Interferon-free direct-acting antiviral therapy for acute hepatitis C virus infection in HIV-infected individuals: A literature review

Dramatic rises in hepatitis C virus (HCV) coinfection rates in human immunodeficiency virus (HIV)-infected individuals have been observed recently, largely attributable to increasing recreational drug use combined with increased testing for HCV. In the era of direct-acting antiviral (DAA) therapy, treatment of acute HCV infection in HIV-infected individuals with short durations of these drugs may potentially reduce the disease and economic burden associated with HCV infection as well as reducing the likelihood of onward HCV transmission. We performed an extensive literature search of PubMed, Embase and Google Scholar up to 05 September 2017 for clinical trials of acute HCV infection in HIV-infected individuals. In the studies identified, rates of sustained virologic response at 12 weeks post-treatment (SVR12) ranged from 21% with 6 weeks of therapy up to 92% with 12 weeks of therapy with sofosbuvir and ribavirin. Ledipasvir/sofosbuvir for 6 weeks achieved an SVR of 77%. No HIV-related events occurred regardless of whether patients were receiving antiretroviral therapy (ART) and DAAs were well tolerated. Data is currently limited with regards to optimal regimens and durations of therapy, which need to be tailored based on potential interactions with concurrent ART and consideration for the fact that patients with higher baseline HCV RNA levels may require an extended duration of treatment.     

Expression of common housekeeping genes is affected by disease in human hepatitis C virus‐infected liver

Background: Comparative gene expression is commonly determined with reference to the expression of a housekeeping gene (HKG), the level of which is assumed to be unregulated. There are little data to date on the effect of disease on the expression of classic HKGs in hepatitis C virus (HCV)‐infected human liver. Aims: To identity HKGs stable across a wide spectrum of disease in human HCV‐infected liver. Methods: β‐Actin, hypoxanthine phosphoribosyltransferase 1 (HPRT1), glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH), splicing factor arginine/serine‐rich 4, β‐glucuronidase and 18S ribosomal RNA (18S rRNA) were measured by real‐time polymerase chain reaction in liver biopsy tissue. Samples were categorised for inflammation, fibrosis and steatosis, and allocated into groups with mild or severe liver disease. Values were analysed using Spearman's rank correlation, NormFinder, BestKeeper and geNorm programs. Results: All genes performed well in the samples of patients with low disease activity, but HPRT1, β‐actin, GAPDH and 18S rRNA ranked poorly in samples with severe fibrosis or inflammation. Conclusions: Our results indicate that liver disease affects the expression of common HKGs and that β‐glucuronidase and splicing factor arginine/serine‐rich 4 are the most stable HKGs from this group for studies of gene expression in HCV‐infected human liver.     

MicroRNAs in hepatic pathophysiology

MicroRNAs (miRNAs) are a group of small non‐coding RNAs that range in length from 20 to 25 nucleotides. MicroRNAs are specific for multiple cellular functions, including cell generation, differentiation, multiplication, carcinogenesis, and apoptosis. Many researchers have recently reported that the aberrant expression of miRNAs in hepatic tissue was related to the pathogenesis of liver disease, including viral hepatitis, hepatocellular carcinoma, and fatty liver disease. Multiple studies have proposed that an analysis of circulating miRNAs may be useful for diagnosing etiologies or staging the progression of liver disease, as well as for therapeutic purposes, for example, nucleic acid therapy. This review summarizes and discusses recent advances in the knowledge of miRNAs for chronic liver diseases, with special interest in viral hepatitis, liver fibrosis, and biomarkers.     

ABT-450: a novel agent for the treatment of CHC genotype 1: focus on treatment-experienced patients

Chronic hepatitis C (CHC) constitutes a major health concern. Hepatitis C virus eradication by antiviral treatment can markedly reduce the risk of developing cirrhosis, hepatocellular carcinoma and liver-related death. A plethora of new direct antiviral agents have been developed and are being explored in clinical trials. One of the newest members of this family is the NS3/4A protease inhibitor ABT-450. The multi-targeted approach combining ritonavir-enhanced ABT-450 with ombitasvir and dasabuvir has been evaluated for the treatment of CHC Gt1 in treatment-naïve and treatment-experienced adults. In this article, we sought to discuss the current knowledge on ABT-450-containing regimens, with special emphasis on treatment-experienced CHC Gt1 patients. This new combination was found to be potent, safe and well tolerated. Future Phase III trials with larger sample size in patients with decompensated cirrhosis, non-Gt1, end-stage renal disease and liver transplant recipients are eagerly awaited.     

Ophthalmological complications in hepatitis C virus infection: Side effect of interferon therapy or a direct role of HCV?

Several clinical studies have demonstrated that retinopathy and ophthalmic complications are features that appear mostly as side effects in HCV patients undergoing interferon (IFN) therapy. Here we underline that HCV itself is also able to modulate genes involved in ocular pathologies. Presently an in vitro model of ocular tissue derived cells infected with HCV is missing. The establishment of such in vitro models would be helpful to better understand the mechanisms through which HCV induces optical pathologies in order to specifically target the causes of ocular disease.