916 
Markers of Liver Fibrosis Predict Adverse Liver Outcomes in a Population of HCV+ Individuals with and without HIV Co-infection
D Nunes1,2, D Nunes1,2, G Offner1, K Chambers1, C Reed3, T Heeren3, S Tumilty2, S Stuver3, C Graham4,5, C Graham4,5, C Horsburgh1,2,3, C Horsburgh1,2,3, C Horsburgh1,2,3, Deborah Cotton*1,2,3, Deborah Cotton*1,2,3, Deborah Cotton*1,2,3, and Hepatitis C, HIV And Related Morbidity (CHARM)
1Boston Univ Sch of Med, MA, US; 2Boston Med Ctr, MA, US; 3Boston Univ Sch of Publ Hlth, MA, US; 4Beth Israel Deaconess Med Ctr, Boston, MA, US; and 5Harvard Med Sch, Boston, MA, US
Background: The prognostic value of serological markers of
fibrosis in predicting liver disease outcomes was assessed in a prospective
cohort study of hepatitis C virus (HCV) -infected subjects with and without HIV
infection.
Methods: All subjects currently being followed in the
cohort were included in the analysis. Liver events were defined as new onset
ascites, bacterial peritonitis, encephalopathy, variceal bleeding, liver decompensation, or liver-related mortality. Sera taken at
the time of enrollment were analyzed for hyaluronic acid and YKL-40. These tests
were compared to simple prognostic indices including Child Pugh (CPT) and MELD
scores, and markers of liver fibrosis—aspartate aminotransferase (AST) /alanine aminotransferase (ALT) ratio, and AST to platelet ratio
index (APRI). The ability of each marker to predict an adverse clinical event
was assessed by the area under the receiver operating characteristic curve
(AUROC). Log rank survival analysis was used to assess these data in a time
dependent manner.
Results: We studied 304 subjects of whom 194 (64%) were
male. The mean age was 44 (±7) years. Of the total, 207 subjects (68%) were
co-infected with HIV. Almost all subjects reported injection drug use as their
HCV risk factor. Median follow-up was 3.1 years. Adverse liver events occurred
in 31 subjects with 25 deaths. There were 26 liver events in the HIV-infected
group versus 5 in the HIV-negative group (p
= 0.08). AUROC for each of the assays or indices analyzed are shown in the table.
Comparison of the values showed hyaluronic acid to be
superior to MELD (p <0.001), but
not significantly different to APRI or CPT score (p >0.05). Survival analysis using the cut-off values showed high
predictive value for all of the tests and scores studied (p <0.001).
Conclusions: Serum markers of liver fibrosis are highly
predictive of adverse liver events in HCV-infected individuals with and without
HIV co-infection. Use of these markers to monitor disease progression and
prognosis warrants further study.
AUROC for Evaluated Indices
and Tests
|
Test
|
AUROC (95%CI)
|
Cut-off value
|
Sens
|
Spec
|
|
HA
|
0.928
(0.885-0.970)
|
99
|
90
|
83
|
|
YKL-40
|
0.764
(0.683-0.846)
|
327
|
71
|
70
|
|
APRI
|
0.897
(0.850-0.944)
|
1.53
|
84
|
85
|
|
AST/ALT
|
0.753
(0.669-0.837)
|
1.35
|
71
|
70
|
|
CPT
|
0.838
(0.742-0.935)
|
6
|
54
|
97
|
|
MELD
|
0.842
(0.771-0.914)
|
9
|
81
|
79
|
CPT: Child Pugh Turcotte score
|
