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Journal of Viral Hepatitis Dec 2015Hepatitis E viral infection can lead to a chronic infection in immunocompromised patients, resulting in progressive liver disease and cirrhosis. Isolated cases have... (Review)
Review
Hepatitis E viral infection can lead to a chronic infection in immunocompromised patients, resulting in progressive liver disease and cirrhosis. Isolated cases have shown that treatment with ribavirin or pegylated interferon-α can result in viral eradication. This systematic review evaluated efficacy and safety of both treatments in chronic hepatitis E. A systematic literature search was performed on PubMed, Web of Science and clinicaltrials.gov for articles and abstracts. The keywords '"Hepatitis E" or HEV' AND 'ribavirin or Rebetol or Copegus' OR 'pegylated interferon OR peginterferon' were combined. The primary outcome was sustained viral response (SVR). Secondary endpoints include rapid viral response (RVR), relapse rates and side effects. Twenty-four studies matched our criteria, representing a total of 105 ribavirin-treated and 8 pegylated interferon-treated patients. The majority of patients had a solid organ transplant. Sixty-four per cent of ribavirin-treated patients achieved a SVR at 6 months after treatment cessation compared to 2/8 peginterferon-treated patients. Ribavirin was relatively well tolerated with the main side effect being anaemia, requiring dose reduction in 28% of patients. Peginterferon leads to acute transplant rejection in 2/8 patients. Ribavirin monotherapy appears to be an effective and safe treatment in all immunocompromised patients with chronic hepatitis E. The use of pegylated interferon in transplant patients may lead to transplant rejection and is not recommended. Therefore, ribavirin should be the antiviral treatment of choice in chronic hepatitis E.
Topics: Adult; Antiviral Agents; Female; Graft Rejection; Hepatitis E; Hepatitis E virus; Humans; Interferon alpha-2; Interferon-alpha; Male; Middle Aged; Organ Transplantation; Polyethylene Glycols; RNA, Viral; Recombinant Proteins; Ribavirin; Treatment Outcome
PubMed: 25760481
DOI: 10.1111/jvh.12403 -
Journal of Viral Hepatitis Apr 2021Hepatitis C virus infection (HCV) may be associated with a greater risk of cardiovascular disease (CVD), and the evidence for whether antiviral therapy for HCV could... (Meta-Analysis)
Meta-Analysis
Hepatitis C virus infection (HCV) may be associated with a greater risk of cardiovascular disease (CVD), and the evidence for whether antiviral therapy for HCV could reduce the risk of CVD events is inconsistent. The aim of this meta-analysis was to investigate the association between anti-HCV treatment and the risk of CVD. We searched PubMed, EMBASE and Cochrane Library databases from inception to 20 August 2020. The pooled hazard ratio (HR) with 95% confidence interval (CI) of the risk of CVD events [any CVD, coronary artery disease (CAD) and stroke] was calculated using the random-effects model. A total of eleven studies, including 309,470 subjects, were enrolled in this meta-analysis. Among those, four studies reported on any CVD between anti-HCV-treated and anti-HCV-untreated patients, five studies reported on CAD, and five studies reported on stroke. Also, five studies reported on any CVD between patients with sustained virological response (SVR) and without SVR. Overall, antiviral therapy for HCV was associated with a reduced risk of any CVD (HR = 0.64, 95% CI: 0.50-0.83), CAD (HR = 0.73, 95% CI: 0.55-0.96) and stroke (HR = 0.74, 95% CI: 0.64-0.86). Besides, we found that SVR was associated with a significant decrease in any CVD compared with non-SVR (HR = 0.74, 95% CI: 0.60-0.92). In conclusion, this meta-analysis demonstrated that antiviral therapy for HCV was associated with a reduced risk of CVD events. In addition, the risk of CVD events was lower in individuals with SVR compared with those without SVR.
Topics: Antiviral Agents; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Humans; Sustained Virologic Response
PubMed: 33452699
DOI: 10.1111/jvh.13469 -
Canadian Journal of Gastroenterology =... Oct 2013Depression complicates interferon-based hepatitis C virus (HCV) antiviral therapy in 10% to 40% of cases, and diminishes patient well-being and ability to complete a... (Meta-Analysis)
Meta-Analysis Review
Antidepressant prophylaxis reduces depression risk but does not improve sustained virological response in hepatitis C interferon recipients without depression at baseline: a systematic review and meta-analysis.
BACKGROUND
Depression complicates interferon-based hepatitis C virus (HCV) antiviral therapy in 10% to 40% of cases, and diminishes patient well-being and ability to complete a full course of therapy. As a consequence, the likelihood of achieving a sustained virological response (SVR [ie, permanent viral eradication]) is reduced.
OBJECTIVE
To systematically review the evidence of whether pre-emptive antidepressant prophylaxis started before HCV antiviral initiation is beneficial.
METHODS
Inclusion was restricted to randomized controlled trials in which prophylactic antidepressant therapy was started at least two weeks before the initiation of HCV antiviral treatment. Studies pertaining to patients with active or recent depressive symptoms before commencing HCV antiviral therapy were excluded. English language articles from 1946 to July 2012 were included. The MEDLINE, Embase and Cochrane Central databases were searched. Where possible, meta-analyses were conducted evaluating the effect of antidepressant prophylaxis on SVR and major depression as well as on Montgomery-Asberg Depression Rating Scale and Beck Depression Index scores at four, 12 and 24 weeks. The Cochrane Collaboration tool was used to assess bias risk.
RESULTS
Six randomized clinical trials involving 522 patients met the inclusion criteria. Although the frequency of on-treatment clinical depression was decreased with antidepressant prophylaxis (risk ratio 0.60 [95% CI 0.38 to 0.93]; P=0.02; I2=24%), no benefit to SVR was identified (risk ratio 1.08 [95% CI 0.74 to 1.57]; P=0.69; I2=58%).
CONCLUSION
This practice is not justified to improve SVR in populations free of active depressive symptoms leading up to HCV antiviral therapy.
Topics: Antidepressive Agents; Antiviral Agents; Depressive Disorder; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Humans; Interferons; Risk
PubMed: 24106729
DOI: 10.1155/2013/832689 -
Leukemia Jun 2021Data on the efficacy and safety of interferon (IFN)-α for the treatment of essential thrombocythemia (ET) and polycythemia vera (PV) are inconsistent. We conducted a... (Meta-Analysis)
Meta-Analysis
Data on the efficacy and safety of interferon (IFN)-α for the treatment of essential thrombocythemia (ET) and polycythemia vera (PV) are inconsistent. We conducted a systematic review and meta-analysis and searched MEDLINE and EMBASE via Ovid, Scopus, COCHRANE registry of clinical trials, and Web of Science from inception through 03/2019 for studies of pegylated IFN (peg-IFN) and non-pegylated IFN (non-peg-IFN) in PV and ET patients. Random-effects models were used to pool response rates for the primary outcome of overall response rate (ORR) defined as a composite of complete response, partial response, complete hematologic response (CHR) and partial hematologic response. Peg-IFN and non-peg-IFN were compared by meta-regression analyses. In total, 44 studies with 1359 patients (730 ET, 629 PV) were included. ORR were 80.6% (95% confidence interval: 76.6-84.1%, CHR: 59.0% [51.5%-66.1%]) and 76.7% (67.4-84.0%; CHR: 48.5% [37.8-59.4%]) for ET and PV patients, respectively. In meta-regression analyses results did not differ significantly for non-peg-IFN vs. peg-IFN. Annualized rates of thromboembolic complications and treatment discontinuation due to adverse events were low at 1.2% and 8.8% for ET and 0.5% and 6.5% for PV patients, respectively. Both peg-IFN and non-peg-IFN can be effective and safe long-term treatments for ET and PV.
Topics: Antiviral Agents; Humans; Interferon-alpha; Polycythemia Vera; Thrombocythemia, Essential
PubMed: 32868875
DOI: 10.1038/s41375-020-01020-4 -
Alimentary Pharmacology & Therapeutics May 2013Chronic hepatitis C (CHC) infection is a risk factor for both the development of end-stage liver disease and hepatocellular carcinoma (HCC). Globally, approximately 170... (Review)
Review
BACKGROUND
Chronic hepatitis C (CHC) infection is a risk factor for both the development of end-stage liver disease and hepatocellular carcinoma (HCC). Globally, approximately 170 million people are chronically infected with the hepatitis C virus (HCV), and the majority of these individuals come from the western Pacific and Southeast Asia regions (94.6 million persons combined). CHC is an understudied and underappreciated health problem in many Asian countries and in the US, where Asians represent one of the fastest growing groups of new Americans.
AIM
To perform a systematic review of the current literature on the epidemiology, diagnosis and screening, clinical characteristics and response to anti-viral therapy of Asians with CHC.
METHODS
Using a PubMed search of 'hepatitis C' and 'Asia,' 341 original manuscripts published in peer-reviewed journals were identified, and 99 were selected based on their relevance.
RESULTS
Many Asian CHC patients do not have easily identifiable risk factors and may be underdiagnosed. Rates of HCV infection in Asians on community screening in the US are unexpectedly high, and there is a high prevalence of HCV genotype 6 in Southeast Asia and Southern China. HCV-infected Asians tend to present at older age and may have higher risk of HCC; however, they respond better to anti-viral therapy than non-Asians across all HCV genotypes.
CONCLUSIONS
Given the high HCV endemicity in Asia, lack of identifiable risk factors and favourable treatment response rates in Asians, we advocate the screening for HCV infection of all Asians who come from areas where HCV prevalence is ≥2%.
Topics: Age Factors; Antiviral Agents; Asian People; Hepatitis C, Chronic; Humans; Prevalence; Risk Factors
PubMed: 23557103
DOI: 10.1111/apt.12300 -
International Journal of Cancer Mar 2017Antiviral therapy with interferon based therapies (IBT) has shown potential in improving survival in patients who have undergone resection or locoregional therapy for... (Meta-Analysis)
Meta-Analysis Review
Antiviral therapy with interferon based therapies (IBT) has shown potential in improving survival in patients who have undergone resection or locoregional therapy for hepatitis C-associated hepatocellular carcinoma (HCV-HCC). However, this benefit has not been definitively ascribed to sustained viral response (SVR). Since IBT has been replaced with new directly acting agents (DAA), which are more efficacious in the treatment of HCV, we sought to better determine the prognostic impact of SVR in HCV-HCC. A systematic search of MEDLINE and EMBASE from inception through October 2015 was performed to identify studies that described the impact of presence of SVR in patients who underwent curative treatment of HCV-HCC. Summary hazard ratio (HR) with 95% confidence intervals (CI) was estimated for recurrence-free survival (RFS) and overall survival (OS) utilizing a random-effects model. After reviewing 858 abstracts, ten studies which included a total of 1,794 patients were selected and data was extracted. Of these ten studies, the impact of SVR on RFS and OS was reported in eight and seven studies respectively. In a meta-analysis which included 1,519 patients, SVR was associated with improved OS (HR 0.18; 95% CI 0.11-0.29, I = 2%). We also found that SVR was associated with better RFS in a meta-analysis (1,241 patients; HR 0.50; 95% CI 0.40-0.63, I = 0). In conclusion, SVR is associated with improved OS and RFS in patients with HCV who have undergone resection or locoregional therapy for HCC. Newer DAA therapies which offer increased tolerability and viral eradication should be considered as adjunctive therapy.
Topics: Aged; Antiviral Agents; Carcinoma, Hepatocellular; Cohort Studies; Disease-Free Survival; Female; Hepatectomy; Hepatitis C, Chronic; Humans; Interferons; Liver Neoplasms; Male; Middle Aged; Prognosis; Remission Induction; Viral Load; Viremia
PubMed: 27861842
DOI: 10.1002/ijc.30521 -
International Journal of Infectious... Aug 2014Antiretroviral therapy (ART) reduces the morbidity and mortality of patients infected with HIV. Standard ART includes either nevirapine or efavirenz, however the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Antiretroviral therapy (ART) reduces the morbidity and mortality of patients infected with HIV. Standard ART includes either nevirapine or efavirenz, however the efficacy of these drugs is limited in patients receiving rifampin treatment for tuberculosis (TB). We compared the efficacy and safety of nevirapine- and efavirenz-based ART regimens in patients co-infected with both HIV and TB through a systematic review and meta-analysis.
METHODS
A comprehensive search of the literature was carried out to identify clinical trials comparing the efficacy and safety of nevirapine- and efavirenz-based ART regimens in HIV-associated TB. Eligible clinical studies included at least one primary or secondary event; the primary event was virological response and secondary events were TB treatment outcomes, mortality, and safety profile.
RESULTS
This meta-analysis compared five randomized clinical trials and four retrospective clinical trials. Both included patients co-infected with HIV and TB; 833 received nevirapine, while 1424 received efavirenz. The proportion of patients achieving a virological response by the end of the follow-up was higher in the efavirenz group: plasma viral load <400 copies/ml, risk ratio (RR) 1.10, 95% confidence interval (CI) 1.03-1.17 (p = 0.004); plasma viral load<50 copies/ml, RR 1.07, 95% CI 0.98-1.16 (p = 0.146). No significant differences were found in either mortality (RR 0.70, 95% CI 0.44-1.13, p = 0.142) or TB treatment outcomes (RR 1.01, 95% CI 0.96-1.06, p = 0.766). Due to adverse advents, nevirapine-based regimens significantly increased the risk of discontinuation of assigned ART (RR 0.43, 95% CI 0.23-0.81, p = 0.009).
CONCLUSIONS
Although efavirenz-based ART was associated with more satisfactory virological outcomes, nevirapine-based ART could be considered an acceptable alternative for patients for whom efavirenz cannot be administered.
Topics: Alkynes; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Antitubercular Agents; Benzoxazines; CD4 Lymphocyte Count; Clinical Trials as Topic; Coinfection; Cyclopropanes; HIV Infections; Humans; Nevirapine; Rifampin; Treatment Outcome; Tuberculosis; Viral Load
PubMed: 24911886
DOI: 10.1016/j.ijid.2014.04.020 -
Liver International : Official Journal... Jul 2013To increase cure rates for Hepatitis C, barriers to treatment adherence and completion must be identified and overcome. (Review)
Review
BACKGROUND
To increase cure rates for Hepatitis C, barriers to treatment adherence and completion must be identified and overcome.
AIMS
This study systematically reviewed evidence on the psychological, lifestyle and social determinants of achieving viral eradication with antiviral therapy.
METHODS
An electronic search strategy was used to identify relevant studies that examined psychological, lifestyle and social factors related to achieving a sustained virological response (SVR).
RESULTS
Thirty-four studies that matched our criteria were identified. Of the factors that predict response to treatment, Asian ethnicity was an independent predictor of SVR. We found an indirect relationship between diet and SVR, with non-responders to treatment consuming more polyunsaturated fatty acids, fats and carbohydrates than those who attained SVR. The effect of alcohol consumption relied on the amount consumed; fewer than 30 grams daily had no effect on SVR, whereas >70 grams daily had an adverse impact on a patient's ability to achieve SVR, with termination rates up to 44% in those who drank >2 drinks a day. Patients with psychiatric illnesses had comparable SVR rates to controls if they continued psychological therapy (average 42%), although discontinuation rates were high with 11 studies reporting rates from 14 to 48%.
CONCLUSIONS
There are major gaps in current knowledge of the impact of variables such as diet, exercise, attitudes and coping skills on cure rates in chronic Hepatitis C. Those who drink limited amounts of alcohol or have psychiatric disorders should be offered treatment for their disease, with adjunctive education and support to improve treatment completion.
Topics: Adaptation, Psychological; Alcohol Drinking; Antiviral Agents; Comorbidity; Diet; Exercise; Health Behavior; Health Knowledge, Attitudes, Practice; Hepatitis C, Chronic; Humans; Life Style; Medication Adherence; Patient Education as Topic; Risk Factors; Social Behavior; Treatment Outcome
PubMed: 23581550
DOI: 10.1111/liv.12138 -
The Lancet. Gastroenterology &... Nov 2018There are concerns around poorer response to direct-acting antiviral (DAA) therapy for hepatitis C virus infection among people who use drugs. This systematic review... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There are concerns around poorer response to direct-acting antiviral (DAA) therapy for hepatitis C virus infection among people who use drugs. This systematic review assessed DAA treatment outcomes among people with recent drug use and those receiving opioid substitution therapy.
METHODS
Bibliographic databases and conference presentations were searched for observational studies and clinical trials assessing DAA treatment completion, sustained virological response (SVR), and loss to follow-up among people with recent drug use (injecting or non-injecting) and those receiving opioid substitution therapy. Meta-analysis was used to pool estimates and meta-regression to explore heterogeneity.
FINDINGS
38 eligible studies, with 3634 participants, were included. The definition of recent drug use varied across studies, with drug use in the past 6 months and at the initiation of or during DAA therapy most commonly used. Among individuals with recent injecting or non-injecting drug use (21 studies; 1408 participants), treatment completion was 97·5% (95% CI 96·6-98·3) and SVR was 87·7% (95% CI 84·2-91·3). Among individuals receiving opioid substitution therapy (36 studies; 2987 participants), treatment completion was 97·4% (95% CI 96·5-98·3) and SVR was 90·7% (95% CI 88·5-93·0). Among individuals with recent injecting drug use (eight studies; 670 participants), treatment completion was 96·9% (95% CI 95·6-98·2) and SVR was 87·4% (95% CI 82·0-92·8). In meta-regression analysis, clinical trials (vs observational studies; adjusted odd ratio 2·18, 95% CI 1·27-3·75; p=0·006) and higher mean or median age (1·07, 1·02-1·12; p=0·008) were significantly associated with higher SVR. Clinical trials (0·45, 0·22-0·94; p=0·033) and older age (0·94, 0·88-0·99; p=0·034) were also significantly associated with a lower proportion of participants lost to follow-up.
INTERPRETATION
Response to DAA therapy was favourable among people with recent drug use (including those who inject) and those receiving opioid substitution therapy, supporting broadening access in these populations.
FUNDING
The Kirby Institute, UNSW Sydney, and National Health and Medical Research Council of Australia.
Topics: Antiviral Agents; Hepatitis C, Chronic; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Abuse, Intravenous; Sustained Virologic Response
PubMed: 30245064
DOI: 10.1016/S2468-1253(18)30304-2 -
BMC Health Services Research Oct 2019Direct Acting Antiviral (DAAs) drugs have a much lower burden of treatment and monitoring requirements than regimens containing interferon and ribavirin, and a much... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Direct Acting Antiviral (DAAs) drugs have a much lower burden of treatment and monitoring requirements than regimens containing interferon and ribavirin, and a much higher efficacy in treating hepatitis C (HCV). These characteristics mean that initiating treatment and obtaining a virological cure (Sustained Viral response, SVR) on completion of treatment, in non-specialist environments should be feasible. We investigated the English-language literature evaluating community and primary care-based pathways using DAAs to treat HCV infection.
METHODS
Databases (Cinahl; Embase; Medline; PsycINFO; PubMed) were searched for studies of treatment with DAAs in non-specialist settings to achieve SVR. Relevant studies were identified including those containing a comparison between a community and specialist services where available. A narrative synthesis and linked meta-analysis were performed on suitable studies with a strength of evidence assessment (GRADE).
RESULTS
Seventeen studies fulfilled the inclusion criteria: five from Australia; two from Canada; two from UK and eight from USA. Seven studies demonstrated use of DAAs in primary care environments; four studies evaluated integrated systems linking specialists with primary care providers; three studies evaluated services in locations providing care to people who inject drugs; two studies evaluated delivery in pharmacies; and one evaluated delivery through telemedicine. Sixteen studies recorded treatment uptake. Patient numbers varied from around 60 participants with pathway studies to several thousand in two large database studies. Most studies recruited less than 500 patients. Five studies reported reduced SVR rates from an intention-to-treat analysis perspective because of loss to follow-up before the final confirmatory SVR test. GRADE assessments were made for uptake of HCV treatment (medium); completion of HCV treatment (low) and achievement of SVR at 12 weeks (medium).
CONCLUSION
Services sited in community settings are feasible and can deliver increased uptake of treatment. Such clinics are able to demonstrate similar SVR rates to published studies and real-world clinics in secondary care. Stronger study designs are needed to confirm the precision of effect size seen in current studies. Prospero: CRD42017069873.
Topics: Antiviral Agents; Community Health Services; Health Services Research; Hepatitis C; Humans; Mass Screening; Primary Health Care; Randomized Controlled Trials as Topic
PubMed: 31660966
DOI: 10.1186/s12913-019-4635-7