The authors drew two separate conclusions

from this article: first, that it further demonstrates a clear link between TLR4 status and the development of hepatic steatosis and steatohepatitis, and second, that it has demonstrated a fructose-specific effect. We remain uncertain of either of these conclusions. Richard D. Johnston*, Ian Roxadustat nmr A. MacDonald†, Guruprasad P. Aithal*, * Nottingham Digestive Diseases Centre and Biomedical Research Unit, University Hospital, Nottingham, UK, † School of Biomedical Sciences, The University of Nottingham Medical School, Nottingham, UK. “
“We read with great interest the article by Afzali et al.,1 who showed that increased serum uric acid levels are associated with a higher incidence of cirrhosis-related hospitalization or death or with the presence of elevated serum

liver enzymes. Their results indeed provide novel data for ABT 263 improving our understanding of the relationship between serum uric acid and chronic liver disease. However, whether hyperuricemia is a direct cause of chronic liver disease or just a marker remains unclear; it is also unclear whether hypouricemic therapy is effective for the prevention of chronic liver disease. Recently, we conducted an experimental study to investigate the effect of hypouricemic therapy on the prevention of nonalcoholic fatty liver disease (NAFLD), which is the most prevalent chronic liver disease in Western countries. We successfully established a Mongolian gerbil model of NAFLD induced by a high-fat diet. A nearly 4-fold increase in serum uric

acid levels was observed in Mongolian gerbils fed the high-fat diet versus controls fed a standard diet (102.99 ± 42.02 versus 26.00 ± 20.59 μmol/L, P < 0.001). When the animals fed a high-fat diet were treated with allopurinol and benzbromarone, two drugs used clinically to lowering uric acid levels, serum uric acid levels significantly decreased from 102.99 ± 42.02 μmol/L in animals fed the high-fat diet to 56.94 ± 29.71 μmol/L in the treated animals (P = 0.02). Celastrol Serum biochemical analyses showed that total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were significantly reduced by hypouricemic therapy (for both, P < 0.01; Fig. 1A), whereas serum alanine aminotransferase (ALT), triglyceride (TG), and glucose (GLU) levels were not affected (Fig. 1A,B). Notably, serum creatinine (Cr) and blood urea nitrogen (BUN) levels were significantly increased in the therapy group, and this indicates that hypouricemic therapy may cause deterioration of renal function (Fig. 1B). Hepatic histology was analyzed to explore the effect of hypouricemic therapy on NAFLD. The hematoxylin and eosin staining of liver tissues from the NAFLD group showed that simple fatty liver (predominantly macrovesicular) occurred with various degrees of fat deposition, whereas the degree of hepatic steatosis in the therapy group was significantly ameliorated (Fig. 1C).