Although nonalcoholic fatty liver disease (NAFLD) is closely linked to obesity, around 10%-20% of nonobese Americans and Asians still develop NAFLD. Data on this special group are limited. We therefore studied the severity and clinical outcomes of nonobese NAFLD patients. Consecutive NAFLD patients who underwent liver biopsy were prospectively recruited. We used the NASH Clinical Research Network system to score the histology. The Asian body mass index cutoff of 25 kg/m 2 was used to define nonobese NAFLD. Among 307 recruited NAFLD patients, 72 (23.5%) were nonobese. Compared to obese patients, nonobese patients had lower NAFLD activity score (3.3 6 1.3 vs. 3.8 6 1.2; P 5 0.019), mainly contributed by steatosis (1.7 6 0.8 vs. 2.0 6 0.8; P 5 0.014) and presence of hepatocyte ballooning (60.9% vs. 73.4%; P 5 0.045). Similarly, nonobese patients had lower fibrosis stage (1.3 6 1.5 vs. 1.7 6 1.4; P 5 0.004), serum cytokeratin-18 fragments (283 vs. 404 U/L; P < 0.001) and liver stiffness measurement by transient elastography (6.3 vs. 8.6 kilopascals; P < 0.001). By multivariate analysis in nonobese patients, only elevated serum triglyceride level was independently associated with higher NAFLD activity score (adjusted odds ratio [OR], 1.644; P 5 0.021), whereas elevated creatinine level was the only factor associated with advanced fibrosis (adjusted OR, 1.044; P 5 0.025). After a median follow-up of 49 months, 6 patients died, 2 developed hepatocellular carcinoma, and 1 had liver failure, all of whom were in the obese group. Conclusion: Nonobese NAFLD patients tend to have less-severe disease and may have a better prognosis than obese patients. Hypertriglyceridemia and higher creatinine are the key factors associated with advanced liver disease in nonobese patients. (HEPATOLOGY 2017;65:54-64) SEE EDITORIAL ON PAGE 4 N onalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in the world. (1) It can progress to nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma (HCC). (2,3) Furthermore, patients with NAFLD have increased risk of cardiovascular events, other malignancies, and mortality. (4) NAFLD is strongly associated with obesity, metabolic syndrome (MetS), and cardiovascular risk factors and is more common in obese patients. (5,6) Nonetheless, a smaller, but significant, proportion of patients develop NAFLD despite having a relatively normal body mass Abbreviations: BMI, body mass index; CK-18, cytokeratin-18; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HDL, high-density lipoprotein; IQR, interquartile range; JNK, c-Jun N-terminal kinase; kPa, kilopascals; LSM, liver stiffness measurement; MetS, metabolic syndrome; NAFLD, nonalcoholic fatty liver disease; NAS, NAFLD Activity Score; NASH, nonalcoholic steatohepatitis; OR, odds ratio; PNPLA3, patatin-like phospholipase domain-containing protein 3; PPV, positive predictive value; TE, transient elastography; TM6SF2, transmembrane 6 superfamily antigen 2.

One-fifth of the general non-obese Chinese population has NAFLD. Non-obese patients with NAFLD do not have a higher risk of steatohepatitis or advanced fibrosis. Patients with risk factors of advanced fibrosis such as metabolic syndrome and PNPLA3 G allele carriage should be assessed for severe NAFLD.

Liver stiffness measurement alone can confidently exclude significant and advanced fibrosis in NAFLD patients. Using FM VCTE in patients with high liver stiffness can increase the positive predictive value to rule in F2-4 and F3-4.

Portal hypertension is the central driver of complications in patients with chronic liver diseases and cirrhosis. The diagnosis of portal hypertension has important prognostic and clinical implications. In particular, screening for varices in patients with portal hypertension can effectively reduce the morbidity and mortality of variceal bleeding. In this article, we review the invasive and non-invasive methods to assess portal hypertension. Hepatic venous pressure gradient remains the gold standard to measure portal pressure but is invasive and seldom performed outside expert centers and research settings. In recent years, a number of non-invasive tests of fibrosis have shown good correlation with liver histology. They also show promise in identifying patients with portal hypertension and large varices. As a result, the latest Baveno VI consensus guidelines endorse the use of liver stiffness measurement by transient elastography and platelet count as initial assessment to select patients for varices screening. On the other hand, the performance of non-invasive tests in assessing the response to non-selective beta-blockers or transjugular intrahepatic portosystemic shunting is either suboptimal or unclear.

An 18-month-old girl presented with a maculopapular rash 10 days after carbamazepine treatment. Initially, she was suspected of having a viral rash owing to associated fever. She deteriorated rapidly and was suspected of having anticonvulsant hypersensitivity syndrome or Stevens-Johnson syndrome. She developed features compatible with toxic epidermal necrolysis rapidly over 24 to 36 hours. Carbamazepine was then stopped. She responded immediately to high-dose intravenous pulse methylprednisone treatment. We discuss the controversy in the management of anticonvulsant hypersensitivity syndrome, toxic epidermal necrolysis, or Stevens-Johnson syndrome with high-dose corticosteroids, intravenous immunoglobulin, and antibiotics. (J Child Neurol 2004; 19:619-623).