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Cureus May 2022Non-alcoholic fatty liver disease (NAFLD) is a broad term encompassing hepatic steatosis and non-alcoholic steatohepatitis (NASH), a form of chronic hepatitis. This may,... (Review)
Review
Non-alcoholic fatty liver disease (NAFLD) is a broad term encompassing hepatic steatosis and non-alcoholic steatohepatitis (NASH), a form of chronic hepatitis. This may, unfortunately, lead to terminal complications like cirrhosis and hepatocellular carcinoma (HCC). NAFLD is strongly associated with obesity, type 2 diabetes (T2DM), hypertension, and metabolic syndrome. The growing prevalence of NAFLD, its associated conditions, and its complications are alarming. The insulin sensitizer group "thiazolidinediones" has shown some therapeutic benefits in this condition. This systematic review is intended to focus on the clinical efficacy of this group in patients with NAFLD, employing PubMed, Google Scholar, and the Cochrane Library as databases. We discovered 10 randomized control trials (RCTs; nine involving pioglitazone and one involving rosiglitazone) involving 887 participants. All studies varied in duration from 6 to 24 months. Most of the involved trials had a small number of participants, and the intrinsic quality of the studies was mixed. Pioglitazone consistently improved histological parameters and normalized liver transaminases, although evidence supporting the benefits of other drugs in this class was minimal. Thiazolidinediones, particularly pioglitazone, have proven efficacious in patients with NAFLD/NASH. However, more extensive trials need to be carried out to investigate this drug class's benefits further. Unfortunately, this drug has attendant side effects like weight gain and fractures, limiting its widespread use; hence, careful selection for likely candidates is imperative.
PubMed: 35765391
DOI: 10.7759/cureus.25380 -
Clinical Therapeutics Dec 2023Alcohol-associated hepatitis (AH) is a unique presentation of cholestatic steatohepatitis with liver dysfunction and malaise preceded by heavy alcohol intake. Although...
PURPOSE
Alcohol-associated hepatitis (AH) is a unique presentation of cholestatic steatohepatitis with liver dysfunction and malaise preceded by heavy alcohol intake. Although AH exists on a spectrum, in its most severe form, 28-day mortality approaches 50%. Clinical trials of therapeutic interventions over the last 50 years have yielded few durable therapies, none of which convey benefit beyond the short term.
METHODS
A qualitative systematic review was performed via searches of PubMed, the International Clinical Trials Registry Platform, and ClinicalTrials.gov for therapeutic interventions for AH.
FINDINGS
Prior to 2005, clinical trial results for AH were identified within PubMed. From 2005 to the present, trials were well catalogued within online registries and included information regarding trial status (eg, complete, terminated, actively enrolling). Most clinical trials for AH have used existing medications broadly targeting pathogenic themes of AH (eg, inflammation, cell death) in an off-label manner. The trend of initially promising pilot studies answered by larger trials showing lack of efficacy or safety signals have ended the hopes of many new therapeutics. The emergence of theragnostics to identify patients who may benefit from existing therapies and trials of agents with novel mechanisms of action, including epigenetic modifications and hyaluronic acid signaling targeted to AH pathogenesis, are currently under investigation.
IMPLICATIONS
This review of AH treatments details the historical interventions and clinical trials that have led to the current treatment algorithm and active studies shaping the therapeutic pipeline for AH.
Topics: Humans; Hepatitis, Alcoholic; Clinical Trials as Topic
PubMed: 37980219
DOI: 10.1016/j.clinthera.2023.10.013 -
Minerva Gastroenterologica E Dietologica Sep 2020Worldwide, patients are tested for acute and chronic diseases using a series of basic blood assays. The most common liver tests are serum alanine aminotransferase (ALT)...
Worldwide, patients are tested for acute and chronic diseases using a series of basic blood assays. The most common liver tests are serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), also called transaminases. These tests are indicators of hepatocellular injury and their increase requires further investigations. The aim of this descriptive review is to highlight and remind the importance of liver transaminases in daily practice. A systematic literature search of the main international databases was performed. We looked for papers that involved transaminases, either in the normal range or in case of increased level and focused on their use in clinical practice. A narrative review of this topic was written. Multiple studies have demonstrated that the presence of an elevated ALT was associated with increased liver-related mortality. The normal ALT level ranges from 29 to 33 IU/L in males and 19 to 25 IU/L in females. The investigations imposed by a high level of transaminases includes testing for viral hepatitis A, B, C and E, assessment for nonalcoholic fatty liver disease and alcoholic liver disease, screening for autoimmune hepatitis, hemochromatosis, Wilson's disease and alpha-1 antitrypsin deficiency. Hepatotoxic drugs consumption also should be excluded. Furthermore, the utility of transaminases is evident in the assessment of the outcome after treatment of each specific liver disease. Beside the role in the first diagnostic step of liver injuries, the utility of liver transaminases is also maintained during the follow-up of liver diseases and in their prognostic assessment.
Topics: Alanine Transaminase; Algorithms; Aspartate Aminotransferases; Humans; Liver Diseases
PubMed: 31994373
DOI: 10.23736/S1121-421X.20.02660-4 -
Acta Endocrinologica (Bucharest,... 2020The aim of the present study was to systematically review the effects of Realsil (silybin-phospholipid-vitamin E complex) on liver enzymes in patients with NAFLD or NASH. (Review)
Review
THE EFFECTS OF REALSIL (SILYBIN-PHOSPHOLIPID-VITAMIN E COMPLEX) ON LIVER ENZYMES IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) OR NON-ALCOHOLIC STEATO-HEPATITIS (NASH): A SYSTEMATIC REVIEW AND META-ANALYSIS OF RCTS.
BACKGROUND
The aim of the present study was to systematically review the effects of Realsil (silybin-phospholipid-vitamin E complex) on liver enzymes in patients with NAFLD or NASH.
METHODS
We searched Web of Science, MEDLINE, Google Scholar, Cochrane Library, Science Direct, ProQuest, Scopus, and 1868 articles were found up to December 2018. Four studies that examined the effect of Realsil intake on liver enzymes among NAFLD or NASH patients were included. Exclusion criteria include: animal studies, studies with the design other than clinical trials, studies on non-adult individuals, studies that assess the effect of vitamin E, silybin, or phospholipid solely, studies that examined the effect of Realsil on other outcomes, or studies with insufficient data.
RESULTS
The analysis demonstrated that Realsil intake led to a significant decrease in Gamma-Glutamyl Transpeptidase (GGT) levels (standardized mean difference (SMD) =-0.37; 95% confidence interval (CI]): -0.68 to -0.06). Realsil intake non-significantly decrease alanine transaminase (ALT) levels (SMD=-1.02 U/L; 95% CI: -2.23 to 0.20) and non-significantly increase aspartate aminotransferase (AST) levels (SMD = 0.17 U/L; 95% CI: -0.26-0.61).
CONCLUSION
Realsil intake was associated with a significantly decreased circulating GGT level without any significant effect on AST and ALT levels.
PubMed: 33029240
DOI: 10.4183/aeb.2020.223 -
Liver Transplantation : Official... Jul 2023Alcohol accounts for a large disease burden in hepatology and liver transplantation (LT) and across the globe. Clinical evaluations and decisions about LT candidacy are...
Alcohol accounts for a large disease burden in hepatology and liver transplantation (LT) and across the globe. Clinical evaluations and decisions about LT candidacy are challenging because they rely on detailed psychosocial assessments and interpretations of psychiatric and substance use disorder data, which often must occur rapidly according to the acuity of end-stage liver disease. Such difficulties commonly occur during the process of candidate selection and liver allocation, particularly during early LT (eLT) in patients with acute alcohol-associated hepatitis (AAH). Patients with AAH commonly have very recent or active substance use, high short-term mortality, psychiatric comorbidities, and compressed evaluation and treatment timetables. LT clinicians report that patients' alcohol-associated insight (AAI) is among the most relevant psychosocial data in this population, yet no studies exist examining how LT teams define and use AAI in eLT or its effect on clinical outcomes. In April 2022, we searched Ovid MEDLINE, Elsevier Embase, EBSCOhost PsycInfo and CINAHL, and Wiley Cochrane Central Register of Controlled Trials for reports describing AAH populations who underwent eLT, which also described psychosocial evaluation parameters. The searches retrieved 1603 unique reports. After eligibility screening, 8 were included in the qualitative analysis. This systematic review reveals that AAI is a poorly defined construct that is not measured in a standardized way. Yet it is a commonly cited parameter in articles that describe the psychosocial evaluation and decision-making of patients undergoing eLT for AAH. This article also discusses the general challenges of assessing AAI during eLT for AAH, existing AAI definitions and rating scales, how AAI has been used to date in the broader hepatology and LT literature, and future areas for clinical and research progress.
Topics: Humans; Liver Transplantation; Hepatitis, Alcoholic; Comorbidity
PubMed: 37016758
DOI: 10.1097/LVT.0000000000000144 -
Journal of Gastrointestinal Cancer Mar 2024Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths globally, including Australia. The absence of a consensus clinical practice guideline (CPG)...
BACKGROUND
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths globally, including Australia. The absence of a consensus clinical practice guideline (CPG) specific to HCC management poses challenges in reducing morbidity, mortality, and improving patient recovery. This systematic review aims to evaluate the existing evidence and assess the potential of published guidelines, including those with an international scope, to provide guidance for healthcare professionals in Australia.
METHODS
Electronic search of MEDLINE, Embase, Cochrane Library, Google Scholar, and PubMed was conducted. Peer-reviewed English language articles from 2005 to June 2022 were included if they described management of HCC as part of an evidence-based overall management plan or CPG. The quality of the included CPGs was assessed by the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool.
RESULTS
Twenty-one articles from 16 regions throughout the world were included in this review. All included guidelines (n = 21, 100%) recommended evaluating cirrhosis, hepatitis B, and hepatitis C as potential risk factors of HCC. Obesity and non-alcoholic fatty liver disease were recommended by 19 CPGs (91%) as risk factor for HCC. Fourteen guidelines (67%) endorsed using the BCLC staging system. Eighteen guidelines (86%) recommended a multidisciplinary approach for the management of HCC. Eighteen guidelines (86%) advised that surveillance using ultrasound should be implemented in all cirrhotic patients every 6 months regardless of the cause of cirrhosis. AGREE II mean overall assessment score was 90% indicating that all guidelines included were highly recommended in majority of domains.
CONCLUSIONS
The included CPGs provided a comprehensive approach, emphasizing the evaluation of risk factors, utilization of the BCLC staging system, and the importance of a multidisciplinary approach. Regular surveillance using ultrasound for cirrhotic patients was widely recommended. An understanding of contemporary international CPGs can prioritize aspects of the management of HCC to assist healthcare professionals to develop a national guideline to enable standardized, comprehensive, and evidence-based care for patients with HCC.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Practice Guidelines as Topic; Risk Factors; Australia
PubMed: 37480425
DOI: 10.1007/s12029-023-00961-0 -
Journal of Crohn's & Colitis Mar 2024Inflammatory bowel disease [IBD] comprises an immune-mediated group of chronic gastrointestinal disorders. Patients with IBD may experience extraintestinal... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Inflammatory bowel disease [IBD] comprises an immune-mediated group of chronic gastrointestinal disorders. Patients with IBD may experience extraintestinal manifestations, such as hepatobiliary complications. This meta-analysis aims to assess the prevalence of different hepatic manifestations in IBD patients.
METHODS
For this systematic review and meta-analysis, PubMed, Scopus, Web of Science, and Embase were searched until July 20, 2022, by specifying keywords for IBD, hepatic manifestations, and study type. Full texts of cohort studies in English that examined the prevalence of different hepatic manifestations were included in this study. The primary outcome was the overall prevalence of hepatic manifestations in IBD patients. For the statistical analysis, a proportion by random effect model meta-analysis was performed. The registration number for the protocol of this study in PROSPERO is CRD42022369595.
RESULTS
From the 4421 articles retrieved from the primary search, 118 met the inclusion criteria and were included in the final analysis. After a pooled analysis of 1 729 128 patients, the overall prevalence of hepatic manifestations was 3.49% (95% confidence interval [CI]: 3.31-3.68%; I2: 99.55%). The pooled prevalence of non-alcoholic fatty liver disease in 228 216 patients was 26.1% [95% CI: 22.1-30.2%; I2: 99.018%]. After pooled analysis of 9642 patients, the prevalence of primary sclerosing cholangitis was 1.67% [95% CI: 1.47-1.88%; I2: 99.10%]. The pooled prevalence of biliary stones was 4.1% [95% CI: 3.6-4.7%; I2: 97.43%]. Autoimmune hepatitis (0.51% [95% CI: 0.26-0.75%]; I2: 85.36%) and portal vein thrombosis (0.21% [95% CI: 0.08-0.33%]; I2: 97.95%) are considered as rare manifestations.
CONCLUSION
This study summarizes the prevalence and importance of different hepatic manifestations in IBD patients. These findings are crucial for the management of extraintestinal manifestations, especially hepatic manifestations, in IBD patients.
Topics: Humans; Inflammatory Bowel Diseases; Prevalence; Research Design; Liver Diseases
PubMed: 37695111
DOI: 10.1093/ecco-jcc/jjad157 -
Pancreatology : Official Journal of the... Sep 2020Available estimates of coexistent alcohol-related pancreatitis (ALP) and alcohol-related liver disease (ALD) vary widely, and factors that determine coexistent disease... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Available estimates of coexistent alcohol-related pancreatitis (ALP) and alcohol-related liver disease (ALD) vary widely, and factors that determine coexistent disease are largely unknown. We performed a systematic review of published literature with the primary aim to generate robust estimates for coexistent alcohol-related chronic pancreatitis (ACP) and alcohol-related cirrhosis (ALC).
METHODS
We searched PubMed, EMBASE, and Web of Science databases from inception until February 2018. Studies included were those in English-language, sample size ≥25 and allowed calculation of the coexistent disease. Pooled estimates were calculated using a random-effects model approach.
RESULTS
Twenty-nine (including 5 autopsy studies) of 2000 eligible studies met inclusion criteria. Only 6.9% included patients were female. Fifteen studies enabled calculation of ACP in ALC, and 11 for ALC in ACP. Pooled prevalence of ACP in ALC was 16.2% (95% CI 10.4-24.5) overall, and 15.5% (95% CI 8.0-27.7) when data were limited to clinical studies. Corresponding prevalence for ALC in ACP was 21.5% (95% CI 12.0-35.6) and 16.9% (95% CI 11.5-24.3), respectively. There was significant heterogeneity among studies (I - 65-92%). Pooled prevalence for ALP in ALD or ALD in ALP in clinical studies were 15.2% and 39%, respectively. None of the studies reported outcomes in patients with coexistent disease.
CONCLUSION
A sizeable fraction of patients with ACP or ALC have coexistent disease. Future studies should define the prevalence of coexistent disease in women and minority populations, and the consequences of coexistent disease on clinical presentation and short- and long-term outcomes.
Topics: Female; Hepatitis, Alcoholic; Humans; Liver Cirrhosis, Alcoholic; Male; Pancreatitis, Alcoholic
PubMed: 32800649
DOI: 10.1016/j.pan.2020.07.412 -
Nutrients Feb 2023The increasing burden of nonalcoholic fatty liver disease (NAFLD) requires innovative management strategies, but an effective pharmacological agent has yet to be found.... (Review)
Review
The increasing burden of nonalcoholic fatty liver disease (NAFLD) requires innovative management strategies, but an effective pharmacological agent has yet to be found. Apart from weight loss and lifestyle adjustments, one isomer of the vitamin E family-alpha-tocopherol-is currently recommended for nondiabetic steatohepatitis patients. Another member of the vitamin E family, tocotrienol (T3), has anti-inflammatory and antioxidant properties that reach beyond those of alpha-tocopherol, making it a potential agent for use in NAFLD management. This systematic review aimed to provide an overview of the effects of T3 supplementation on NAFLD from both clinical and preclinical perspectives. A literature search was performed in October 2022 using PubMed, Scopus and Web of Science. Original research articles reporting NAFLD outcomes were included in this review. The search located 12 articles (8 animal studies and 4 human studies). The literature reports state that T3 isomers or natural mixtures (derived from palm or annatto) improved NAFLD outcomes (liver histology, ultrasound or liver profile). However, the improvement depended on the severity of NAFLD, study period and type of intervention (isomers/mixture of different compositions). Mechanistically, T3 improved lipid metabolism and prevented liver steatosis, and reduced mitochondrial and endoplasmic reticulum stress, inflammation and ultimately liver fibrosis. In summary, T3 could be a potential agent for use in managing NAFLD, pending more comprehensive preclinical and human studies.
Topics: Animals; Humans; Non-alcoholic Fatty Liver Disease; Tocotrienols; alpha-Tocopherol; Liver; Vitamin E
PubMed: 36839192
DOI: 10.3390/nu15040834 -
Alcohol and Alcoholism (Oxford,... May 2022Chronic alcohol consumption may result in liver injury and chronic liver disease, but other factors are likely to influence disease progression. Malnutrition,...
AIMS
Chronic alcohol consumption may result in liver injury and chronic liver disease, but other factors are likely to influence disease progression. Malnutrition, specifically micronutrient deficiency, is frequently associated with both alcohol use disorder and chronic liver disease. We hypothesize that micronutrient deficiencies may affect the progression of liver disease in this population.
METHODS
Systematic integrative review of the medical literature; electronic search of MEDLINE 1950-2021; studies investigating role of any micronutrient in the acceleration of alcohol-related liver injury in humans or animals. Studies which specifically related to alcoholic hepatitis were excluded. Outcomes were extracted and recorded in tabulated form and discussed narratively.
RESULTS
We identified 46 studies investigating the role of micronutrient deficiencies in the pathogenesis of alcohol-related liver disease. Specific micronutrients which were identified included folic acid or related B vitamins (n = 9 studies), Vitamin D (n = 9 studies), magnesium (n = 8 studies), zinc (n = 8 studies) and selenium (n = 12 including one systematic review). Observational evidence suggests a potential role of magnesium deficiency in accelerating alcohol-related liver injury with weak or negative evidence for other micronutrients.
CONCLUSIONS
Magnesium deficiency may increase the risk of alcohol-related liver injury and adverse liver outcomes. However, currently, there is insufficient evidence to support magnesium supplementation except for clinically relevant magnesium deficiency. Long-term prospective cohort studies assessing the impact of micronutrients on liver disease progression in patients with alcohol use disorder are lacking and may help determine whether there is a causal role for micronutrient deficiencies in alcohol-related liver injury.
Topics: Alcoholism; Dietary Supplements; Disease Progression; Humans; Liver Diseases; Magnesium; Magnesium Deficiency; Malnutrition; Micronutrients; Prospective Studies; Vitamins
PubMed: 34491307
DOI: 10.1093/alcalc/agab060