Ribavirin Dose Research Articles

Efficacy of Plant Tissue Culture Techniques for Eliminating Black Mulberry Idaeovirus (BMIV) from Infected Black Mulberry (Morus nigra)

Obtaining virus-free plants is a crucial step in disease management that enables reliable and profitable fruit farming. The present study applied various in vitro virus elimination protocols, including apical shoot culture, chemotherapy, thermotherapy, cryotherapy, and their combination, to eliminate black mulberry Idaeovirus (BMIV) from sour black mulberry. First, a shoot tip (0.5–2 mm) culture protocol was optimized, and four ribavirin concentrations (0, 10, 20, and 30 mg/L) were investigated over five weeks as a form of chemotherapy (ch). For the first thermotherapy treatment (Ch + Th1st), chemotherapy treatment was followed by a gradual increase in the temperature (24–33 °C). In another experiment (Th2nd + Ch), in vitro shoots were incubated in the dark for two weeks at two different temperatures (35 ± 1 °C and 37 ± 1 °C, for one week each). Subsequently, the shoot tips were incubated with various ribavirin doses. Finally, cryotherapy (Cr) was used with or without immersing the shoot tips in liquid nitrogen. A two-step RT-PCR was performed to assess the presence of the virus in 7–8-week-old in vitro plants. Th2nd + Ch significantly increased the shoot tip burst and plant survival/morphogenesis compared to the other treatments. Except for the application of cryotherapy, the protocols eliminated BMIV in different proportions, and the highest virus elimination rate (50%) was obtained by applying 30 mg/L ribavirin during the Ch + Th1st treatment. These findings are essential in preventing the dissemination of the virus and enabling the safe movement of germplasm around the world.

Systematic Evaluation of Guidelines for the Diagnosis and Treatment of Hepatitis E Virus Infection.

The hepatitis E virus (HEV) is a zoonotic disease, and infection with HEV in humans primarily causes acute infections and can progress to chronic manifestation in immunocompromised individuals. Over the past decade, guidelines for diagnosing and treating HEV infection have been developed. This study aimed to systematically assess the quality of current guidelines for diagnosing and treating HEV infection, and we analyzed the differences in guideline quality and primary recommendations and explored possible reasons for these differences. Guidelines published between 2013 and 2022 were searched, and studies were identified using selection criteria. The study assessed the quality of the included guidelines using the Appraisal of Guidelines for Research and Evaluation tool, extracted the primary recommendations in the guidelines, determined the highest level of evidence supporting the recommendations, and reclassified the evidence using the Oxford Centre for Evidence-Based Medicine grading system. Seven guidelines were included in the final analysis. The quality of the guidelines varied widely. The discrepancies may have been caused by the lack of external experts, the failure to consider influencing factors in guideline application, and the lack of consideration of the public's opinion. Analysis of the heterogeneity in primary recommendations revealed differences in algorithms for managing chronic HEV infection, the dosage of ribavirin, and a low level of evidence supporting the primary recommendations. Guideline quality and primary recommendations vary considerably. Refinement by guideline developers and researchers would facilitate updating and applying guidelines for diagnosing and treating HEV infection.

Impact of ITPA gene polymorphism for predicting anemia and treatment outcome in HCV infected patients taking Sofosbuvir Ribavirin therapy

BackgroundGlobally, 80 million people are suffering from chronic Hepatitis C virus (HCV) infection. Sofosbuvir ribavirin-based anti-HCV therapy is associated with anemia and other adverse effects. Polymorphisms of Inosine triphosphatase (ITPA) gene may cause functional impairment in the Inosine triphosphate pyrophosphatase enzyme, resulting in enhanced sustained viral response (SVR) and protection from ribavirin-associated anemia in patients on therapy. The study objective was to investigate the effect of Inosine triphosphatase gene polymorphism on SVR achievement, hemoglobin decline and ribavirin dose reduction in patients on therapy.MethodsThis prospective cohort study was of 170 hepatitis C infected patients received 6-month sofosbuvir ribavirin therapy. Patient viral load, reduction in ribavirin amount, liver function test, and complete blood count were noted monthly. Inosine triphosphatase variants rs1127354 and rs7270101 were assessed through the restriction fragment length polymorphism and confirmed using Sanger sequencing. The impact of polymorphism on cumulative reduction of ribavirin, and anti-HCV therapy outcome were studied.ResultsA total of 74.3% of patients had ITPA rs1127354 CC genotype, 25.7% were CA and AA 0%. The frequency of ITPA genotype rs7270101-AA was 95%, AC 5%, and CC was 0%. ITPA rs1127354-CA had a notably positive impact on SVR achievement with a zero-relapse rate. ITPA rs1127354-CA genotype was significantly (P ˂0.05) protective against ≥ 2 g/dl Hb reduction from baseline to 1st, 2nd and 6th months of therapy. During treatment, Hb reduction ≥ 10 g/dl was frequently observed in rs1127354-CC genotype and rs7270101-AA genotype patients. Ribavirin dose reduction was significantly (P ˂0.05) high in rs1127354-CC genotype as compared to genotype CA whereas no significant difference was observed in ribavirin dose reduction in rs7270101 AA and non-AA genotype. Patient baseline characteristics such as age, body mass index, rs1127354-CC genotype, and baseline Hb were significantly associated with significant Hb reduction.ConclusionPretreatment evaluation of ITPA polymorphism can be a diagnostic tool to find out patients at risk of anemia and improve treatment adherence. ITPA genotype rs1127354-CA contributes to improved compliance with ribavirin dose and protects against hemoglobin decline in HCV patients while taking ribavirin-based therapy. However, ITPA rs1127354, rs7270101 polymorphism have no significant impact on SVR achievement.

Associations of ITPA gene polymorphisms with outcomes among chronic hepatitis C patients treated with Peg-interferon/ribavirin: A 5-year follow-up study.

To investigate associations between inosine triphosphatase (ITPA) gene polymorphisms and long-term outcomes among chronic hepatitis C (CHC) patients in Northeast China treated with Peg-interferon (IFN)/ribavirin (RBV). CHC patients who received Peg-IFN-2a/RBV treatment during between 2011 and 2013 at 5 hepatitis centers in Northeast China were enrolled. ITPA single nucleotide polymorphisms rs1127354 and rs7270101 from all patients were detected and their associations with 5-year outcomes were analyzed. A total of 635 patients, including 421 infected with hepatitis C virus (HCV) genotype 1 and 214 infected with non-genotype 1 were included. No significant differences were observed in the distribution frequencies of ITPA rs1127354 variants and ITPase activity between patients with HCV genotype 1 and non-genotype 1. In patients who received more than 80% of the planned RBV dose, the 5-year virological response rate and the improvement in liver fibrosis were higher in those with ITPA rs1127354 non-CC with ITPase activity <25% compared with these outcomes in patients with ITPA rs1127354 CC with 100% ITPase activity. Multiple regression analysis revealed that HCV genotype non-1, low baseline HCV ribose nucleic acid (RNA) levels (≤4 × 105 IU/mL), interleukin-28B rs12979860 CC genotype, low baseline liver fibrosis (Fibroscan 0-2), and ITPA rs1127354 non-CC genotype were independent predictors for a high long-term virological response rate, whereas interleukin-28B rs12979860 CC genotype, ITPA rs1127354 non-CC genotype, and low baseline liver fibrosis were independent predictors for improvement of liver fibrosis. ITPA rs1127354 polymorphisms is predictors of long-term outcomes in CHC patients treated with Peg-IFN/RBV.

Screening of Cirrhotic Compensated Hepatitis C Virus Infected Patients Who Received Oral Direct Acting Antiviral Drugs for Hepatocellular Carcinoma and Other Malignancies

Abstract Background HCV is now recognized as a major factor in the development of severe liver damage as chronic infection is associated with the development of hepatic steatosis, cirrhosis and hepatocellular carcinoma. Aim of the Work screening of our patients for the incidence of hepatocellular carcinoma and other malignancies during or after end of treatment with orally direct acting antiviral drugs to prove or disprove this allegation. Patients and Methods This retrospective observational study was performed at Maadi Military Hospital during the period from July 2015 to July 2016 including 290 naive compensated cirrhotic hepatitis C virus infected patients with no prior history of hepatocellular carcinoma or any other malignancy and divided into 5 groups: Group (A) patients treated with combined sofosbuvir and ribavirin for 24 weeks. Group (B) patients treated with combined sofosbuvir and daclatasvir and low dose ribavirin for 12 weeks. Group(C) patients treated with combined sofosbuvir and ledipasvir with weight based ribavirin for 12 weeks. Group (D) patients with chronic renal failure on regular hemodialysis treated with combined ompitasvir+paritaprevir+ritonavir and low dose ribavirin for 12 weeks. Group (E) patients with the same criteria were taken from the waiting list of treatment and studied as the control group and were subjected to the same investigations and follow up. Results Highly significant increase in HCC prevalence in A group (23.3%) during follow up period. Significant increase in HCC prevalence in B group (8%) during follow up period. Non-significant difference in HCC prevalence in C group; during follow up period. In group D; non-significant difference in HCC prevalence during treatment and follow up periods. There was no detected occurrence of HCC or any other malignancies during the course of the study in group E. Conclusion Increased HCV detection combined with the availability of simple, well-tolerated treatment regimens can potentially reduce the need for liver transplantation and reduce HCV-related mortality. No evidence of an increased risk of de novo HCC by patients treated with interferon free SOF-based regimens. However, cirrhosis was strongly associated with the short-term development of HCC after HCV eradication. Treatment of HCV in patients with CKD is highly effective, with SVR12 rates similar to those seen in patients without CKD. The role of SVR by DAAs on the incidence or recurrence of hepatocellular carcinoma (HCC) is still a matter of debate, although it is known that SVR does not eliminate the risk of HCC.

Efficacy of Sofosbuvir and Ribavirin in Children Presenting with Hepatitis C at Tertiary Care Hospital, Faisalabad

Objectives: To assess efficacy, safety, and outcome of combination of Sofosbuvir and Ribavirin in various genotypes, in children with hepatitis C infection. Study design and setting: It was a quasi-experimental study, conducted at the Gastroenterology and Hepatology Department, Children Hospital Faisalabad, from August 2017 to August 2021. Methodology: 50 confirmed cases of HCV infection aged 5 to 18 years, were given an oral dose of Sofosbuvir and Ribavirin daily for 12 weeks. PCR was assessed at 4 weeks (for Rapid Viral Response (RVR)) and repeated at 8 weeks and 12 weeks (for Early Viral Response (EVR)) and again 12 weeks after the completion of therapy for Sustained Viral Response (SVR)). Primary outcome was the number who achieved an SVR at 12 weeks (SVR12) after completion of treatment with a viral load below quantitation level. Results: Genotype 3 was found in 80% , type 1 in 6% , type 2 in 4% and 10% were untypeable. All children were PCR positive at presentation; 96% became PCR negative at 4 weeks (RVR), while 100 percent were negative at 8 weeks, 12 weeks (EVR), and SVR 12 weeks after completion of 12 week course was 100%. Conclusion: Although majority of patients were Genotype 3, 12 week course of Sofosbuvir and Ribavirin of hepatitis C-infected children was highly effective, with 100 percent PCR-negative cases at 8 weeks and 12 weeks with only minor side effects, and, SVR of 100% twelve weeks after completion of therapy.

Matrine combined with Osthole inhibited the PERK apoptosis of splenic lymphocytes in PCV2-infected mice model

BackgroundPorcine circovirus type 2 (PCV2) is one of the major pathogens commonly found in pigs, which causes immunosuppression and apoptosis. Vaccination and a single drug cannot totally prevent and treat PCV2 infection. Our previous in vitro study reported that the synergistic anti-PCV2 effect of Matrine and Osthole was better than that of Matrine or Osthole alone, This study was aimed to evaluate the synergistic anti-PCV2 effect as well as the underline molecular mechanism of Matrine and Osthole in Kunming (KM) mice model infected with PCV2. KM mice were randomly divided into 8 groups namely control group, PCV2 infected, Matrine combined with Osthole high dose treatment (40 mg/kg + 12 mg/kg), medium dose treatment (20 mg/kg + 6 mg/kg), low dose treatment (10 mg/kg + 3 mg/kg), Matrine treatment (40 mg/kg), Osthole treatment (12 mg/kg) and Ribavirin positive control (40 mg/kg) groups. PCV2 was intraperitoneally (i.p.) injected in all mice except the control group. 5 days of post-infection (dpi), mice in different treatment groups were injected i.p. with various doses of Matrine, Osthole and Ribavirin once daily for the next 5 consecutive days.ResultsThe synergistic inhibitory effect of Matrine and Osthole on PCV2 replication in mouse liver was significantly heigher than that of Matrine and Osthole alone. The expression of GRP78, p-PERK, p-eIF2α, ATF4, CHOP, cleaved caspase-3 and Bax proteins were significantly reduced, while that of Bcl-2 was significantly increased in Matrine combined with Osthole groups, which alleviated the pathological changes caused by PCV2, such as interstitial pneumonia, loss of spleen lymphocytes, infiltration of macrophages and eosinophils.ConclusionsThe synergistic anti-apoptotic effect of Matrine and Osthole was better than their alone effect, Both Matrine and Osthole had directly inhibited the expression of PCV2 Cap and the apoptosis of spleen cells induced by PCV2 Cap through the PERK pathway activated by endoplasmic reticulum (ER) GRP78. These results provided a new insight to control PCV2 infection and provide good component prescription candidate for the development of novel anti-PCV2 drugs.

Fatigue in Patients with Chronic Hepatitis C.

This study aimed to explore the factors associated with fatigue in chronic hepatitis C patients before and at 4, 8, 12, 16, 20, and 24 weeks after antiviral therapy. The study employed a prospective and repeated-measures design. The Chinese version of the brief fatigue inventory (BFI-C) and the Pittsburg sleep quality index (PSQI) were employed to collect data. Pegylated Interferon plus Ribavirin dosages and serum values (hemoglobin, alanine aminotransferase [ALT], and aspartate aminotransferase [AST]) were monitored before and during the antiviral therapy at 4, 8, 12, 16, 20, and 24 weeks. The study enlisted 115 patients as participants. Multivariate analysis indicated that gender, educational level, body mass index (BMI), and hemoglobin level were significant determinants of patients' fatigue. When hemoglobin levels in the patients decreased in week 4 and continued to fall to the nadir at week 12, it prompted the healthcare providers to assess their fatigue levels and initiate proactive interventions as needed.

Micro-elimination of hepatitis C in patients with chronic kidney disease: an Egyptian single-center study

Background and aimsMicro-elimination of hepatitis C in renal patients is crucial. This study aims to assess the efficacy and safety of directly acting antivirals in chronic kidney disease patients and the effect of treatment on kidney functions.ResultsThis prospective cohort study included 77 chronic HCV-infected patients with chronic kidney disease. Patients were consented and treated for 12 weeks with either sofosbuvir and daclatasvir ± ribavirin if glomerular filtration rate was > 30 mL/min per 1.73m2 or ritonavir-boosted paritaprevir-ombitasvir-ribavirin if it was < 30 mL/min per 1.73m2. Patients were divided into two categories (responders versus non-responders). Predictors of response to treatment were statistically analyzed through logistic regression analysis. Sixty-two patients received ritonavir-boosted paritaprevir-ombitasvir-ribavirin, 3 received sofosbuvir and daclatasvir, and 12 received sofosbuvir and daclatasvir plus ribavirin. Most patients were on hemodialysis (n = 36) while 31 were stage 3 kidney disease. All patients completed their treatment course; ribavirin doses were adjusted or stopped in patients who developed anemia (40%). Seventy-two patients (93.5%) achieved sustained virological response 12 weeks following end-of-treatment. Five patients (6.5%) were non-responders, 4 of whom were on hemodialysis (p = 0.179). All non-responders were on ritonavir-boosted paritaprevir-ombitasvir-ribavirin. The mean serum creatinine level at weeks 4 and 8 of treatment demonstrated significant improvement compared to pretreatment values (p < 0.001) in patients on conservative therapy.ConclusionTreatment of chronic kidney disease patients for chronic hepatitis C with directly acting antivirals is safe, efficacious with high response rates and likely to improve renal functions if started early in the course of kidney disease.

Study the response of Qurevo (ombitasvir, paritaprevir, and ritonavir) in end-stage renal disease patients with hepatitis C virus

BackgroundOut of the 185 million people infected with hepatitis C virus (HCV) worldwide according to the World Health Organization (WHO), Egypt had the highest prevalence of HCV reaching 13% of its population with an estimated number of 12 million people. The prevalence of HCV infection among hemodialysis (HD) patients ranged from 6 to 60%. HD patients have an increased overall mortality risk if they have chronic HCV when compared to those without HCV infection. Treatment of HCV with the new direct-acting antiviral agent (DAA) therapy Qurevo “ombitasvir/paritaprevir/ritonavir” with ribavirin in ESRD was approved in many countries compared to traditional HCV treatment that faced restrictions in the setting of chronic kidney disease (CKD).Aim of the studyTo evaluate the efficacy and safety of Qurevo/ribavirin regimen in HCV-infected HD patients.Patients and methodsA prospective cohort study evaluated the outcome of 12-week ombitasvir (NS5A inhibitor)/paritaprevir (NS3/4A protease inhibitor)/ritonavir with ribavirin combination therapy for 50 HCV-infected HD patients, over a period of 15 months from December 2016 to February 2018. The primary endpoint was sustained virologic response 12 weeks after therapy (SVR12) and after 24 weeks of therapy (SVR24).ResultsThe SVR12 rate was 96% (48/50); 2 patients (4%) were non-responders to treatment at SVR12, and another 2 (4%) were relapsers after SVR12. As regards the adverse events, the most frequent were fatigue/asthenia in 44 patients (88%) and worsening anemia (Hb dropped to < 10 g/dl) in 42 patients (84%). GIT upset occurred in 10 patients (20%), sleep disorders in 8 patients (16%), decreased appetite in 8 patients (16%), respiratory distress in 6 patients (12%), headache and dizziness in 6 patients (12%), and muscle spasms in 4 patients (8%). Itching (pruritus) occurred in 3 patients (6%). Death occurred in 4 patients (8%) after SVR24 most probably not due to DAA but may be due to myocardial infarction, pulmonary edema, severe hypotension on hemodialysis sessions, and shock due to blood loss in retroperitoneal hematoma following peritoneal dialysis not related to DAA therapy. Hepatic decompensation, hypersensitivity (angioedema), teratogenicity, and drug interactions did not occur in any patient (0%). Other events occurred in 11 patients (22%). They were parenchymal liver changes in ultrasound at the end of therapy after being normal before therapy (in 3 patients), thrombocytopenia, increased alkaline phosphatase, hiccough, deterioration of hypertension, urinary tract infection, lower limb cellulitis, vaginal bleeding, and chest infection (in 1 patient each). SVR12 was achieved in 100% of patients who had to stop or modify the ribavirin dose; this means that ribavirin absence did not affect the SVR in these patients.ConclusionOur results confirm the efficacy of Qurevo “ombitasvir/paritaprevir/ritonavir” with ribavirin combination therapy in ESRD patients (on regular hemodialysis) with HCV infection with anemia as the most frequent adverse event.

Hepatitis E case series: A UK experience.

The incidence of hepatitis E continues to increase and in immunocompromised patients can lead to chronic infection. Management of hepatitis E has evolved over time, with the first step being a reduction of immunosuppression followed by treatment with ribavirin. The European Association for the Study of Liver guidelines support treatment with ribavirin although the optimum dose and regime is unknown. This series reviews eight chronically infected cases treated between 2018 and 2021 in two UK centres (Ipswich Hospital and Addenbrooke's Hospital). Treatment response was defined primarily as sustained virological response at 12 weeks (SVR12) following the cessation of treatment and secondly as sustained virological response at 24 weeks (SVR24). The median dose of ribavirin given daily was 600 mg. The management of five of the eight cases was in line with the guidelines, and treatment was stopped after 12 weeks. Two of these five patients achieved SVR (40%). The remaining three cases were given a 24-week course based on clinical judgement, and all achieved SVR (100%). The three patients who relapsed received a second 24-week course of treatment and achieved SVR. Therefore, with a 24-week course, a 100% treatment success rate was attained. In chronic hepatitis E, a 24-week course of ribavirin would achieve optimum clearance rates with a single course of treatment. Ensuring the highest dose of ribavirin as possible (aiming to reach 800 mg daily) and attempts to reduce immunosuppressive therapy safely may also be relevant to achieving SVR.

Assessment of efficacy and safety of daclatasvir, sofusbuvir and ribavirin regimen for 12 weeks as compared to daclatasvir and sofusbuvir combination regimen for 24 weeks in decompensated cirrhotic patients due to hepatitis C virus genotype 3 infection

Background: Assessment of efficacy and safety of daclatasvir+sofosbuvir+ribavirin (DCV+ SOF+ RBV) for 12 weeks as compare to daclatasvir and sofusbuvir for 24 weeks in decompensated cirrhotic patients due to hepatitis C virus (HCV) genotype 3 infection.Methods: An observational, prospective, COHORT study over 1 year, in decompensated cirrhosis due to G3-HCV infected adult patients. Treatment was a combination of sofosbuvir 400 mg/day+daclatasvir 60 mg/day, with or without a weight-adjusted dosing of ribavirin for 12 or 24 weeks. The primary efficacy endpoint was sustained virologic response rates 12 weeks after therapy (SVR 12). The primary safety endpoint was treatment withdrawal rates secondary to severe adverse events.Results: The 32 patients were screened and 2 were excluded, one patient due to associated HBV+, one patient due to severe anemia. 30 patients were randomized. All 30 randomized patients were divided into two groups. Group 1 was given SOF+DCV+RBV for 12 weeks while group 2 patients were given SOF+DCV for 24 weeks. 81.8% of the participants in the group1 achieved SVR 12. The 90.9% of the participants in the group 2 achieved SVR12 (p=1). No other patient or treatment basal variables influenced the treatment effectiveness. No patient treatment withdrawal secondary to severe adverse events was observed.Conclusions: Both the regimen SOF+DCV with or without RBV are highly efficacious and safe. Addition of RBV can reduce the treatment duration to 12 weeks, and it will further improve compliance and more convenient for the patients.

Clinical Pharmacist’s Role in Successful Retreatment of Glecaprevir/Pibrentasvir Virologic Failure with Prolonged Treatment Duration and Low Dose Ribavirin in Hepatitis C Patient with End-Stage Renal Disease: A Case Report

Clinical Pharmacist’s Role in Successful Retreatment of Glecaprevir/Pibrentasvir Virologic Failure with Prolonged Treatment Duration and Low Dose Ribavirin in Hepatitis C Patient with End-Stage Renal Disease: A Case Report

Antiviral Combination Clinically Better Than Standard Therapy in Severe but Not in Non-Severe COVID-19.

PurposeDefinitive antiviral treatment is not available for COVID-19 infection, with the exception of remdesivir, which still evokes many doubts. Various monotherapy or combination therapies with antivirals or other agents have been tried. The present study aims to evaluate the therapeutic potential of hydroxychloroquine and lopinavir–ritonavir in combination with ribavirin in mild–severe COVID-19.Patients and MethodsA single-center, open-label, parallel-arm, stratified randomized controlled trial evaluated the therapeutic potential of combination antiviral therapies. Enrolled patients in the severe category were randomized into three groups: (A) standard treatment, (B) hydroxychloroquine+ribavirin+standard treatment, or (C) lopinavir+ritonavir+ribavirin+standard treatment; while the non-severe category comprised two groups: (A) standard treatment or (B) hydroxychloroquine+ribavirin. Combination antivirals were given for 10 days and followed for 28 days. The primary endpoints were safety, symptomatic and laboratory recovery of organ dysfunctions, and time to SARS-CoV-2 RT-PCR negative report.ResultsIn total, 111 patients were randomized: 24, 23, and 24 in severe categories A, B, and C, respectively, and 20 in each of the non-severe groups. Two patients receiving ribavirin experienced drug induced liver injury, and another developed QT prolongation after hydroxychloroquine. In the severe category, 47.6%, 55%, and 30.09% in A, B, and C groups, respectively, showed symptomatic recovery, compared to 93.3% and 86.7% in A and B groups, respectively, in the non-severe category at 72 hours (P>0.05).ConclusionThough the results failed to show statistical superiority of the antiviral combination therapies to that of the standard therapy in both the severe and non-severe categories in symptomatic adult patients of COVID-19 due to very small sized trial, clinically hydroxychloroquine+ribavirin therapy is showing better recovery by 7.4% than standard therapy in the former category. However, results do indicate the benefit of standard therapy in the non-severe category by 6.6%. Furthermore, the dose of ribavirin needs to be reconsidered in the Indian population.

Treatment of Chronic Hepatitis C Virus Using Direct Acting Antivirals in Geriatric Egyptian Patients.

There is high proportion of geriatric patients who acquired chronic hepatitis C virus infection. There is a shortage in evidence- based data as regards direct-acting antivirals in this group of patients. The aim was to assess safety, efficacy, and tolerability of direct acting antiviral drugs in Egyptian geriatric patients. This prospective study was performed on 177 patients with chronic hepatitis C and administrated different regimens of direct acting antivirals. Patients were divided into two groups: Group I: patients below 65 years old (N = 143), and Group II: patients > 65 years old (N = 34). Pretreatment history taking, baseline characteristics, and investigations were done for both groups. Follow up was made to detect treatment efficacy and adverse effects. Geriatric group were found to have more comorbidities (diabetes mellitus, hypertension, and cardiomyopathy); also liver cirrhosis. Minor adverse effects occurred in both groups without significant difference included fatigue, insomnia, headache, and dizziness. Vomiting, diarrhea, and skin rash occurred in group II more than group I. Leucopenia, thrombocytopenia, jaundice, and significant anemia occurred without significant difference between both groups. Eighteen patients (25%) of 72 patients who took ribavirin had to reduce ribavirin dose or to stop it. The overall treatment response in the entire study was 97.7% without significant difference between both groups. Direct acting antivirals are recommended regardless the age. These drugs are effective and tolerable in elderly patients. Attention to other comorbidities, drug-drug interactions, and follow up are recommended.

Effective treatment of acute hepatitis E by ribavirin in a patient complicated with renal impairment: a case report

AbstractBackgroundHepatitis E infections are the most common cause of acute viral hepatitis worldwide. High‐risk patients such as the immunocompromised or those with a background of liver disease co‐infected with hepatitis E virus (HEV) have particularly high morbidity and mortality rates. Currently, there are no approved treatments for acute infections. Although ribavirin is proposed as a viable option, dosing in renally impaired patients is not well established.AimTo present a case describing ribavirin use in the treatment of acute hepatitis E infection, complicated by acute kidney injury.Clinical detailsA 56‐year‐old man presented to hospital with severely deranged liver function tests and jaundice. Serology tests confirmed diagnoses of acute hepatitis E and ribavirin was commenced. Acute renal impairment developed and ribavirin was reduced to 200 mg p.o. in the morning and 400 mg p.o. at night for a total of four weeks. A total of 12 weeks’ therapy was completed.OutcomesLiver function tests (LFTs) showed drastic and significant improvement within one week of commencing ribavirin. Levels largely normalised by four weeks of therapy. No adverse events were reported throughout ribavirin therapy and HEV reactivation was not observed.ConclusionRibavirin may be an effective and safe treatment for acute hepatitis E infections with concurrent acute kidney impairment. In this case, adjusting ribavirin doses to renal function led to a good clinical outcome, as highlighted by the normalisation of LFTs. Further studies are required to establish an appropriate ribavirin dosing regimen among patients with HEV, particularly in the context of renal impairment.

Ribavirin Therapy in Immunodeficient Patients with Chronic Hepatitis E Virus Infection

Hepatitis E virus (HEV) infection, usually self-limiting in immunocompetent individuals, may adopt a chronic course in immunodeficient patients. A low threshold for HEV screening in immunodeficient patients is advocated so early management can be initiated to minimise liver injury. This retrospective, observational study evaluated all cases (n=11) of chronic HEV diagnosed in immunodeficient patients in 2 university hospitals in Bristol, UK between February 2014 and October 2017. We report our experiences in the management of chronic HEV including ribavirin use. No patients achieved viral clearance spontaneously or with reduction of immunosuppression and so all were treated with ribavirin. The median time between chronic HEV diagnosis and initiation of ribavirin was 91 days (range, 1–293 days). The median ribavirin dose at initiation was 1000 mg/day (range 800-1200 mg/day) and at cessation was 900 mg/day (range 600–1200 mg/day), reduced due to anaemia. Different end points guided treatment cessation including negative HEV RNA PCR serology +/- negative stool HEV RNA PCR +/- biochemical remission at various time points. Following ribavirin therapy, HEV relapse occurred in 1 patient. The mean duration of ribavirin therapy, excluding the patient who was re-treated, was 4.6 months. One significant adverse event of severe anaemia requiring transfusion was observed. This case series supports the use of ribavirin monotherapy for chronic HEV in immunodeficient patients. Anaemia commonly developed prompting ribavirin dose reduction. We advocate 2 consecutive negative serum and stool HEV RNA PCR results sampled at 4 weekly intervals to guide ribavirin cessation.

Sofosbuvir-based therapies in genotype 2 hepatitis C virus cirrhosis: A real-life experience with focus on ribavirin dose.

This study aimed to investigate the efficacy and safety of sofosbuvir‐based therapies for the treatment of cirrhosis from hepatitis C virus (HCV) genotype 2 infection. Data of all consecutive HCV genotype 2 cirrhotic patients who started sofosbuvir‐based treatments between January 2015 and March 2017 in eight Italian tertiary hospitals were collected retrospectively. Overall, 273 patients (Child A: 94.5%) were enrolled. In the 194 subjects treated with sofosbuvir/ribavirin, median initial ribavirin dosage was 13.9 mg/kg/day, and therapy duration was 16 weeks. Sustained virological response (SVR) rates were 93.8% in intention‐to‐treat (ITT) and 95.3% in per‐protocol (PP) analyses for the 129 treatment‐naïve patients, and 96.9% (ITT) and 98.4% (PP) for the 65 treatment‐experienced subjects. Adverse events were reported in 142 patients (73.2%), but only 1.5% discontinued treatment. Eighty‐eight subjects with treatment‐induced anemia (mild: 34.5%, moderate: 7.7%, severe: 3.1%) had to reduce ribavirin dosage, but SVR rates were comparable to the weight‐based dose group, both in ITT (95.4% and 94.3%) and PP (97.7% and 95.2%) analyses, respectively. Moreover, ITT and PP SVR rates were similar between shorter (<20 weeks) (94.1% and 96.0%, respectively) and prolonged (≥20 weeks) regimens (95.7% and 96.7%, respectively). SVR rates in the 79 subjects treated with sofosbuvir/daclatasvir (without ribavirin) were similar (ITT: 96.2%; PP: 97.4%, respectively), without de novo/worsening anemia. In conclusion, in a real‐life study centered on genotype 2 patients with well‐compensated cirrhosis, sofosbuvir‐based regimens were associated with good SVR and tolerability rates, regardless of previous antiviral treatments, without a significant impact of on treatment ribavirin dose reductions.

Analysis of the clinical features and the risk factors of severe adenovirus pneumonia in children

Objective: To analyze the clinical characteristics, risk factors for critical illness and death of severe adenovirus pneumonia in children, so as to provide clinical evidences for early diagnosis and reliable treatment. Methods: A total of 75 pediatric cases with severe adenovirus pneumonia admitted to Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January to October 2019 were studied. The clinical features, laboratory and imaging data, therapeutic approaches, efficacy of the treatments and prognosis were investigated retrospectively. Patients were divided into severe group and critical group. Chi square test and Mann-Whitney U rank sum test were used to analyze the data of the two groups. The risk factors for critical illness and death were analyzed by univariate and multivariate Logistic regression. Results: Among the 75 children, there were 52 males and 23 females, aged from 3 months to 8 years, including 30 of severe cases and 45 of critical case. The positive rate of adenovirus antigen in nasopharyngeal swab was 21% (15/72), and the positive rate of serum adenovirus IgM antibody was only 13% (10/75). However, the positive rate of adenovirus nucleic acid in nasopharyngeal swab was 75% (21/28). What is more, the positive rates of metagenomics next generation sequencing (mNGS) in plasma and bronchoalveolar lavage fluid were 92% (33/36) and 96% (54/56), respectively, of which 95% (63/66) were confirmed as adenovirus type 7. Relatively high dose of ribavirin and integrated therapeutic approaches (respiratory support, glucocorticoids, immunoglobulin and organ supportive therapies) were used. The recovery rate was 77% (58/75), the improvement rate was 8% (6/75) and the mortality rate was 15% (11/75). The proportion of children with the duration of fever longer than 3 days after ribavirin treatment in the critical group was significantly higher than that in the severe group(51% (18/35) vs. 8% (2/26), χ2=12.949, P<0.05). The risk factors for critical illness were younger than 4 years, longer duration of fever before and after admission to PICU, oxygenation index<300 mmHg (1 mm Hg=0.133 kPa), ferritin>1 000 μg/L, lactate dehydrogenase (LDH)>1 500 U/L, 5 lung lobes involvement, pleural effusion and (or) air leakage (all P<0.05). Among them, 5 lung lobes involvement was the independent risk factor for critical illness (adjusted OR=49.641, 95%CI 4.186-588.618, P=0.002). Risk factors for death included longer duration of fever after being admitted to PICU, oxygenation index<100 mmHg, ferritin>2 000 μg/L, interleukin (IL)-6>100 ng/L, LDH>1 500 U/L, pleural effusion and (or) air leakage (all P<0.05). Among them, IL-6>100 ng/L was the independent risk factor for the mortalities of critically ill children (adjusted OR=16.094, 95%CI 2.059-25.787, P=0.008). Conclusions: The mortality rate of severe pediatric adenovirus pneumonia caused by adenovirus type 7 is high. High positive rates of adenovirus nucleic acid in nasopharyngeal swabs and mNGS in plasma or bronchoalveolar lavage fluid contribute to early diagnosis, and mNGS can also be used for serotyping. Younger children under 4 years of age, persistent fever, extensive pulmonary lesions and significantly increased inflammatory cytokines such as IL-6 are warning indicators for critical illness and poor prognosis. Relatively high dose of ribavirin combined with integrated therapeutic approaches are beneficial for prognosis.

Association of inosine triphosphate pyrophosphatase gene polymorphisms with ribavirin combined with direct-acting antiviral agent in treatment of hepatitis C patients with hemolytic anemia

Objective To investigate the influencing factors for ribavirin (RBV)-induced hemolytic anemia in the treatment of chronic hepatitis C, and to provide a reference for the early prediction of ribavirin-related hemolytic anemia in clinical practice. Methods A total of 49 patients with chronic hepatitis C who attended or were hospitalized in Hebei Petrochina Central Hospital from January 2018 to July 2019 and received antiviral therapy with direct-acting antiviral agent (DAA) and RBV were enrolled, with a major allele of C allele and a minor allele of A allele at the rs1127354 locus of the inosine triphosphate pyrophosphatase (ITPA) gene, and the patients with AA and AC genotypes were compared with those with CC genotype. During treatment, RBV was reduced to 600 mg when hemoglobin (Hb) level was Results A total of 49 patients were enrolled in this study, among whom 22 had chronic hepatitis C and 27 had liver cirrhosis, with a sustained virologic response (SVR) rate of 95.9%. The dose of RBV was reduced in 3 patients (2 in the AA/AC group and 1 in the CC group) due to anemia, and RBV was withdrawn in 3 patients (1 in the AA/AC group and 2 in the CC group); all these 6 patients had liver cirrhosis and finally achieved SVR. During the anti-HCV therapy with DAA+RBV, there was relatively mild RBV-related hemolysis, and the maximum reduction in Hb from baseline was compared between the patients with AA/AC genotype at ITPA rs1127354 and those with CC genotype, which showed no significant difference between the two groups (Z=-0.18, P=0.87). Conclusion During the treatment with RBV+DAA, RBV is withdrawn or reduced for liver cirrhosis patients due to anemia, and no obvious statistical relation is observed between ITPA genotype and the maximum reduction in Hb from baseline. Therefore, detection of ITPA genotype before the application of RBV does not improve safety during treatment, and it is not recommended to perform conventional detection of ITPA gene polymorphisms.