Summary
Background
With the development of direct‐acting anti‐virals (DAAs), almost all patients with chronic hepatitis C virus (HCV) infection can achieve sustained viral response (SVR).
Aim
To ...evaluate the short‐term risk of HCC among patients with SVR by DAAs, including those with cirrhosis or previous HCC.
Methods
This large‐scale, multicentre cohort study included 1,675 consecutive patients who achieved SVR by treatment with interferon‐free sofosbuvir‐based regimens, divided into groups with (n = 152) or without previous HCC (n = 1,523). The Kaplan‐Meier method and Cox proportional hazard analysis were used to calculate the cumulative HCC incidence and related factors of HCC.
Results
During the follow‐up period (median: 17 months), 46 (2.7%) patients developed HCC. The 1‐year cumulative rates of de novo HCC were 0.4% and 4.9% for the noncirrhosis and cirrhosis groups respectively (log‐rank test: P < 0.001). For cirrhotic patients, serum α‐fetoprotein level at the end of treatment (EOT‐AFP) was the strongest predictor of de novo HCC. The 1‐year cumulative de novo HCC rates were 1.4% and 13.1% in the EOT‐AFP < 9.0 ng/mL and ≥ 9.0 ng/mL groups (cut‐off value) respectively (log‐rank test: P < 0.001). The 1‐year cumulative rates of HCC recurrence were 6.5% and 23.1% for the noncirrhosis and cirrhosis groups respectively (log‐rank test: P = 0.023). For cirrhotic patients, previous HCC characteristics were significantly associated with HCC recurrence. In contrast, sex, age and metabolic features did not influence de novo HCC or recurrence.
Conclusions
For cirrhotic patients after elimination of HCV, serum EOT‐AFP level and previous HCC characteristics would be useful markers for predicting de novo HCC or recurrence.
Linked ContentThis article is linked to Tan and Lim paper. To view this article visit https://doi.org/10.1111/apt.14437.
Myocarditis is a principal cause of heart disease among young adults and is often a precursor of heart failure due to dilated cardiomyopathy. We show here that complement is critical for the ...induction of experimental autoimmune myocarditis and that it acts through complement receptor type 1 (CR1) and type 2 (CR2). We also found a subset of CD44(hi)CD62L(lo) T cells that expresses CR1 and CR2 and propose that both receptors are involved in the expression of B and T cell activation markers, T cell proliferation and cytokine production. These findings provide a mechanism by which activated complement, a key product of the innate immune response, modulates the induction of an autoimmune disease.
Summary
Background
Antiviral treatment is recommended for chronic hepatitis C patients with advanced fibrosis to reduce and prevent cirrhosis‐related complications.
Aim
To evaluate the efficacy and ...safety of telaprevir (TVR)‐based triple therapy for patients with advanced fibrosis in a clinical practice setting.
Methods
This prospective, multicentre study consisted of 102 patients with advanced fibrosis (METAVIR score F3‐4) who were infected with HCV genotype 1b. All received 12 weeks of TVR in combination with 24 weeks of pegylated interferon (PEG‐IFN) α2b and ribavirin (RBV).
Results
The sustained virological response (SVR) rate was 69.6% (71 of 102). Notably, for treatment‐naïve and prior relapse patients the SVR rate was over 80%. Previous treatment response, interleukin 28B polymorphism (rs8099917) and rapid virological response (undetectable HCV RNA at week 4) were independently associated with SVR. To achieve SVR, an adequate dosage of PEG‐IFNα2b (≥1.2 μg/kg/week) and RBV (≥7.5 mg/kg/day) is preferable; however, the mean weight‐adjusted TVR dosage had little impact on treatment outcome. Although severe blood cytopaenia and a dermatological disorder were frequently found, the rate of discontinuation due to adverse effects was 12.7%. The inosine triphosphatase CC allele (rs1127354) was independently associated with the development of severe anaemia, and lower serum albumin level (<35 g/L) was associated with the occurrence of infection.
Conclusions
The great gain in the SVR rate by telaprevir‐based triple therapy offsets the problems with adverse effects; thus, it should be considered as a potent treatment protocol for patients with advanced fibrosis, especially for those with treatment‐naïve and prior relapse.
A liver biopsy is currently considered the definitive diagnostic modality for establishing the severity of hepatic fibrosis. We analysed the diagnostic sensitivity and accuracy of ultrasound (US) ...using both low frequency and high frequency probes as a repeatable, inexpensive, and reliable method to determine the fibrosis stage in chronic liver disease and then compared our results with the histological findings. A total of 103 patients with chronic liver disease (60 males and 43 females, average age 51 years old) who had undergone both a liver biopsy and US with 2-5 MHz frequency and 5-12 MHz frequency probes were prospectively evaluated in this study. An US scoring system using both the low frequency and high frequency probes was performed by evaluating the edge, surface and parenchymal texture of the liver. Each score was obtained by evaluating three parameters; the bluntness of the liver edge, the irregularity of the surface and the coarseness of the parenchymal texture were evaluated and then compared with the histological findings. The US scores of the liver edge (rs: 0.6668), liver surface (rs: 0.9007) and liver parenchymal texture (rs: 0.8853) correlated significantly with the fibrosis stage obtained based on the biopsy findings. The accumulated US scores of these three parameters, however, was found to be the most reliable indicator (rs: 0.9524). Patients with an accumulated score of 6.5 or more were all found to have fibrosis stage 4 in which the accuracy of our scoring system for correctly predicting cirrhosis was found to be 100% sensitive. When an accumulated US score of 3 was interpreted to indicate mild fibrosis (a fibrosis score of 0 or 1), all 42 patients with stage 0 or 1 fibrosis were found to have an accumulated US score of 3 or less (a probability of 100%) and 42 of 53 patients with a score of 3 or less were found to have stage 0 or 1 fibrosis (specificity of 79.2%). An ultrasound evaluation of the liver fibrosis stage based on the scoring system using both low and high frequency probes was found to be a reliable and effective alternative to the histological staging in chronic liver diseases.
Interleukin (IL)-12 exerts a potent proinflammatory effect by stimulating T-helper (Th) 1 responses. This effect is believed to be mediated primarily through the activation of STAT4 and subsequent ...production of interferon (IFN)-gamma. Methods and Results- We examined the role of IL-12 receptor (IL-12R) signaling in the development of murine experimental autoimmune myocarditis (EAM) induced by cardiac myosin immunization. Both IL-12Rbeta1-deficient mice and STAT4-deficient mice were resistant to the induction of myocarditis. Treatment with exogenous IL-12 exacerbated disease. We questioned whether IFN-gamma is required for the disease-promoting activity of IL-12. On the contrary, we found that IFN-gamma suppresses EAM. Lack of IFN-gamma due to either depletion with an antibody or a genetic deficiency exacerbated myocarditis. Spleens from IFN-gamma-deficient mice immunized with cardiac myosin showed increased cellularity; greater numbers of CD3+, CD4+, CD8+, and IL-2-producing cells; and heightened ability to produce cytokines on stimulation in vitro. Treatment of mice with recombinant IFN-gamma suppressed the development of myocarditis.
IL-12/IL-12R/STAT4 signaling promotes the development of EAM. In contrast, IFN-gamma plays a protective role. The disease-limiting effects of IFN-gamma might be explained by its ability to control the expansion of activated T lymphocytes.
Summary
Favourable efficacy and safety profiles for simeprevir in combination with pegylated interferon alpha (PEG‐IFNα) and ribavirin (triple therapy) have been shown in clinical trials. This study ...was carried out to evaluate the effectiveness of simeprevir‐based triple therapy for patients with prior telaprevir treatment failure. This multicentre, observational cohort consisted of 345 consecutive Japanese patients infected with HCV genotype 1b, including 20 who had experienced telaprevir‐based triple therapy. Amino acid substitutions in the NS3/4A region were identified by direct sequencing at the time of relapse or breakthrough in treatment with telaprevir and at the initiation of treatment with simeprevir. Patients were stratified according to prior response to PEG‐IFNα and ribavirin. Of the 20 patients with telaprevir treatment failure, 10 (50.0%) achieved sustained virological response at week 12 after the end of treatment (SVR12). For patients treatment naïve 3/4 (75.0%) or with prior relapse 1/1 (100%) or partial response 5/6 (83.3%) to PEG‐IFNα and ribavirin, almost all achieved SVR12, mainly because of the improvement of treatment adherence, especially to direct‐acting antiviral agent and ribavirin. However, of the nine patients with prior null response to PEG‐IFNα and ribavirin, only one (11.1%) achieved SVR12, despite all having received an adequate treatment dosage, and five (55.6%) achieved rapid virological response. The treatment outcome of simeprevir‐based triple therapy for HCV genotype 1b patients with prior telaprevir failure depended on the prior response to PEG‐IFNα and ribavirin. For patients with prior null response to PEG‐IFNα and ribavirin, retreatment with simeprevir‐based triple therapy is not a useful option.
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