Temporal liver stiffness improvements observed during antiviral HBV therapy
medwireNews: Serial liver stiffness (LS) measurement is a useful tool for monitoring longitudinal improvements in advanced fibrosis among patients receiving antiviral treatment for chronic hepatitis B virus (HBV) infection, say researchers.
Jun Yong Park (Yonsei University College of Medicine, Seoul, Korea) and colleagues explain that “LB [liver biopsy] has been the gold standard for assessing liver fibrosis in the past few decades; however, LB can have limited diagnostic accuracy resulting from sampling error and inter-observational variation and is an impractical procedure to repeat.”
They therefore used Fibroscan, which provides LS measurements, to investigate liver fibrosis improvement during 5 years of antiviral treatment in 120 nucleos(t)ide analog-naïve chronic HBV patients with histologically advanced fibrosis (stage ≥F3), high viral load (HBV DNA ≥2000 IU/ml), and normal liver enzyme levels (<2 times the upper normal limit).
They found that 90.0% of patients had a decrease in LS values after 5 years of treatment with lamivudine or entecavir.
The greatest improvement occurred during the first year, when LS values fell significantly from an average pretreatment level of 14.5 kPa to 11.3 kPa at year 1 (p<0.001).
The degree of fibrosis improvement subsequently slowed, but was still significant, relative to the previous year, for the next 4 years, with mean LS values of 9.6 kPa at year 2 (p<0.001), 9.3 kPa at year 3 (p<0.001), 8.6 kPa at year 4 (p<0.001), and 8.3 kPa at year 5 (p<0.037).
Just over half (53.4%) of patients achieved the primary study endpoint of 5-year fibrosis improvement, defined by the researchers as an LS value below 7.2 kPa (<F3) at year 5.
And the team notes that the rate of 5-year fibrosis improvement was significantly higher among patients with F3 fibrosis than among those with F4 histological cirrhosis, at 86.7% versus 48.5% (p=0.048), even though the degree of fibrosis improvement after 5 years was greater in F4 than F3 patients (−6.9 vs −3.2 kPa, p=0.001).
On multivariate analysis, adjusted for baseline platelet count and fibrosis stage, baseline LS value was the only significant predictor of 5-year fibrosis improvement, at an odds ratio of 0.91 (p=0.014).
Using area under the receiver operating characteristic curve analysis, Park and team calculated an optimal baseline cutoff LS value of 12 0 kPa to predict fibrosis improvement.
Patients with a baseline LS value below this level were significantly more likely to experience fibrosis improvement than those with a higher LS value, at 81.5% versus 29.0% (p<0.001).
Writing in The American Journal of Gastroenterology, the researchers point out that nucleotide analog therapy is generally only recommended for hepatitis B e antigen (HBeAg)-positive patients with liver enzymes at least twice the upper normal limit and HBV DNA levels of at least 20,000 IU/mL or HBeAg-negative patients with HBV DNA levels of at least 2000 IU/mL.
Yet, in this study, chronic HBV patients with advanced fibrosis or cirrhosis and normal liver enzyme levels “experienced significant annual improvement of fibrosis,” while those with low LS values were more likely than those with high values to experience 5-year fibrosis improvement during treatment.
“Therefore, we should cautiously consider early intervention with [nucleotide analog] therapy in patients with sufficiently high HBV DNA and normal or slightly elevated liver enzymes […] in early stages of advanced fibrosis (LS value <12 kPa),” they say.
Park et al conclude that “LS measurement was a useful method for monitoring long-term improvement of fibrosis in [chronic HBV] patients in our study, as this parameter is accurate, noninvasive, and reproducible.”
They continue: “Future research should focus on investigating the development of cirrhosis-related complications and [hepatocellular carcinoma] in these patients who show improvement of fibrosis monitored by Fibroscan.”
By Laura Cowen
medwireNews is an independent medical news service provided by Springer Healthcare. © 2017 Springer Healthcare part of the Springer Nature group