Ludwig, Jürgen

Among 210 deaths in infants aged 2 weeks to 2 years in Olmsted County, Minnesota, during the 20-year period 1946 through 1965, review of the clinical and pathologic reports disclosed 37 instances of sudden, unexpected, unexplained death (SUUD). The incidence rate was 1.2/1,000 live births. The death occurred between midnight and noon in 90% of cases, and all but one of the children were found dead in bed. Some seasonal variation was noted. Autopsy was done in 75% of the 210 instances, including 86% (32) of the SUUD cases. More than two thirds of the cases of SUUD coming to autopsy had some evidence of an infectious disease, but these findings were minimal and in no case sufficient in themselves to cause death. Therefore, it was concluded that a second factor is necessary to initiate the sequence of events that leads to death, although the specific trigger mechanisms are unknown and may be quite variable.

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.