Ribavirin Treatment Research Articles

Changes in miR-122 and Cholesterol Expression in Chronic Hepatitis C Patients after PegIFN-Alpha/Ribavirin Treatment.

The hepatitis C virus (HCV) is known as a main etiological cause of chronic hepatitis. HCV infection disturbs cholesterol metabolism of the host, which is frequently observed in patients suffering from chronic hepatitis C (CHC). The course of viral infections remains under strict control of microRNA (miRNA). In the case of HCV, miR-122 exerts a positive effect on HCV replication in vitro. The purpose of this study was to investigate the impact of peginterferon alpha (pegIFN-α) and ribavirin treatments on the expression of miR-122 and the cholesterol level in the peripheral blood mononuclear cells (PBMCs) of CHC patients. We report here that the level of miR-122 expression in the PBMCs decreased after the antiviral treatment in comparison to the pretreated state. Simultaneously, the level of cholesterol in the PBMCs of CHC patients was higher six months following the treatment than it was pretreatment. Consequently, it seems that the decrease of miR-122 expression in the PBMCs of CHC patients is one of the antiviral effects connected with the pegIFN-alpha/ribavirin treatments.

Evaluation of 10 years of parainfluenza virus, human metapneumovirus, and respiratory syncytial virus infections in lung transplant recipients.

Respiratory tract infection with pneumoviruses (PVs) and paramyxoviruses (PMVs) are increasingly associated with chronic lung allograft dysfunction (CLAD) in lung transplant recipients (LTRs). Ribavirin may be a treatment option but its effectiveness is unclear, especially with respect to infection severity. We retrospectively analyzed 10 years of PV/PMV infections in LTRs. The main end points were forced expiratory volume in 1 second (FEV1) at 3 and 6 months postinfection, expressed as a percentage of pre‐infection FEV1 and incidence of new or progressed CLAD 6 months postinfection. A total of 139 infections were included: 88 severe infections (63%) (defined as >10% FEV1 loss at infection) and 51 mild infections (37%) (≤10% FEV1 loss). Overall postinfection CLAD incidence was 20%. Associations were estimated on postinfection FEV1 for ribavirin vs no ribavirin (+13.2% [95% CI: 7.79; 18.67]) and severe vs mild infection (−11.1% [95% CI: −14.76; −7.37]). Factors associated with CLAD incidence at 6 months were ribavirin treatment (odds ratio (OR [95% CI]) 0.24 [0.10; 0.59]), severe infection (OR [95% CI] 4.63 [1.66; 12.88]), and mycophenolate mofetil use (OR [95% CI] 0.38 [0.14; 0.97]). These data provide valuable information about the outcomes of lung transplant recipients with these infections and suggests possible associations of ribavirin use and infection severity with long‐term outcomes. Well‐designed prospective trials are needed to confirm these findings.

Abstract B06: Repositioning the FDA-approved antiviral drug ribavirin as targeted therapy for nasopharyngeal carcinoma

Abstract Purpose: Nasopharyngeal carcinoma (NPC) is a squamous cell carcinoma that is often diagnosed at an advanced stage, leading to poor disease-free and overall survival. Accumulating literature suggests that elevated protein expression of enhancer of zeste homolog 2 (EZH2), eukaryotic initiation factor 4E (eIF4E), and inosine-5’-monophosphate dehydrogenase (IMPDH)—proteins implicated in myriad cancers—correlates with poor prognosis in NPC. These three proteins are modulated by the Food and Drug Administration-approved antiviral drug ribavirin, which has recently been repositioned by our laboratory and others as a promising anticancer agent. Based on this intersection of molecular signature and drug targets, we investigated the potential of ribavirin as a therapeutic agent for NPC. Experimental Design: We assessed antineoplastic efficacy of ribavirin on six human NPC cell lines in vitro using cellular growth assays, flow cytometry, and scratch wound assays. Mechanistic pathways involved were investigated using genomic expression datasets, Western blots, and enzymatic activity assays. The effects of combining ribavirin with radiation were assessed using clonogenic assays and flow cytometry. Finally, we evaluated the effects of ribavirin on tumor growth in vivo using two human cell line-derived xenograft models. Results: Ribavirin significantly decreased NPC cellular proliferation and migratory capacity in addition to promoting cell cycle arrest and cell death. Modulation of the EZH2, Snail, eIF4E, and IMPDH pathways was observed in response to ribavirin treatment. Ribavirin significantly enhanced the cytotoxic effects of radiation therapy in NPC. Most importantly, ribavirin significantly reduced flank tumor growth in two NPC xenograft models. Conclusions: Our work suggests that ribavirin has potent anticancer effects in NPC and could represent a safe and promising addition to current NPC treatment regimens. Citation Format: Sakibul Huq, Joshua Casaos, Michael Peters, Yuanxuan Xia, Andy Ding, Manuel Morales, Noah Gorelick, Riccardo Serra, Tianna Zhao, Wataru Ishida, Alexander Perdomo-Pantoja, Arba Cecia, Chenchen Ji, Ian Suk, David Sidransky, Mariana Brait, Henry Brem, Nicolas Skuli, Betty Tyler. Repositioning the FDA-approved antiviral drug ribavirin as targeted therapy for nasopharyngeal carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr B06.

Real-world efficacy, safety, and clinical outcomes of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin combination therapy in patients with hepatitis C virus genotype 1 or 4 infection: The Turkey experience experience

mbitasvir/paritaprevir/ritonavir (OMV/PTV/r) ± dasabuvir (DSV) ± ribavirin (RBV) combination has demonstrated excellent rates of sustained virologic response (SVR) and a very good safety profile in patients with the chronic hepatitis C virus (HCV) genotype 1 or 4 infections. We aimed to investigate the effectiveness and safety of OMV/PTV/r ± DSV ± RBV combination regimen in a real-world clinical practice. Data from HCV genotype 1 and 4 patients treated with OMV/PTV/r ± DSV ± RBV (n=862) in 34 centers across Turkey between April 1, 2017 and August 31, 2018 were recorded in a large national database. Demographic, clinical, and virologic data were analyzed. The mean age of the patients was 55.63, and 430 patients (49.9%) were male. The majority had HCV genotype 1b infection (77.3%), and 66.2% were treatment-naïve. Non-cirrhosis was present at baseline in 789 patients (91.5%). SVR12 rate was 99.1% in all patients. Seven patients had virologic failure. No significant differences were observed in SVR12 according to HCV genotypes. HCV RNA was undetectable at treatment week 4 in 90.9%, at treatment week 8 in 98.5%, and at the end of treatment (EOT) in 98.9%. SVR12 ratio was significantly higher in the non-cirrhotic patients compared to that in the compensated cirrhotic patients. Rates of adverse events (AEs) in the patients was 59.7%. The present real-life data of Turkey for the OBV/PTV/r ± DSV ± RBV treatment of patients with HCV genotype 1b, 1a, or 4 infection from 862 patients demonstrated high efficacy and a safety profile.

Efficiency of eradication of Raspberry bushy dwarf virus from infected raspberry (Rubus idaeus) by in vitro chemotherapy, thermotherapy and cryotherapy and their combinations

Raspberry bushy dwarf virus (RBDV) is one of the few horizontally transmitted plant viruses and is difficult to eradicate from infected raspberry (Rubus idaeus) by conventional methods because of its ability to infect meristematic cells in the apical dome. This virus is present where ever raspberry is grown and its adverse effects on quality and yield of the crop has necessitated development of methods to eradicate RBDV from infected stock plants. We applied ribavirin treatment (30 mg/L for 2 weeks—chemotherapy), thermotherapy (24 °C for 8 h in dark and 39 °C for 16 h with light for 2 weeks), cryotherapy (droplet vitrification of shoot tips) and their different combinations to assess the efficiency of virus eradication from an infected raspberry genotype. Virus testing was done on plantlets in tissue culture after 3–4 months following plant regeneration and repeated in half the population of virus-free plants in the greenhouse, 1 year after the initial test. Results showed that ribavirin treatment severely affected plant regeneration, resulting in low efficiency of virus eradication (10.6% regenerated plantlets free of RBDV out of all explants treated). When it was combined with thermotherapy, plant regeneration was significantly improved, resulting in higher efficiency of virus eradication (44.4%). When the shoot tips subjected to these two treatments were cryopreserved and regenerated, virus eradication efficiency further improved to 58.5%. The control of this treatment where plant material was not treated in liquid nitrogen produced the highest efficiency of virus eradication (78.8%), partly because of better plant regeneration. Thermotherapy and cryotherapy when applied alone failed to remove the virus from infected material; however, when combined, 48.6% efficiency of virus eradication was recorded. Inclusion of in vitro thermotherapy in combination with chemotherapy or cryotherapy or both is important to improve efficiency of RBDV eradication from infected raspberry. Nevertheless this virus can be eradicated by different approaches, and our results are useful for planning virus eradication programmes based on the efficiency of eradication. It is important to test the virus status after greenhouse acclimation, as virus may be suppressed and not completely eliminated in some treatments at tissue culture stage, as shown in ribavirin treatment in our research. Eradication of Raspberry bushy dwarf virus from infected red raspberry is possible by chemotherapy, but the efficiency can be significantly improved when combined with thermotherapy or cryotherapy, or both.

Evidence of the Extrahepatic Replication of Hepatitis E Virus in Human Endometrial Stromal Cells.

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide. The tropism of HEV is not restricted to the liver, and the virus replicates in other organs. Not all the extrahepatic targets for HEV are identified. Herein, we found that non-decidualized primary human endometrial stromal cells (PHESCs), which are precursors for the decidua and placenta, are susceptible to HEV infection. PHESCs, isolated from healthy non-pregnant women (n = 5), were challenged with stool-derived HEV-1 and HEV-3. HEV RNA was measured by qPCR, and HEV capsid protein was assessed by flow cytometry, immunofluorescence (IF), and ELISA. HEV infection was successfully established in PHESCs. Intracellular and extracellular HEV RNA loads were increased over time, indicating efficient replication in vitro. In addition, HEV capsid protein was detected intracellularly in the HEV-infected PHESCs and accumulated extracellularly over time, confirming the viral assembly and release from the infected cells. HEV-1 replicated more efficiently in PHESCs than HEV-3 and induced more inflammatory responses. Ribavirin (RBV) treatment abolished the replication of HEV in PHESCs. In conclusion, PHESCs are permissive to HEV infection and these cells could be an endogenous source of HEV infection during pregnancy and mediate HEV vertical transmission.

Interferon Response in Hepatitis C Virus-Infected Hepatocytes: Issues to Consider in the Era of Direct-Acting Antivirals.

When interferons (IFNs) bind to their receptors, they upregulate numerous IFN-stimulated genes (ISGs) with antiviral and immune regulatory activities. Hepatitis C virus (HCV) is a single-stranded, positive-sense RNA virus that affects over 71 million people in the global population. Hepatocytes infected with HCV produce types I and III IFNs. These endogenous IFNs upregulate a set of ISGs that negatively impact the outcome of pegylated IFN-α and ribavirin treatments, which were previously used to treat HCV. In addition, the IFNL4 genotype was the primary polymorphism responsible for a suboptimal treatment response to pegylated IFN-α and ribavirin. However, recently developed direct-acting antivirals have demonstrated a high rate of sustained virological response without pegylated IFN-α. Herein, we review recent studies on types I and III IFN responses in HCV-infected hepatocytes. In particular, we focused on open issues related to IFN responses in the direct-acting antiviral era.

Respiratory syncytial virus and human metapneumovirus after allogeneic hematopoietic stem cell transplantation: Impact of the immunodeficiency scoring index, viral load, and ribavirin treatment on the outcomes.

Respiratory viral infections are a major cause of morbidity and mortality among stem cell transplant recipients. While there is a substantial amount of information on prognostic factors and response to ribavirin therapy is available for RSV infections, this information is largely lacking for hMPV. In total, 71 patients were included in this study: 47 patients with RSV and 24 with hMPV. Forty-one patients presented as an upper respiratory tract infection (URTI) and 30 as a primary lower respiratory tract infection (LRTI). Patients were stratified as per ISI criteria into low-, moderate-, and high-risk groups. Twenty-two patients in the URTI cohort received treatment with ribavirin (mainly oral), and 19 patients received no antiviral therapy. The decision for antiviral treatment was at the discretion of the attending physician. All 30 patients with primary LRTI and 10 patients with secondary LRTI were treated with ribavirin, 95% with the intravenous formulation. 45% of these patients received additional treatment with intravenous immunoglobulins. The viral load was assessed indirectly by using the CT value of the RT-PCR. In the cohort, as whole 11.5% suffered a virus-associated death, 5% in the URTI group, and 20% in the LRTI group. Sixty-day mortality was significantly higher in the ISI high-risk group (log-rank P=.05). Mortality was independent of the type of virus (P=.817). Respiratory failure with an indication for mechanical ventilation developed in 11.5%, this risk was independent of the type of virus. Progression from URTI to LRTI was observed in 24% of cases with a significantly higher risk (75%) in the ISI high group (log-rank P=.001). In the ISI high-risk group, treatment with ribavirin significantly reduced the risk of progression (log-rank P<.001). Neither the type of virus nor the viral load in the nasopharyngeal swab impacted the risk of progression (P=.529 and P=.141, respectively). The detection of co-pathogens in the BAL fluid was borderline significant for mortality (P=.07). We could detect no differences between RSV and hMPV with respect to progression to LRTI, risk of respiratory failure or need for mechanical ventilation and virus-associated death. The ISI index is of predictive value in hMPV patients with a high ISI score and treatment with oral ribavirin has an equivalent protective effect in RSV and hMPV patients. Treatment of LRTI with intravenous ribavirin results in a similar outcome in RSV- and hMPV-infected patients. We could not detect any benefit of adjunctive treatment with immunoglobulins in both primary and secondary LRTI. No role of viral load as an independent prognostic marker could be detected either for progression to LRTI or death.

Prospective observational study on the pharmacokinetic properties of the Irrua ribavirin regimen used in routine clinical practice in patients with Lassa fever in Nigeria

IntroductionLassa fever (LF) is a severe and often fatal systemic disease in humans and affects a large number of countries in West Africa. Treatment options are limited to supportive care...

Ten Years of Ribavirin Treatment for Pneumovirus and Paramyxovirus Infections in Lung Transplant Recipients

Respiratory tract infection with respiratory syncytial virus (RSV), human metapneumo virus (hMPV) or parainfluenza virus (PIV) are increasingly associated with chronic lung allograft dysfunction in the form of bronchiolitis obliterans syndrome (BOS) in lung transplant recipients (LTR). Ribavirin as treatment option is under debate since its effectiveness is unclear, especially in light of infection severity. We retrospectively analyzed 10 years of RSV, hMPV and PIV infections in LTR in our center. Main endpoints were FEV1 at 3 and 6 months post-infection, expressed as a percentage of pre-infection FEV1 (by hierarchical linear mixed model) and incidence of new or progressed BOS 6 months post infection (by logistic regression). Patients with acute rejection < 3 mo. or transplantation <6 mo. prior to infection or with concomitant fungal infection were excluded. Time since transplantation, virus type (RSV, hMPV or PIV), viral co-infection, bacterial co-infection, presence of BOS prior to infection, severe or mild infection, follow-up time point (three vs. six months), tacrolimus use, mycophenolate mofetil (MMF) use, and ribavirin treatment (any form) were used as covariates in the multivariable models. A total of 139 infections were included, 88 (63%) with a severe infection (defined as a >10% FEV1 decline at infection), and 51 (37%) with a mild infection (≤10% FEV decline). Median [IQR] FEV1 decline during infection was notable and similar across the viruses (RSV 14% [22], hMPV 15% [14], PIV 16% [20]. Overall post-infection BOS incidence was 20% (27% for severe, 10% for mild). There were no virus related deaths. The linear mixed model found estimated associations on post-infection FEV1 for ribavirin treatment vs. no ribavirin (+13.2% [7.79;18.67]) and severe infection vs. mild infection (-11.1% [-14.76; -7.37). Ribavirin treatment (aOR 0.24 [0.10-0.59]), severe infection (aOR 4.63 [1.66;12.88]) and surprisingly also MMF use (aOR 0.38 [0.14;0.97]) were factors associated with new or progressed BOS at 6 months. LTR with a mild infection tended to recover well, regardless of antiviral therapy. We conclude that ribavirin should be considered as treatment option to possibly prevent allograft dysfunction in LTR with severe RSV, hMPV or PIV infection. We found no reason to discontinue MMF during these infections.

Monitoring Crimean-Congo haemorrhagic fever virus RNA shedding in body secretions and serological status in hospitalised patients, Turkey, 2015.

IntroductionCrimean-Congo haemorrhagic fever (CCHF) is a tick-borne disease in Africa, Asia, the Balkan peninsula, the south-east of Europe and the Middle East, with mortality rates of 3–30%. Transmission can also occur through contact with infected animals or humans.AimThis observational, prospective case series aimed to investigate detectable viral genomic RNA in whole-body fluids and antibody dynamics in consecutive daily samples of patients diagnosed with CCHF until discharge from hospital.MethodsWe tested 18 patients and 824 swabs and sera with RT-PCR and 125 serum samples serologically.ResultsThe longest duration until clearance of viral RNA was 18 days from serum collection and 18, 15, 13, 19 and 17 days, respectively, from nasal, oral, genital (urethral or vaginal) and faecal swab, and urine. In seven patients, viral load decreased in serum at the same time as it increased in urine or persisted at the same logarithmic values. Despite clearance in serum, viral RNA was detected in faeces and genital swabs in two and three patients, respectively. Viral clearance from body fluids occurred earlier than from serum in eight patients on ribavirin treatment. The shortest seroconversion time was 3 days after symptom onset for IgM and IgG. Seroconversion of IgG occurred until Day 14 of symptoms.ConclusionWe report persistence of viral RNA in urine, faeces and genital swabs despite serum clearance. This may indicate a need for extending isolation precautions, re-evaluating discharge criteria and transmission risk after discharge, and considering oral swabs as a less invasive diagnostic alternative.

Efficacy and Safety of Omibtasvir, Paritaprevir and Ritonavir Combination with Ribavirin for Treatment of Chronic Hepatitis C Patients

Abstract Background: The highest prevalence of chronic Hepatitis C Virus (HCV) was reported in Egypt. DAAs has been avail-able, with a reported 12 weeks sustained virologic response (12w-SVR) above 95% after treatment for 12 weaks. Aim of Study: Aim of the current study was to evaluate evaluate efficacy of the 2-DAAs combination of ombitasvir, paritaprevir (co-dosed with ritonavir) with ribavirin in treatment of chronic HCV patients and evaluate correlation between virologic failure and risk factors. Patients and Methods: Chronic HCV patients (n=100) were enrolled in the current study. All patients received 25mg ombitasvir, 150mg paritaprevir, and 100mg ritonavir orally once daily plus Ribavirin 600-1000mg) for 12 weaks. Response was assessed 12 weeks after end of treatment by SRT-PCR. Results: The interferon-free regimen of ombitasvir/ pari-taprevir/ritonavir + ribavirin for 12 weeks achieved sustained virologic response in 91% of patients. Conclusion: In conclusion, the 12-week 2-DAA regimen of OBV/PTV/r and DSV achieved an SVR12 rate of 91% in previously untreated patients with HCV infection. Liver Cirrhosis has negative impact on 12 weeks-SVR. Conflict of Interest: The authors have no conflict of interest related to this publication.

Inhibition of cardiomyocyte differentiation of human induced pluripotent stem cells by Ribavirin: Implication for its cardiac developmental toxicity

Ribavirin has been proven to be an antiviral treatment, whereas there are still risks of hemolysis and congenital malformation. Abnormal cardiac development contributes to the occurrence and development of many heart diseases. However, there is so far no evidence that ribavirin induces human cardiac developmental toxicity. Herein, we employed the cardiac differentiation model of human induced pluripotent stem cells (hiPSCs) to determine the impact of ribavirin on heart development. Our data showed that ribavirin at clinically high concentrations (5 and 10 μM) significantly inhibited the proliferation and differentiation of hiPSCs from mesoderm to cardiac progenitor cells and cardiac progenitor cells to cardiomyocytes, but not from pluripotent status to mesoderm. Meanwhile, DCFH-DA staining revealed that ribavirin could increase ROS content in the mid-phase of differentiation. In addition, ribavirin treatment (1, 5 and 10 μM) remarkably caused DNA damage which was shown by the increase of γH2AX-positive cells and upregulation of the p53 during the differentiation of hiPSCs from mesoderm to cardiac progenitor cells. Moreover, exposuring to ribavirin (5 and 10 μM) markedly upregulated the expression of lncRNAs Gas5 in both mid-phase and late phase of differentiation and HBL1 in the mid-phase. In conclusion, our results suggest that ribavirin is detrimental in cardiac differentiation of hiPSCs, which may be associated with DNA damage, upregulated p53 and increased Gas5. It may provide the evidence for the rational clinical application of ribavirin.

Time course alterations of virus sequences and immunoglobulin titers in a chronic hepatitis E patient.

HepatitisE virus (HEV) can cause chronic infection in immunocompromised hosts. However, the dynamics of HEV during persistent infection is not well understood. To elucidate time course alterations in virus sequences and anti-HEV antibodies during persistent infection, we analyzed the HEV sequences and titers of anti-HEV antibodies from a chronic hepatitisE patient. Serum samples were obtained from a chronic hepatitisE patient under corticosteroid therapy for neurological disease. The titers of anti-HEV antibodies (immunoglobulinA, immunoglobulinM, and immunoglobulinG) in serum samples were detected by enzyme immunoassay. The full or near-full nucleotide sequences of HEV isolated from consecutive serum samples were identified and compared. Phylogenetic analysis was also performed. Alterations of anti-HEV antibodies from a chronic hepatitisE patient were different from those previously reported in acute hepatitisE patients. The virus sequence was unchanged in the period without treatment, but nucleotide mutations were observed after ribavirin treatment was started. In addition, the sequence of this strain had extremely high identity to that isolated from swine liver in Japan. Virus mutations in HEV emerged after ribavirin treatment was started. Sequence analysis may useful for deciding the treatment strategy for chronic hepatitisE patients who did not eliminate the virus with 3months of RBV treatment and inferring the origin of the infection. This report provides insights into the chronicity of hepatitisE, and the impact of persistent infection and ribavirin treatment on the emergence of virus mutations.

Efficacy of Ombitasvir/Paritaprevir/Ritonavir plus Ribavirin in Treatment of Chronic Hepatitis C Patients with End Stage Renal Disease on Regular Hemodialysis

Background: Hepatitis C virus (HCV) infection is associated with more significant morbidity and mortality among dialysis patients than in healthy populations. The fixed-dose tablet (ombitasvir/ paritaprevir/ritonavir) in combination with ribavirin was effective and generally well tolerated in treatment of chronic HCV infected patients with end stage renal disease (ESRD) on hemodialysis. However, limited published data are known about the usefulness of this regimen for treatment of HCV patients with ESRD on hemodialysis. Aim of the work: The aim of this study was to evaluate the safety and efficacy of treatment regimen of ombitasvir (OBV) 25 mg /paritaprevir (PTV) 150 mg /ritonavir (RTV) 100 mg plus generic ribavirin (RBV) 200 mg in Egyptian HCV-infected naive patients with ESRD on regular hemodialysis. Patients and methods: A prospective cohort study involved 40 chronic HCV on regular hemodialysis patients, who were eligible for treatment with combined oral antiviral therapy. Results: The results showed that thirty-five patients [35/40(87.5%)] completed 12 weeks of HCV therapy; they had a virological response at end of therapy and sustained virological response. Anemia was the main observed side effect which lead to discontinuation of the treatment in five patients (12.2%). As these patients were not responding to anemia correction measures (blood transfusion, erythropoietin-stimulating agents, and modification of RBV dose). Conclusion: OBV/PTV/RTV plus Ribavirin can be used in treatment of chronic HCV patients with ESRD on regular hemodialysis.

Incidence of depression in patients with hepatitis C treated with direct-acting antivirals.

Objective:Depression has been associated with hepatitis C, as well as with its treatment with proinflammatory cytokines (i.e., interferon). The new direct-acting antiviral agents (DAAs) have minimal adverse effects and high potency, with a direct inhibitory effect on non-structural viral proteins. We studied the incidence and associated factors of depression in a real-life prospective cohort of chronic hepatitis C patients treated with the new DAAs.Methods:The sample was recruited from a cohort of 91 patients with hepatitis C, of both sexes, with advanced level of fibrosis and no HIV coinfection, consecutively enrolled during a 6-month period for DAA treatment; those euthymic at baseline (n=54) were selected. All were evaluated through the depression module of the Patient Health Questionnaire (PHQ-9-DSM-IV), at three time points: baseline, 4 weeks, and end-of-treatment.Results:The cumulative incidence (95%CI) of major depression and any depressive disorder during DAA treatment was 13% (6.4-24.4) and 46.3% (33.7-59.4), respectively. No differences were observed between those patients with and without cirrhosis or ribavirin treatment (p > 0.05). Risk factors for incident major depression during DAA treatment included family depression (relative risk 9.1 [1.62-51.1]), substance use disorder (11.0 [1.7-73.5]), and baseline PHQ-9 score (2.1 [1.1-3.1]).Conclusions:The findings of this study highlight the importance of screening for new depression among patients receiving new DAAs, and identify potential associated risk factors.

Direct-acting antiviral therapy for hepatitis C: The initial experience of the University of Cape Town/Groote Schuur Hospital Liver Clinic, South Africa.

An estimated 600 000 South Africans are chronically infected with hepatitis C virus (HCV). To date, accurate prevalence data are lacking, but emerging data suggest a significant burden in key populations. Historically, pegylated interferon and ribavirin treatment was challenging, with access limited. The advent of all-oral, short-course direct-acting antiviral (DAA) therapy has revolutionised the management of HCV, being well tolerated and highly effective, although initial cost was a prohibitive factor. To report our initial 2-year experience with DAA therapy at the University of Cape Town/Groote Schuur Hospital Liver Clinic, South Africa (SA). Patients who were viraemic for HCV were offered access to DAA therapy. All relevant demographic, virological, serological and clinical laboratory data were captured in a registry. Liver fibrosis was assessed non-invasively with the FibroScan. DAA regimens were prescribed according to current guidance based on HCV genotype (GT), prior treatment history and degree of fibrosis. On treatment, virological response was recorded and a sustained virological response (SVR) was defined as an undetectable HCV RNA at least 12 weeks after the end of treatment. We report on the first 210 patients treated. Their median (interquartile range (IQR)) age was 52 (42 - 61) years and 65% were male, with men significantly younger than women at 50 (42 - 59) years v. 58 (47 - 67) years, respectively (p=0.001). All GTs were observed, with 1 and 5 most prevalent at 45% and 20%, respectively, and GTs 2, 3 and 4 frequencies of 7%, 11% and 17%, respectively. Extensive subtype diversity for GTs 2 and 4 was present. The median (IQR) HCV viral load was log10 5.9 IU/mL (5.4 - 6.5). A significant proportion of patients (39%) had advanced fibrosis or cirrhosis, with 11% F3 fibrosis and 28% F4. Of those with cirrhosis, 12% were decompensated with Childs-Pugh B or C disease. Of the patients, 19% were HIV co-infected and 2% HBV co-infected. In total, 13% were treatment experienced. The majority of patients were treated with sofosbuvir and ledipasvir (38%), daclatasvir (36%) or velpatasvir (± voxilaprevir, 9%). Less frequent combinations included partitaprevir, ritonavir, ombitasvir ± dasbuvir (11%) and sofosbuvir/ribavirin (5%). The per-protocol SVR was 96% (98% if sofosbuvir/ribavirin is excluded). The majority of treatment failures occurred with GT-4, notably subtype 4r. Mild side-effects were reported in 10% of patients, with none discontinuing therapy. DAA therapy for HCV in a pan-genotypic group of patients, many with advanced liver disease, was highly effective. Our outcomes correspond with existing trial and real-world data for similar treatment. DAA therapy and access need rapid upscaling in SA, especially targeting key populations at point of care.

Clinical Manifestations, Pathogenesis and Treatment of Hepatitis E Virus Infections.

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis throughout the world. Most infections are acute but they can become chronic in immunocompromised patients, such as solid organ transplant patients, patients with hematologic malignancy undergoing chemotherapy and those with a human immunodeficiency virus (HIV) infection. Extra-hepatic manifestations, especially neurological and renal diseases, have also been described. To date, four main genotypes of HEV (HEV1-4) were described. HEV1 and HEV2 only infect humans, while HEV3 and HEV4 can infect both humans and animals, like pigs, wild boar, deer and rabbits. The real epidemiology of HEV has been underestimated because most infections are asymptomatic. This review focuses on the recent advances in our understanding of the pathophysiology of acute HEV infections, including severe hepatitis in patients with pre-existing liver disease and pregnant women. It also examines the mechanisms leading to chronic infection in immunocompromised patients and extra-hepatic manifestations. Acute infections are usually self-limiting and do not require antiviral treatment. Conversely, a chronic HEV infection can be cleared by decreasing the dose of immunosuppressive drugs or by treating with ribavirin for 3 months. Nevertheless, new drugs are needed for those cases in which ribavirin treatment fails.

Somatic pain associated with initiation of interferon-alpha (IFN-α) plus ribavirin (RBV) therapy in chronic HCV patients: A prospective study

ObjectiveThis study is aimed to investigate the association between interferon-alpha (IFN-α) plus ribavirin (RBV) treatment and emergence of somatic pain symptoms in patients with hepatitis C virus (HCV) over a 24-week treatment. MethodIn this prospective cohort study, 297 patients with HCV were evaluated at baseline and 2nd, 4th, 8th, 12th, 16th, 20th, and 24th week with structured Mini-International Neuropsychiatric Interview for Major Depressive Disorder (MDD) diagnosis and the Neurotoxicity Rating Scale (NRS) for somatic symptoms. ResultsEighty-seven out of the 297 patients (29%) developed IFN-α induced depression and had significantly higher somatic pain symptoms as early as the 2nd week and at all the assessment time points (p ​< ​.001). Most depressed patients perceived greatest somatic pain at the 8th week of treatment. Moreover, NRS somatic pain scores after initial therapy strongly correlated with NRS somatic pain scores at all other assessment time points (p ​< ​.001). ConclusionIFN-α therapy induce significant somatic pain as early as the 2nd week of treatment in HCV patients who later developed MDD. Thus, initial NRS somatic pain score after initiation of IFN-α treatment may serve as a reference for the susceptibility of the individual to IFN-α induced depression.

A comparison of hepatitis E and A in a teaching hospital in Northwestern Romania. Acute hepatitis E - a mild disease?

Background and aimsThe incidence of locally acquired hepatitis E has increased in recent years across Europe. There are only few data on hepatitis E in Romania. The purpose of our research was to describe and compare hepatitis E and hepatitis A in adult patients.MethodsWe included all consecutive adult patients with hepatitis E and hepatitis A admitted to the Teaching Hospital of Infectious Diseases, Cluj-Napoca, Romania between January 2017 and August 2019.ResultsHepatitis E incidence increased in 2018–2019 compared to 2017. The average age in hepatitis E (n=48) patients was 50.6 versus 39.1 years in hepatitis A (n=152, not including 262 minors) and two-thirds of the patients in both groups were men. Compared to hepatitis A, patients with hepatitis E presented significantly less modified AST and ALT, bilirubin, prothrombin index and INR levels. We found more comorbidities in hepatitis E patients adjusted for age and gender. Severe forms were found in 5 (3.3%) hepatitis A patients, compared to 12 (25%) of hepatitis E patients, of which 3 died. Ribavirin treatment was considered in 9 patients with acute-on-chronic hepatitis E, immunosuppression, cancers or neurological manifestations, showing good results.ConclusionsWe observed an increased number of hepatitis E cases. Although laboratory results were less modified compared to hepatitis A, we found a higher number of severe hepatitis E cases. Ribavirin treatment seems to be beneficial in patients with preexisting conditions.