-
The Cochrane Database of Systematic... Aug 2021Vitamin D deficiency is often reported in people with chronic liver diseases. Improving vitamin D status could therefore be beneficial for people with chronic liver... (Review)
Review
BACKGROUND
Vitamin D deficiency is often reported in people with chronic liver diseases. Improving vitamin D status could therefore be beneficial for people with chronic liver diseases.
OBJECTIVES
To assess the beneficial and harmful effects of vitamin D supplementation in adults with chronic liver diseases.
SEARCH METHODS
We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index-Science. We also searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. We scanned bibliographies of relevant publications and enquired experts and pharmaceutical companies as to additional trials. All searches were up to November 2020.
SELECTION CRITERIA
Randomised clinical trials that compared vitamin D at any dose, duration, and route of administration versus placebo or no intervention in adults with chronic liver diseases. Vitamin D could have been administered as supplemental vitamin D (vitamin D (cholecalciferol) or vitamin D (ergocalciferol)), or an active form of vitamin D (1α-hydroxyvitamin D (alfacalcidol), 25-hydroxyvitamin D (calcidiol), or 1,25-dihydroxyvitamin D (calcitriol)).
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. We used GRADE to assess the certainty of evidence.
MAIN RESULTS
We included 27 randomised clinical trials with 1979 adult participants. This review update added 12 trials with 945 participants. We assessed all trials as at high risk of bias. All trials had a parallel-group design. Eleven trials were conducted in high-income countries and 16 trials in middle-income countries. Ten trials included participants with chronic hepatitis C, five trials participants with liver cirrhosis, 11 trials participants with non-alcoholic fatty liver disease, and one trial liver transplant recipients. All of the included trials reported the baseline vitamin D status of participants. Participants in nine trials had baseline serum 25-hydroxyvitamin D levels at or above vitamin D adequacy (20 ng/mL), whilst participants in the remaining 18 trials were vitamin D insufficient (less than 20 ng/mL). Twenty-four trials administered vitamin D orally, two trials intramuscularly, and one trial intramuscularly and orally. In all 27 trials, the mean duration of vitamin D supplementation was 6 months, and the mean follow-up of participants from randomisation was 7 months. Twenty trials (1592 participants; 44% women; mean age 48 years) tested vitamin D (cholecalciferol); three trials (156 participants; 28% women; mean age 54 years) tested vitamin D; four trials (291 participants; 60% women; mean age 52 years) tested 1,25-dihydroxyvitamin D; and one trial (18 participants; 0% women; mean age 52 years) tested 25-hydroxyvitamin D. One trial did not report the form of vitamin D. Twelve trials used a placebo, whilst the other 15 trials used no intervention in the control group. Fourteen trials appeared to be free of vested interest. Eleven trials did not provide any information on clinical trial support or sponsorship. Two trials were funded by industry. We are very uncertain regarding the effect of vitamin D versus placebo or no intervention on all-cause mortality (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.51 to 1.45; 27 trials; 1979 participants). The mean follow-up was 7 months (range 1 to 18 months). We are very uncertain regarding the effect of vitamin D versus placebo or no intervention on liver-related mortality (RR 1.62, 95% CI 0.08 to 34.66; 1 trial; 18 participants) (follow-up: 12 months); serious adverse events such as hypercalcaemia (RR 5.00, 95% CI 0.25 to 100.8; 1 trial; 76 participants); myocardial infarction (RR 0.75, 95% CI 0.08 to 6.81; 2 trials; 86 participants); thyroiditis (RR 0.33, 95% CI 0.01 to 7.91; 1 trial; 68 participants); circular haemorrhoidal prolapse (RR 3.00, 95% CI 0.14 to 65.9; 1 trial; 20 participants); bronchopneumonia (RR 0.33, 95% CI 0.02 to 7.32; 1 trial 20 participants); and non-serious adverse events. The certainty of evidence for all outcomes is very low. We found no data on liver-related morbidity such as gastrointestinal bleeding, hepatic encephalopathy, hepatorenal syndrome, ascites, or liver cancer. There were also no data on health-related quality of life. The evidence is also very uncertain regarding the effect of vitamin D versus placebo or no intervention on rapid, early, and sustained virological response in people with chronic hepatitis C.
AUTHORS' CONCLUSIONS
Given the high risk of bias and insufficient power of the included trials and the very low certainty of the available evidence, vitamin D supplementation versus placebo or no intervention may increase or reduce all-cause mortality, liver-related mortality, serious adverse events, or non-serious adverse events in adults with chronic liver diseases. There is a lack of data on liver-related morbidity and health-related quality of life. Further evidence on clinically important outcomes analysed in this review is needed.
Topics: Adult; Dietary Supplements; Female; Hepatitis C, Chronic; Humans; Male; Middle Aged; Quality of Life; Vitamin D
PubMed: 34431511
DOI: 10.1002/14651858.CD011564.pub3 -
Current Opinion in Pharmacology Oct 2021Severe alcoholic hepatitis is the most severe form of alcohol-related liver disease. Corticosteroids remain the first choice of treatment. However, they are only... (Review)
Review
Severe alcoholic hepatitis is the most severe form of alcohol-related liver disease. Corticosteroids remain the first choice of treatment. However, they are only effective in a subset of patients and are associated with an increased infection risk. Furthermore, nonresponders to corticosteroids have a poor prognosis with a mortality of 70% over 6 months. As such, there is a high need for a more personalized use of corticosteroids and the development and identification of alternative therapeutic strategies. In this review, we summarize the recent and ongoing randomized controlled trials concerning the treatment of severe alcoholic hepatitis.
Topics: Adrenal Cortex Hormones; Hepatitis, Alcoholic; Humans
PubMed: 34365226
DOI: 10.1016/j.coph.2021.06.011 -
Cureus May 2021Renal and hepatic functions are often mingled through both the existence of associated primary organ diseases and hemodynamic co-relationship. The primary objective of... (Review)
Review
Renal and hepatic functions are often mingled through both the existence of associated primary organ diseases and hemodynamic co-relationship. The primary objective of this study was to sum up the relationship between autoimmune hepatitis (AIH) on renal tubular acidosis (RTA) and the stages of the disease. A systematic review was performed for 24 trials. A total of 3687 patients were included. The incidence of RTA occurring and short-term mortality reduction was seen in two groups; for an overall effect: Z = 2.85 (P = 0.004) a total 95% CI of 0.53 [0.34, 0.82]. Only one patient with alcoholic liver cirrhosis was found to have an incomplete type of RTA. Test for overall effect: Z = 2.28 (P = 0.02) 95% CI of 2.83 [1.16, 6.95]. A reduction in fatal infections with dual therapy of corticosteroid plus N-acetylcysteine (NAC) test for overall effect: Z = 3.07 (P = 0.002) with 95% CI of 0.45 [0.27, 0.75]. Autoimmune diseases are the most frequent underlying cause of secondary RTA in adults. The primary renal disease must be actively excluded in all patients with hepatic failure by aggressive clinical and laboratory evaluations.
PubMed: 34079685
DOI: 10.7759/cureus.15287 -
Annals of Surgery Open : Perspectives... Jun 2021To systematically review and compare the overall (OS) and disease-free (DFS) survival after hepatic resections for hepatocellular carcinoma (HCC) of patients with...
OBJECTIVE
To systematically review and compare the overall (OS) and disease-free (DFS) survival after hepatic resections for hepatocellular carcinoma (HCC) of patients with nonalcoholic fatty liver disease (NAFLD) versus other risk factors.
BACKGROUND
Different clinical and tumor characteristics are associated with HCC in the setting of NAFLD in comparison to other risk factors. It is still unclear whether these differences impact patient survival after radical hepatectomies.
METHODS
Randomized controlled trials and observational studies published in the English literature between July 1980 and June 2020 were searched using multiple databases. Patients' baseline characteristics and the hazard ratios (HRs) of the OS and DFS were extracted and meta-analyses were performed.
RESULTS
Fifteen retrospective cohort studies with a total of 7226 patients were included. Among them, 1412 patients (19.5%) had NAFLD and 5814 (80.4%) had other risk factors (eg, viral hepatitis B or C, alcoholic cirrhosis, or cryptogenic cirrhosis). Summary statistics showed that patients with NAFLD had better DFS (HR = 0.81; 95% CI: 0.70-0.94; = 0.006) and OS (HR = 0.78; 95% CI: 0.67-0.90; = 0.001) than the control group. Subgroups analyses also indicated that the OS favored NAFLD patients versus patients with viral hepatitis B or C (HR = 0.80; 95% CI: 0.67-0.96; = 0.017) or alcoholic and cryptogenic cirrhosis (HR = 0.68; 95% CI: 0.47-1.0; = 0.05).
CONCLUSION
After hepatic resections for HCC, NAFLD patients have better DFS and OS than patients with other risk factors. Subgroup analysis and meta-regression suggested that the survival advantage of NAFLD patients was more pronounced in studies published after 2015 and from Asian centers.
PubMed: 37636554
DOI: 10.1097/AS9.0000000000000065 -
Journal of Hepatology Sep 2021Despite a marked reduction in new cases of cirrhosis caused by HCV infection, over 500,000 new cirrhosis cases in this category were estimated globally in 2019. This... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Despite a marked reduction in new cases of cirrhosis caused by HCV infection, over 500,000 new cirrhosis cases in this category were estimated globally in 2019. This contribution quantifies the relationship between alcohol use and the progression of liver disease in people with HCV infections.
METHODS
The causal impact of different levels of alcohol use on cirrhosis has previously been established. The quantification of this relationship was undertaken based on a systematic search of the literature and a meta-analysis. We limited our search to longitudinal and case-control studies with biologically verified outcomes. Different sensitivity analyses were conducted to check on key assumptions and on the generalizability of the relationship.
RESULTS
Alcohol use has a dose-dependent relationship with incident cirrhosis, which is linear on the log-linear level, and thus exponential on the level of odds ratios or other risk indicators. Each standard drink of 12 grams of pure alcohol per day increases the risk by about 11%. The results were stable regardless of the statistical model used, level of adjustment, quality of the study, or outcome (i.e., cirrhosis, decompensated cirrhosis, liver-related death).
CONCLUSIONS
Alcohol use has a marked impact on the progression of HCV infections to cirrhosis and more severe liver outcomes.
LAY SUMMARY
Alcohol consumption has a significant impact on the progression of liver disease in people with HCV infections. Each alcoholic drink per day is associated with an increase in the risk of cirrhosis of 11%.
Topics: Alcohol Drinking; Hepatitis C; Humans; Liver Diseases; Risk Factors
PubMed: 33892007
DOI: 10.1016/j.jhep.2021.04.018 -
Journal of Gastroenterology and... Jul 2021The rising incidence of chronic liver disease (CLD) has increased the need for early recognition. This systematic review assesses the diagnostic accuracy of the enhanced...
BACKGROUND AND AIMS
The rising incidence of chronic liver disease (CLD) has increased the need for early recognition. This systematic review assesses the diagnostic accuracy of the enhanced liver fibrosis (ELF) test in cases of advanced fibrosis and cirrhosis due to multiple etiologies in at-risk populations.
METHODS
Studies evaluating the ELF accuracy in identifying advanced fibrosis or cirrhosis, defined as METAVIR stage F ≥ 3 and F = 4 or equivalent, in patients with non-alcoholic fatty liver disease (NAFLD), alcohol liver disease (ALD), or viral hepatitis were included. Liver biopsy was used as the reference standard. Medline and Embase databases were searched. The QUADAS-2 tool was used as a framework to assess risk of bias and applicability. The area under the receiver operator curve (AUROC) was extracted as a summary measure of diagnostic accuracy.
RESULTS
Thirty-six studies were included: 11 hepatitis C, 4 hepatitis B, 9 NAFLD, 2 ALD, and 10 mixed. The ELF test showed good diagnostic performance in detecting advanced fibrosis in patients with viral hepatitis (AUROC 0.69 to 0.98) and excellent performance in NAFLD (AUROC 0.78 to 0.97) and ALD (AUROC from 0.92 to 0.94). There is also evidence of good diagnostic performance for detecting cirrhosis in patients with viral hepatitis (AUROC 0.63 to 0.99), good performance in NAFLD (AUROC 0.85 to 0.92), and excellent performance in patients with ALD (AUROC 0.93 to 0.94).
CONCLUSION
This systematic review supports the use of the ELF test across a range of CLD as a possible alternative to liver biopsy in selected cases.
Topics: Algorithms; Biomarkers; Biopsy; Hepatitis, Viral, Human; Humans; Hyaluronic Acid; Liver Cirrhosis; Liver Diseases, Alcoholic; Non-alcoholic Fatty Liver Disease; Peptide Fragments; Procollagen; Prognosis; Severity of Illness Index; Tissue Inhibitor of Metalloproteinase-1
PubMed: 33668077
DOI: 10.1111/jgh.15482 -
Cureus Sep 2020Background Severe alcoholic hepatitis is a condition with a very high mortality rate and there is a paucity of evidence regarding efficacy and safety of most available...
Background Severe alcoholic hepatitis is a condition with a very high mortality rate and there is a paucity of evidence regarding efficacy and safety of most available therapeutic options. The present systematic review and meta-analysis aims to assess the survival benefit of granulocyte colony stimulating factor (G-CSF) in patients with severe alcoholic hepatitis. Methods Studies involving adult patients receiving G-CSF for severe alcoholic hepatitis were searched in MEDLINE, Ovid journals, MEDLINE nonindexed citations, and Cochrane Central Register of Controlled Trials and Database of Systematic Reviews. Pooling was conducted by both fixed and random effects model. Results The initial search identified 543 reference articles; of these 24 relevant articles were selected and reviewed. Data was extracted from four studies ( = 136) which met the inclusion criteria. In the pooled analysis, the 90-day survival in the G-CSF group was 80.03% (95% CI = 69.93-88.49) compared to 40.92% (95% CI = 29.76-52.58) in the Standard Medical Therapy (SMT) group. At 28 days, the Model for End-Stage Liver Disease (MELD) score lowered by 4.89 (95% CI = 4.13-5.64) in the G-CSF group compared to 4.00 (95% CI = 3.25-4.75) in the SMT group. Child-Turcotte-Pugh score declined by 2.26 (95% CI = 1.90-2.63) in the G-CSF group after 28 days compared to 0.91 (95% CI = 0.59-1.23) in the SMT group. At 28 days, Maddrey Discriminant Function score lowered by 39.79 (95% CI = 34.22-45.36) in the G-CSF group compared to 12.39 (95% CI = 6.90-17.88) in the SMT group. Conclusions In patients with severe alcoholic hepatitis, G-CSF therapy resulted in significantly improved 90-day survival compared to SMT. It also demonstrated significant reduction in severity indices (Child-Turcotte-Pugh, MELD, and Maddrey discriminant function) after 28 days of treatment. There certainly is a need for further studies, including development of personalized therapeutic dosing schedules, for G-CSF administration.
PubMed: 33083176
DOI: 10.7759/cureus.10474 -
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 -
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 -
JHEP Reports : Innovation in Hepatology Oct 2020Granulocyte colony-stimulating factor (G-CSF) treatment has been proposed as a therapeutic option for patients with severe alcoholic hepatitis (AH). The aim of this...
BACKGROUND & AIMS
Granulocyte colony-stimulating factor (G-CSF) treatment has been proposed as a therapeutic option for patients with severe alcoholic hepatitis (AH). The aim of this study was to synthesise available evidence on the efficacy of G-CSF in AH.
METHODS
This is a meta-analysis of randomised controlled trials evaluating the risk of death at 90 days and the risk of infection.
RESULTS
Seven studies were included. Of a total of 396 patients, 336 had AH, 197 patients were treated with G-CSF, and 199 received placebo or pentoxifylline. In overall meta-analysis, G-CSF therapy was associated with a reduced risk of death at 90 days (odds ratio [OR] 0.28; 95% CI 0.09-0.88; = 0.03). There was high heterogeneity between studies ( <0.001; = 80%). Five studies were performed in Asia and 2 in Europe. In the subgroup analysis of studies performed in Asia, G-CSF was associated with a reduced risk of death (OR 0.15; 95% CI 0.08-0.28; <0.001; heterogeneity: = 0.5, = 0%). In European studies, G-CSF tended to increase mortality compared with controls, although the difference was not significant (OR 1.89; 95% CI 0.90-3.98; = 0.09; heterogeneity: = 0.8, = 0%). In Asian studies, occurrence of infection was less frequent in G-CSF patients than in controls (OR 0.12; 95% CI 0.06-0.23; <0.001; heterogeneity: = 0.7, = 0%), whilst in European studies, this occurrence was not statistically different (OR 0.92; 95% CI 0.50-1.68; = 0.78; heterogeneity: = 0.5, = 0%). In sensitivity analyses, excluding studies that included patients with acute-on-chronic liver failure (ACLF) other than AH, patients with less severe AH, or patients with non-response to corticosteroids, results were similar to those of overall analyses, both for mortality and occurrence of infection.
CONCLUSIONS
Granulocyte colony-stimulating factor therapy may improve the prognosis of patients with severe AH. However, owing to the high heterogeneity observed in the overall analysis caused by conflicting results between the Asian and European studies, G-CSF cannot currently be recommended for AH, particularly in Europe. Whether these differences can be explained by ethnic differences or disparities in patient selection and disease severity remains unclear.
LAY SUMMARY
The main finding of this meta-analysis is that the use of granulocyte colony-stimulating factor (G-CSF) is associated with a mortality reduction of more than 70% at 3 months amongst patients with alcoholic hepatitis (AH) compared with controls who did not receive this therapy. However, owing to the high heterogeneity observed in the overall analysis caused by conflicting results between the Asian and European studies, G-CSF cannot currently be recommended for patients with AH, particularly in Europe. Whether these differences can be explained by ethnic differences or disparities in patient selection and disease severity remains unclear.
PubMed: 32775975
DOI: 10.1016/j.jhepr.2020.100139