Summary
Background
Hepatitis C virus (HCV) clearance with IFN‐based therapies reduces the incidence of hepatocellular carcinoma (HCC). There has been some debate if IFN‐free therapy with ...direct‐acting antivirals alters the risk for HCC.
Aim
To investigate the HCC incidence in cirrhotic HCV patients who cleared HCV with direct‐acting antivirals vs untreated controls.
Methods
We prospectively monitored 373 patients with chronic hepatitis C who received IFN‐free therapies with direct‐acting antiviral after January 2014. A retrospective control cohort of untreated cirrhotic patients was recruited out of 3715 HCV patients who were followed at our centre between 2007 and 2013, with similar HCC screening protocols.
Results
158 direct‐acting antiviral‐treated and 184 control patients with liver cirrhosis were included in this analysis. The groups did not differ in gender and genotype distribution, severity of liver disease and prevalence of diabetes mellitus. Patients were followed up for a median of 440 (range 91‐908) and 592 (range 90‐1000) days. HCCs developed in 6 and 14 patients during follow‐up, resulting in an incidence of 2.90 vs 4.48 HCCs per 100 person‐years. In the direct‐acting antiviral‐treated group, there was no new case of HCC later than 450 days after treatment initiation. In multivariate analysis, higher MELD‐Scores and AFP‐levels were independently associated with HCC development. Transplant‐free patient survival was similar in both groups.
Conclusions
IFN‐free direct‐acting antiviral therapy of chronic hepatitis C does not alter the short‐term risk for HCC in patients with liver cirrhosis. A reduced HCC incidence may become evident after more than 1.5 years of follow‐up.
Linked ContentThis article is linked to Kao and Su and Mettke and Wedemeyer papers. To view these articles visit https://doi.org/10.1111/apt.14565 and https://doi.org/10.1111/apt.14582.
Chronic hepatitis delta represents the most severe form of chronic viral hepatitis. The current treatment of hepatitis delta virus (HDV) infection consists of the use of interferons and is largely ...unsatisfactory. Several new compounds are currently in development for the treatment of HDV infection. However, surrogate markers that can be used to develop clinical endpoints in HDV infection are not well defined. In the current manuscript, we aimed to evaluate the existing data on treatment of HDV infection and to suggest treatment goals (possible “trial endpoints”) that could be used across different clinical trials.
Summary
Chronic hepatitis D is caused by coinfection of hepatitis B and hepatitis D virus. While HDV is the dominant virus over HBV in the majority of cases, mechanisms and consequences of viral ...dominance are largely unknown. We aimed to investigate associations between viral dominance patterns and patients’ characteristics and inflammatory features; 109 HDV‐infected patients treated with PEG‐IFNa‐2α within the international multicentre, prospective HIDIT‐2 trial were studied. Patients were classified as D‐ or B‐dominant if the viral load of one virus exceeded that of the other virus by more than 1log10. Otherwise, no viral dominance (ND) was described. We used Luminex‐based multiplex technology to study 50 soluble immune mediators (SIM) in pretreatment samples of 105 HDV RNA‐positive patients. Dominance of HDV was evident in the majority (75%) of cases. While only 7% displayed B‐dominance, 17% showed nondominance. D‐dominance was associated with downregulation of 4 interleukins (IL‐2ra, IL‐13, IL‐16 and IL‐18) and 5 chemokines/cytokines (CTACK (CCL27), MCP‐1 (CCL2), M‐CSF, TRAIL and ICAM‐1) while no analyte was increased. In addition, D‐dominance could be linked to a delayed HDV RNA response to pegylated interferon as patients with B‐dominance or nondominance showed higher early HDV RNA responses (61% at week 12) than D‐dominant patients (11%; P < .001). In conclusion, this study revealed unexpected effects of viral dominance on clinical and immunological features in chronic hepatitis delta patients. Individualizing PEG‐IFNa‐2α treatment duration should consider viral dominance. Overall, our findings suggest an activated but exhausted IFN system in D‐dominant patients.
Hepatitis E has always been related to morbidity in pregnant women. Its epidemiology is not well understood in Brazil. Therefore, we tested sera from 209 pregnant women and 199 female blood donors, ...collected at a single center in Curitiba, Brazil. The Wantai assay was used for testing the anti‐hepatitis E virus (anti‐HEV), immunoglobulin G (IgG), and an in‐house polymerase chain reaction process for testing HEV RNA. Anti‐HEV was detected in 22.5% of the total group, 19% in the pregnant women group, and 26% in the blood donor group (P = 0.11), a much higher prevalence when compared with other studies in Brazil. Demographical analysis showed that 92.4% were born in the South Region of Brazil, 4.9% in the Southeast, and 2.7% were distributed over other regions of the country. With respect to their origin, 99% were from the South, 0.7% from the Southeast, and 0.2% from the Central‐West regions. Income, education, race, number of pregnancies, and abortion did differ significantly when comparing both the groups (P < 0.001). Age >30 (P = 0.012) and the number (>3) of pregnancies (P = 0.008) were related to anti‐HEV positivity. All anti‐HEV IgG–positive females were HEV RNA negative. In conclusion, HEV positivity was found in one out of five young women, which showed an urgent need for further epidemiological studies in Brazil.
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