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To review evidence on the diagnosis and management of nonalcoholic fatty liver disease (NAFLD), the most common cause of chronic liver disease in human beings.
The literature was searched for clinical trials and review articles on NAFLD. Levels I and II evidence indicates the benefit of both lifestyle and pharmacologic interventions for NAFLD and n...
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Context 1
... the major causes of elevated serum trans- aminases and liver steatosis are excluded, the most likely diagnosis is NAFLD (Figure 1). Clinical sus- picion is strengthened by this patient's lifestyle and clinical and biochemical features (metabolic syn- drome). Given his age and associated factors, he will most likely require referral for consideration of liver biopsy if 6 months of diet and exercise fail to help him reach therapeutic targets. Every ...
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Simple Summary
The prevalence of intrahepatic cholangiocarcinoma (iCCA) is rising. About 50% of iCCA arise in patients without known risk factors. We hypothesized that nonalcoholic fatty liver disease (NAFLD) and its most aggressive phenotype (NASH) could be risk factors for iCCA, similarly to other liver malignancies. We verified whether the preva...
Citations
... Cross-sectional studies of NASH patients have shown that 30-40% present with advanced liver fibrosis, and 10-15% have established cirrhosis [9][10][11]. It is estimated that NASH is the underlying cause of approximately 80% of cryptogenic cirrhosis cases, accounting for 10%-20% of all cirrhosis cases and progressing to advanced fibrosis in 32%-37% of patients [12]. There is growing recognition that NAFLD is a heterogeneous disease with multiple pathogenic pathways, leading to diverse disease manifestations among patients [13]. ...
... A liver biopsy can be used to perform a comparative analysis of NAFLD after intervention in comparison to the time of diagnosis and to determine if fibrosis exists. In patients who have risk factors that can lead to NAFLD progression, histological evaluation is the best monitoring option [89]. ...
Nonalcoholic fatty liver disease (NAFLD), also named metabolic dysfunction-associated fatty liver disease (MAFLD), is a progressive disease spectrum encompassing simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. It is a clinically silent disease leading to multiple extra-hepatic complications/comorbidities. It is an independent risk factor for cardiovascular disease (CVD), increasing susceptibility to hypertension, atherosclerosis, arrhythmia, myocardial dysfunction, cardiac valve deformation, and venous thrombosis through putative mechanisms including systemic inflammation, endothelial dysfunction, oxidative stress, insulin resistance, and altered lipid metabolism. Eventually, it increases the CVD prevalence, incident, and fatality, contributing to a huge health care burden. In fact, CVD is becoming the leading cause of mortality among patients with NAFLD. Other cardiometabolic risk factors coexisting with NAFLD may also accelerate the synergistic development of CVD, which warrants assessment targeting hypertension, diabetes mellitus (DM), obesity, and dyslipidemia to be an integral part of NAFLD care. Monitoring metabolic biomarkers (glucose, glycosylated hemoglobin [HbA1c], insulin, lipids, and lipoproteins), cardiovascular (CV) risk scores (American College of Cardiology/American Heart Association [ACC/AHA] or Framingham), and subclinical atherosclerosis (coronary artery calcification [CAC], carotid intima-media thickness [CIMT], and carotid plaque) are recommended for risk prediction and reduction. There is no universally accepted treatment for NAFLD, and lifestyle changes with weight loss of at least 10% are the mainstay of management. Combination therapy of ezetimibe and statins have a cardioprotective effect and help reduce liver fat. Despite being an emerging risk factor for CVD and its rapidly increasing pattern affecting a quarter of the global population, NAFLD remains overlooked and undetected, unlike the other traditional risk factors. Hence, we conducted a comprehensive narrative review to shed more light on the importance of screening CVD in NAFLD patients. PubMed indexed relevant articles published from 2002 to 2022 (20 years) were searched in April 2022 using medical subject headings (MeSH) as "nonalcoholic fatty liver disease" [Mesh] AND "cardiovascular diseases" [Mesh]. Evidence from 40 observational studies, three clinical trials, one case series, 45 narrative reviews, four systematic reviews and meta-analyses, three systematic reviews, and one meta-analysis were summarized on the epidemiologic data, pathophysiologic mechanisms, clinical features, diagnostic modalities, overlapping management, perceived challenges and health literacy regarding the CVD risk attributed to NAFLD.
... Given that prognosis from chronic liver disease is dictated primarily by fibrosis severity, the challenge facing primary care physicians is the identification of patients with significant liver disease amongst those identified as being "at For patients with NAFLD and non-significant fibrosis (Brunt ≤F2 disease), the appropriate preventative interventions are weight loss and exercise [172,173] and these can be ably delivered in primary care [174] obviating the need for referral for specialist care. ...
... The pattern of referrals identified in this study is likely to be common across industrialised countries. In NAFLD, for patients with non-significant disease, the appropriate preventative interventions are weight loss and exercise [172,173] and these can be delivered effectively in primary care [174] ...
The health, societal and economic consequences of chronic liver disease (CLD) are substantial and increasing exponentially. Cirrhosis is typically detected in the latter stages when prognosis is poor. Timely diagnosis is hindered by reliance on non-discriminatory tests for fibrosis. I explored the role of non-invasive tests (NITs) of liver fibrosis in primary care to promote earlier disease detection. In this thesis, a systematic review revealed a paucity of published studies evaluating NIT in the community setting. A national survey demonstrated that UK specialists consider current fibrosis assessment methods to be sub-optimal, and NIT are important in improving disease stratification in primary care. To benchmark standard care, a one-year retrospective study of GP referrals for non-alcoholic fatty liver disease (NAFLD) established 93% of referrals to have non-significant fibrosis (Brunt ≤ F2) as assessed by liver specialists. Over two-thirds had a low-risk FIB-4 (<1.30) and could have avoided referral, although a quarter of patients with indeterminate FIB-4 (1.30 – 3.25) had significant liver fibrosis suggesting patients in this subgroup warrant further evaluation. As part of the Camden and Islington liver working group, I developed and evaluated a NAFLD pathway that employs FIB-4 and ELF to identify patients with advanced fibrosis or cirrhosis (Brunt ≥ F3 fibrosis). The pathway processed nearly 1500 patients over two years, resulting in a reduction in the proportion of total patients referred and an 81% decrease in referral of patients with non-significant fibrosis. The pathway achieved a 5-fold increase in the referral of patients with advanced fibrosis and 3-fold increase in the detection of liver cirrhosis. To further extrapolate these findings, I developed a probabilistic decision analytical model which tested FIB-4, ELF and fibroscan, either alone or in combination in primary care pathways. Cost consequence analyses revealed all strategies to be clinically effective and cost-saving compared to standard care.
... 13 The current standard of care (SOC) for managing NAFLD mainly includes caloric restriction of 25-30 kcal/ kg/day ideal body weight and moderate physical activity. 14 Although there are no well-established guidelines recommendations for managing NAFLD, 15 medications that are mainly prescribed include antioxidants (e.g. vitamins E and C, betaine), insulin-sensitizing agents (thiazolidinediones and metformin), lipid-lowering agents (statins, orlistat, probucol), choleretic agents such as ursodeoxycholic acid (UCDA), and medications with anti-inflammatory (pentoxifylline) or anti-fibrotic (angiotensin-receptor blockers) potential. ...
Purpose:
Non-alcoholic fatty liver disease (NAFLD) and steatohepatitis are two forms of fatty liver disease with benign and malignant nature, respectively. These two conditions can cause an increased risk of liver cirrhosis and hepatocellular carcinoma. Given the importance and high prevalence of NAFLD, it is necessary to investigate the results of different studies in related scope to provide a clarity guarantee of effectiveness. Therefore, this systematic review and meta-analysis aim to study the efficacy of various medications used in the treatment of NAFLD.
Methods:
A systematic search of medical databases identified 1963 articles. After exclusion of duplicated articles and those which did not meet our inclusion criteria, eta-analysis was performed on 84 articles. Serum levels of alanine aminotransferase (ALT), aspartate amino transferase (AST) were set as primary outcomes and body mass index (BMI), hepatic steatosis, and NAFLD activity score (NAS) were determined as secondary outcomes.
Results:
Based on the P-score of the therapeutic effects on the non-alcoholic steatohepatitis (NASH), we observed the highest efficacy for atorvastatin, tryptophan, orlistat, omega-3 and obeticholic acid for reduction of ALT, AST, BMI, steatosis and NAS respectively.
Conclusion:
This meta-analysis showed that atorvastatin. life-style modification, weight loss, and BMI reduction had a remarkable effect on NAFLD-patients by decreasing aminotransferases.
... Ultasound has 80% specificity and 99% sensitivity (Samson et al., 2011) NAFLD is usually an incidental finding when an abdominal scan is done for some other suspected pathology. It can be associated with abnormal LFTs but even advanced cases may present with normal LFTs (Grattagliano et al., 2007). Recently there has been a proposed role of subfamily of FGFs in liver metabolism, which includes FGF19 & FGF21. ...
Background: mellitus (T2DM) patients; most likely cause is the frequent occurrence of obesity and insulin resistance in T2DM. Weight reduction by diet and exercise is effective in preve NAFLD in diabetics. Bariatric surgery is recommended in obese patients to reverse NAFLD. There is evidence that drugs used as hypoglycemic agents for T2DM thiazolidinediones (TZDs), glucagon peptide even treat NAFLD. Screening for progression in fatty liver diseases by LFT and ultrasound is now recommended. Fibroblast growth factor (FGF21) Conclusion: liver diseases are one of the common complications of type 2 Diabetes mellitus. Early diagnosis and screening can prevent serious complications such as cirrhosis and liver failure or hepatocellular carcinoma. Ef such as Sitagliptin has shown to improve NAFLD. FGF21 levels correlate with hepatic and peripheral insulin resistance and is markedly increased in obesity and type II diabe Copyright © 2016, Samia Perwaiz Khan and Dunesh Kumar permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
... Ultasound has 80% specificity and 99% sensitivity (Samson et al., 2011) NAFLD is usually an incidental finding when an abdominal scan is done for some other suspected pathology. It can be associated with abnormal LFTs but even advanced cases may present with normal LFTs (Grattagliano et al., 2007). Recently there has been a proposed role of subfamily of FGFs in liver metabolism, which includes FGF19 & FGF21. ...
Background: mellitus (T2DM) patients; most likely cause is the frequent occurrence of obesity and insulin resistance in T2DM. Weight reduction by diet and exercise is effective in preve NAFLD in diabetics. Bariatric surgery is recommended in obese patients to reverse NAFLD. There is evidence that drugs used as hypoglycemic agents for T2DM thiazolidinediones (TZDs), glucagon peptide even treat NAFLD. Screening for progression in fatty liver diseases by LFT and ultrasound is now recommended. Fibroblast growth factor (FGF21) Conclusion: liver diseases are one of the common complications of type 2 Diabetes mellitus. Early diagnosis and screening can prevent serious complications such as cirrhosis and liver failure or hepatocellular carcinoma. Ef such as Sitagliptin has shown to improve NAFLD. FGF21 levels correlate with hepatic and peripheral insulin resistance and is markedly increased in obesity and type II diabe Copyright © 2016, Samia Perwaiz Khan and Dunesh Kumar permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
... However in between group analysis, using unpaired t test, there was no statistically significant difference present (p>0.05). The outcome was in accordance with most of the studies carried where lifestyle intervention was the mainstay of treatment 37,38,39,40 . In this study marked weight reduction may be due to instructions to strictly adhere to prescribed diet (20-25 kcal/kg/body weight) 7,8,41 and exercise (Brisk walk) for 40 minutes 4-5 times per week 8,9 . ...
... 6 NASH probably causes ~80% of cases of cryptogenic cirrhosis, which accounts for 10-20% of all cirrhosis and progresses to advanced fibrosis in 30-37% of patients. 7 The risk of developing decompensated cirrhosis is 5-10% and that for hepatocellular carcinoma is 1-2%. 8 There is currently no FDA-approved treatment available for NASH. ...
Background/purpose
Dipeptidyl peptidase 4 (DPP-4) expression is directly associated with hepatic lipogenesis and liver injury in nonalcoholic steatohepatitis (NASH). This study has been designed to elucidate the histological improvement of NASH with the DPP-4 inhibitor sitagliptin.
Materials and methods
In this open-label randomized control trial, paired liver biopsy was taken from 40 NASH patients. Sitagliptin 100 mg was given once daily to the SL group and no sitagliptin was given to the L group for 1 year. Patients from both groups were encouraged to exercise moderately and advised to avoid saturated fat, excessive sugar, soft drinks, fast food, and refined carbohydrates to reduce weight.
Results
Steatosis improved in the SL group (from 2.3±0.6 to 1.2±0.8; P=0.000) and the L group (from 2.1±0.6 to 1.6±0.9; P=0.008), ballooning decreased from 1.8±0.6 to 1.3±06 (P=0.002) in the SL group, but not in the L group. Nonalcoholic fatty liver disease activity score (NAS) attenuated in both groups: the SL group (from 5.8±0.9 to 3.9±1.4; P=0.000) and the L group (from 5.3±0.6 to 4.6±1.2; P=0.009). NAS improvement was much higher in the SL group (1.9±1.4) than in the L group (0.7±1.1) (P=0.006), with NAS improving by ≥2 in 13 patients from the SL group and five patients from the L group (P=0.01). Improvement was irrespective of diabetes. Regression analysis explored that sitagliptin had odds of 6.38 and weight reduction had odds of 4.51 for NAS reduction.
Conclusion
Sitagliptin 100 mg once daily for 1 year ameliorates NAS by improving steatosis and ballooning, irrespective of diabetes. Sitagliptin has stronger efficacy than that of weight reduction.
... There are no biochemical parameters that allow accurate diagnosis of steatosis. NAFLD is often accompanied by moderate elevation of serum alanine aminotransferase (ALT), gamma-glutamyl transferase (γGT) [83] and an ALT/AST ratio < 1 [84], as well as levels of triglycerides and cholesterol that exceed the normal range. However, a significant number of subjects may present normal parameters of the liver while suffering from advanced forms of liver disease. ...
... However, a significant number of subjects may present normal parameters of the liver while suffering from advanced forms of liver disease. Liver ultrasound has a high sensitivity (89%) and specificity (93%) for the diagnosis of steatosis, but not for the diagnosis of fibrosis (sensitivity 77%, specificity 89%) [84]. Moreover, while ultrasound is highly effective in determining the presence of fat in the liver parenchyma, it does not provide information regarding the likelihood of disease progression. ...
Non-alcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease in industrialized countries. NAFLD progresses through the inflammatory phase of non-alcoholic steatohepatitis (NASH) to fibrosis and cirrhosis, with some cases developing liver failure or hepatocellular carcinoma (HCC). Liver biopsy remains the gold standard approach to a definitive diagnosis of NAFLD and the distinction between simple steatosis and NASH. The pathogenesis of NASH is still not clear. Several theories have been proposed ranging from the "Two Hit Theory" to the "Multiple Hit Theory". However, the general consensus is that the gut microbiota, oxidative stress, and mitochondrial damage play key roles in the pathogenesis of NASH. The interaction between the gut epithelia and some commensal bacteria induces the rapid generation of reactive oxygen species (ROS). The main goal of any therapy addressing NASH is to reverse or prevent progression to liver fibrosis/cirrhosis. This problem represents the first "Achilles' heel" of the new molecules being evaluated in most ongoing clinical trials. The second is the inability of these molecules to reach the mitochondria, the primary sites of energy production and ROS generation. Recently, a variety of non-pharmacological and pharmacological treatment approaches for NASH have been evaluated including vitamin E, the thiazolidinediones, and novel molecules related to NASH pathogenesis (including obeticholic acid and elafibranor). Recently, a new isoform of human manganese superoxide dismutase (MnSOD) was isolated and obtained in a synthetic recombinant form designated rMnSOD. This protein has been shown to be a powerful antioxidant capable of mediating ROS dismutation, penetrating biological barriers via its uncleaved leader peptide, and reducing portal hypertension and fibrosis in rats affected by liver cirrhosis. Based on these distinctive characteristics, it can be hypothesized that this novel recombinant protein (rMnSOD) potentially represents a new and highly efficient adjuvant therapy to counteract the progression from NASH to HCC.
... [5,6] Nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD, is characterized by hepatocellular damage, inflammation and liver fibrosis that can progress to cirrhosis. [7][8][9] The pathogenesis of NASH is multifactorial, inflammatory activation clearly plays a pivotal role in the disease progression. Chronic inflammation interplaying with increased oxidative stress, cytokine production, direct lipotoxicity and autoimmunity is implicated in NAFLD pathophysiology by increasing NASH. ...
Background and Objectives
To observe the effect of Pentoxifylline for 1 year on hepatic histological activity and fibrosis of nonalcoholic steatohepatitis (NASH).
Materials and Methods
A single center, open label Randomized Control Trial. Patients were included if they had ultrasonographic evidence of fatty liver and nonalcoholic fatty liver disease activity score (NAS) ≥ 5 on liver histology. A total of 35 patients were selected; 25 of PL (Experimental) group and 10 of L (Control) group. PL group received 400 mg pentoxifylline thrice daily along with lifestyle modification and there was only lifestyle modification for the L group. After one year, NAS and fibrosis was compared in both groups.
Results
In PL group, NAS improved 2.10 ± 1.07; whereas in L group, NAS was 0.90 ± 0.99 (
Conclusion
Pentoxifylline for 1 year improves the hepatic histological activity but not fibrosis of NASH patients.
