Altering retinol binding protein 4 levels in hepatitis C: Inflammation and steatosis matter

Abstract

Both hepatitis C virus (HCV) infection and retinol-binding protein 4 (RBP4) might contribute to insulin resistance (IR), how RBP4 links to IR in HCV infection remain elusive. A joint study of a prospective cohort of 842 chronically HCV-infected (CHC) patients (with 842 controls) and a line of HCV core transgenic mice was conducted. Of 842 patients, 771 had completed anti-HCV therapy and 667 had sustained virological responses (SVRs). Compared with controls, CHC patients had lower RBP4 levels. At baseline, age (95% CI β: −0.87~−0.317), BMI (0.516~2.036), triglycerides (0.03~0.127), neutrophil-to-lymphocyte ratio (NLR) (1.561~7.327), and estimated glomerular filtration rate (eGFR) (−0.342~−0.149) levels were associated with RBP4 levels in CHC patients. At 24-week post-therapy, male sex (0.652~8.129), BMI (0.199~1.254), triglycerides (0.039~0.088), uric acid (0.599~3.067), eGFR (−0.247 ~−0.14) levels, and fibrosis-4 (−3.602~−0.039) scores were associated with RBP4 levels in SVR patients; compared with baseline, except genotype 3 HCV-infected patients, SVR patients had increased RBP4 levels, which were comparable with controls, while no HOMA-IR index alteration was noted after SVR. The HCV core transgenic mice exhibited nonobese hepatic steatosis, had higher hepatic RBP4 expression, higher serum levels of RBP4 and triglycerides, but comparable HOMA-IR levels than non-transgenic littermates. In conclusion, steatosis, sex, age, uric acid, NLR, and FIB-4 levels were associated with HCV-related RBP4 levels; BMI, triglycerides, and eGFR levels were associated with non-HCV-related RBP4 levels. Reversal of low RBP4 levels after SVR was evident in non-genotype 3 HCV-infected patients. Steatosis and inflammation linked with metabolic alteration other than IR, determined RBP4 levels in HCV-infected patients.

Identification of the Representative Primary Biliary Cholangitis Cohort in Taiwan: A Comparison of Four Nationwide Cohorts

“…Second, hepatitis B virus (HBV) infection is hyperendemic, and hepatitis C virus (HCV) infection is wide spread in Taiwan [ 26 ]. Both HBV [ 27 ] and HCV infections [ 28 , 29 ] are associated with many hepatic and extrahepatic complications, which might bias the outcomes in all four PBC cohorts. Third, some primary sclerosing cholangitis (PSC) patients with cirrhosis might have been categorized into C4, while the portion of PSC in C4 should be negligible, since PSC is very rare in Taiwan [ 30 ].…”

Association between Hepatitis C Virus Infection and Esophageal Cancer: An Asian Nationwide Population-Based Cohort Study

“…Hepatitis C virus (HCV) is a human pathogen responsible for acute and chronic liver disease that infects an estimated 150 million individuals worldwide [ 8 ]. In addition to hepatic complications such as steatosis, cirrhosis, and hepatocellular carcinoma (HCC), HCV causes extrahepatic complications, including mixed cryoglobulinemia [ 9 ], dyslipidemia, diabetes [ 10 ], obesity, cardiovascular events [ 11 ], and neurological manifestations [ 12 ]. Moreover, HCV infection is associated with many extrahepatic malignancies, including lymphoid [ 13 ], head and heck [ 14 ], thyroid [ 15 ], lung, pancreas, kidney [ 13 ], and gastric cancers [ 16 ], B-cell non-Hodgkin’s lymphomas, and intrahepatic cholangiocarcinoma [ 17 ].…”