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.     

Diagnosis and classification of non‐alcoholic fatty liver disease and non‐alcoholic steatohepatitis: Current concepts and remaining challenges

The high prevalence of non‐alcoholic fatty liver disease (NAFLD) has made the condition an important public health issue. Two clinical entities are manifestations of NAFLD, namely, non‐alcoholic fatty liver (NAFL) and non‐alcoholic steatohepatitis (NASH). The former tends to be benign and non‐progressive while the latter can progress to cirrhosis, which in rare cases gives rise to hepatocellular carcinoma. The diagnosis of NAFLD is based on: (i) a history of no or limited daily alcohol intake (<20 g for women and <30 g for men); (ii) presence of hepatic steatosis by imaging or by histology; and (iii) exclusion of other liver diseases. NAFL is defined histologically by the presence of bland, primarily macrovesicular, hepatocellular fatty change, while NASH features fatty change with inflammation and evidence of hepatocyte injury, such as ballooning degeneration. Presence of fibrosis is a sign of chronicity. Thus, the diagnosis of NAFL/NASH rests on clinicopathological criteria; it always requires both clinical and biopsy‐based information. NAFLD could be both the result and the cause of metabolic syndrome, with a vicious cycle operating between these conditions. Remaining challenges are: (i) the lack of a clear threshold alcohol intake for defining “non‐alcoholic”; (ii) a lacking consensus for the classification of fatty liver disease; and (iii) absence of a histological definition of NASH, which currently remains the gold standard for the diagnosis. Further challenges include the overlap of the criteria for NAFLD and alcoholic liver disease as many obese individuals also consume considerable volumes of alcohol.     

Modification of a simple clinical scoring system as a diagnostic screening tool for non‐alcoholic steatohepatitis in Japanese patients with non‐alcoholic fatty liver disease

Aims/Introduction

We reinvestigated the clinical usefulness of the modified NAFIC scoring system, modified by changing the weightage assigned to the fasting serum insulin level based on the importance of hyperinsulinemia in the pathogenesis of non‐alcoholic steatohepatitis (NASH), in Japanese patients with non‐alcoholic fatty liver disease (NAFLD) who had undergone liver biopsy.

Materials and Methods

The NAFIC score is conventionally calculated as follows: serum ferritin ≥200 ng/mL (female) or ≥300 ng/mL (male), 1 point; serum fasting insulin ≥10 μU/mL, 1 point; and serum type IV collagen 7 s ≥5.0 ng/mL, 2 points. A total of 147 patients with NAFLD who had undergone liver biopsies were included in the estimation group. To validate the modified scoring system, 355 patients from nine hepatology centers in Japan were also enrolled.

Results

In the estimation group, 74 (50.3%) patients were histologically diagnosed as having NASH, whereas the remaining 73 (49.7%) were diagnosed as not having NASH. As the percentage of NASH patients increased not only among participants with serum insulin levels greater than 10 μU/mL, but also in those with serum levels greater than 15 μU/mL, we advocated use of the modified NAFIC score, as follows: serum fasting insulin 10–15 μU/mL, 1 point and ≥15 μU/mL, 2 points. The modified NAFIC score showed improved sensitivity and negative predictive value for the diagnosis of NASH. This finding was also confirmed in the validation group.

Conclusions

The modified NAFIC scoring system could be a clinically useful diagnostic screening tool for NASH.     

Non-alcoholic fatty liver disease and thyroid dysfunction: A systematic review

Thyroid hormones are totally involved in the regulation of body weight, lipid metabolism, and insulin resistance. Therefore it is anticipated that thyroid hormones may have a role in the pathogenesis of non alcoholic fatty liver disease (NAFLD) and non alcoholic steatohepatitis (NASH). In this study, we reviewed the current literature on the association between thyroid dysfunction and NAFLD/NASH. A search for English language medical literature reporting an association between thyroid dysfunction and NAFLD/NASH in humans was conducted across PubMed, ISI Web of Science, and Scopus in August, 2013. Out of 140 studies initially identified through the search, 11 relevant articles were included in the final review. Thyroid dysfunctions in the form of overt or subclinical hypothyroidism are prevalent among patients with NAFLD/NASH. Hypothyroidism appears to be an independent risk factor for NAFLD/NASH in some studies; however, other newly published studies failed to find such an association. The results of the studies on the role of thyroid abnormalities in NAFLD/NASH are inconsistent, and further research is recommended to determine the relationship between hypothyroidism and NAFLD/NASH and the underlying mechanisms.