Professional society guidelines recommend semiannual screening for hepatocellular carcinoma (HCC) in patients with cirrhosis; however, studies suggest underuse of screening in clinical practice. Our study's aim was to characterize reasons for HCC screening underuse among patients with cirrhosis. We conducted a retrospective cohort study of patients with cirrhosis diagnosed with HCC in two large health systems from 2011 to 2019. We classified screening receipt as consistent, inconsistent, or no screening in the year before HCC diagnosis. We categorized reasons for screening underuse as a potential failure at each of the following steps required for HCC screening: receipt of regular outpatient care, recognition of liver disease, recognition of cirrhosis, screening orders in patients with cirrhosis, and adherence to screening ultrasound appointments. Among 1,014 patients with cirrhosis with HCC, only 377 (37.2%) had regular outpatient care in the year before HCC presentation. Consistent screening was observed in 93 (24.7%) patients under regular outpatient care, whereas 161 (42.7%) had inconsistent screening and 123 (32.6%) no screening. We found screening underuse related to failures at each step in the screening process, although nearly half (49.6%) were due to lack of screening orders in patients with known cirrhosis. Conclusion: The most common reasons for HCC screening underuse in patients with cirrhosis are lack of regular outpatient care and lack of screening orders in those with known cirrhosis, highlighting the need for interventions targeted at these steps to increase HCC screening use. (Hepatology Communications 2021;0:1-9).
Nonalcoholic steatohepatitis
(NASH) is the fastest growing cause
of hepatocellular carcinoma (HCC) in the United States. Changes in
N
-glycosylation on specific glycosites of serum proteins
have been investigated as potential markers for the early detection
of NASH-related HCC. Herein, we report a glycopeptide with a Sialyl
Lewis structure derived from serum haptoglobin (Hp) as a potential
marker for NASH related HCCs among 95 patients with NASH, including
46 cirrhosis, 32 early-stage HCC, and 17 late-stage HCC. Hp immuno-isolated
from patient serum was analyzed using LC-HCD-PRM-MS/MS followed by
data analysis
via
Skyline software. Two glycopeptides
involving site N184 and four glycopeptides involving site N241 were
significantly changed in patients with HCC
vs
NASH
cirrhosis (
P
< 0.05). The two-marker panel using
N
-glycopeptide N241_A4G4F2S4 showed the best performance
for HCC detection when combined with α-fetoprotein (AFP), with
an improved estimated area under the curve (AUC) = 0.898 (95% CI:
0.835, 0.951), compared to the AUC of 0.790(95% CI, 0.697 0.872) using
AFP alone (
P
= 0.048). At 90% specificity, the combination
of N241_A4G4F2S4 + AFP had an improved sensitivity of 63.3%, compared
to the sensitivity of 52.3% using AFP alone. When using three markers,
the panel of AFP + N241_A2G2F1S2 + N241_A4G4F2S4 yielded an estimated
AUC of 0.928 (95% CI: 0.877, 0.970). Our findings indicated that N241_A4G4F2S4
may play an important role in distinguishing HCC from NASH cirrhosis.
Aberrant specific N-glycosylation, especially the increase in fucosylation on specific peptide sites of serum proteins have been investigated as potential markers for diagnosis of nonalcoholic steatohepatitis (NASH)-related HCC. We have combined a workflow involving broad scale marker discovery in serum followed by targeted marker evaluation of these fucosylated glycopeptides. This workflow involved an LC-Stepped HCD-DDA-MS/MS method coupled with offline peptide fractionation for large-scale identification of N-glycopeptides directly from pooled serum samples (each n=10) as well as differential determination of N-glycosylation changes between disease states. We then evaluated the fucosylation level of the glycoprotein ceruloplasmin among 62 patient samples (35 cirrhosis, 27 early-stage NASH HCC) by LC-Stepped HCD-PRM-MS/MS to quantitatively analyze 18 targeted glycopeptides. Of these targets, we found the ratio of fucosylation of a tri-antennary glycopeptide from site N762, involving N762_ HexNAc(5)Hex(6)Fuc(2)NeuAc(3) (P=0.0486), increased significantly from cirrhosis to early HCC. This fucosylation ratio of a tri-antennary glycopeptide in CERU could be a potential biomarker for further validation in a larger sample set and could be a promising candidate for early detection of NASH HCC.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.