Screening for liver fibrosis in primary care: Focus on subjects above 40 and with metabolic risk factors.

Chronic liver diseases (CLD) are an important cause of the overall morbidity and mortality and account for approximately 2 million deaths per year worldwide. The Risk factors for CLD are well known and highly prevalent: 43% of the global population are current drinkers, and two‐thirds engage in heavy episodic drinking. Furthermore, 8.5% of the global population have diabetes, one‐third are overweight and 10% are obese. The commonest causes of CLD are alcohol‐related liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD), followed by chronic hepatitis B and C. Despite the vast number of people at risk for ALD and NAFLD, 75% of the patients are still diagnosed at an advanced stage of disease when they already have decompensated cirrhosis. There is thus an urgent need to change the paradigm of current diagnosis of CLD: subjects at risk should be screened and diagnosis of CLD should be made early before cirrhosis occurs. This would enable initiation of specific measures or treatments to prevent disease progression and improve survival, including antiviral therapy for HBV or HCV, alcohol abstinence in ALD, lifestyle changes and treatment of diabetes and obesity in NAFLD. The development of non‐invasive methods for detecting liver fibrosis has been a major advance in Hepatology over the last decade. Transient elastography (TE), allowing liver stiffness measurement (LSM), is a well validated and widely available point‐of‐ care technique that seems well suited for such purpose. In their pioneer proof‐of‐concept study, Roulot et al. have shown that TE was an acceptable and accurate tool for detecting liver fibrosis and cirrhosis not only in patients with known CLD but also in presumably healthy subjects without known liver disease. In this issue of the UEG journal, Llop et al. screened for liver fibrosis, using TE, 11,440 adult subjects from the general population, seen in 18 primary care centres in Spain. This study is a nested study within the PREVHEP‐ETHON (Epidemiological sTudy of Hepatic infectiONs; NCT02749864) Cohort, designed to evaluate the prevalence of HCV in a representative cohort of the Spanish population between July 2015 and April 2017. Stages of fibrosis were defined according to established LSM criteria, as follows: >8 kPa = significant fibrosis, >10 kPa = advanced fibrosis or suggestive compensated advanced chronic liver disease (cACLD), and >15 kPa = cirrhosis or highly suggestive cACLD. The cohort was composed of mostly middle age women (mean age 50 years; female 58%), with approximately 22% being obese, 9% having harmful alcohol use, and 2% viral hepatitis. Overall, more than 5% had LSM values suggestive of fibrosis, with prevalence of significant fibrosis, advanced fibrosis and cirrhosis of 5.6%, 2.9% and 1.2%, respectively, a finding consistent with those of previous European studies. Like in these studies, age (above 50) was a major risk factor for the presence of fibrosis. Interestingly, when the authors analysed the subgroup of patients below 40, prevalence of significant fibrosis, advanced fibrosis and cirrhosis was almost twice lower than in the total population: 3.2%, 1.0% and 0.3%, respectively. These findings are in keeping with those of a 2.7% prevalence of significant fibrosis (LSM > 8 kPa) in a recently published cohort of young UK adults. Overall, these results suggest that liver fibrosis rarely occurs before 40 and that screening for fibrosis should focus on populations above 40. Given, the large sample of the cohort, the largest to date, the authors were able to perform subgroup analyses to focus on subjects without known liver disease. When they analysed the subgroup (n = 10,190) without harmful alcohol consumption or viral hepatitis, obese subjects showed a higher prevalence of significant fibrosis (9.4% vs. 3.7%; p < 0.001), advanced fibrosis (5.3% vs. 1.8%; p < 0.001) and cirrhosis (1.7% vs. 0.9%; p = 0.003). Interestingly, the prevalence of fibrosis increased with the number of metabolic risk factors and metabolic unhealthy status as previously reported. For instance, prevalence of significant fibrosis and cirrhosis increased from 2.3% to 19.3% and 0.6% to 2.9%, respectively, when 4 risk factors (obesity, type 2 diabetes, hypertension and dyslipidemia) were present as compared to no risk factor. Similarly, prevalence of significant fibrosis and cirrhosis increased from 2.7% to 10.2% and 0.5% to 1.9%, respectively, in metabolically unhealthy obese as compared to metabolically healthy non obese. Unfortunately, controlled attenuation parameter (CAP) was not measured at the time of LSM, thus no data regarding the prevalence of steatosis was available. However, NAFLD likely was the leading cause for underlying liver disease in these patients. In addition, in subjects with harmful alcohol use, metabolic syndrome remained an independent risk factor for significant fibrosis and cirrhosis, as already suggested. Finally, it should be stressed that a non‐negligible proportion of patients in this cohort (n = 9877, 86.3%) had normal transaminase levels. Interestingly, the prevalence of significant fibrosis, advanced fibrosis, and cirrhosis (4.6% 2.1% and 1%, respectively), as well as risk