studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 1231A
2098
A novel mouse model for the study of pediatric Non-Alcoholic
Fatty Liver Disease (NAFLD)
Veronica Marin 1 , Natalia Rosso 1 , Matteo Dal Ben 1 , Alan Raseni 2 ,
Cristina Degrassi 3 , Claudio Tiribelli 1,4 , Silvia Gazzin 1 ; 1 Fondazione
Italiana Fegato, Trieste, Italy; 2 S.C.Laboratorio Analisi
Cliniche, IRCCS Burlo Garofalo, Trieste, Italy; 3 Medical Research
Institute, Trieste, Italy; 4 Department of Medical Science, University
of Trieste, Trieste, Italy
The increasing prevalence of pediatric NAFLD is considered
a booming problem with worrying future outcome. Consistent
pediatric models to mimic the clinical condition, as well as
studies considering eventual gender differences, are still lacking.
The aim of this study is to develop and characterize a
Juvenile NAFLD model. Males (M) and females (F) C57BL/6
mice, immediately after weaning were randomly assigned to
control (CTRL) or high-fat high-carbohydrate diet (HFHCD).
Animals had ad-libitum food for 16wks access. Body-weight,
glycaemia, insulinemia, triglycerides, total cholesterol, HDL-C,
LDL-C, ALT and liver histology were screened every 4wks and
compared to CTRL. Soon after the 1 st week, HFHCD induced
a significant bodyweight gain in both genders. Males, after
4wks presented also hyperplasia of epididymal fat-pads and
after week 12 th , a significant hepatomegaly. Males showed
earlier alteration of glycemia, insulinemia, lipid profile and
ALT (Table1). Interestingly, comparable body/blood alterations
were observed in females only at the 16 th week. Liver histology
showed in both genders a mixed macro-microvesicular steatosis
increasing steadily after the 8 th week. Inflammatory cells foci
were observed in males from the beginning and increased over
the time. On the contrary, inflammation was absent in females.
Surprisingly, both genders developed progressive fibrosis starting
from the 8 th week and rising steadily over the time. This
juvenile NAFLD model progresses faster than those previously
reported in adults. A clear gender difference was found in the
onset of the liver injury. Even if the final outcome was comparable
between genders (fibrosis grade 2), males presented early
signs of liver injury, whereas females did not.
was January 2004 to March 2014. The total number of abnormal
results for both caeruloplasmin and A1AT, defined as a
value below the lower limit of normal, were assessed and subsequent
diagnosis evaluated from medical records. The value
for caeruloplasmin varied during the study, however the majority
of samples were < 0.17 g/L. For A1AT deficiency the limit
was < 0.9 g/L. Results During the study period caeruloplasmin
was ordered on 2444 patients. The mean age of patients was
46.4 years, 56.4% were male and 76 tests (3.1%) were abnormal.
Plasma copper was performed on 41 patients (53.9%),
however 36 (87.8%) were simultaneous with caeruloplasmin.
Only 13 patients (17.1%) underwent 24-hour urinary copper
measurement with 9 (69.2%) elevated. 21 patients (27.6%)
had a liver biopsy, and 3 (14.3%) had hepatic copper quantification.
Only 1 patient had WD confirmed. Other diagnoses
included viral hepatitis (32.3%), alcohol (26.3%), drug induced
liver injury (10.5%) and NAFLD (7.9%). The positive predictive
value of a low caeruloplasmin level for WD was 1.4%. A1AT
levels were requested for 3247 patients. The mean age of
patients was 47 years, 55.9% were male and 88 tests (2.7%)
were abnormal. Genotyping was performed on 55 patients
(62.5%) with MZ (41.8%) most prevalent followed by MM
(38.2%). Only 1 patient had ZZ genotype and was diagnosed
with A1AT deficiency. Five patients had SZ genotype however
only three had this noted in medical records. Of the 21 patients
with MM genotype, 6 have been referred for further genotyping
of rare genetic variants. 1 has shown MM procida
. Other
diagnoses included viral hepatitis (44.3%), NAFLD (18.2%),
alcohol (11.4%) and drug induced liver injury (6.8%). The
positive predictive value of a low A1AT level to detect ZZ genotype
was 1.8%. Conclusion Caeruloplasmin and A1AT have
very low detection rates when used as screening tests within the
hepatology department of a tertiary hospital. The use of these
investigations should be limited to patients in whom initial liver
screen is negative and clinical suspicion remains.
Disclosures:
Leon A. Adams - Patent Held/Filed: Quest diagnostics
The following authors have nothing to disclose: Tim Mitchell, John Beilby, Gary P.
Jeffrey, George Garas, John Joseph, Ric Rossi, Gerry C. MacQuillan
Disclosures:
The following authors have nothing to disclose: Veronica Marin, Natalia Rosso,
Matteo Dal Ben, Alan Raseni, Cristina Degrassi, Claudio Tiribelli, Silvia Gazzin
2099
The real world experience of screening investigations
for Wilson’s disease and α1-antitrypsin deficiency
within a tertiary liver unit – is it worthwhile?
Tim Mitchell 1 , John Beilby 2 , Gary P. Jeffrey 1 , Leon A. Adams 1 ,
George Garas 1 , John Joseph 2 , Ric Rossi 2 , Gerry C. MacQuillan 1 ;
1 Sir Charles Gairdner Hospital, Nedlands, WA, Australia; 2 Path-
West, Nedlands, WA, Australia
Introduction Wilson’s disease (WD) and α1-antitrypsin (A1AT)
deficiency are rare but important causes of liver disease. The
phenotypic presentation is varied and diagnosis can be difficult.
Despite limitations as screening tests, caeruloplasmin
and A1AT levels have been performed routinely at this center
among patients presenting with liver disease. We reviewed the
yield of these investigations to guide future ordering practices.
Methods All serum caeruloplasmin and A1AT levels requested
by the hepatology department at a tertiary hospital from the
state reference laboratory were reviewed. The study period
2100
Relapse of Porphyria Cutanea Tarda After Achieving
Remission With Phlebotomy or Low Dose Hydroxychloroquine
Ashwani K. Singal 1 , Eric Gou 2 , Maira Rizwan 1 , Marisol Albuerne 2 ,
Csilla Kormos Hallberg 3 , Karl E. Anderson 3,2 ; 1 Gastroenterology
and Hepatology, UAB, Birmingham, AL; 2 Internal Medicine,
UTMB, Galveston, TX; 3 Preventive Medicine, UTMB, Galveston, TX
Background: Porphyria cutanea tarda (PCT) is due to inhibition
of hepatic uroporphyrinogen decarboxylase (UROD) and is
effectively treated by phlebotomy (to serum ferritin of