How to identify the NASH patient?
The fibrosis-4 (FIB-4) index is a biomarker test that uses outcomes from standard and easily available blood serum tests to generate a score that is correlated with the degree of liver damage in people with a variety of liver diseases. A score can be derived from age, AST and ALT, and platelet counts, and can be used as an indicator of NASH. However, only 36% of PCPs had knowledge of either this or the NAFLD Fibrosis Score (NFS), a non-invasive scoring system that takes into consideration age, hyperglycemia, body mass index, platelet count, albumin and AST/ALT ratio, as diagnostic determinants of NAFLD. In endocrinologists and gastroenterologists, these tests were familiar to 58% and 82%, respectively. However, only 18% of PCPs, 30% of endocrinologists and 65% gastroenterologists reported using these tests in clinical practice. There were significant differences between physician groups (P < 0.0001) in both of these cases. Given that many physicians do not opt for liver biopsy, these non-invasive tests could be crucial to more widespread patient identification. Both of these tests are recommended in the 2018 guidelines as clinically useful tools and decision aids that should be used to differentiate patients at higher risk of advanced fibrosis or cirrhosis. Thus, the lack of awareness in this area is of real concern.
Imaging studies are also an important part of the workup for NAFLD, and while imaging is used by 98% of gastroenterologists, only 83% and 82% of endocrinologists and PCPs, respectively, use the technique. Again, a significant difference (P < 0.0004) was seen between physician groups. Outside of liver biopsy in the gastroenterology cohort, vibration-controlled transient elastography [VCTE (FibroScan®)] and computed tomography-guided ultrasound were the techniques most commonly employed (Figure 3).
Figure 3 Diagnostic techniques used in non-alcoholic steatohepatitis physicians of different specialties.
MRE: Magnetic resonance elastography; VCTE: Vibration-controlled transient elastography; CT: Computed tomography.
While the survey sample was small, some clear trends emerged. Although the prevalence of NAFLD and NASH is high in the general population, there are no widely accepted screening processes, even in high-risk patients. As well as exacerbating under-diagnosis and under-treatment, the absence of a standardized screening system contributes to the inadequacy of the numbers of patients available for clinical trials. Currently, trials in NAFLD and NASH tend to recruit and enroll patients who already have, or are very likely to have, a diagnosis. Therefore, to optimize enrollment, an improved process for patient identification would be of great value. This need not involve invasive procedures; rather, the focus should be on identifying those individuals who are most likely to meet clinical trial eligibility criteria. This key subset of patients then can be referred for biopsy to obtain a definitive histological diagnosis. As up to 25% of patients with NAFLD are expected to show evidence of NASH on biopsy, such a screening algorithm is perhaps the most efficient and cost-effective way to identify appropriate patients. It is estimated this process would allow the screening of up to 120000 patients annually, which would greatly aid drug developers and researchers in populating clinical studies in the coming years (Figure 4).
Figure 4 The non-alcoholic steatohepatitis patient recruitment screening pathway.
LFT: Liver function test; FBC: Full blood count; INR: International normalized ratio; PT: Prothrobmin time; PTT: Partial thromboplastin time; CAP: Controlled attenuation parameter; PCV: Porcine circovirus; NAFLD: Non-alcoholic fatty liver disease; FIB: Fibrosis.