The treatment of chronic hepatitis C (CHC) has been revolutionized in an era of all-oral direct-acting antivirals (DAAs) since 2014. Satisfactory treatment efficacy and tolerability can be provided by novel DAAs. Nevertheless, there are still some unmet needs and emerging issues in the treatment of CHC in the DAA era. Certain hard-to-cure populations are prone to have inferior treatment responses, including patients with severe liver decompensation, active hepatocellular carcinoma (HCC), and hepatitis C virus (HCV) genotype 3 (HCV-3) infection and those who experience multiple DAA treatment failures. Hepatitis B virus (HBV) reactivation during and after DAA treatment has raised concern regarding the use of prophylactic antivirals against HBV throughout DAA treatment. However, the standard strategy for the use of prophylactic antivirals is not uniform across regional guidelines. In the post-sustained virological response (SVR) period, HCC still occurs in a substantial proportion of patients. Due to the relatively short follow-up period, the net benefit of the achievement of an SVR by DAAs in the reduction of extrahepatic manifestations has not yet been determined. Attention must also be paid to HCV reinfection, particularly in high-risk populations. The most critical and unmet need for HCV elimination is the large gap in the HCV care cascade at the population level. To accomplish the World Health Organization (WHO)’s goal for HCV elimination by 2030, the expansion of access to HCV care requires a continuous effort to overcome practical and political challenges.

OBJECTIVETo evaluate the relationship between uric acid (UA) and peripheral arterial disease (PAD) in Chinese patients with coronary heart disease (CHD).

METHODSUA levels and PAD were evaluated in 3251 Chinese hospitalized patients with CHD (age > or = 50 years). PAD was diagnosed when the ankle-brachial index was < 0.9 but patients with an ankle-brachial index of > 1.4 were excluded because of false negative rate. Potential confounding variables with P < 0.10 were adjusted for multivariate analysis.

RESULTSIn univariate analysis, UA levels were higher in patients with PAD than in those without PAD (349.80 micromol/L +/- 128.45 micromol/L vs. 323.00 micromol/L +/- 110.72 micromol/L, P < 0.001). Rate of hyperuricemia in patients with PAD and without PAD were 31.62% and 22.48% (P < 0.001) respectively. Prevalence rates of PAD for quintiles of UA level were 23.2%, 27.4%, 36.1%, 43.2% and 72.7%, respectively (P-trend < 0.05). With UA level as a continuous variable, the multivariate-adjusted odds ratio for PAD was 1.002 (95% confidence interval: 1.001 - 1.002) (P < 0.001). The optimal cut-off point for UA as determined by the receiver operating characteristic curve, was 227.2 micromol/L. The sensitivity and specificity at this cut-off point were 84.6% and 20.3%, respectively. The area under curve was 0.521 (95% confidence interval: 0.504 - 0.547) and the multivariate-adjusted odds ratio for PAD for UA above this level was 1.292 (95% confidence interval: 1.047 - 1.596) (P < 0.01). The results, however, after exclusion those cases who used diuretics, were similar.

CONCLUSIONElevated uric acid level seemed a significant and independent risk factor for PAD in Chinese hospitalized patients with CHD (age > or = 50 years).

Analysis of Variance ; Ankle Brachial Index ; China ; Coronary Disease ; blood ; complications ; Humans ; Hyperuricemia ; complications ; Middle Aged ; Odds Ratio ; Peripheral Vascular Diseases ; etiology ; Prevalence ; ROC Curve ; Risk Factors ; Sensitivity and Specificity ; Uric Acid ; blood

During the clinical trial development of directly acting antivirals (DAAs), evidence regarding the treatment efficacy in chronic hepatitis C patients with hepatocellular carcinoma (HCC) was scarce because these patients have always been excluded. Apart from the clinical trials, more HCC patients are currently being treated in daily practice, given that these treatments are highly effective and involve well-tolerated regimens. Large scale, real-world studies have demonstrated potentially suboptimal antiviral treatment efficacy in HCC patients who received DAAs. It is postulated that the impairment of the bioavailability of DAAs may account for the inferior treatment response. However, the results could not be generalized across all studies. The differing results were attributed to diverse patient characteristics, suboptimal regimens or imprecise definitions of active cancer statuses at the time of treatment initiation. Additional large-scale studies that utilize the treatment of choice in clearly defined HCC patients with different disease severities are warranted to clarify the issue.
Antiviral Agents ; Biological Availability ; Carcinoma, Hepatocellular ; Hepatitis C, Chronic ; Humans ; Treatment Outcome

Hepatitis C virus (HCV) infection is one of the major etiologies of hepatocellular carcinoma (HCC) with approximately 30% of HCC being due to HCV infection worldwide. HCV eradication by antivirals greatly reduces the risk of HCC; nevertheless, HCC remains to occur in chronic hepatitis C (CHC) patients who have achieved a sustained virological response (SVR). The proportion of post-SVR HCC among newly diagnosed HCC patients is increasing in the direct-acting antiviral (DAA) era and might be due to preexisting inflammatory and fibrotic liver backgrounds, immune dysregulation between host and virus interactions, as well as host epigenetic scars, genetic predispositions and alternations. By means of applying surrogate markers and adopting risk stratification, HCC surveillance should be consistently performed in high-risk populations. In this review, we discuss the possible molecular mechanism, risk factors, and HCC surveillance strategy for HCC development after HCV eradication in CHC patients.