studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 1293A
is a common finding which can be associated with chronic
liver disease but referral practices vary. Aim: to investigate
referral practices, prevalance of liver disease and three, five
and 10 year mortality of minimally deranged ALT. Methods All
LFT results requested by primary care in Newcastle between
1 st January and 31 st December 2003 were collected. Patients
with at least one ALT in the range 41-90IU/L were flagged
and the patients subsequently referred to Gastroenterology or
Hepatology were identified and case notes reviewed. Mortality
was investigated by matching ALT41-90 patients by age,
gender and GP practice to patients with normal range ALT.
Up to date mortality data was collected and three, five and
10 year mortality rates for both groups were calculated and
compared using chi-square tests. Results In 2003, 56,131 LFTs
were checked by primary care in Newcastle. Of these, 5,489
unique patients (9.8%) had an ALT in the range 41-90, while in
986 (1.8%) ALT was >90. Of the ALT41-90 patients, only 331
(6%) were referred to Gastroenterology or Hepatology within a
year. Casenotes were available for review in 309 (93%). 179
(58%) had evidence of significant liver disease and 22 (7%)
had established cirrhosis. Mortality: 1,195 (21.7%) ALT41-
90 patients were matched to normal ALT controls. Mean ALT
was 55.6 (SD 15.9) and 22.1 (SD 7.7) in the ALT41-90 and
normal groups respectively. Mean age was 50.2 (SD 14.1) in
both groups. There was no statistically significant difference
in the three, five or 10 year mortality between the ALT41-90
patients and the normal ALT patients (see table). Conclusions
Minimally deranged ALT is associated with a high risk of liver
pathology in asymptomatic patients but many of these patients
are not referred to a specialist. We did not find that a minimally
deranged ALT was associated with significantly higher
mortality rates at three, five or 10 years but it is possible that
this would be observed after longer follow-up. It would be valuable
to study the relative benefits of other methods of screening
for asymptomatic liver disease, in particular the combination of
aspartate aminotransferase (AST) with ALT in the AST:ALT ratio.
key pathological processes in NAFLD. We sought to determine
whether changes in VLDL profiles predict NAFLD disease progression.
Methods: We evaluated VLDL profiles of127 patients
from a single center NAFLD registry, and examined VLDL size
and subclass particle concentrations in relation with biopsy-determined
NASH and liver fibrosis. Results: NASH was associated
with larger VLDL size, but not higher concentration. In
a multivariate model, every nm increase in mean VLDL size
was associated with 2% increase in the relative risk of NASH
(95% CI 1.01–1.03, p = 0.002). A decrease in small VLDL
particle concentration was associated with more advanced
liver fibrosis. Every nmol/L decrease in the concentration of
small VLDL particles was associated with 2% increase (95% CI
1.003–1.04, p = 0.03) in the relative risk of stage 2 or above
fibrosis. Mean VLDL size and small VLDL particle concentration
alone performed equally well as cytokeratin-18 (CK18) and
NAFLD fibrosis score (NFS) in predicting both NASH and significant
liver fibrosis (Figure). The incorporation of VLDL measurements
improves the predictive value of existing NASH and
fibrosis indicators. Conclusions: The development of NASH is
associated with an increase in mean VLDL size, whereas the
progression of liver fibrosis is associated with a decrease in
the concentration of small VLDL particles. Profiles of circulating
VLDL may be used as biomarkers for NAFLD.
A. Comparison of CK18, VLDL size and the combination of both
in predicting NASH (NAS score ≥ 4). B. Comparison of NFS,
small VLDL concentration and the combination of both in predicting
significant liver fibrosis (stage 2 or above).
Mortality of normal ALT vs ALT41-90
Disclosures:
The following authors have nothing to disclose: James G. Orr, Richard C.
Thomas, David Jones, Mark Hudson
2227
Steatohepatitis and liver fibrosis are predicted by the
size and subclass concentration of very low density lipoprotein
in nonalcoholic fatty liver disease
Zhenghui G. Jiang 1 , Elliot B. Tapper 1 , Margery A. Connelly 2 , Carolina
F. Pimentel 1 , Linda Feldbrügge 1 , Misung Kim 3 , Sarah Krawczyk
3 , Nezam H. Afdhal 1 , Simon C. Robson 1 , Mark A. Herman 3 ,
James Otvos 2 , Kenneth Mukamal 4 , Michelle Lai 1 ; 1 Gastroenterology
and Hepatology, Beth Israel Deaconess Medical Center,
Harvard Medical School, Boston, MA; 2 LabCorp, Raleigh, NC;
3 Endocrinology, Beth Israel Deaconess Medical Center, Harvard
Medical School, Boston, MA; 4 General Internal Medicine, Beth
Israel Deaconess Medical Center, Harvard Medical School, Boston,
MA
Background: A major challenge in the management of nonalcoholic
fatty liver disease (NAFLD) is to identify patients at
risk for disease progression characterized by steatohepatitis
(NASH) and early liver fibrosis. Very low density lipoprotein
(VLDL) is produced exclusively from the liver, and influenced by
Disclosures:
Margery A. Connelly - Employment: LabCorp
Nezam H. Afdhal - Advisory Committees or Review Panels: Trio Helath Care;
Board Membership: Journal Viral hepatitis; Consulting: Merck, EchoSens, BMS,
Achillion, GlaxoSmithKline, Springbank, Gilead, AbbVie; Grant/Research Support:
Gilead; Stock Shareholder: Springbank
Simon C. Robson - Grant/Research Support: Pfizer, NIH, Dainippon; Independent
Contractor: Biolegend, EMD Millipore, Mersana; Management Position:
eBioscience; Speaking and Teaching: ACP, Elsevier, ATC; Stock Shareholder:
Nanopharma, Puretech
Mark A. Herman - Speaking and Teaching: Pfizer
The following authors have nothing to disclose: Zhenghui G. Jiang, Elliot B.
Tapper, Carolina F. Pimentel, Linda Feldbrügge, Misung Kim, Sarah Krawczyk,
James Otvos, Kenneth Mukamal, Michelle Lai