Effects of proprotein convertase subtilisin/kexin type-9 inhibitors on fatty liver

BACKGROUND: Many studies have investigated the progression of nonalcoholic fatty liver disease (NAFLD) and its predisposing risk factors, but the conclusions from these studies have been conflicting. More challenging is the fact that no effective treatment is currently available for NAFLD. AIM: To determine the effects of proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibitors on fatty infiltration of the liver. METHODS: This retrospective, chart review-based study was conducted on patients, 18-year-old and above, who were currently on PCSK9 inhibitor drug therapy. Patients were excluded from the study according to missing pre- or post-treatment imaging or laboratory values, presence of cirrhosis or rhabdomyolysis, or development of acute liver injury during the PCSK9 inhibitor treatment period; the latter being due to false elevation of liver function markers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Radiographic improvement was assessed by a single radiologist, who read both the pre- and post-treatment images to minimize reading bias. Fatty infiltration of the liver was also assessed by changes in ALT and AST, with pre- and post-treatment levels compared by paired t-test (alpha criterion: 0.05). RESULTS: Of the 29 patients included in the study, 8 were male (27.6%) and 21 were female (72.4%). Essential hypertension was present in 25 (86.2%) of the patients, diabetes mellitus in 18 (62.1%) and obesity in 15 (51.7%). In all, patients were on PCSK9 inhibitors for a mean duration of 23.69 ± 11.18 mo until the most recent ALT and AST measures were obtained. Of the 11 patients who received the radiologic diagnosis of hepatic steatosis, 8 (72.73%) achieved complete radiologic resolution upon use of PCSK9 inhibitors (mean duration of 17.6 mo). On average, the ALT level (IU/L) decreased from 21.83 ± 11.89 at pretreatment to 17.69 ± 8.00 at post-treatment (2-tailed P = 0.042) and AST level (IU/L) decreased from 22.48 ± 9.00 pretreatment to 20.59 ± 5.47 post-treatment (2-tailed P = 0.201). CONCLUSION: PCSK9 inhibitors can slow down or even completely resolve NAFLD.