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Cureus Apr 2024Acute hepatitis can result from a wide variety of noninfectious causes that include, but are not limited to, drugs (drug-induced hepatitis), alcohol (alcoholic...
Acute hepatitis can result from a wide variety of noninfectious causes that include, but are not limited to, drugs (drug-induced hepatitis), alcohol (alcoholic hepatitis), immunologic (autoimmune hepatitis, primary biliary cholangitis), or as a result of indirect insult secondary to biliary tract dysfunction (cholestatic hepatitis), pregnancy-related liver dysfunction, shock, or metastatic disease. In clinical settings, these causes are not uncommon to overlap with each other or are masked by obviously visible causes in medical history. We reported our scenario of a patient who has a heavy history of alcohol use and presented with alcohol withdrawal symptoms and a marked elevation of liver enzymes. Interestingly, further investigations suggested Wilson's disease could be an underlying culprit of acute hepatitis in this patient. This case again emphasized that Wilson's disease can be masked under multiple causes and various scenarios, which alerts clinicians that a broad approach should be made for every case of acute hepatitis.
PubMed: 38803772
DOI: 10.7759/cureus.59025 -
Hepatology Research : the Official... May 2024It is not uncommon to encounter outpatients in the hepatology department with harmful alcohol habits. When treating such chronic liver disease (CLD) patients, an...
AIM
It is not uncommon to encounter outpatients in the hepatology department with harmful alcohol habits. When treating such chronic liver disease (CLD) patients, an adequate intervention method for harm reduction of alcohol use, such as brief intervention (BI) or BI and nalmefene, should be considered. This study aimed to elucidate the clinical effectiveness of BI for CLD patients affected by harmful alcohol use.
METHODS
From June 2021 to 2023, 123 Japanese CLD outpatients (hepatitis B virus : hepatitis C virus : alcoholic liver disease : others = 32:18:42:31) with an Alcohol Use Disorders Identification Test (AUDIT) score of ≥8 at the initial interview and a repeat interview with AUDIT 9 months later were enrolled. Clinical features related to patient behavior following the initial AUDIT interview were retrospectively evaluated, and compared between patients without and with BI treatment.
RESULTS
For the non-BI and BI groups, baseline AUDIT score (median 10 [interquartile range (IQR) 9-13] vs. 12 [IQR 10-17], p = 0.016) and relative change in AUDIT score (median 0 [IQR -3 to 2] vs. -3 [IQR -7 to 0], p < 0.01) showed significant differences, whereas there was no significant difference between the groups for AUDIT score at the time of the second interview (p = 0.156). Following BI, significant improvements were observed for items 1, 2, 3, 4, 5, 8, and 10 of AUDIT (each p < 0.05).
CONCLUSION
Patients with an alcohol use disorder as well as those with alcohol dependency who received BI showed a significant decline in AUDIT score, although the score of the follow-up AUDIT indicated continued alcohol use disorder. In addition to BI, medication with nalmefene should be considered, based on individual factors.
PubMed: 38801372
DOI: 10.1111/hepr.14060 -
Journal of Gastroenterology and... May 2024Natural killer (NK) cells are one of the key members of innate immunity that predominantly reside in the liver, potentiating immune responses against viral infections or... (Review)
Review
Natural killer (NK) cells are one of the key members of innate immunity that predominantly reside in the liver, potentiating immune responses against viral infections or malignant tumors. It has been reported that changes in cell numbers and function of NK cells are associated with the development and progression of chronic liver diseases (CLDs) including non-alcoholic fatty liver disease, alcoholic liver disease, and chronic viral hepatitis. Also, it is known that the crosstalk between NK cells and hepatic stellate cells plays an important role in liver fibrosis and cirrhosis. In particular, the impaired functions of NK cells observed in CLDs consequently contribute to occurrence and progression of hepatocellular carcinoma (HCC). Chronic infections by hepatitis B or C viruses counteract the anti-tumor immunity of the host by producing the sheddases. Soluble major histocompatibility complex class I polypeptide-related sequence A (sMICA), released from the cell surfaces by sheddases, disrupts the interaction and affects the function of NK cells. Recently, the MICA/B-NK stimulatory receptor NK group 2 member D (NKG2D) axis has been extensively studied in HCC. HCC patients with low membrane-bound MICA or high sMICA concentration have been associated with poor prognosis. Therefore, reversing the sMICA-mediated downregulation of NKG2D has been proposed as an attractive strategy to enhance both innate and adaptive immune responses against HCC. This review aims to summarize recent studies on NK cell immune signatures and its roles in CLD and hepatocellular carcinogenesis and discusses the therapeutic approaches of MICA/B-NKG2D-based or NK cell-based immunotherapy for HCC.
PubMed: 38800890
DOI: 10.1111/jgh.16584 -
Aging May 2024Alcoholic liver disease (ALD) has a complex pathogenesis. Although early-stage ALD can be reversed by ceasing alcohol consumption, early symptoms are difficult to...
Alcoholic liver disease (ALD) has a complex pathogenesis. Although early-stage ALD can be reversed by ceasing alcohol consumption, early symptoms are difficult to detect, and several factors contribute to making alcohol difficult to quit. Continued alcohol abuse worsens the condition, meaning it may gradually progress into alcoholic hepatitis and cirrhosis, ultimately, resulting in irreversible consequences. Therefore, effective treatments are urgently needed for early-stage ALD. Current research mainly focuses on preventing the progression of alcoholic fatty liver to alcoholic hepatitis and cirrhosis. However, challenges remain in identifying key therapeutic targets and understanding the molecular mechanisms that underlie the treatment of alcoholic hepatitis and cirrhosis, such as the limited discovery of effective therapeutic targets and treatments. Here, we downloaded ALD microarray data from Gene Expression Omnibus and used bioinformatics to compare and identify the hub genes involved in the progression of alcoholic fatty liver to alcoholic hepatitis and cirrhosis. We also predicted target miRNAs and long non-coding RNAs (lncRNAs) to elucidate the regulatory mechanisms (the mRNA-miRNA-lncRNA axis) underlying this progression, thereby building a competitive endogenous RNA (ceRNA) mechanism for lncRNA, miRNA, and mRNA. This study provides a theoretical basis for the early treatment of alcoholic hepatitis and cirrhosis and identifies potential therapeutic targets.
Topics: Humans; Liver Diseases, Alcoholic; Gene Regulatory Networks; MicroRNAs; RNA, Long Noncoding; Early Diagnosis; RNA, Messenger; Computational Biology; Disease Progression; Gene Expression Profiling; Gene Expression Regulation; RNA, Competitive Endogenous
PubMed: 38795390
DOI: 10.18632/aging.205861 -
Cellular and Molecular Gastroenterology... May 2024There is limited information on how the liver-to-gut axis contributes to alcohol-associated liver disease (AALD). We previously identified that high-mobility group box-1...
BACKGROUND & AIMS
There is limited information on how the liver-to-gut axis contributes to alcohol-associated liver disease (AALD). We previously identified that high-mobility group box-1 (HMGB1) undergoes oxidation in hepatocytes and demonstrated elevated serum levels of oxidized HMGB1 ([O] HMGB1) in alcoholic patients. Since interleukin-1 beta (IL-1B) increases in AALD, we hypothesized hepatocyte-derived [O] HMGB1 could interact with IL-1B to activate a pro-inflammatory program that, besides being detrimental to the liver, drives intestinal barrier dysfunction.
RESULTS
Alcohol-fed Rage mice exhibited decreased nuclear factor kappa B signaling, a pro-inflammatory signature, and reduced total intestinal permeability, resulting in protection from AALD. In addition, [O] HMGB1 bound and signaled through the receptor for advanced-glycation end-products (RAGE) in myeloid cells, driving hepatic inflammation, intestinal permeability, and increased portal blood lipopolysaccharide in AALD. We identified that [O] HMGB1 formed a complex with IL-1B, which was found in the livers of patients with acute alcoholic hepatitis and mice with AALD. This complex originated from the liver, because it was absent in the intestine when hepatocytes did not produce [O] HMGB1. Mechanistically, the complex bound RAGE in Kupffer cells and macrophages induces a pro-inflammatory program. Moreover, it bound RAGE in intestinal macrophages and epithelial cells, leading to intestinal inflammation, altered intestinal epithelial cell tight junction protein expression, increased intestinal permeability, and elevated portal blood lipopolysaccharide, enhancing AALD pathogenesis.
CONCLUSIONS
We identified a protein complex of liver origin that amplifies the pro-inflammatory feedback loop in AALD; therefore, targeting this complex could have significant therapeutic potential.
PubMed: 38788899
DOI: 10.1016/j.jcmgh.2024.05.010 -
Cureus May 2024Background The hepatoprotective function of polyherbal formulation Liv.52 in chronic liver diseases is well recognized in published literature. The objective of this...
Background The hepatoprotective function of polyherbal formulation Liv.52 in chronic liver diseases is well recognized in published literature. The objective of this open-label, phase IV study was to further strengthen and validate its safety and effectiveness using a large patient pool in a real-world scenario and provide scientific data on symptomatic improvement and supportive treatment in liver function with improvement in quality of life. Methods Adult patients of either sex with one or more clinical symptoms like fatigue, nausea, anorexia, abdominal pain or discomfort, muscle cramps, jaundice, or any other signs and symptoms with a history suggestive of mild-to-moderate hepatic disorders like alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), drug-induced hepatotoxicity, or hepatitis were treated with two Liv.52 DS tablets (oral) twice daily for 12 weeks. Results Out of the 1000 enrolled patients, 962 (96%) completed the study with the following subgroups ALD: 375 (38.9%), NAFLD: 379 (39.3%), drug-induced hepatotoxicity: 78 (8.1%), hepatitis: 130 (13.5%). The mean age of enrolled patients was 37.7 years, and the majority of them, 785 (78.5%) were men. The common adverse events observed (with >1.5% incidence) in the study were abdominal pain: 26 (2.6%) and headache: 17 (1.7%). Liv.52 showed statistically significant improvement (P<0.0001) in various clinical signs and symptoms in the majority of patients namely, fatigue: 357/723 (49%), anorexia: 485/620 (78.2%), jaundice: 48/52 (92%). Majority of the patients showed significant improvements from baseline to end of 12 weeks in the liver function test parameters namely, aspartate aminotransferase: 633/840 (75.36%), alanine aminotransferase: 592/729 (81.21%), serum bilirubin: 244/347 (70.32%), alkaline phosphatase: 279/355 (78.59%) with P<0.0001 for all parameters. Statistically significant improvement (P<0.005) was also seen in all the components of the chronic liver disease questionnaire (CLDQ) scores from baseline to 12 weeks. Conclusions The study demonstrated that Liv.52 was hepatoprotective and well tolerated in the study population after treatment for 12 weeks. Significant improvements were seen in clinical signs and symptoms, laboratory parameters of liver function, and CLDQ scores from baseline to 12 weeks. No significant or new safety signals emerged from this study.
PubMed: 38784689
DOI: 10.7759/cureus.60898 -
Vox Sanguinis May 2024Transfusion-related acute lung injury is an infrequent adverse reaction observed in patients receiving blood products. The lung injury can range in severity and can be...
BACKGROUND AND OBJECTIVES
Transfusion-related acute lung injury is an infrequent adverse reaction observed in patients receiving blood products. The lung injury can range in severity and can be associated with both mortality and mortality. All blood products except albumin have been linked to cases of transfusion-related acute lung injury. In fact, albumin may be used as a salvage modality in severe transfusion-related acute lung injury. We report an alcoholic patient who developed lung injury following treatment with albumin in the setting of hypoalbuminaemia.
MATERIALS AND METHODS
A 41-year-old male with alcoholic liver disease was admitted for severe ascites and alcoholic hepatitis. Chest x-ray showed small pleural effusions at the lung bases with no overt pulmonary oedema. He received high doses of furosemide for lower extremity oedema. The patient received a total of two albumin infusions to augment the diuresis effect.
RESULTS
He subsequently developed acute hypoxic respiratory failure with imaging showing interstitial and airspace abnormalities concerning for pulmonary oedema. He showed no additional signs of volume overload and was treated supportively until the condition improved.
CONCLUSION
This is the first reported case of albumin-associated lung injury proximally related to albumin infusion. We aim to increase awareness of this possible sequelae among physicians.
PubMed: 38779759
DOI: 10.1111/vox.13684 -
Journal of Multidisciplinary Healthcare 2024To analyse clinical manifestations of unexplained abnormal liver function and perform hepatobiliary histopathology procedures on patients to evaluate the value of liver...
OBJECTIVE
To analyse clinical manifestations of unexplained abnormal liver function and perform hepatobiliary histopathology procedures on patients to evaluate the value of liver biopsy in diagnosing the aetiology of unexplained abnormal liver function.
METHODS
A convenience sampling method was used to retrospectively collect the data of patients who were diagnosed with unexplained abnormal liver function and who received liver biopsy in the Pathology Department of Tianjin Second People's Hospital, China, between March 2022 and July 2023 to analyse liver pathology and clinical manifestations.
RESULTS
A total of 1302 patients were included in this study, which mainly included 11 diseases: autoimmune liver disease (74 cases, 5.68%), drug-induced liver injury (DILI) (204 cases, 15.67%), cancer (237 cases, 18.20%), non-alcoholic fatty liver disease (104 cases, 7.99%), non-alcoholic steatohepatitis (74 cases, 5.68%), viral hepatitis (490 cases, 37.63%), other types of hepatitis (30 cases, 2.30%), cholestatic liver disease (17 cases, 1.31%), alcoholic liver disease (15 cases, 1.15%), hepatic cyst (5 cases, 0.38%) and Gilbert syndrome (4 cases, 0.31%). The success rate of liver biopsy sampling was 100%, and (1.52 ± 0.130) tissue strips were sampled. The average operating time was 11.52 minutes. The percutaneous liver biopsy did not significantly increase short-term liver function index values (serum γ-glutamyl transpeptidase, total bilirubin, alanine transaminase, aspartate aminotransferase, alkaline phosphatase). Ninety-two patients had a small amount of liver subcapsular fluid, but there was no progress after medical treatment.
CONCLUSION
Ultrasound-guided percutaneous liver biopsy has value in the diagnosis of unexplained abnormal liver function. Viral hepatitis, cancer and DILI are the most common causes of unexplained abnormal liver function. Liver biopsy does not aggravate the organic and functional impairment of the liver.
PubMed: 38779307
DOI: 10.2147/JMDH.S460338 -
Liver Transplantation : Official... May 2024The Sustained Alcohol use post-Liver Transplant (SALT) and the High-Risk Alcohol Relapse (HRAR) scores were developed to predict return to alcohol use after liver...
BACKGROUND AIMS
The Sustained Alcohol use post-Liver Transplant (SALT) and the High-Risk Alcohol Relapse (HRAR) scores were developed to predict return to alcohol use after liver transplant (LT) for alcohol associated liver disease (ALD).
METHODS
A retrospective analysis of deceased donor LT 10/2018 to 4/2022 was performed. All patients (pts) underwent careful pre-LT psychosocial evaluation. Data on alcohol use, substance abuse, prior rehabilitation, and legal issues were collected. Post-LT, all were encouraged to participate in rehabilitation programs and underwent interval phosphatidylethanol (PeTH) testing. Pts with ALD were stratified by < or > 6 month sobriety prior to listing. Those with <6 month were further stratified as acute alcoholic hepatitis (AH) by NIAAA criteria and non-AH. The primary outcome was utility of the SALT (<5 vs. ≥5) and HRAR (<3 vs. ≥3) scores to predict return to alcohol use (+PeTH) within 1 year after LT.
RESULTS
Of the 365 LT, 86 had > 6 month sobriety and 85 had <6 month sobriety; 41 with AH and 44 non-AH. In those with AH, the mean time of abstinence to LT was 58 days, and 71% failed prior rehabilitation. Following LT, return to drinking was similar in the AH (24%) compared to <6M non-AH (15%) and >6M ALD (22%). Only 4% had returned to heavy drinking. The accuracy of both the SALT and HRAR scores to predict return to alcohol was low (accuracy 61-63%) with poor sensitivity (46% and 37%), specificity (67-68%), positive predictive value (22-26%) with moderate negative predictive value (NPV) (81-83%), respectively with higher NPVs (95%) in predicting return to heavy drinking.
CONCLUSIONS
Both SALT and HRAR scores had good NPV in identifying patients at low risk for recidivism.
PubMed: 38775570
DOI: 10.1097/LVT.0000000000000407 -
Revista Da Associacao Medica Brasileira... 2024The aim of the study was to compare the epidemiology and clinical profiles of hospital admissions in a single Brazilian Hepatology Unit from the period 2014-2017 to...
OBJECTIVE
The aim of the study was to compare the epidemiology and clinical profiles of hospital admissions in a single Brazilian Hepatology Unit from the period 2014-2017 to 2019-2022.
METHODS
A retrospective analysis of hospital database from the abovementioned periods was done. The study included patients over the age of 18 years who were hospitalized due to complications of diseases such as viral hepatitis, alcoholic disease, nonalcoholic fatty liver disease, and autoimmune liver and drug-induced hepatitis.
RESULTS
In both study periods, middle-aged males were predominant and were younger than females. In the first period (2014-2017), hepatitis C (33.5%) was the most prevalent cause of admission, followed by alcoholic liver disease (31.7%). In the second period (2019-2022), nonalcoholic fatty liver disease (38%) and alcoholic liver disease (27.6%) were the most frequent causes of admission. No changes were observed in the proportion of alcoholic liver disease or drug-induced hepatitis in both study periods. The prevalence of viral hepatitis decreased in both genders, with hepatitis C decreasing from 32.4 to 9.7% for males and 35.4 to 10.8% for females, and OR=0.2; 95%CI 0.1-0.3 for both males and females. Similarly, the prevalence of hepatitis B decreased from 19.1 to 8.1% and OR=0.3; 95%CI 0.2-0.5 for males and 8.2 to 3.7% and OR=0.4; 95%CI 0.1-0.9 for females. The prevalence of autoimmune liver diseases increased only in males, from 2.1 to 5.9% and OR=2.9; 95%CI 1.2-6.6.
CONCLUSION
Over the past 4 years, there has been a shift in hospital admission profile at a Brazilian Hepatology Unit, with a decrease in viral hepatitis and an increase in autoimmune diseases and nonalcoholic fatty liver disease. Males were more affected at younger ages than females. Furthermore, ascites was the most prevalent cause of complications in both periods analyzed.
Topics: Humans; Male; Female; Brazil; Middle Aged; Retrospective Studies; Adult; Liver Diseases; Hospitalization; Aged; Prevalence; Chronic Disease; Sex Distribution; Young Adult; Liver Diseases, Alcoholic; Age Distribution; Adolescent; Hepatitis, Autoimmune
PubMed: 38775508
DOI: 10.1590/1806-9282.20231430