In the Journals

SVR after HCV therapy reduces extrahepatic mortality, manifestations

Results of a recent systematic review and meta-analysis showed that sustained virologic response after hepatitis C therapy can reduce extrahepatic manifestations including insulin resistance and cardiovascular risks.

“Extrahepatic manifestations in HCV-infected patients are either rare but very severe on the short term ... or very frequent with a potential severity on the mid-long term,” Patrice Cacoub, MD, from the Hôpital La Pitié-Salpêtrière, France, and colleagues wrote. “In most cases, they are independent of the severity of the liver disease. Antiviral therapy can reduce hepatic manifestations of HCV and also many extrahepatic manifestations related to HCV when SVR is achieved.”

Cacoub and colleagues conducted a search of the Embase and Medline databases for studies published between 1989 and June 2017. They included 48 studies in the final meta-analysis.

Analysis of four studies showed that SVR correlated with a significant reduction in extrahepatic mortality (OR = 0.44; 95% CI, 0.28-0.67) with little heterogeneity and moderate strength of evidence.

Data from another four studies showed that SVR had a significant effect on insulin resistance among patients without diabetes (OR = 0.42; 95% CI, 0.33-0.53) with homogeneity and moderate strength of evidence. Additionally, seven studies showed that SVR had a significant protective effect on diabetes frequency at follow-up (OR = 0.34; 95% CI, 0.21-0.56) with moderate strength of evidence.

Regarding cryoglobulinemia vasculitis, SVR had a significant effect on complete remission (OR = 20.76; 95% CI, 6.73-64.05) and correlated with any observed improvement (OR = 27.24; 95% CI, 10.99-67.53).

One study showed that SVR had a significant effect on the incidence of major adverse cardiovascular events (OR = 0.37; 95% CI, 0.59-0.84) and another showed a significant reduction in the incidence of ischemic events (OR = 0.7; 95% CI, 0.07-0.31).

Though limited to one large data set, the researchers also found that SVR after interferon-based therapy reduced the risk for renal impairment events (OR = 0.15; 95% CI, 0.7-0.31).

“Although progressive hepatic fibrosis is responsible for most HCV morbidity and mortality, studies with a 5-year to 12-year follow-up have suggested that noncirrhotic patients in particular benefit from a significant decrease in mortality on achieving SVR,” Cacoub and colleagues concluded. “In future clinical trials, longer-term follow-up of patients, and more extensive reporting of a variety of clinical outcomes, will be vital to promote a more thorough understanding of the risk–benefit profiles of these treatments.” – by Talitha Bennett

Disclosure: Cacoub reports he received consulting and lecturing fees from AbbVie, Astra Zeneca, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Janssen, Merck Sharp & Dohme, Roche, Servier and Vifor; and received grants from French National Center for Scientific Research (CNRS), Inserm, Université Pierre et Marie Curie, ANRS and World Health Organization. Please see the full study for the other authors’ relevant financial disclosures.

Results of a recent systematic review and meta-analysis showed that sustained virologic response after hepatitis C therapy can reduce extrahepatic manifestations including insulin resistance and cardiovascular risks.

“Extrahepatic manifestations in HCV-infected patients are either rare but very severe on the short term ... or very frequent with a potential severity on the mid-long term,” Patrice Cacoub, MD, from the Hôpital La Pitié-Salpêtrière, France, and colleagues wrote. “In most cases, they are independent of the severity of the liver disease. Antiviral therapy can reduce hepatic manifestations of HCV and also many extrahepatic manifestations related to HCV when SVR is achieved.”

Cacoub and colleagues conducted a search of the Embase and Medline databases for studies published between 1989 and June 2017. They included 48 studies in the final meta-analysis.

Analysis of four studies showed that SVR correlated with a significant reduction in extrahepatic mortality (OR = 0.44; 95% CI, 0.28-0.67) with little heterogeneity and moderate strength of evidence.

Data from another four studies showed that SVR had a significant effect on insulin resistance among patients without diabetes (OR = 0.42; 95% CI, 0.33-0.53) with homogeneity and moderate strength of evidence. Additionally, seven studies showed that SVR had a significant protective effect on diabetes frequency at follow-up (OR = 0.34; 95% CI, 0.21-0.56) with moderate strength of evidence.

Regarding cryoglobulinemia vasculitis, SVR had a significant effect on complete remission (OR = 20.76; 95% CI, 6.73-64.05) and correlated with any observed improvement (OR = 27.24; 95% CI, 10.99-67.53).

One study showed that SVR had a significant effect on the incidence of major adverse cardiovascular events (OR = 0.37; 95% CI, 0.59-0.84) and another showed a significant reduction in the incidence of ischemic events (OR = 0.7; 95% CI, 0.07-0.31).

Though limited to one large data set, the researchers also found that SVR after interferon-based therapy reduced the risk for renal impairment events (OR = 0.15; 95% CI, 0.7-0.31).

“Although progressive hepatic fibrosis is responsible for most HCV morbidity and mortality, studies with a 5-year to 12-year follow-up have suggested that noncirrhotic patients in particular benefit from a significant decrease in mortality on achieving SVR,” Cacoub and colleagues concluded. “In future clinical trials, longer-term follow-up of patients, and more extensive reporting of a variety of clinical outcomes, will be vital to promote a more thorough understanding of the risk–benefit profiles of these treatments.” – by Talitha Bennett

Disclosure: Cacoub reports he received consulting and lecturing fees from AbbVie, Astra Zeneca, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Janssen, Merck Sharp & Dohme, Roche, Servier and Vifor; and received grants from French National Center for Scientific Research (CNRS), Inserm, Université Pierre et Marie Curie, ANRS and World Health Organization. Please see the full study for the other authors’ relevant financial disclosures.