Ruxolitinib in Alleviating the Cytokine Storm of Hemophagocytic Lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening syndrome classified into primary HLH and secondary HLH. Secondary HLH is always caused by autoimmune disease, infections, or cancer. The first-line therapy for secondary HLH is the HLH 2004 protocol, including dexamethasone, etoposide, and supportive therapy. However, up to 30% of patients, especially pediatric patients, remain unresponsive to first-line treatment, and the mortality rate reaches 50% in children with HLH. Furthermore, some children who have special conditions, such as an active virus infection, are not suitable for immunosuppressants treatment. Recently, several HLH-promoting cytokines have been identified, including interferon-γ, interleukin-2, and interleukin-6. Janus kinase 1 and 2 control the signaling of many cytokines, notably interferon-γ, interleukin-2, and interleukin-6. Janus kinase 1 and 2 inhibitors, such as ruxolitinib, have been successfully used to treat HLH in mice. Here, we report that a boy, diagnosed with HLH and high titer of hepatitis B virus-DNA copies, improved quickly, and the cytokine storm of HLH was alleviated after receiving ruxolitinib. Five days after ruxolitinib treatment, entecavir was introduced and serum titer results of hepatitis B virus-DNA returned negative. With 3 months of ruxolitinib treatment and following-up 1 year, the boy's situation maintained sustained remission. In this study, it is suggested that ruxolitinib might be a first-line drug, which could alleviate the cytokine storm of HLH. This treatment may be ushering in the age of glucocorticosteroid-free HLH treatment, which is particularly meaningful for children because it avoids the side effects of glucocorticosteroid.

Relationship between serum aminotransferase levels and metabolic disorders in northern China.

BACKGROUND/AIMS: Increasing evidence suggests an association between elevated serum aminotransferase levels and metabolic disorders (metabolic syndrome, hyperlipidemia and diabetes mellitus). However, the significance of relatively low levels of aminotransferases in relation to metabolic disorders has not been fully investigated in the general population. We investigated the association between serum aminotransferase levels and metabolic disorders using data from a survey in Jilin Province, China. MATERIALS AND METHODS: In 2007, a prospective survey was conducted throughout Jilin, China, covering both urban and rural areas. A total of 3835 people, 18-79 years old, were undergoing real-time ultrasonography, blood tests, and interviews with a structured questionnaire. RESULTS: Serum aminotransferase levels within the normal range were associated with metabolic syndrome independent of age, occupation, cultural and educational level, income, body mass index, waist circumference, smoking, and alcohol intake. Compared with the lowest level (< 20 IU/L), the adjusted odds ratios for alanine aminotransferase levels of 20-29, 30-39, 40-49, and >50 IU/L were 1.92, 2.50, 2.97, and 3.52 in men, and 1.38, 1.54, 3.06, and 2.62 in women, respectively. Near-normal serum aminotransferase levels associated with hyperlipidemia, non-alcoholic fatty liver disease, and diabetes mellitus were also found in the study. CONCLUSIONS: Normal to near-normal serum aminotransferase levels are associated with metabolic disorders. Serum alanine aminotransferase levels of 21-25 IU/L for men and 17-22 IU/L for women are suggested as cut-off levels that detect metabolic disorders affecting the liver.