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The Lancet. Gastroenterology &... Sep 2022Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and the leading cause of liver-related morbidity and mortality. We aimed to predict... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and the leading cause of liver-related morbidity and mortality. We aimed to predict the burden of NAFLD by examining and estimating the temporal trends of its worldwide prevalence and incidence.
METHODS
In this systematic review and meta-analysis, we searched MEDLINE, EMBASE, Scopus, and Web of Science without language restrictions for reports published between date of database inception and May 25, 2021. We included observational cross-sectional or longitudinal studies done in study populations representative of the general adult population, in whom NAFLD was diagnosed using an imaging method in the absence of excessive alcohol consumption and viral hepatitis. Studies were excluded if conducted in paediatric populations (aged <18 years) or subgroups of the general population. Summary estimates were extracted from included reports by KR and independently verified by HA using the population, intervention, comparison, and outcomes framework. Primary outcomes were the prevalence and incidence of NAFLD. A random-effects meta-analysis was used to calculate overall and sex-specific pooled effect estimates and 95% CIs.
FINDINGS
The search identified 28 557 records, of which 13 577 records were screened; 299 records were also identified via other methods. In total, 72 publications with a sample population of 1 030 160 individuals from 17 countries were included in the prevalence analysis, and 16 publications with a sample population of 381 765 individuals from five countries were included in the incidence analysis. The overall prevalence of NAFLD worldwide was estimated to be 32·4% (95% CI 29·9-34·9). Prevalence increased significantly over time, from 25·5% (20·1-31·0) in or before 2005 to 37·8% (32·4-43·3) in 2016 or later (p=0·013). Overall prevalence of NAFLD was significantly higher in men than in women (39·7% [36·6-42·8] vs 25·6% [22·3-28·8]; p<0·0001). The overall incidence of NAFLD was estimated to be 46·9 cases per 1000 person-years (36·4-57·5); 70·8 cases per 1000 person-years (48·7-92·8) in men and 29·6 cases per 1000 person-years (20·2-38·9) in women (p<0·0001). There was considerable heterogeneity between studies of both NAFLD prevalence (I=99·9%) and NAFLD incidence (I=99·9%).
INTERPRETATION
Worldwide prevalence of NAFLD is considerably higher than previously estimated and is continuing to increase at an alarming rate. Incidence and prevalence of NAFLD are significantly higher among men than among women. Greater awareness of NAFLD and the development of cost-effective risk stratification strategies are warranted to address the growing burden of NAFLD.
FUNDING
Canadian Institutes of Health.
Topics: Adult; Canada; Child; Cross-Sectional Studies; Female; Humans; Incidence; Male; Non-alcoholic Fatty Liver Disease; Prevalence
PubMed: 35798021
DOI: 10.1016/S2468-1253(22)00165-0 -
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 -
Hepatology (Baltimore, Md.) Nov 2020Chronic hepatitis B virus (HBV), hepatitis C virus (HCV), nonalcoholic fatty liver disease (NAFLD), and alcohol-associated liver disease (ALD) are main causes of chronic...
BACKGROUND AND AIMS
Chronic hepatitis B virus (HBV), hepatitis C virus (HCV), nonalcoholic fatty liver disease (NAFLD), and alcohol-associated liver disease (ALD) are main causes of chronic liver disease. We assessed the global incidence, mortality, and disability-adjusted life-years (DALYs) related to chronic liver disease (primary liver cancer [LC] and cirrhosis).
APPROACH AND RESULTS
We obtained data from the 2017 Global Burden of Disease study. In 2017, there were 2.14 million liver-related deaths (2.06-2.30 million), representing an 11.4% increase since 2012 (16.0% increase in LC deaths; 8.7% increase in cirrhosis deaths). LC and cirrhosis accounted for 38.3% and 61.7%, respectively, of liver deaths (LC and cirrhosis deaths were related to HBV [39% and 29%], HCV [29% and 26%], ALD [16% and 25%], and NAFLD [8% and 9%]). Between 2012 and 2017, age-standardized incidence rate, age-standardized death rate (ASDR), and age-standardized DALY rate increased for LC from 11.1 to 11.8, 10.1 to 10.2, and 250.4 to 253.6 per 100,000, respectively. Although age-standardized incidence rate for cirrhosis increased from 66.0 to 66.3, ASDR and age-standardized DALY rate decreased from 17.1 to 16.5 and 532.9 to 510.7, respectively. The largest increase in ASDR for LC occurred in Eastern Europe (annual percent change [APC] = 2.18% [0.89%-3.49%]), whereas the largest decrease occurred in high-income Asia Pacific (APC = -2.88% [-3.58 to -2.18%]). ASDR for LC-NAFLD and ALD increased annually by 1.42% (1.00%-1.83%) and 0.53% (0.08-0.89), respectively, whereas there were no increases for HBV (P = 0.224) and HCV (P = 0.054). ASDR for cirrhosis-NAFLD increased (APC = 0.29% [0.01%-0.59%]) but decreased for ALD (APC = -0.44% [-0.78% to -0.40%]), HCV (APC = -0.50% [-0.81% to -0.18%]), and HBV (APC = -1.43% [-1.71% to -0.40%]).
CONCLUSIONS
From 2012 to 2017, the global burden of LC and cirrhosis has increased. Viral hepatitis remains the most common cause of liver deaths, and NAFLD is the most rapidly growing contributor to liver mortality and morbidity.
Topics: Disease Progression; Global Burden of Disease; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Incidence; Liver Cirrhosis; Liver Diseases, Alcoholic; Liver Neoplasms; Mortality; Non-alcoholic Fatty Liver Disease; Quality-Adjusted Life Years; Risk Factors
PubMed: 32043613
DOI: 10.1002/hep.31173 -
Cureus Jul 2019Severe alcoholic hepatitis (SAH) is associated with significant morbidity and mortality, yet the treatment options available are very limited. Past studies have... (Review)
Review
Severe alcoholic hepatitis (SAH) is associated with significant morbidity and mortality, yet the treatment options available are very limited. Past studies have evaluated the efficacy of infliximab in such patients; however, they were limited by sample size. Our aim was to perform a systematic review of these studies to assess the role of infliximab in patients with SAH. We conducted a literature search using electronic database engines including Ovid, PubMed, Scopus, MEDLINE and Cochrane Library from inception to October 2018 to identify published articles addressing outcomes in patients treated for alcoholic hepatitis with infliximab. The primary outcome reviewed was one-month mortality. Secondary outcomes included rate and type of infection; cause of mortality; levels of aspartate aminotransferase, alanine aminotransferase, bilirubin and tumor necrosis factor-α; and Maddrey discriminant function. Five studies including two randomized controlled trials and three case series were included in our analysis with a total sample size of 70 patients. One-month mortality ranged from 10% to 17% in patients who received a single dose of infliximab with or without prednisone compared to 38% in patients who received three doses of infliximab in combination with prednisone. A single dose of infliximab was associated with an infection rate of 10% to 26% in contrast to an 89% rate with three doses of infliximab. Infliximab, when used in a single dose, could potentially be an alternative agent for the management of SAH in a large group of patients who have contraindications such as gastrointestinal bleeding, uncontrolled diabetes or an active hepatitis infection. It might also have a role in the prevention of hepatorenal syndrome. There is a need for larger trials to evaluate the role of infliximab in a cohort of patients who are not candidates for prednisolone therapy.
PubMed: 31516791
DOI: 10.7759/cureus.5082 -
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 -
Alimentary Pharmacology & Therapeutics Jan 2020The liver has a critical role in the metabolism of glucose and lipids. Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection leads to a spectrum of liver...
BACKGROUND
The liver has a critical role in the metabolism of glucose and lipids. Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection leads to a spectrum of liver disease including chronic hepatitis, cirrhosis and hepatocellular carcinoma. Metabolic syndrome (MetS) has a rising incidence owing to an epidemic of type 2 diabetes mellitus (T2DM) and obesity. Non-alcoholic fatty liver disease is a liver manifestation of MetS and has become the most common cause of chronic liver disease worldwide.
AIM
To summarise the interplay among hepatitis viruses, MetS and its components.
METHODS
We searched the literature about HBV, HCV infection, MetS, fatty liver and its components from PubMed.
RESULTS
With respect to the viral replication cycle, lipids are important mediators between viral entry and hepatocyte in HCV infection, but not in HBV infection. Thus, HCV infection is inversely associated with hyperlipidaemia and lipid rebound occurs following sustained viral response induced by interferon-based therapy or direct antiviral agents. In addition, HCV infection is positively associated with insulin resistance, hepatic steatosis, MetS and the risk of T2DM and atherosclerosis. In contrast, HBV infection may protect infected subjects from the development of MetS and hepatic steatosis. Accumulating evidence suggests that HBV infection is inversely associated with lipid metabolism, and exhibits no conclusive association with insulin resistance or the risk of T2DM and arteriosclerosis.
CONCLUSIONS
In patients with viral hepatitis and concurrent metabolic diseases, a multidisciplinary approach should be given rather than simply antiviral treatment.
Topics: Antiviral Agents; Carcinoma, Hepatocellular; Diabetes Mellitus, Type 2; Hepacivirus; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Incidence; Liver Cirrhosis; Liver Neoplasms; Metabolic Diseases; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease; Obesity
PubMed: 31746482
DOI: 10.1111/apt.15575 -
International Journal of Molecular... Feb 2024Cannabidiol (CBD), a non-psychoactive phytocannabinoid abundant in , has gained considerable attention for its anti-inflammatory, antioxidant, analgesic, and... (Review)
Review
Cannabidiol (CBD), a non-psychoactive phytocannabinoid abundant in , has gained considerable attention for its anti-inflammatory, antioxidant, analgesic, and neuroprotective properties. It exhibits the potential to prevent or slow the progression of various diseases, ranging from malignant tumors and viral infections to neurodegenerative disorders and ischemic diseases. Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease, and viral hepatitis stand as prominent causes of morbidity and mortality in chronic liver diseases globally. The literature has substantiated CBD's potential therapeutic effects across diverse liver diseases in in vivo and in vitro models. However, the precise mechanism of action remains elusive, and an absence of evidence hinders its translation into clinical practice. This comprehensive review emphasizes the wealth of data linking CBD to liver diseases. Importantly, we delve into a detailed discussion of the receptors through which CBD might exert its effects, including cannabinoid receptors, CB1 and CB2, peroxisome proliferator-activated receptors (PPARs), G protein-coupled receptor 55 (GPR55), transient receptor potential channels (TRPs), and their intricate connections with liver diseases. In conclusion, we address new questions that warrant further investigation in this evolving field.
Topics: Humans; Cannabidiol; Receptors, Cannabinoid; Cannabis; Digestive System Diseases; Liver Diseases, Alcoholic; Receptor, Cannabinoid, CB1
PubMed: 38397045
DOI: 10.3390/ijms25042370 -
JHEP Reports : Innovation in Hepatology Sep 2022Non-alcoholic steatohepatitis (NASH) is associated with increased mortality and a high clinical burden. NASH adversely impacts patients' health-related quality of life...
BACKGROUND & AIMS
Non-alcoholic steatohepatitis (NASH) is associated with increased mortality and a high clinical burden. NASH adversely impacts patients' health-related quality of life (HRQoL), but published data on the humanistic burden of disease are limited. This review aimed to summarise and critically evaluate studies reporting HRQoL or patient-reported outcomes (PROs) in populations with NASH and identify key gaps for further research.
METHODS
Medline, EMBASE, the Cochrane Library and PsycINFO were searched for English-language publications published from 2010 to 2021 that reported HRQoL/PRO outcomes of a population or subpopulation with NASH.
RESULTS
Twenty-five publications covering 23 unique studies were identified. Overall, the data showed a substantial impact of NASH on HRQoL, particularly in terms of physical functioning and fatigue, with deterioration of physical and mental health as NASH progresses. Prevalent symptoms, including fatigue, abdominal pain, anxiety/depression, cognition problems, and poor sleep quality, adversely impact patients' ability to work and perform activities of daily living and the quality of relationships. However, some patients fail to attribute symptoms to their disease because of a lack of patient awareness and education. NASH is associated with high rates of comorbidities such as obesity and type 2 diabetes, which contribute to reduced HRQoL. Studies were heterogeneous in terms of diagnostic methods, population, outcomes, follow-up time, and measures of HRQoL/utility. Most studies were rated 'moderate' at quality assessment, and all evaluable studies had inadequate control of confounders.
CONCLUSIONS
NASH is associated with a significant HRQoL burden that begins early in the disease course and increases with disease progression. More robust studies are needed to better understand the humanistic burden of NASH, with adequate adjustment for confounders that could influence outcomes.
LAY SUMMARY
Non-alcoholic steatohepatitis (NASH) has a significant impact on quality of life, with individuals experiencing worse physical and mental health compared with the general population. NASH and its symptoms, which include tiredness, stomach pain, anxiety, depression, poor focus and memory, and impaired sleep, affect individuals' relationships and ability to work and perform day-to-day tasks. However, not all patients are aware that their symptoms may be related to NASH. Patients would benefit from more education on their disease, and the importance of good social networks for patient health and well-being should be reinforced. More studies are needed to better understand the patient burden of NASH.
PubMed: 36039144
DOI: 10.1016/j.jhepr.2022.100525 -
Clinical and Molecular Hepatology Jul 2023Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional... (Meta-Analysis)
Meta-Analysis
BACKGROUND/AIMS
Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional meta-analysis (MA) and individual patient-level data MA (IPDMA), we compared liver-related outcomes and mortality between CHB-FL and CHB-no FL patients.
METHODS
We searched 4 databases from inception to December 2021 and pooled study-level estimates using a random- effects model for conventional MA. For IPDMA, we evaluated outcomes after balancing the two study groups with inverse probability treatment weighting (IPTW) on age, sex, cirrhosis, diabetes, ALT, HBeAg, HBV DNA, and antiviral treatment.
RESULTS
We screened 2,157 articles and included 19 eligible studies (17,955 patients: 11,908 CHB-no FL; 6,047 CHB-FL) in conventional MA, which found severe heterogeneity (I2=88-95%) and no significant differences in HCC, cirrhosis, mortality, or HBsAg seroclearance incidence (P=0.27-0.93). IPDMA included 13,262 patients: 8,625 CHB-no FL and 4,637 CHB-FL patients who differed in several characteristics. The IPTW cohort included 6,955 CHB-no FL and 3,346 CHB-FL well-matched patients. CHB-FL patients (vs. CHB-no FL) had significantly lower HCC, cirrhosis, mortality and higher HBsAg seroclearance incidence (all p≤0.002), with consistent results in subgroups. CHB-FL diagnosed by liver biopsy had a higher 10-year cumulative HCC incidence than CHB-FL diagnosed with non-invasive methods (63.6% vs. 4.3%, p<0.0001).
CONCLUSION
IPDMA data with well-matched CHB patient groups showed that FL (vs. no FL) was associated with significantly lower HCC, cirrhosis, and mortality risk and higher HBsAg seroclearance probability.
Topics: Humans; Carcinoma, Hepatocellular; Hepatitis B Surface Antigens; Hepatitis B, Chronic; Liver Neoplasms; Hepatitis B virus; Antiviral Agents; Liver Cirrhosis; Fatty Liver; DNA, Viral
PubMed: 37157776
DOI: 10.3350/cmh.2023.0004 -
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