A Pragmatic Approach Identifies a High Rate of Nonalcoholic Fatty Liver Disease With Advanced Fibrosis in Diabetes Clinics and At‐Risk Populations in Primary Care

Abstract

Noninvasive serum biomarkers (nonalcoholic fatty liver disease fibrosis score [NFS], fibrosis 4 score [FIB‐4], or enhanced liver fibrosis [ELF] test) are recommended as first‐line tools to determine the risk of advanced fibrosis in nonalcoholic fatty liver disease. We aimed to assess the utility of a pragmatic approach to screening for clinically significant fibrosis in primary care and diabetes clinics. We recruited 252 patients from an endocrine clinic or primary care facility. Anthropometric measurements, ELF test, ultrasound, and liver stiffness measurements (LSMs) were performed. Clinically significant fibrosis was defined as LSM ≥8.2 kPa or ELF ≥9.8. A subgroup of patients underwent liver biopsy (n = 48) or had imaging diagnostic of cirrhosis (n = 14). Patients were 57.3 ± 12.3 years old with a high prevalence of metabolic syndrome (84.5%), type 2 diabetes (82.5%), and body mass index (BMI) ≥40 kg/m2 (21.8%). LSM met quality criteria in 230 (91.3%) patients. NFS and FIB‐4 combined had a high negative predictive value (90.0%) for excluding LSM ≥8.2 kPa. However, 84.1% of patients had indeterminate or high NFS or FIB‐4 scores requiring further assessment. LSM ≥8.2 kPa and ELF ≥9.8 were present in 31.3% and 28.6% of patients, respectively. Following adjustment for age, BMI, sex, and presence of advanced fibrosis, older age was independently associated with ELF ≥9.8 (adjusted odds ratio, 1.14; 95% confidence interval, 1.06‐1.24), whereas increasing BMI was independently associated with LSM ≥8.2 kPa (adjusted odds ratio, 1.15; 95% confidence interval, 1.01‐1.30). Concordant LSM <8.2 kPa and ELF <9.8 and concordant LSM ≥8.2 kPa and ELF ≥9.8 had a high negative predictive value (91.7%) and positive predictive value (95.8%) for excluding and identifying clinically significant fibrosis, respectively. Conclusion: Simple scoring tools alone lack accuracy. LSM accuracy is influenced by severe obesity, whereas age impacts the ELF test. Further studies are required to confirm whether combining LSM and ELF may enhance accuracy and confidence in identifying clinically significant fibrosis. (Hepatology Communications 2018; 00:000‐000)

Nonalcoholic Fatty Liver Disease: Interface Between Primary Care and Hepatology Clinics

“…Among the 143 patients referred for NAFLD, steatosis or fatty liver, age‐specific FIB‐4 and NFS scores were provided or could be calculated using information in the referral for 54 (37.8%) patients. Twenty‐one patients had concordant “low” scores; the negative predictive value of NFS and FIB‐4 in combination for excluding definite/probable advanced fibrosis was 90.5%. Compared to those with concordant “low” scores at referral, patients with “indeterminate”/“high” FIB‐4 and/or NFS scores were 5.7 (95% CI: 1.1‐28.9; P = 0.036) times more likely to be diagnosed as having definite or probable advanced fibrosis.…”

“…In the hepatology clinic, patients underwent a clinical assessment that included anthropometric measurements, laboratory tests (routine biochemical, hematological, and serological assays), transient elastography, and liver imaging (computed tomography, magnetic resonance imaging, and/or ultrasound). Transient elastography was performed using FibroScan technology (Echosens, Paris, France) as previously described . At our center, LSM ≥8.2 kPa are used to identify clinically significant fibrosis (LSM ≥ 9.5 kPa for advanced fibrosis, and >13 kPa to indicate cirrhosis) .…”

Non‐invasive tests for liver fibrosis in NAFLD: Creating pathways between primary healthcare and liver clinics

“…It should be kept in mind that FIB‐4 and NFS do not adequately rule‐in advanced fibrosis (with a high rate of false‐positive results), thus further assessment with a more specific test is required in case of positive results. Several tests have been proposed for these cases, including ELF TM , Fibrometer® and TE . For instance, in a large, prospective study of a UK primary care referral pathway in 1,452 patients with NAFLD, Srivastava et al recently showed that a two‐step pathway (FIB‐4 followed by ELF TM performed in those with an indeterminate (score 1.3‐3.25) FIB‐4) reduced unnecessary referrals to liver specialists by 81%, and also markedly increased (five‐fold) the accurate referral of cases with advanced fibrosis.…”

“…Several tests have been proposed for these cases, including ELF TM , 24,25 Fibrometer® 26 and TE. 23,[25][26][27] For instance, in a large, prospective study of a UK primary care referral pathway in 1,452 patients with NAFLD, Srivastava et al 24 recently showed that a two-step pathway (FIB-4 followed by ELF TM performed in those with an indeterminate (score 1.3-3.25) FIB-4) reduced unnecessary referrals to liver specialists by 81%, and also markedly increased (five-fold) the accurate referral of cases with advanced fibrosis. Importantly, because of the dual FIB-4 or NFS cut-offs, a significant proportion of patients (around 30%) fall in the intermediate risk category and cannot be correctly classified (indeterminate results).…”

“…28 Also, the use of FIB-4 or NFS may lead to a higher proportion of patients in the intermediate category. 25 Thus, the direct use of a more specific test seems more suited to this setting ( Figure 2B). This screening strategy has been tested by systematically performing liver stiffness measurements using TE in consecutive type 2 diabetes patients seen at diabetes clinics in Hong Kong (n = 1918) 29 and in France (n = 705).…”