Sofosbuvir-Based Therapy Leads to Rapid LOXL2 Decline in Cirrhosis

SAN FRANCISCO, CA—Rapid declines in serum/plasma lysyl oxidase-like-2 (LOXL2) levels were seen in patients with hepatitis C virus (HCV) and cirrhosis who were treated with sofosbuvir (SOF)-based therapy, reported authors of a new study presented at The Liver Meeting® 2015.

The declines were “consistent with a theoretical decline in hepatic fibrogenesis,” noted lead study author Nezam H. Afdhal, MD, from Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, and coauthors. 

“Decreases in LOXL2 levels were observed by the end of treatment and were sustained during the post-treatment follow-up period,” Dr. Afdhal noted. “A greater LOXL2 decline was associated with higher baseline LOXL2 and ALT levels, prior transplantation, and with serum compared to plasma samples.”

Serum LOXL2 is a “key driver” in liver fibrosis pathways, Dr. Afdhal explained; LOXL2 levels are associated with hepatitis B virus (HBV)-related fibrosis and LOXL2 levels decline with tenofovir therapy. 

The researchers sought to assess changes in LOXL2 levels among patients with HCV cirrhosis who experience sustained virologic response (SVR) to sofosbuvir-based therapy.They studied a total of 371 HCV-infected cirrhotic patients who had achieved SVR12 in 4 trials:

·         Study GS-US-337-0121 (SIRIUS): ledipasvir (LDV)/SOF + ribavirin (RBV) for 12 vs. LDV/SOF for 24 weeks 

·         Study GS-US-337-0123 (SOLAR-1): LDV/SOF + RBV for 12 weeks vs. 24 weeks

·         Study GS-US-334-0125: SOF + RBV for 48 weeks

·         Study GS-US-334-016: SOF + RBV for 24 weeks

LOXL2 levels in serum or plasma were taken at baseline, end of treatment, and SVR12, using VIDAS® immunoassay. A “LOXL2 response” was defined as a ≥25% decline from baseline to SVR12. 

A total of 96% of patients had genotype 1 HCV, and 4% had genotypes 2, 3 or 4, Dr. Afdhal reported.

“LOXL2 levels decreased in 83% of patients following SOF-based antiviral therapy,” reported Dr. Afdhal. “The median relative decline from baseline to SVR12 was 23%.”

In a multivariate model, LOXL2 response was significantly associated with baseline LOXL2 level (odds ratio [OR] 2.69; 95% CI: 1.89, 3.82; P<0.001), prior liver transplantation (OR 2.08; 95% 1.04, 4.17; P=0.039), baseline ALT (U/L; OR 1.69; 95% CI: 1.09, 2.61; P=0.019), and type of specimen (serum vs. plasma; OR 11.8, 95% CI: 3.8, 37.0; P<0.001).