icon-folder.gif   Conference Reports for NATAP  
  The International Liver Congress™
EASL - European Association for the
Study of the Liver
June 23-26 2021
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NASH Fibrosis Rate 2% in General Population
of Spain-1.3% With Treatable Fibrosis

  EASL International Liver Congress, June 23-26, 2021
Mark Mascolini
By merging calculations from two large Spanish databases, researchers determined that 2% of the general population in Spain has nonalcoholic steatohepatitis (NASH) with significant (F2-F4) fibrosis [1]. About 1.3% of the population has treatable (F2-F3) NASH fibrosis.
The multicenter Spanish team that conducted this study noted that metabolic-associated fatty liver disease (MAFLD) has become the most prevalent chronic liver disease in the world, affecting about one quarter of the global population. But the precise prevalence of MAFLD or NASH (the progressive form of MAFLD) remains to be established country by country. Also, the relative contribution of MAFLD to NASH is still uncertain.
The Spanish researchers aimed to produce an updated and reliable estimate of NASH prevalence in Spain's general population. The study strategy involved combining data from two cohorts, first, a general-population cohort of 12,246 people (ETHON) who had transient elastography (TE) in 2015-2017. TE, the researchers noted, is the most widely used noninvasive test to estimate liver fibrosis rates in population-based studies. The second cohort was a real-world group of 501 people with biopsy-proved NASH from 5 Spanish tertiary care centers in 2015-2020.
ETHON provided 11,440 cohort members with reliable TE measures. Median age in this group stood at 54 years and 58% were women. Most cohort members, 88%, were Caucasian, and median body mass index (BMI) measured 26.1 kg/m2, putting most cohort members in the overweight or obese ranges. Median liver stiffness measure (LSM) stood at 4.5 kPa (normal is 2 to 6 kPa [2]) and median core attenuation parameter (CAP) at 247 dB/m (steatosis grade S1, the least advanced grade; see [2]). The researchers believe CAP from transient elastography (TE) is a sensitive means of detecting steatosis.
Among these 11,440 people from Spain's generation population, 5.61% has an LSM at or above 8 kPa (indicating F2 or greater fibrosis with NASH). The researchers focused on this group of 643 people for further study. To figure the proportion of F2-F4 NASH attributable to MAFLD, the researchers eliminated people with other causes of F2-F4 fibrosis, like viral hepatitis and alcohol use, then calculated the ratio of remaining patients to total patients with LSM at or above 8 kPa. This math yielded a MAFLD-attributable proportion of 57.3%.
Next the research team multiplied the 5.61% general population prevalence of F2-F4 fibrosis with NASH by 0.573 (the 57.3% MAFLD-attributable proportion) to estimate that 3.21% of the general population with LSM at or above 8 kPa and CAP at or above 250 dB/m has F2-F4 NASH fibrosis attributable to MAFLD.
The investigators then turned to the 501-person cohort with biopsy-proved NASH and determined proportions with F0, F1, F2, F3, and F4 fibrosis in four LSM ranges: 8-10 kPa, 10.1-15 kPa, 15.1-20 kPa, and 20+ kPa. The proportion of people with advanced fibrosis climbed steadily in each higher LSM bracket. But even among people in the most advanced LSM group (20+ kPa), 39% still did not have cirrhosis (F4 fibrosis).
Of these 501 people with biopsy-proved NASH, 389 (78%) had an LSM at or above 8 kPa. Among these 389 cohort members, 246 (63%) had F2 or worse fibrosis and 85 (21.8%) had F4 fibrosis. Fifty-two of the 389 people (13.4%) with an LSM at or above 8 kPa were F0, 91 (23.4%) were F1, 70 (18.0%) were F2, and 91 (23.4%) were F3.
Finally, the researchers merged results in cohort 1 (general population) and cohort 2 (biopsy-proved NASH) to figure that 2.03% of the general population has significant (F2-F4) NASH fibrosis, 1.33% has treatable (F2-F3) NASH fibrosis, and 0.70% has cirrhosis (F4).
The multicenter team noted that their study is limited by the arbitrary choice of a CAP threshold of 250 dB/m; the literature yields no clear consensus on the optimal threshold. And because of the makeup of their study populations, the researchers counseled that results should be applied with caution to multiethnic populations and populations with higher prevalence of alcoholic disease.
But with those limitations in mind, the investigators believe their estimates "provide an accurate picture of the current prevalence of NASH in Spain" based on the biggest European population-based and biopsy-proved NASH numbers analyzed to date. They hope their findings offer a good reference point for therapeutic planning in European populations when NASH therapies become available.
1. Rivera J, Calleja JL, Aller R, et al. Prevalence estimation of significant fibrosis due to non-alcoholic steatohepatitis combining transient elastography and histology. EASL International Liver Congress, June 23-26, 2021. Abstract OS-2337.
2. Memorial Sloan Kettering Cancer Center. Understanding your FibroScan results. https://www.mskcc.org/cancer-care/patient-education/understanding-your-fibroscan-results