Higher kidney disease risk persists in people cured of hepatitis C

People with hepatitis C remain at higher risk of chronic kidney disease after clearing or being cured of hepatitis C and people with genotype 1 infection have a higher risk of kidney disease before and after being cured of hepatitis C, a large US study has reported.

The study investigators say that people who have been cured of hepatitis C need to be recognised as having a higher risk of chronic kidney disease and monitored accordingly.

Hepatitis C virus can cause kidney damage by several mechanisms, including inflammation of blood vessels and over-production of immune system proteins called cryoglobulins that can block small blood vessels.

Previous studies have shown that the risk of chronic kidney disease and acute kidney failure is higher in people with hepatitis C than the general population, but these studies have not explored whether people who have been cured of hepatitis C have a similar risk of kidney disease as people who still have the virus.

It’s also unclear if the risk of chronic kidney disease is affected by hepatitis C genotype, as studies have produced conflicting results.

Researchers in Taiwan used data from the US National Health and Nutrition Examination Study (NHANES) to analyse the risk of chronic kidney disease in a large study cohort representative of the US population.

The study cohort consisted of 44,998 people included in NHANES surveys between 1999 and 2018 who had records of kidney function and hepatitis C antibody and RNA testing. Those with HCV antibodies and a negative HCV RNA result were defined as having resolved hepatitis C (either spontaneously cleared or cured by treatment).

The cohort consisted of 44,157 people without hepatitis C, 255 with resolved hepatitis C and 586 with chronic hepatitis C.

People with hepatitis C (including resolved hepatitis C) were older (51 vs 46 years), more often male, more likely to have high blood pressure, to have cardiovascular disease or a previous history of stroke, chronic hepatitis B and HIV. The prevalence of albuminuria, a sign of kidney damage, was higher in people with hepatitis C but there was no difference in the rate of reduced kidney function.

Fifteen per cent of the entire study population had kidney disease, defined as reduced kidney function (eGFR < 60 ml/min/1.73m²) or a urinary albumin/creatinine ratio greater than 30mg/g. The prevalence of kidney disease was higher in people with resolved kidney disease (23.5%) and chronic HCV (20%). Multivariable analysis showed that the risk of chronic kidney disease was 40% higher in people with resolved HCV and 26% higher in people with chronic HCV after adjusting for age, sex, race, body mass index, diabetes, high blood pressure, cardiovascular disease stroke and HIV.

Diabetes, cardiovascular disease, hypertension and HIV were each more substantial risk factors for chronic kidney disease than hepatitis C, raising the risk by between 60 and 150%.

In 586 people with detectable HCV RNA, 62% had genotype 1 infection, 8.5% genotype 2, 9% other genotypes and 19% had a missing genotype result. Twenty-three per cent of people with genotype 1 had chronic kidney disease compared to 12% of those with genotype 2 and 7% of those with other genotypes. People with genotype 1 had a 41% higher risk of chronic kidney disease compared to those without hepatitis and were more than twice as likely to have chronic kidney disease compared to people with other genotypes.

The study did not find that the risk of kidney disease increased in later periods but the investigators say that more research is needed to detect whether sofosbuvir-based treatment has any negative impact on kidney disease risk in people who have been cured of hepatitis C.