Liver stiffness and liver fat (steatosis) in people with chronic hepatitis C virus (HCV) infection both improve significantly after treatment with direct-acting antivirals (DAAs) resulting in sustained virological response (SVR), investigators from Japan report in Alimentary Pharmacology and Therapeutics. Both measures of liver health were assessed six months after SVR. Improvement was associated with a reduction in ALT levels and an increase in platelet count.
It is currently unclear whether SVR following HCV therapy with DAAs is associated with improvements in steatosis – the accumulation of fat in the liver. Steatosis in its more severe form can promote the development of cirrhosis and hepatocellular carcinoma and might prevent the regeneration of the liver after curing hepatitis C. Steatosis is also associated with an increased risk of cardiovascular disease.
Steatosis is associated with obesity, high lipid or glucose levels, high alcohol intake and type 2 diabetes in all populations but is also present in people with hepatitis C as a consequence of viral infection. Steatosis is present in around half of people with hepatitis C and is more prevalent in people with hepatitis C genotype 3 infection. Some studies have suggested that in untreated people with hepatitis C genotype 3, steatosis is a marker for more aggressive fibrosis. In genotype 1 infection, steatosis is more often a marker of metabolic problems such as diabetes.
Abnormal fat deposits in the liver.
- 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.
Whereas there is evidence that liver damage in the form of fibrosis begins to improve after hepatitis C infection is eliminated, it is less clear that steatosis diminishes after DAA treatment.
Investigators from Japan designed a prospective study involving 198 people with SVR after DAA therapy. The study participants were treated between 2015 and 2016. Most (58%) were women and the median age was 72 years. All the participants had HCV monoinfection with genotypes 1 or 2.
Liver stiffness and steatosis were assessed using MRI imaging (proton density fat fraction – PDFF – for steatosis) at baseline and again 24 weeks after SVR. Blood chemistry, including ALT and platelet count, was also monitored at these time points.
There were significant improvements in blood chemistry between baseline and SVR24. Median ALT declined from 30 IU/L to 14 IU/L (p < 0.001), whereas platelet count increased from 16.4 x104/mm3 to 17.5 x104/mm3.
Median liver stiffness was 3.10 kPa at baseline and 2.80 kPa at the end of follow-up, a significant reduction. Likewise, median PDFF at the start of the study was 2.4%, falling to 1.9% by SVR24.
Significant improvements in steatosis between baseline and the end of follow-up were seen regardless of the severity of baseline liver stiffness (p < 0.001). Moreover, steatosis also improved regardless of HCV genotype.
A total of 28 people had clinical fatty liver disease at baseline (PDFF > 5.2%). Approximately 70% of these people did not have fatty liver disease at the end of follow-up.
Between baseline and SVR24, steatosis improved in 138 people and increased in 59 individuals. People with a decrease had higher baseline steatosis values than people in whom steatosis did not improve (2.6% vs 19%, p < 0.001).
For the purposes of comparison, the investigators also evaluated liver stiffness and steatosis values in nine people without SVR after DAA therapy. There were no significant changes in either measure between baseline and 24SVR.
“Liver stiffness based on magnetic resonance elastography decreased from baseline to SVR24 in patients with chronic HCV infection who received direct-acting anti-viral therapy and achieved SVR,” conclude the authors. “In addition, MRI-determined PDFF values significantly decreased between baseline to SVR24 in the same cohort. Thus, liver steatosis decreased in patients with HCV who have demonstrated viral eradication after direct-acting anti-viral therapy. Further studies are warranted to confirm these findings in other populations.”