The severity of serious fibrosis varied between studies, with prevalence of cirrhosis in one study [22] being less than half that in the other studies Seven studies evaluated its performance in the identification of cirrhosis or cirrhosis /severe

fibrosis although only 4 of these reported AUROC values. One study reported results for the identification of patients with no or mild fibrosis. The AUROCs for the 3 studies identifying cirrhosis were discrepant −0.78, 0.80 and 0.93. The median AUC for predicting severe fibrosis/cirrhosis =0.79 (range 0.69-0.93). Overall the LRs and predictive values showed that HA was better at excluding cirrhosis/ severe fibrosis than detecting it, with NPVs consistently high ~90% for cirrhosis.

There are two direct comparisons of a panel find more and HA. These showed differing results. In the larger study [25] there was no significant difference between panel (Fibrotest) and HA at both identifying cirrhosis and moderate /severe fibrosis. In the other study [28] most of the panel tests had greater AUC values in predicting cirrhosis than HA alone (but 95% CI were overlapping) but at lower levels of fibrosis the performance of HA and panels are more similar. Overall HA was better at identifying cirrhosis alone than moderate/severe fibrosis (AUROC ~ 0.80) or milder fibrosis. ii) Other single markers There were more limited data on five other single markers, with only three studies presenting AUROC analyses. Prothrombin buy YAP-TEAD Inhibitor 1 index had high LR + and predictive values in the identification of cirrhosis in two studies. One study reported performance of TIMP1 and

PIIINP in the same population of patients as single markers and as part of a panel. The study found that the AUROC values were next lower than in other studies of the same markers [29]. However this study population differed from the other studies in having a very high alcohol consumption over a long period of time Marker panels Cirrhosis/severe fibrosis (Figure 1, Table 3). Eight studies assessed the performance in detecting cirrhosis/severe fibrosis, five of which reported AUROCs. Four studies were external validations of previously derived panels [25, 27–30]. Several panels (Fibrotest, Fibrometer, Hepascore, ELF) showed promise in detection of cirrhosis with AUROCs >0.9, although one was small (ELF n = 64), and one showed no statistically significant difference to HA in direct comparison (Fibrotest). Common components of these panels are HA (in 3 panels), alpha macroglobulin (in 2 panels), GGT (in 2 panels). One panel (Tran index) reported a very high specificity and PPV compared to other panels.