ABSTRACTNonalcoholic fatty liver disease (NAFLD) affects 25% of the global adult population with a range of 13.5% in Africa and 31.8% in the Middle East. Nonalcoholic fatty liver disease is closely ...associated with a constellation of metabolic comorbidities which includeobesity, type 2 diabetes mellitus, hypertension, and hypercholesteremia. In fact, the increasing number of metabolic comorbidities not only increases the prevalence of NAFLD but also places patients at higher risk for progressive liver disease. As such, NAFLD is presently among the top etiologies for hepatocellular carcinoma and an indication for liver transplantation (LT) in the United States. Therefore, the following recommendations are made based on our current knowledge of NAFLD and its consequences(1) the evaluation of the risk of liver disease progression can be affected by patientʼs ethnic origin and sex; (2) fibrosis in NAFLD is the most important predictor of mortality; (3) we recommend that individuals who present with features of metabolic syndrome in the presence of elevated liver enzymes should be screened for NAFLD and, more importantly, nonalcoholic steatohepatitis (NASH); (4) we recommend that NAFLD patients, especially those with multiple risk factors, should be screened for cardiovascular diseases and managed accordingly; (5) comorbidities in NAFLD/NASH patients who are considered for LT need to be assessed in the pretransplant and posttransplant settings because these factors can affect waitlist mortality, resource utilization, as well as posttransplant complications, morbidity, and perhaps, mortality; (6) any attempt to decrease the incidence of NAFLD should ideally address the development of obesity in childhood and early adulthood, favoring the adoption of healthy lifestyles through comprehensive health policy programs.
Background and Aims
The beneficial effect of Hepatitis C virus (HCV) eradication by direct antiviral agents (DAAs) on liver fibrosis is well defined. Despite this, the impact of viral eradication in ...both hepatic and extra‐hepatic metabolic features is underreached. This systematic review aimed to synthesize the evidence on the impact of HCV eradication by DAAs on liver steatosis, carotid atherosclerosis, glucidic impairment, dyslipidaemia, and weight gain.
Methods
A systematic search of the existing literature (up to December 2022) identified 97 original studies that fulfilled the inclusion criteria.
Results
Whereas total cholesterol and low‐density lipoprotein (LDL) seem to increase after viral eradication, the cardiovascular damage expressed as carotid plaques and intima‐media thickness seems to improve. Otherwise, the effect on liver steatosis, glucidic homeostasis, and weight seems to be strictly dependent on the presence of baseline metabolic disorders.
Conclusion
Despite high heterogeneity and relatively short follow‐up of included studies, we can conclude that the presence of metabolic risk factors should be strictly evaluated due to their impact on liver steatosis, glucidic and lipid homeostasis, and on weight gain to better identify patients at risk of liver disease progression despite the virus eradication.
Non-alcoholic fatty liver disease(NAFLD) is the most frequent cause of liver disease in the Western world. Furthermore, it is increasing worldwide, paralleling the obesity pandemic. Though highly ...frequent, only about one fifth of affected subjects are at risk of developing the progressive form of the disease, non-alcoholic steatohepatitis with fibrosis. Even in the latter, liver disease is slowly progressive, though, since it is so prevalent, it is already the third cause of liver transplantation in the United States, and it is predicted to get to the top of the ranking in few years. Of relevance, fatty liver is also associated with increased overall mortality and particularly increased cardiovascular mortality. The literature and amount of published papers on NAFLD is increasing as fast as its prevalence, which makes it difficult to keep updated in this topic. This review aims to summarize the latest knowledge on NAFLD, in order to help clinicians understanding its pathogenesis and advances on diagnosis and treatment.
Background & Aims
No multi‐national prospective study of drug‐induced liver injury (DILI) has originated in Europe. The design of a prospective European DILI registry, clinical features and ...short‐term outcomes of the cases and controls is reported.
Methods
Patients with suspected DILI were prospectively enrolled in the United Kingdom, Spain, Germany, Switzerland, Portugal and Iceland, 2016–2021. DILI cases or non‐DILI acute liver injury controls following causality assessment were enrolled.
Results
Of 446 adjudicated patients, 246 DILI patients and 100 had acute liver injury due to other aetiologies, mostly autoimmune hepatitis (n = 42) and viral hepatitis (n = 34). DILI patients (mean age 56 years), 57% women, 60% with jaundice and 3.6% had pre‐existing liver disease. DILI cases and non‐DILI acute liver injury controls had similar demographics, clinical features and outcomes. A single agent was implicated in 199 (81%) DILI cases. Amoxicillin‐clavulanate, flucloxacillin, atorvastatin, nivolumab/ipilimumab, infliximab and nitrofurantoin were the most commonly implicated drugs. Multiple conventional medications were implicated in 37 (15%) and 18 cases were caused by herbal and dietary supplements. The most common single causative drug classes were antibacterials (40%) and antineoplastic/immunomodulating agents (27%). Overall, 13 (5.3%) had drug‐induced autoimmune‐like hepatitis due to nitrofurantoin, methyldopa, infliximab, methylprednisolone and minocycline. Only six (2.4%) DILI patients died (50% had liver‐related death), and another six received liver transplantation.
Conclusions
In this first multi‐national European prospective DILI Registry study, antibacterials were the most commonly implicated medications, whereas antineoplastic and immunomodulating agents accounted for higher proportion of DILI than previously described. This European initiative provides an important opportunity to advance the study on DILI.
Background and aims
The role of portal vein thrombosis (PVT) in the natural history of cirrhosis is controversial. There are few prospective studies validating risk factors for development of PVT. We ...analysed the incidence, factors associated with PVT development and its influence on cirrhosis decompensations and orthotopic liver transplant (OLT)‐free survival.
Methods
In this prospective observational study between January 2014 and March 2019, 445 consecutive patients with chronic liver disease were screened and finally 241 with cirrhosis included. Factors associated with PVT development and its influence on cirrhosis decompensations and OLT‐free survival by time dependent covariate coding were analysed.
Results
Majority of patients belonged to Child‐Pugh class A 184 (76.3%) and the average MELD score was 10 ± 5. Previous cirrhosis decompensations occurred in 125 (52.1%), 63 (26.1%) were on NSBB and 59 (27.2%) had undergone banding for bleeding prophylaxis. Median follow‐up was 29 (1‐58) months. Cumulative incidence of PVT was 3.7% and 7.6% at 1 and 3 years. Previous decompensation of cirrhosis and low platelet counts but not NSBB independently predicted the development of PVT. During follow‐up, 82/236 (34.7%) patients developed cirrhosis decompensations. OLT‐free survival was 100% and 82.8% at 3 years, with and without PVT respectively. MELD score, but not PVT, independently predicted cirrhosis decompensations (HR 1.14; 95%CI:1.09‐1.19) and OLT‐free survival (HR 1.16;95%CI:1.11‐1.21).
Conclusion
Previous decompensations of cirrhosis and thrombocytopenia predict PVT development in cirrhosis suggesting a pathophysiologic role for severity of portal hypertension. PVT development did not independently predict cirrhosis decompensations or lower OLT‐free survival.
Background and Aims: Although hepatic steatosis (HS) has an association with hepatitis C virus (HCV) infection, an association with hepatitis B virus (HBV) is controversial. We performed a ...meta‐analysis to evaluate HS prevalence and risk factors, in HBV infection.
Methods: Standard guidelines for performance of meta‐analyses were followed. Studies with HS assessed by histology were included. Pooled odd ratios (OR) and standardized mean differences (SMD) were obtained with the random‐effects model and DerSimonian‐Laid method.
Results: Seventeen out of 21 studies were included, comprising 4100 HBV infected patients. Overall HS prevalence was 29.6%. Eight studies also included 945 HCV infected patients, showing decreased risk of HS in HBV versus HCV patients (OR 0.55, 95%CI 0.45–0.67, P < 0.001). In HBV, HS positively associated with male gender (OR 1.74, 95%CI 1.28–2.38, P < 0.001), body mass index (SMD 2.17, 95%CI 1.23, 3.11, P < 0.001), obesity (OR 6.59, 95%CI 3.51–12.257, P = 0.003), diabetes (OR 2.62, 95%CI 1.37–4.00, P = 0.004), glycemia (SMD 0.84, 95%CI 0.00, 1.67, P = 0.049), triglycerides (SMD 1.18, 95%CI 0.48, 1.89, P = 0.001), cholesterol (SMD 0.88, 95%CI 0.31, 1.45, P = 0.003), moderate alcohol consumption (OR 1.54, 95%CI 1.10–2.15, P = 0.011) and negatively with HBV DNA (SMD −74.12, 95%CI −82.93, −65.31, P < 0.001). HS had no association with aminotransferases, HBeAg, genotype or hepatic histology, necroinflammation or fibrosis.
Conclusion: HS in HBV seems to be as frequent as in the general population, and lower than in HCV infected patients, relating to metabolic factors but not with hepatic histology severity. A puzzling strong negative association between viral load and HS, may even suggest a protective effect of the virus on HS.
The exclusion of other chronic liver diseases including “excess” alcohol intake has until now been necessary to establish a diagnosis of metabolic dysfunction-associated fatty liver disease (MAFLD). ...However, given our current understanding of the pathogenesis of MAFLD and its rising prevalence, “positive criteria” to diagnose the disease are required. In this work, a panel of international experts from 22 countries propose a new definition for the diagnosis of MAFLD that is both comprehensive and simple, and is independent of other liver diseases. The criteria are based on evidence of hepatic steatosis, in addition to one of the following three criteria, namely overweight/obesity, presence of type 2 diabetes mellitus, or evidence of metabolic dysregulation. We propose that disease assessment and stratification of severity should extend beyond a simple dichotomous classification to steatohepatitis vs. non-steatohepatitis. The group also suggests a set of criteria to define MAFLD-associated cirrhosis and proposes a conceptual framework to consider other causes of fatty liver disease. Finally, we bring clarity to the distinction between diagnostic criteria and inclusion criteria for research studies and clinical trials. Reaching consensus on the criteria for MAFLD will help unify the terminology (e.g. for ICD-coding), enhance the legitimacy of clinical practice and clinical trials, improve clinical care and move the clinical and scientific field of liver research forward.
Diet, Microbiota, Obesity, and NAFLD: A Dangerous Quartet Machado, Mariana Verdelho; Cortez-Pinto, Helena
International Journal of Molecular Sciences,
2016-Apr-01, 2016-04-01, 20160401, Letnik:
17, Številka:
4
Journal Article, Book Review
Recenzirano
Odprti dostop
Recently, the importance of the gut-liver-adipose tissue axis has become evident. Nonalcoholic fatty liver disease (NAFLD) is the hepatic disease of a systemic metabolic disorder that radiates from ...energy-surplus induced adiposopathy. The gut microbiota has tremendous influences in our whole-body metabolism, and is crucial for our well-being and health. Microorganisms precede humans in more than 400 million years and our guest flora evolved with us in order to help us face aggressor microorganisms, to help us maximize the energy that can be extracted from nutrients, and to produce essential nutrients/vitamins that we are not equipped to produce. However, our gut microbiota can be disturbed, dysbiota, and become itself a source of stress and injury. Dysbiota may adversely impact metabolism and immune responses favoring obesity and obesity-related disorders such as insulin resistance/diabetes mellitus and NAFLD. In this review, we will summarize the latest evidence of the role of microbiota/dysbiota in diet-induced obesity and NAFLD, as well as the potential therapeutic role of targeting the microbiota in this set.
PDF
