate the protective effects of on fatty liver and hepatitis in chronic alcohol-induced hepatotoxicity. The physiological compounds of...
This study was performed to investigate the protective effects of on fatty liver and hepatitis in chronic alcohol-induced hepatotoxicity. The physiological compounds of a mixture of aqueous and 60% ethanol (2:8, /) extracts of (EA) were identified as kestose, raffinose, kaempferol and quercetin glucoside, and kaempferol di-glucoside by UPLC Q-TOF MS. The EA regulated the levels of lipid metabolism-related biomarkers such as total cholesterol, triglyceride, low-density lipoprotein (LDL), and high-density lipoprotein (HDL)-cholesterol in serum. Also, EA ameliorated the levels of liver toxicity-related biomarkers such as glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and total bilirubin in serum. EA improved the antioxidant system by reducing malondialdehyde contents and increasing superoxide dismutase (SOD) levels and reduced glutathione content. EA improved the alcohol metabolizing enzymes such as alcohol dehydrogenase, acetaldehyde dehydrogenase, and cytochrome P450 2E1 (CYP2E1). Treatment with EA alleviated lipid accumulation-related protein expression by improving phosphorylation of AMP-activated protein kinase (p-AMPK) expression levels. Especially, EA reduced inflammatory response by regulating the toll-like receptor-4/nuclear factor kappa-light-chain-enhancer of activated B cells (TLR-4/NF-κB) signaling pathway. EA showed an anti-apoptotic effect by regulating the expression levels of B-cell lymphoma 2 (BCl-2), BCl-2-associated X protein (BAX), and caspase 3. Treatment with EA also ameliorated liver fibrosis via inhibition of transforming growth factor-beta 1/suppressor of mothers against decapentaplegic (TGF-β1/Smad) pathway and alpha-smooth muscle actin (α-SMA). Therefore, these results suggest that EA might be a potential prophylactic agent for the treatment of alcoholic liver disease.
Topics: Mice; Animals; Kaempferols; Liver; Mice, Inbred C57BL; Fatty Liver, Alcoholic; Ethanol; Fatty Liver; Inflammation; Cholesterol; Glucosides; Biomarkers; Oxidative Stress
PubMed: 38542468
DOI: 10.3390/ijms25063496 -
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