*The use of 18F-fluorodeoxyglucose positron emission tomography and computed tomography imaging for the detection of inflammation in steatotic livers as an indicator of non-alcoholic steatohepatitis*

Non-alcoholic fatty liver disease (NAFLD) has been used as a general name for
conditions ranging from simple steatosis through non-alcoholic steatohepatitis
(NASH) to end-stage liver disease (cirrhosis). Simple steatosis is a rather
benign condition as less then 5% shows progression to steatohepatitis. NASH
proves to be more dangerous, as leads to cirrhosis in approximately 20% after
8-10 years of follow up. More then 30% of patients with end stage liver disease
(cirrhosis) develop liver related morbidity and mortality. In spite of intense
research, the mechanism that causes progression of simple steatosis to NASH
remains unclear. In 1998 Day launched the two-hit-theory, stating that two
succeeding wallops have to be delivered to the liver to cause NASH. The first
hit, development of hepatic steatosis, consists of the accumulation of
triglycerides in the liver. Inflammation is the response to the second hit,
formation of reactive oxygen species (ROS) and mitochondrial damage. The first
step in establishing the diagnosis is physical examination and blood tests,
directed to exclude other liver diseases: Increased waist-to-hip-ratio, mildly
elevated transaminases and increased fasting glucose and hyperinsulinaemia
should rise the suspicion of hepatic steatosis and it can be confirmed by
radiologic imaging, with 1H-MR-spectroscopy as the most promising technique.
Although a number of serological markers and imaging techniques can be helpful
in distinguishing NASH from simple steatosis, a non-invasive tool to
differentiate simple steatosis and NASH in an early stage is unavailable. To
identify inflammation a liver biopsy still remains the gold standard.

The primary objective is to study if non-diabetic patients with biopsy-proven
NASH have higher hepatic FDG-uptake as compared to non-diabetic patients with
biopsy-proven non-inflammatory steatosis?
Secondary Objectives are (1) to study the association between hepatic
FDG-uptake and the degree of inflammation in the liver biopsies, (2) to study
the association between hepatic FDG-uptake and 1H-MRS-measured hepatic fat
content and (3) to study the association between the parameters measured by
imaging (PET/1H-MRS) and circulating markers of metabolism, including insulin
resistance and transaminases, and markers of inflammation?

Observational single center pilot study

Participating patients will have to bring 3 visits to the VUmc. Duration of
these visits ranges from 45 minutes to a maximum of 4 hours. Subjects have to
abstain from heavy physical activities (e.g. sports) 24-h prior to the visits
and remain fasted as indicated. Visits will be scheduled in accordance with the
participants schedule and preferably in the morning, so the fasting period can
be at nights. FDG-PET CT-scan delivers an amount of approximately 4
milliSievert of ionizing radiation to the patient. Furthermore the contrast
that is used may cause irritation at the injection place, nausea, minor
allergic reaction and in rare cases severe allergic reactions. An oral glucose
tolerance tests will be performed to determine glucose tolerance status (2*
hours test time). Prior to and during the OGTT patients will be allowed a
restricted regime of water intake. Participants will be presented with a light
meal and coffee/tea after testing.