Blood Test May Predict Response to HCV Treatment

Lara C. Pullen, PhD

May 18, 2015

Serum levels of oxidized low-density lipoprotein (oxLDL) may predict sustained virologic response (SVR) in patients with chronic hepatitis C virus (HCV) infection who receive interferon (IFN)-based therapy. Although an association between LDL and SVR has been documented previously, the new data uncover a mechanism for the link: oxLDL limits the cell-to-cell spread of infection, thereby improving the likelihood of SVR.

"From a clinical point of view, we have identified a novel predictor of SVR after interferon-based treatment of chronic hepatitis C. Although interferon-free regimens now offer higher SVR rates and fewer side effects compared with interferon-containing regimens, they are also much more costly. Thus, peg-IFN may continue to be used for some time, especially in settings where cost is an issue," write Philipp Solbach, MD, from the Medizinische Hochschule Hannover in Germany, and colleagues.

The researchers published the results of their HCV and serum oxLDL study in the May issue of Cellular and Molecular Gastroenterology and Hepatology. They evaluated 379 patients from the Individually Adapted Therapy Duration for the Treatment of Chronic Hepatitis C Genotype 1 Infection (INDIV-2) study.

The investigators found that baseline oxLDL in patients with chronic HCV genotype 1 infection is an independent predictor of response to the combination pegylated interferon plus ribavirin (peg-IFN/RBV) treatment. Median serum oxLDL was 7.1 mU/L in patients who achieved SVR compared with 5.9 mU/L in patients who did not achieve SVR (P < .0001).

The authors went on to investigate an explanation for the association. Previous studies have suggested that oxLDL levels might reflect inflammation in patients infected with HCV. Alternatively, the investigators questioned whether oxLDL might increase the sensitivity of replicating HCV to interferon.

Neither of these hypotheses proved to be correct. Instead, the investigators determined that the endogenous oxLDL acts as an HCV entry inhibitor, and thus helps drive the loss of infected cells during the untreated steady state.

Because the newer therapies are so much more expensive than IFN-based regimens, the authors suggest that IFN therapies will continue to be used, and therefore there is a need for a tool that distinguishes those individuals who are likely to respond to IFN therapy from those who will require the newer drugs.

However, in an accompanying editorial, Markus von Schaewen, MD, and Alexander Ploss, PhD, from Princeton University in New Jersey, disagree about the importance of the biomarker and focus attention instead on the importance of the virology.

"Clinicians, especially in resource-limited environments, may take oxLDL or LDL serum levels into consideration for treatment decisions although these predictors are unlikely to broadly affect such decisions in real-world settings. The significance of this study lies more in adding to our understanding the pathophysiology of HCV. The authors' data indicate that oxLDL is likely not only the molecule responsible for the previously observed positive correlation between LDL serum levels and SVR in IFN-based treatment regimens, but also that this effect is possibly due to an oxLDL-mediated inhibition of HCV cell-to-cell spread," write Dr von Schaewen and Dr Ploss.

This study was funded by a grant from the Germany Center for Infection. Several coauthors have various financial relationships with MSD/Merck and Roche. The other authors and editorialists have disclosed no relevant financial relationships.

Cell Mol Gastroenterol Hepatol. 2015;1:285-294. Article full text, Editorial full text

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