Non‐alcoholic fatty liver disease: a review of epidemiology,risk factors,diagnosis and management

Due to the rising prevalence of obesity and type II diabetes mellitus, non‐alcoholic fatty liver disease is becoming the leading cause of chronic liver disease in the Western world. In some patients, simple steatosis can result in non‐alcoholic steatohepatitis which over time can lead to liver cirrhosis and its associated sequelae, including hepatocellular carcinoma. Early identification and management of patients at risk with intensive dietary and lifestyle modification are essential to prevent the development of advanced liver disease and its complications. In this review, we will discuss the epidemiology of non‐alcoholic fatty liver disease, pathogenesis, diagnosis, management and surveillance strategies to offset the morbidity and mortality of this disease, as well as liver and non‐liver‐related complications.     

Non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world. It is closely associated with metabolic syndrome. The alarming epidemics of diabetes and obesity have fueled an increasing prevalence of NAFLD, particularly among these high-risk groups. Histologically, NAFLD encompasses a disease spectrum ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), which is characterized by hepatocyte injury, inflammation, and variable degrees of fibrosis on liver biopsy. Non-alcoholic steatohepatitis can progress to cirrhosis in a fraction of patients. There is currently little understanding of risk factors for disease progression and the disease pathogenesis has not been fully defined. Liver biopsy remains the gold standard for diagnosis. Weight loss, dietary modification, and the treatment of underlying metabolic syndrome remain the mainstays of therapy once the diagnosis is established. There are no well-established pharmacological agents for treatment of NASH, although this is a subject of ongoing research.     

Clinical application of magnetic resonance elastography in chronic liver disease

Recent evidence highlighted that the accurate assessment of liver fibrosis is important for evaluating the progression of chronic liver disease. During the past decade, many non‐invasive methods have been developed to reduce the need for core‐needle biopsy in fibrosis staging and to overcome its limitations, such as invasiveness, high cost, low reproducibility, and poor patient consent. The diagnostic performance of magnetic resonance elastography (MRE) is promising for use in clinical practice to evaluate not only liver fibrosis, but also survival and major clinical end‐points such as liver decompensation, portal hypertension, development of hepatocellular carcinoma, and surgical outcomes. Together with other clinical markers, MRE can be used to better categorize patients with advanced fibrosis and cirrhosis, and assign them to different classes of risk for significant clinical outcomes. This review discusses clinical applications of MRE in the management strategy of patients with chronic liver disease.     

Transitional features of histologic type of non-alcoholic fatty liver disease in Korean young men

Background and Aim: The prevalence of non‐alcoholic fatty liver disease (NAFLD) is increasing in Korea as the dietary pattern and lifestyle become more Westernized and the obese population increases. The spectrum of NAFLD ranges from asymptomatic steatosis to non‐alcoholic steatohepatitis (NASH) and cirrhosis. Schwimmer et al. divided NASH into three types according to the histological characteristics, such as adult type, pediatric type and overlap type. We investigated clinical and histologic features of NAFLD patients in Korean young men. Methods: A total of 64 male patients under age 30 years, diagnosed as NAFLD by a liver biopsy, were reviewed retrospectively. NASH was diagnosed by NAFLD activity score (NAS), and NASH patients were classified with Schwimmer's histological classification. Results: Pathological features of liver biopsy revealed NASH in most cases (59 cases, 92.2%) including 29 cases (45.3%) of borderline NASH and 30 cases (46.9%) of definite NASH. The definite NASH group showed significantly high aspartate aminotransferase/alanine aminotransferase levels compared to the borderline NASH group. There were four cases (6.8%) of pediatric type, 17 cases (28.8%) of adult type, and 38 cases (64.4%) of overlap type in the NASH group. NAS was 3.75 ± 0.05 in the pediatric type, 4.29 ± 1.16 in the adult type and 4.87 ± 1.21 in the overlap type, and the overlap type showed a higher NAS than the pediatric type. The fibrosis stage was significantly higher in the overlap type than the other types. Conclusion: Most Korean young men with NAFLD turned out to have borderline or definite NASH. More than half of the NASH cases showed overlap type in Korean young men.     

Clinical usage of serum ferritin to assess liver fibrosis in patients with non‐alcoholic fatty liver disease: Proceed with caution

Serum ferritin was recently reported to have low diagnostic accuracy for the detection of advanced fibrosis in patients with non‐alcoholic fatty liver disease (NAFLD). To corroborate these findings, we investigated the diagnostic accuracy of serum ferritin levels for detecting liver fibrosis in NAFLD patients utilizing a large Japanese cohort database. A total 1201 biopsy‐proven NAFLD patients, seen between 2001 and 2013, were enrolled into the Japan Study Group of NAFLD. Analysis was performed on data from this cohort comparing between serum ferritin levels and hepatic histology. Serum ferritin increased with increasing histological grade of steatosis, lobular inflammation and ballooning. Multivariate analyses revealed that sex differences, steatotic grade and fibrotic stage were independently associated with serum ferritin levels (P < 0.0001, <0.0001, 0.0248, respectively). However, statistical analyses performed using serum ferritin levels demonstrated that the area under the receiver–operator curve for detecting fibrosis was not adequate for rigorous prediction. Several factors including sex differences, steatosis and fibrosis were found to correlate with serum ferritin levels. Therefore, serum ferritin may have low diagnostic accuracy for specifically detecting liver fibrosis in NAFLD patients due to the involvement of multiple hepatocellular processes.     

Advances in noninvasive methods for diagnosing nonalcoholic fatty liver disease

The prevalence of nonalcoholic fatty liver disease (NAFLD), one of the most common chronic liver diseases worldwide, has been increasing. In terms of pathological changes, NAFLD can be divided into simple steatosis, nonalcoholic steatohepatitis (NASH) and liver cirrhosis. Hepatocyte damage and inflammatory activity are the main characteristics for evaluating the progress of liver disease. Early and effective diagnosis of the disease is quite important. Pathological findings based on liver biopsy or resected specimens are considered the gold standard for diagnosing and staging steatosis, fibrosis and cirrhosis; however, it is invasive and may lead to related complications. Non‐imaging methods such as clinical features and biochemical tests, and imaging methods such as ultrasonography, FibroScan, computed tomography and magnetic resonance imaging are the commonly used noninvasive alternatives, being relatively novel, safe and reliable. In this review, we summarized the benefits and shortcomings of these non‐invasive methods for the evaluation of NAFLD.     

Histopathological characteristics of non-alcoholic fatty liver disease in children: Comparison with adult cases

Aim: Non-alcoholic steatohepatitis (NASH) has been classified pathologically into type 1 (characterized by ballooning and perisinusoidal fibrosis) and type 2 (characterized by portal inflammation and portal fibrosis). Reportedly, type 2 NASH has been the most commonly observed histopathological feature in pediatric non-alcoholic fatty liver disease (NAFLD). While only a few studies have documented the histopathology of pediatric NAFLD so far, appropriate histopathological classification or characteristics of pediatric NAFLD, and the disease incidence correlation with race or ethnicity are still controversial. Methods: In this study, we compared the clinical and histopathological characteristics of NAFLD in 34 pediatric and 23 adult cases. Results: We found that pediatric steatosis was more severe than adult steatosis. Perisinusoidal fibrosis was significantly milder in pediatric cases than in adult cases. Lobular inflammation and ballooning was found to be milder in pediatric cases than in adult cases. On the other hand, portal inflammation was more severe in pediatric cases than in adult cases. The so-called borderline zone 1 NASH, similar to type 2 NASH, was observed in 21% of pediatric subjects; this rate was more than twice that in adult subjects. Fifty percent of pediatric cases showed overlapping features of types 1 and 2 NASH. Intralobular and portal changes showed positive and significant correlations with each other. Serum aminotransferase levels reflected the histopathological severity of NAFLD. Conclusion: We confirmed that pediatric NAFLD exhibits histopathological features that are different from adult NAFLD. The classification consisting of "type 1 NASH" and "type 2 NASH" may be impractical.     

Clinical Cases in Hepatitis: Towards improving liver disease management in Australia

Clinical Cases in Hepatitis 2018 was an interactive educational program for Australian physicians (gastroenterologists, hepatologists, and infectious disease specialists) actively involved in the treatment of liver diseases including hepatitis C virus, hepatitis B virus, and non‐alcoholic steatohepatitis. This educational program sponsored by Gilead Sciences took place on October 12–13, 2018, and provided timely, informative case‐based, and practical education to Australian physicians. This report summarizes keynote lectures from international leaders in the field of hepatitis C virus, hepatitis B virus, and non‐alcoholic steatohepatitis and practical clinical case studies designed to inform and educate Australian physicians on managing challenging patients.     

Paediatric non‐alcoholic fatty liver disease: an overview

Non‐alcoholic fatty liver disease (NAFLD) is a progressive disease that encompasses a spectrum of liver diseases, ranging from simple steatosis to non‐alcoholic steatohepatitis (NASH). Data related to survival in children are scarce, but these data firmly associate NAFLD with higher risks of hepatic and non‐hepatic morbidities and mortalities compared with the general population. More recently, the association between NAFLD and cardiovascular disease among children has increasingly been recognized. Given that obesity is a major risk factor for the disease, paediatric NAFLD is becoming a global issue, paralleling the dramatic rise in obesity worldwide. NASH, which is more common in obese children, has the potential to advance to liver fibrosis and failure. It is unclear why certain patients undergo such transformation but this susceptibility is likely related to an interaction between a genetically susceptible host and the surrounding environment. Currently, treatment is largely conservative and includes lifestyle modification, attainable through healthy weight reduction via diet and exercise. In this review, current knowledge about NAFLD in children is summarized. This review aims to increase the awareness of the medical community about a hidden public health issue and to identify current gaps in the literature while providing directions for future research.