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HCV therapy with SVR reduces the risk of several non-liver-related diseases commonly seen in people with chronic HCV

Michael Carter
06 July 2017

The risk of several non-liver complications associated with chronic hepatitis C virus (HCV) infection is reduced after interferon-based treatment that achieves a sustained virological response (SVR), investigators from the United States report in Gut. “The results of our study emphasise the extra-hepatic benefits of SVR,” comment the authors.

However, early treatment was needed to reduce the risk of several extra-hepatic manifestations (EHM) of HCV infection, including non-Hodgkin lymphoma.

Patients received interferon-based therapies since superseded by safer and more effective direct-acting antivirals (DAAs). “As more patients are treated with DAAs, we expect greater benefits of SVR including reduced risk of EHMs of chronic HCV infection, assuming that the clinical benefits of SVR remain similar for interferon-based compared with interferon-free treatment regimens,” write the investigators. “Our results need to be replicated in a cohort of HCV-infected patients who received DAAs.”



Something that has an effect outside the liver, for example when viral hepatitis affects the kidneys or causes depression.


A type of tumour affecting the lymph nodes.

sustained virological response (SVR)

Undetectable hepatitis C RNA after treatment has come to an end. Usually SVR refers to RNA remaining undetectable for 24 weeks (six months) after ending treatment and is considered to be a cure. SVR4 and SVR12 refer to RNA remaining undetectable for 4 and 12 weeks respectively. 

Chronic HCV infection is associated with serious liver disease, including cirrhosis and hepatocellular carcinoma. The infection can also increase the risk of several extra-hepatic illnesses.

Antiviral therapy (AVT) achieving a sustained virological response (undetectable HCV viral load 12 weeks after the completion of therapy) is associated with normalisation of liver function and a reduced risk of liver disease. The effect of therapy and SVR on rates of extra-hepatic conditions linked to chronic HCV infection is unclear.

Investigators from the United States Department of Veterans Affairs, therefore, designed a retrospective study involving people with a positive HCV RNA test between 1999 and 2009. The risk of eight extra-hepatic manifestations of HCV infection was compared between people with SVR and non-SVR patients. HCV therapy was based on interferons.

The eight extra-hepatitic conditions of interest to the investigators were:

  • Mixed cryoglobulinaemia – a blood disorder.
  • Glomerulonephritis – renal disease involving the parts of the kidneys that filter blood.
  • Porphyria cutanea tarda (PCT) – the most common type of porphyria.
  • Lichen planus – an itchy rash
  • Non-Hodgkin lymphoma (NHL).
  • Diabetes mellitus.
  • Coronary heart disease.
  • Stroke.

The study population comprised 161,000 HCV RNA-positive people, of whom 31,000 received AVT, with 10,500 people attaining SVR.

Most non-hepatic disorders were rare, with an incidence below 1 per 1000 person-years of follow-up. Overall, rates were lower among people who received HCV therapy compared to non-treated people. The lowest incidence was observed in people with SVR, with the exception of coronary heart disease and stroke.

After adjustment for potential confounders, people with SVR, compared to untreated people, had a lower risk of the following extra-hepatic disorders:

  • Mixed cryoglobulinaemia (aHR = 0.61; 95% CI, 0.39 - 0.94).
  • Glomerulonephritis (aHR = 0.62; 95% VI, 0.48 - 0.79).
  • PCT (aHR = 0.41; 95% CI, 0.20 - 0.83).
  • Non-Hodgkin lymphoma (aHR = 0.64; 95% CI, 0.43 - 0.95).
  • Diabetes (aHR = 0.82; 95% CI, 0.76 - 0.88).
  • Stroke (aHR = 0.84; 95% CI, 0.74 - 0.94).

When the analysis was restricted to treated people, individuals with SVR, compared to non-SVR patients, had a lower risk of:

  • Mixed cryoglobulinaemia (aHR = 0.55; 95% CI, 0.33 - 0.90).
  • Glomerulonephritis (aHR = 0.75; 95% CI, 0.57 - 0.99).
  • PCT (aHR = 0.31; 95% CI, 0.14 - 0.65).
  • Diabetes (aHR = 0.72; 95% CI, 0.65 - 0.78).

Other findings showed the importance of prompt therapy.

Treatment was only protective against the risk of glomerulonephritis and stroke if started within one or two years of infection with HCV. Treatment was only beneficial in reducing the risk of non-Hodgkin lymphoma if started within a year of infection.

“We observed a significant reduction in the risk of several EHMs of chronic HCV with AVT and attainment of SVR,” conclude the authors. “”However, early initiation of AVT may be required…although future studies will need to evaluate the effects of DAAs, the benefits associated with SVR following interferon-based AVT suggest great promise in reducing the risk of EHMs.”


Mahale P et al. The effect of sustained virological response on the risk of extrahepatic manifestations of hepatitis C virus infection. Gut. Online edition,