However it is an important issue and should be borne in mind SRT1720 when looking at results between studies. Clinical implications For preventing and managing

ALD it is important to identify those patients who are drinking hazardously and have clinically silent severe fibrosis/cirrhosis in order to focus interventions, to begin to screen for varices and Hepatocellular carcinoma or to prepare for possible liver transplant. Data presented in this review suggest that marker panels could be used effectively in this situation. It would be clinically useful to patients and clinicians to identify the proportion of hazardous drinkers who have developed liver disease to monitor disease progress more closely and to offer an opportunity for strategies aimed at reduction/abstention. Repeated serum marker measurement showing rise or decline in results may have an impact on lifestyle choices again allowing scope for reduction in alcohol consumption. These are speculative ideas and require further MLN2238 research. This group of patients often has erratic attendance at outpatient and biopsy appointments and may present in settings where invasive tests are inappropriate/difficult (e g prison). Access to non-invasive

tests of liver fibrosis would be useful in the management of such patients. Future research Large studies of patients with ALD need to be designed which can directly compare and validate in external populations, performance of existing markers, the identification of new markers or enhancement of existing tests to identify any, mild or moderate fibrosis. For example, methods such as proteomics and metabonomics may identify markers that can be incorporated into existing or new panels of markers, either in isolation or in combination with quantitative imaging techniques (such as elastography). This process might be facilitated by establishing

an international reference library and quality assurance scheme. The evaluation of diagnostic performance should be accompanied by parallel evaluation of test performance for properties such as reproducibility, stability and linearity. Further work is needed to ascertain the diagnostic performance of markers in primary care setting. The limitations of liver biopsy may create Grape seed extract a glass ceiling for potential non-invasive tests, and future studies should consider use of clinical outcomes as the reference standard. The few studies that have been reported in the literature on performance of serum markers in ALD predicting clinical outcomes rather than fibrosis have shown good performance for some panels of serum markers [27]. Fibrotest, Hepascore and Fibrometer A has been shown to be able to predict liver related mortality at 5 years and 10 years (AUC = 0.79 (95% CI 0.68,0.86) 0.77(95% CI 0.69,0.85) 0.80(95% CI 0.71,0.87) respectively, at least as well as biopsy (AUC 0.77 (95% CI 0.70,0.83). Forns index, APRI and FIB 4 had lower performance in predicting liver related mortality -AUCs 0.40 (95% CI 0.30,0.49), 0.