The correct identification of patients at increased risk of non-alcoholic steatohepatitis (NASH) and advanced fibrosis is a critical step in the assessment of non-alcoholic fatty liver disease ...(NAFLD). Since liver biopsy is invasive, expensive and prone to sampling error, several clinical prediction rules and blood-based biomarkers have been developed as attractive and affordable alternatives for identification of patients at high risk of NASH and advanced fibrosis. Current biomarkers constitute predictive models (e.g. NAFLD fibrosis score, FIB-4 index and BARD score) or direct measures of inflammation (e.g. circulating keratin 18 fragments), or fibrosis (e.g. FibroTest®, ELF™ or Pro-C3 tests). In the clinical setting, biomarkers may discriminate between patients with NASH or advanced fibrosis, predict dynamic changes in NASH/fibrosis over time, and provide long-term prognostic information. Although clinically useful, current biomarker predictions may be influenced by hepatic and extrahepatic conditions (e.g. age, patient comorbidities, and fibrosis or NASH prevalence), which may lead to inaccurate estimates in small subsamples of patients. No highly sensitive and specific tests are available to differentiate NASH from simple steatosis. However, diagnostic accuracy can be improved by combining blood biomarkers. NAFLD fibrosis score and FIB-4 index are both cost-effective and highly sensitive tools to exclude patients with advanced fibrosis. Moreover, their higher scores may identify patients at higher risk of non-liver- and liver-related morbidity and mortality. More expensive tests such as FibroTest or ELF are more specific for detection of patients with significant and advanced fibrosis. Recent efforts have concentrated on “omics” approaches for developing and validating novel biomarkers. Herein, we describe currently available clinical prediction rules and blood-based biomarkers for identifying NASH and advanced fibrosis in patients with NAFLD, discussing their advantages and disadvantages, as well as their potential clinical utility for predicting dynamic changes over time and identifying patients at increased risk of adverse outcomes.
Idiosyncratic drug-induced liver injury (DILI) is common in gastroenterology and hepatology practices, and it can have multiple presentations, ranging from asymptomatic elevations in liver ...biochemistries to hepatocellular or cholestatic jaundice, liver failure, or chronic hepatitis. Antimicrobials, herbal and dietary supplements, and anticancer therapeutics (e.g., tyrosine kinase inhibitors or immune-checkpoint inhibitors) are the most common classes of agents to cause DILI in the Western world. DILI is a diagnosis of exclusion, and thus, careful assessment for other etiologies of liver disease should be undertaken before establishing a diagnosis of DILI. Model for end-stage liver disease score and comorbidity burden are important determinants of mortality in patients presenting with suspected DILI. DILI carries a mortality rate up to 10% when hepatocellular jaundice is present. Patients with DILI who develop progressive jaundice with or without coagulopathy should be referred to a tertiary care center for specialized care, including consideration for potential liver transplantation. The role of systemic corticosteroids is controversial, but they may be administered when a liver injury event cannot be distinguished between autoimmune hepatitis or DILI or when a DILI event presents with prominent autoimmune hepatitis features.
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world and its incidence is increasing rapidly. NAFLD is a spectrum ranging from simple steatosis, which is ...relatively benign hepatically, to nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis. Obesity, insulin resistance, type 2 diabetes mellitus, and dyslipidemia are the most important risk factors for NAFLD. Due to heavy enrichment with metabolic risk factors, individuals with NAFLD are at significantly higher risk for cardiovascular disease. Individuals with NAFLD have higher incidence of type 2 diabetes. The diagnosis of NAFLD requires imaging evidence of hepatic steatosis in the absence of competing etiologies including significant alcohol consumption. Liver biopsy remains the gold standard for diagnosing NASH and for determining prognosis. Weight loss remains a cornerstone of treatment. Weight loss of ∼5% is believed to improve steatosis, whereas ∼10% weight loss is necessary to improve steatohepatitis. A number of pharmacologic therapies have been investigated to treat NASH, and agents such as vitamin E and thiazolidinediones have shown promise in select patient subgroups.
Nonalcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) are both manifestations of end-organ damage of the metabolic syndrome. Through multiple pathophysiological mechanisms, CVD ...and NAFLD are associated with each other. Systemic inflammation, endothelial dysfunction, hepatic insulin resistance, oxidative stress, and altered lipid metabolism are some of the mechanisms by which NAFLD increases the risk of CVD. Patients with NAFLD develop increased atherosclerosis, cardiomyopathy, and arrhythmia, which clinically result in cardiovascular morbidity and mortality. Defining the mechanisms linking these 2 diseases offers the opportunity to further develop targeted therapies. The aim of this comprehensive review is to examine the association between CVD and NAFLD and discuss the overlapping management approaches.
Nonalcoholic fatty liver disease (NAFLD) is a spectrum comprised of isolated steatosis, nonalcoholic steatohepatitis (NASH), advanced fibrosis, and cirrhosis. The majority of NAFLD subjects do not ...have NASH and do not carry a significant risk for liver‐related adverse outcomes (cirrhosis and mortality). Globally, the prevalence of NAFLD is approximately 25%. In Asia, a gradient of high to low prevalence rates is noted from urban to rural areas. Given the prevalence of NAFLD, the clinical and economic burden of NAFLD and NASH can be substantial. With increasing recognition of NASH as an important liver disease, the diagnosis of NASH still requires a liver biopsy that is suboptimal. Although liver biopsy is the most accurate modality to diagnose and stage the severity of NASH, this method suffers from being invasive, costly, associated with potential complications, and plagued with interobserver variability of individual pathological features. A number of noninvasive modalities to diagnose NASH and stage liver fibrosis are being developed. These modalities include predictive models (NAFLD fibrosis score) and serum biomarkers such as enhanced liver fibrosis (ELF). Other tests are based on radiological techniques, such as transient elastography (TE) or magnetic resonance elastography (MRE), which are used to estimate liver stiffness as a potential surrogate of hepatic fibrosis. Although a dynamic field of research, most of these diagnostic modalities have area under the curve ranging between 0.76 and 0.90%, with MRE having the best predictive performance. In summary, developing safe and easily accessible noninvasive modalities to accurately diagnose and monitor NASH and associated fibrosis is of utmost importance in clinical practice and clinical research. These tests are not only important to risk stratify subjects at the greatest risk for progressive liver disease, but also to serve as appropriate surrogate endpoints for therapeutic clinical trials of NASH. (Hepatology 2018;68:349‐360).
Nonalcoholic fatty liver disease (NAFLD) and its progressive form non‐alcoholic steatohepatitis (NASH), are rapidly becoming among the top causes of cirrhosis, hepatocellular carcinoma, and ...indications for liver transplantation. Other than lifestyle modification through diet and exercise, there are currently no other approved treatments for NASH/NAFLD. Although weight loss can be effective, it is difficult to achieve and sustain. In contrast, bariatric surgery can improve metabolic conditions associated with NAFLD, and has been shown to improve liver histology. To have approved regimens for the treatment of NASH/NAFLD, several issues must be addressed. First, all stakeholders must agree on the most appropriate clinical trial endpoints for NASH. Currently, resolution of NASH (without worsening fibrosis) or reduction of fibrosis stage (without worsening NASH) are the accepted endpoints by the regulatory authorities. It is important to recognize the prognostic implication of histologic features of NASH. In this context, although histologic NASH has been associated with advanced fibrosis, it is not an independent predictor of long‐term mortality. In contrast, there are significant data to suggest that fibrosis stage is the only robust and independent predictor of liver‐related mortality. In addition to the primary endpoints, several important secondary endpoints, including noninvasive biomarkers, long‐term outcomes, and patient‐reported outcomes must be considered. In 2018, a few phase 3 clinical trials for the treatment of NASH have been initiated. Additionally, a number of phase 2a and 2b clinical trials targeting different pathogenic pathways in NASH are in the pipeline of emerging therapies. Conclusion: Over the next 5 years, some of these regimens are expected to provide potential new treatment options for patients with NASH/NAFLD. (Hepatology 2018;68:361‐371)
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