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Cancers May 2022Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are the preferred anti-viral agents used as first-line treatments for chronic hepatitis B (CHB). However, the... (Review)
Review
Systematic Review with Meta-Analysis: Comparison of the Risk of Hepatocellular Carcinoma in Antiviral-Naive Chronic Hepatitis B Patients Treated with Entecavir versus Tenofovir: The Devil in the Detail.
Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are the preferred anti-viral agents used as first-line treatments for chronic hepatitis B (CHB). However, the efficacy of these agents in reducing the incidence of hepatocellular carcinoma (HCC) remains unclear. We conducted this meta-analysis to assess the efficacy of anti-viral agent on preventing HCC in CHB. Two investigators independently searched all relevant studies that examined the efficacy of anti-viral agent for preventing HCC using MEDLINE, Embase, and Cochrane Library databases through August 2021. The extracted data were analysed using a random-effects meta-analysis model based on the inverse-variance method (DerSimonian-Laird) and expressed as hazard ratio (HR) and 95% confidence interval (95% CI). We included 19 retrospective studies in the analysis. Although there was substantial heterogeneity between the studies, the overall pooled HR indicated that TDF significantly lowered the risk of HCC (HR: 0.72, 95% CI: 0.58-0.90, I = 66.29%). However, the pooled analysis of propensity score (PS)-matched subpopulations showed no significant differences (HR, 0.83; 95% CI, 0.65-1.06; I = 52.30%) between TDF and ETV. In a subgroup analysis, an interval of over three years in the start point of patient enrolment and excluding alcoholic liver disease patients significantly lowered the HCC risk associated with TDF. In conclusion, TDF may be more effective than ETV at reducing HCC incidence in treatment-naive CHB patients, but this effect was not consistent in the PS-matched subpopulation that reduced heterogeneity. As a result of subgroup analysis, the conflicting findings of previous studies may result from heterogeneous inclusion criteria. Further studies with standardised protocols are needed to reduce the residual heterogeneity.
PubMed: 35681596
DOI: 10.3390/cancers14112617 -
The Lancet. Gastroenterology &... Aug 2022Empirical, updated country-level estimates on the proportion of cirrhosis attributable to viral hepatitis are required. We estimated the prevalence of hepatitis B virus...
BACKGROUND
Empirical, updated country-level estimates on the proportion of cirrhosis attributable to viral hepatitis are required. We estimated the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in patients with cirrhosis at country, regional, and global levels as an approximation for the fractions of cirrhosis attributable to viral hepatitis.
METHODS
In this systematic review, we searched MEDLINE, Embase, Web of Science, and Scielo between Jan 1, 1993, and Aug 1, 2021. Studies were eligible if they reported on the prevalence of both HBV and HCV infection in representative studies of at least 20 patients with cirrhosis. Studies were excluded if they used first-generation HCV assays or were from a selected population of patients with cirrhosis (eg, patients selected based on specific causes, veterans, injecting drug users). Two authors (CJA and CdM) selected and extracted aggregated data from the selected publications. Data were extracted for study recruitment period, age, sex, and cause of cirrhosis, among others. Data about heavy alcohol consumption and non-alcoholic fatty liver disease (NAFLD) were also extracted when available. Aggregated data from studies from key publications were requested from the authors of the original study if selection of patients was unclear or information on causes was missing. We estimated the country-specific prevalence of causes of cirrhosis by pooling study-level data from the same country using a random-effects model. Subsequently, we estimated the regional (WHO region and UN subregion) and global prevalence by weighting the country-specific prevalence by the number of new liver cancer cases that occurred in 2020, as estimated in GLOBOCAN. The study was registered with PROSPERO, CRD42020149323.
FINDINGS
Our database searches identified 21 338 records, and a further nine records were identified by scanning references of key publications. After excluding duplicates and assessing full-text articles for eligibility, 520 publications from 86 countries or territories (and reporting on 1 376 503 patients with cirrhosis) were included in the systematic review. The prevalence of HBV infection was lower among patients with cirrhosis in Europe, the Americas, and Oceania (UN subregional prevalence ranges 3-14%) than in Africa and Asia (8-61%). HCV infection prevalence was heterogenous, even within regions (12-83%). The combined prevalence of HBV and HCV infection exceeded 50% in most Asian and African regions. Globally, among patients with cirrhosis, 42% had HBV infection and 21% had HCV infection. The contribution of heavy alcohol use was highest in Europe (country range 16-78%), the Americas (17-52%), and Oceania (15-37%) and lowest in Asia (0-41%). Data on NAFLD were limited.
INTERPRETATION
HBV and HCV could account for almost two thirds of the global burden of cirrhosis. With the availability of effective interventions for the prevention or treatment of HBV and HCV, the data presented in this study will help to effectively allocate resources towards viral hepatitis elimination and to design interventions at the country level.
FUNDING
International Agency for Research on Cancer, World Health Organization.
Topics: Hepacivirus; Hepatitis B; Hepatitis B virus; Hepatitis C; Hepatitis, Viral, Human; Humans; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Prevalence; United States
PubMed: 35576953
DOI: 10.1016/S2468-1253(22)00050-4 -
Clinical Kidney Journal Apr 2022Patients receiving dialysis for end-stage kidney disease (ESKD) commonly co-exhibit risk factors for hepatic impairment. This systematic review and meta-analysis aimed...
BACKGROUND
Patients receiving dialysis for end-stage kidney disease (ESKD) commonly co-exhibit risk factors for hepatic impairment. This systematic review and meta-analysis aimed to quantify the coexistence of chronic liver disease (CLD) and characterize risk factors and outcomes.
METHODS
We searched the following databases from inception to May 2021: CINAHL, Cochrane Library, Embase, Kings Fund Library, MEDLINE and PubMed. The protocol was pre-registered on PROSPERO (study ID: CRD42020206486). Studies were assessed against three inclusion criteria: adults (>18 years) with ESKD receiving dialysis, primary outcome involving CLD prevalence and publications in English. Moderator analysis was performed for age, gender, study size and publication year. Sensitivity analysis was performed where applicable by removing outlier results and studies at high risk of bias.
RESULTS
Searches yielded 7195 articles; of these 15 met the inclusion criteria. A total of 320 777 patients were included. The prevalence of cirrhosis and non-alcoholic fatty liver disease (NAFLD) was 5% and 55%, respectively. Individuals with CLD had 2-fold higher mortality than those without {odds ratio [OR] 2.19 [95% confidence interval (CI) 1.39-3.45]}. Hepatitis B [OR 13.47 (95% CI 1.37-132.55)] and hepatitis C [OR 7.05 (95% CI 4.00-12.45)], but not diabetes, conferred increased cirrhosis risk. All studies examining NAFLD were judged to be at high risk of bias. We found no data on non-alcoholic steatohepatitis (NASH). Deaths from CLD, cancer and infection were greater among cirrhotic patients.
CONCLUSIONS
CLD is prevalent in dialysis patients. Hepatitis B and C confer increased risk of CLD. The impact of NAFLD and NASH cirrhosis requires further study. CLD is associated with an increased risk of mortality in this setting.
PubMed: 35371444
DOI: 10.1093/ckj/sfab230 -
Frontiers in Pharmacology 2022To explore the relationship between the use of aspirin and the incidence of hepatocellular carcinoma (HCC). MEDLINE, EMBASE, Web of Science and Cochrane CENTRAL... (Review)
Review
To explore the relationship between the use of aspirin and the incidence of hepatocellular carcinoma (HCC). MEDLINE, EMBASE, Web of Science and Cochrane CENTRAL databases were searched systematically from the earliest available date to 13 March 2020. The primary outcome was incidence of HCC, and the secondary outcomes were recurrence and mortality of HCC. The results were expressed as the Hazard Ratio (HR) and 95% confidence interval (CI). Based on the heterogeneity evaluated with the statistic, a meta-analysis was performed using either a random- or fixed-effects model. A total of sixteen articles (2781100 participants) were included. There was lower incidence of HCC in aspirin users than those in non-aspirin users (HR, 0.56; 95% CI, 0.46-0.69; < 0.001). Subgroup analysis further showed that the incidence of liver cancer in patients with alcoholic cirrhosis (HR, 0.14; 95% CI, 0.09-0.22; < 0.001) and virus hepatitis (HR, 0.68; 95% CI, 0.62-0.74; < 0.001) who use aspirin was lower than that of patients who do not use aspirin. In addition, aspirin was found to associate with decreased risk of HCC mortality (HR, 0.71; 95% CI, 0.65-0.78; < 0.001), not HCC recurrence (HR, 0.52; 95% CI, 0.15-1.76; = 0.291). Aspirin use is significantly associated with the low incidence rate of liver cancer.
PubMed: 35300300
DOI: 10.3389/fphar.2022.764854 -
The American Journal of Tropical... Apr 2022COVID-19, a respiratory viral infection, has affected 388 million individuals worldwide as of the February 4, 2022. In this review, we have outlined the important liver...
COVID-19, a respiratory viral infection, has affected 388 million individuals worldwide as of the February 4, 2022. In this review, we have outlined the important liver manifestations of COVID-19 and discussed the possible underlying pathophysiological mechanisms and their diagnosis and management. Factors that may contribute to hepatic involvement in COVID-19 include direct viral cytopathic effects, exaggerated immune responses/systemic inflammatory response syndrome, hypoxia-induced changes, vascular changes due to coagulopathy, endothelitis, cardiac congestion from right heart failure, and drug-induced liver injury. The majority of COVID-19-associated liver symptoms are mild and self-limiting. Thus management is generally supportive. Liver function tests and abdominal imaging are the primary investigations done in relation to liver involvement in COVID-19 patients. However, imaging findings are nonspecific. Severe acute respiratory syndrome coronavirus 2 RNA has been found in liver biopsies. However, there is limited place for liver biopsy in the clinical context, as it does not influence management. Although, the management is supportive in the majority of patients without previous liver disease, special emphasis is needed in those with nonalcoholic fatty liver disease, cirrhosis, hepatocellular carcinoma, hepatitis B and C infections, and alcoholic liver disease, and in liver transplant recipients.
PubMed: 35203056
DOI: 10.4269/ajtmh.21-1240 -
JHEP Reports : Innovation in Hepatology Dec 2021In an attempt to uncover unmet patient needs, this review aims to synthesise quantitative and qualitative studies on patients' quality of life and their experience of...
BACKGROUND & AIMS
In an attempt to uncover unmet patient needs, this review aims to synthesise quantitative and qualitative studies on patients' quality of life and their experience of having liver disease.
METHODS
Three databases (CINAHL, Embase, and PubMed) were searched from January 2000 to October 2020. The methodological quality and data extraction of both quantitative and qualitative studies were screened and appraised using Joanna Briggs Institute instruments for mixed-method systematic reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A convergent, integrated approach to synthesis and integration was used. Studies including patients with autoimmune and cholestatic liver disease, chronic hepatitis B and C, non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma were considered.
RESULTS
The searches produced 5,601 articles, of which 95 (79 quantitative and 16 qualitative) were included in the review. These represented studies from 26 countries and a sample of 37,283 patients. The studies showed that patients´ quality of life was reduced. Unmet needs for information and support and perceived stigmatisation severely affected patients' quality of life.
CONCLUSIONS
Our study suggests changes to improve quality of life. According to patients, this could be achieved by providing better education and information, being aware of patients' need for support, and raising awareness of liver disease among the general population to reduce misconceptions and stigmatisation.
REGISTRATION NUMBER
PROSPERO CRD42020173501.
LAY SUMMARY
Regardless of aetiology, patients with liver diseases have impaired quality of life. This is associated with disease progression, the presence of symptoms, treatment response, and mental, physical, and social factors such as anxiety, confusion, comorbidities, and fatigue, as well as limitations in daily living, including loneliness, low income, stigmatisation, and treatment costs. Patients highlighted the need for information to understand and manage liver disease, and awareness and support from healthcare professionals to better cope with the disease. In addition, there is a need to raise awareness of liver diseases in the general population to reduce negative preconceptions and stigmatisation.
PubMed: 34805816
DOI: 10.1016/j.jhepr.2021.100370 -
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 -
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 -
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