Aim
The predictors for the development of hepatocellular carcinoma (HCC) after direct‐acting antiviral (DAA) treatment were investigated.
Methods
A total of 1174 patients with chronic hepatitis C virus infection were treated with DAA therapy (sofosbuvir and ledipasvir [n = 615], sofosbuvir and ribavirin [n = 380], and daclatasvir and asunaprevir [n = 179]) and achieved sustained virologic response (SVR). The HCC development rate and the factors that might contribute to the development of HCC after the end of DAA treatment were analyzed.
Results
During the median observation period of 537 days, HCC developed in 33 cases. The incidence of HCC was 1.9%, 3.2%, and 4.1% at 1, 1.5, and 2 years after the end of DAA therapy, respectively. Multivariate analysis with pre‐ and post‐treatment factors identified the Fibrosis‐4 (FIB‐4) index (hazard ratio [HR] = 1.09; 95% confidence interval [CI], 1.021–1.178; P = 0.011) and post‐treatment α‐fetoprotein (AFP) (HR = 1.11; 95% CI, 1.054–1.172; P < 0.001) as independent factors that contributed to the development of HCC after DAA therapy. Using these identified parameters, a new scoring system (0 to 2 points) was established. Patients in the high‐score group (2 points) could be identified as having a significantly higher risk of HCC development, and the respective 1‐ and 2‐year cumulative incidence rates of HCC were 6.1% and 14.4%.
Conclusions
A high FIB‐4 index and a high post‐treatment AFP at the end of DAA treatment were the independent predictors for developing HCC after DAA treatment. For patients with these risk factors, extra attention to the possibility of HCC development is needed.
A previous genome-wide association study (GWAS) performed in 963 Japanese individuals (487 primary biliary cholangitis [PBC] cases and 476 healthy controls) identified TNFSF15 (rs4979462) and POU2AF1 (rs4938534) as strong susceptibility loci for PBC. In this study, we performed GWAS in additional 1,923 Japanese individuals (894 PBC cases and 1,029 healthy controls), and combined the results with the previous data. This GWAS, together with a subsequent replication study in an independent set of 7,024 Japanese individuals (512 PBC cases and 6,512 healthy controls), identified PRKCB (rs7404928) as a novel susceptibility locus for PBC (odds ratio [OR] = 1.26, P = 4.13 × 10-9). Furthermore, a primary functional variant of PRKCB (rs35015313) was identified by genotype imputation using a phased panel of 1,070 Japanese individuals from a prospective, general population cohort study and subsequent in vitro functional analyses. These results may lead to improved understanding of the disease pathways involved in PBC, forming a basis for prevention of PBC and development of novel therapeutics.
Increased infiltration of lymphocytes and induction of damage and destruction of hepatocytes by these lymphocytes are characteristic features of chronic viral hepatitis. As chemokines attract lymphocytes to inflamed tissues, we studied macrophage inflammatory protein (MIP)-3alpha, a CC chemokine, in chronic viral hepatitis. The levels of MIP-3alpha were measured in the sera from 40 patients with chronic viral hepatitis and 30 control subjects by an enzyme-linked immunosorbent assay (detection limit of MIP-3alpha=7.8 pg/mL). The kinetics of MIP-3alpha were checked during interferon (IFN) therapy in 25 patients. The levels of MIP-3alpha in the sera were significantly higher in patients with chronic viral hepatitis (39.0 +/- 28.9 pg/mL) than control subjects (15.6 +/- 4.9 pg/mL; P < 0.0001) and in patients with severe (49.6 +/- 49.2 pg/mL) and moderate degree of hepatitis (50.9 +/- 27.1 pg/mL) than in mild disease (16.0 +/- 6.8 pg/mL; P < 0.05). A significant correlation was seen among serum MIP-3alpha levels with the levels of alanine aminotransferase (r=0.509, P < 0.0001), aspartate aminotransferase (r=0.505, P < 0.0001), and degrees of activity of hepatitis (r=0.592, P < 0.0001) and interface hepatitis (r=0.419, P=0.0066). The levels of MIP-3alpha were significantly increased in patients with hepatitis C 2 weeks after the start of therapy in IFN-responders, but, remained almost unchanged in IFN-nonresponders. These findings might be important not only for the understanding of immunoptahogenesis of hepatocellular damage in chronic hepatitis (CH) patients but also for a therapeutic strategy to control the local immune response in the liver. A prognostic value of MIP-3alpha during IFN therapy in patients with chronic hepatitis C is also shown.
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