Liver fibrosis in conjunction with the prosteatotic PNPLA3 variant affects quality of life in patients with NAFLD: prospective liver stiffness-based study

Background:

Non-alcoholic fatty liver disease (NAFLD) belongs to the most common liver diseases, and the PNPLA3 gene variant p.I148 M is associated with higher hepatic fat contents and liver fibrosis. Here, we investigate if hepatic fibrosis and steatosis as well as the PNPLA3 variant affect Health-related Quality of Life (HRQoL) in patients with fatty liver diseases.

Methods:

Prospectively, we recruited individuals with NAFLD/diabetes at our center. All patients filled the battery of HrQoL questionnaires, i.e. SF36, STADI, FIS, PHQ9, and RIS (Regensburg Insomnia Scale). Hepatic steatosis and fibrosis were assessed non-invasively by controlled attenuated parameter (CAP) and liver stiffness measurement (LSM). Patients were stratified using CAp ≥248dB/m, LSM ≥9.2 kPa and LSM ≥13.0 kPa as cut-offs for significant steatosis, fibrosis and cirrhosis, respectively. The variant PNPLA3 p.I148 M was genotyped using a specific TaqMan assay.

Results:

Among 107 patients (57 women, age 60 ± 13 years) 76% presented with significant steatosis, 23% of these showed at least significant fibrosis and 13% cirrhosis. LSM correlated significantly (all P < 0.05) with several QoL aspects: physical functioning (SFpfi), physical component summary (SFPCS), anxiety and depression at present (STADI states) and as personal characteristic (STADI traits). Patients with significant fibrosis scored worse in physical scales and often showed characteristics of major depressive disorder (according to PHQ9) (all P < 0.05). The differences in HRQoL were most pronounced in patients with cirrhosis, who scored worst in physical and mental health scores. Notably, the PNPLA3 polymorphism significantly affected patients' quality of life: Carriers of the prosteatotic PNPLA3 variant were characterized by higher level of physical fatigue (FIS), reported impairments in physical functioning in everyday life and during physical activity, felt more often affected by physical pain (Sfpain) and scored worse in SFPCS (all P < 0.05).

Conclusions:

LSM allows the detection of patients with NAFLD who have impaired quality of life, including depressive states. Since not only HRQoL but also treatment success might be affected, special attention should be paid to identify depressive comorbidities in NAFLD patients. Finally, the PNPLA3 gene variant might represent the first genetic marker for worse HRQoL in the context of NAFLD.