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1.
Interferon-α-induced retinopathy in chronic hepatitis C treatment: summary, considerations, and recommendations.
Rentiya, ZS, Wells, M, Bae, J, Chen, KJ, Chao, AN, Turgeon, N, Shah, SM, Hanout, M
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2019;(3):447-452
Abstract
Interferons are cytokines that regulate the host's response to viral infection, particularly in the setting of the immunologic response to the hepatitis C virus (HCV). While the virus has the ability to evade the host's innate and specific immunity, exogenous interferon-α with combined ribavirin, treatments have been found to achieve a significant sustained viral response in subgroups of patients with chronic HCV. One of the major side effects of interferon-α is an ocular retinopathy characterized by flame-shaped hemorrhages and cotton wool spots visualized on funduscopic examination. There have been documented cases of more severe side effects including optic nerve and retinal artery damage; however, these instances are the minority. We sought to investigate the literature surrounding interferon-induced retinopathy, clinically correlate our findings with two recent cases, and provide recommendations for practitioners who continue to manage chronic HCV patients using interferon-α with combined ribavirin treatments.
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2.
Successful treatment of chronic hepatitis C virus infection with crushed glecaprevir/pibrentasvir administered via a percutaneous endoscopic gastrostomy tube: case report and review of the literature.
Tanaka, Y, Tateishi, R, Koike, K
Clinical journal of gastroenterology. 2019;(6):588-591
Abstract
Glecaprevir (GLE)/pibrentasvir (PIB) is a direct-acting antiviral regimen approved for patients infected with hepatitis C virus. No data are available on the safety and efficacy of this regimen when crushed and administered through a percutaneous endoscopic gastrostomy (PEG) tube. Here, we report a patient who successfully achieved a sustained viral response after treatment with GLE/PIB administered via a PEG tube. A 41-year-old female with chronic hepatitis C viral infection was referred to our department for treatment. She had a history of spina bifida and hydrocephalus, and she received a PEG tube for nutrition and medication due to an aftereffect of hydrocephalus. She received crushed GLE/PIB treatment through a PEG tube for 8 weeks and achieved a sustained viral response 12, without any treatment-related severe adverse events. This is the first documented case treated with GLE/PIB administered through a PEG tube. Based on this case report and a review of the literature, we discuss the safety and efficacy of direct-acting antiviral treatment via a PEG tube.
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3.
Estimating Prevalence of Hepatitis C Virus Infection in the United States, 2013-2016.
Hofmeister, MG, Rosenthal, EM, Barker, LK, Rosenberg, ES, Barranco, MA, Hall, EW, Edlin, BR, Mermin, J, Ward, JW, Ryerson, AB
Hepatology (Baltimore, Md.). 2019;(3):1020-1031
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Abstract
Hepatitis C virus (HCV) infection is the most commonly reported bloodborne infection in the United States, causing substantial morbidity and mortality and costing billions of dollars annually. To update the estimated HCV prevalence among all adults aged ≥18 years in the United States, we analyzed 2013-2016 data from the National Health and Nutrition Examination Survey (NHANES) to estimate the prevalence of HCV in the noninstitutionalized civilian population and used a combination of literature reviews and population size estimation approaches to estimate the HCV prevalence and population sizes for four additional populations: incarcerated people, unsheltered homeless people, active-duty military personnel, and nursing home residents. We estimated that during 2013-2016 1.7% (95% confidence interval [CI], 1.4-2.0%) of all adults in the United States, approximately 4.1 (3.4-4.9) million persons, were HCV antibody-positive (indicating past or current infection) and that 1.0% (95% CI, 0.8-1.1%) of all adults, approximately 2.4 (2.0-2.8) million persons, were HCV RNA-positive (indicating current infection). This includes 3.7 million noninstitutionalized civilian adults in the United States with HCV antibodies and 2.1 million with HCV RNA and an estimated 0.38 million HCV antibody-positive persons and 0.25 million HCV RNA-positive persons not part of the 2013-2016 NHANES sampling frame. Conclusion: Over 2 million people in the United States had current HCV infection during 2013-2016; compared to past estimates based on similar methodology, HCV antibody prevalence may have increased, while RNA prevalence may have decreased, likely reflecting the combination of the opioid crisis, curative treatment for HCV infection, and mortality among the HCV-infected population; efforts on multiple fronts are needed to combat the evolving HCV epidemic, including increasing capacity for and access to HCV testing, linkage to care, and cure.
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4.
Chronic kidney disease in patients with chronic hepatitis C virus infection.
Shahab, O, Golabi, P, Younossi, ZM
Minerva gastroenterologica e dietologica. 2018;(4):376-382
Abstract
Hepatitis C virus (HCV) infection affects many organs in the body, including the liver, kidneys, skin, joints and others. Although the hepatic manifestation of HCV has been widely studied, the extrahepatic manifestations of HCV have not been fully appreciated. Studies have shown that patients with HCV have a higher risk of chronic kidney disease and end-stage renal disease, as well as poorer outcomes after kidney transplantation. Given these findings, it is important to screen HCV patients for presence of renal impairment in a timely manner. Current guidelines recommend screening for kidney disease at the time of HCV diagnosis, along with annual urinalysis and creatinine checks. It is important to note that chronic HCV infection has been associated with a number of renal disorders, including cryoglobulinemic glomerulonephritis, membranoproliferative glomerulonephritis, membranous nephropathy, focal segmental glomerulosclerosis, IgA nephropathy, fibrillary and immunotactoid glomerulopathies, and hepatorenal syndrome. Of these, while HRS can be reversible post-transplantation, cryoglobulinemic glomerulonephritis is common and is primarily caused by mixed cryoglobulinemia. These patients may be asymptomatic or may present with hematuria, proteinuria, nephrotic syndrome, or impaired renal function only detected by laboratory data. In this review, we will provide an up-to-date assessment of these renal complications in patients with HCV infection.
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5.
Update on hepatitis C treatment: systematic review of clinical trials.
Jhaveri, M, Procaccini, N, Kowdley, KV
Minerva gastroenterologica e dietologica. 2017;(1):62-73
Abstract
Chronic hepatitis C is a major public health problem. The chronicity of the hepatitis C can lead to advanced liver disease, cirrhosis and even hepatocellular carcinoma. Chronic hepatitis C is the leading indication of for liver transplantation in the United States. Since the introduction of directly acting antiviral agents (DAAs), there have been there have been dramatic advances in treatment of hepatitis C in terms of tolerability, duration of therapy with significant increases in the rates of sustained virologic response (SVR). This review summarizes the findings of recently published clinical trials of DAAs in the treatment of hepatitis C by genotype and in patients co-infected with HCV/HIV.
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6.
Exceptional serological and radiological response to sorafenib in 2 patients with advanced hepatocellular carcinoma and chronic hepatitis C viral infection: case report and review of the literature.
Atkin, C, Earwaker, P, Pallan, A, Shetty, S, Punia, P, Ma, YT
BMC gastroenterology. 2017;(1):30
Abstract
BACKGROUND In patients with advanced hepatocellular carcinoma (HCC), the multikinase inhibitor sorafenib is the only systemic treatment that has been shown to increase overall survival. However, similar to other tyrosine kinase inhibitors, most patients achieve disease stabilisation radiologically, and only 2-3% of patients achieve a partial response. Recent exploratory subgroup analyses of the large phase 3 trials have demonstrated that patients with chronic hepatitis C virus (HCV) infection associated HCC survive longer than those who are negative for HCV. The mechanism underlying this currently remains unknown. A small number of cases of complete response to sorafenib treatment have now been reported worldwide, however a prolonged response has only been reported in 2 cases, both of whom had HCV-related HCC. CASE PRESENTATION A 55 year old gentleman was diagnosed with hepatocellular carcinoma and concomitant chronic hepatitis C viral infection. He progressed following transarterial chemoemoblisation treatment and was commenced on sorafenib treatment. His serum alphafetoprotein level normalised within 2 months of treatment and he achieved an almost complete radiological response. This response was maintained for 20 months before the patient progressed. A 75 year old lady was diagnosed with advanced hepatocellular carcinoma and concomitant chronic hepatitis C viral infection. She was commenced on sorafenib treatment but required early dose reductions due to palmar plantar erythrodysesthesia, and liver decompensation. Despite this she achieved an excellent serological and radiological response that was maintained for 24 months. CONCLUSIONS Our two cases show that patients with HCV-associated HCC can attain excellent responses to sorafenib treatment that is durable. Furthermore, such exceptional responses can be achieved even with dose reductions and treatment breaks.
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7.
The Challenge of Treating Children With Hepatitis C Virus Infection.
Indolfi, G, Thorne, C, El Sayed, MH, Giaquinto, C, Gonzalez-Peralta, RP
Journal of pediatric gastroenterology and nutrition. 2017;(6):851-854
Abstract
The development of oral hepatitis C virus (HCV) direct-acting antivirals (DAAs) has revolutionized the therapeutic field. Nowadays, multiple safe and highly effective antiviral regimens are commercially available to treat adults with hepatitis C infection. These new regimens for the first time genuinely raise the prospects of eradicating HCV. Many challenges, however, remain from identifying infected individuals to optimizing treatment and ensuring global access to antiviral therapy to all population groups, including children. Recently, in April 2017, the association of sofosbuvir with ribavirin and the fixed-dose combination sofosbuvir/ledipasvir have been approved by the Food and Drug Administration for treatment of children with chronic HCV infection 12 years of age and older. The only drugs currently approved for children younger than 12 years are pegylated interferon and ribavirin. There are 6 registered ongoing pediatric trials assessing safety and efficacy of DAAs, but their current completion timelines are years away. Herein, we summarize the state of the art of DAAs' development for adult and children and highlight the crucial importance of overcoming barriers to treating children with HCV.
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8.
[Porphyria cutanea tarda: the benefit of additional diagnostics].
Vossen, AR, Boesten, LS, Siersema, PD, Nellen, RG
Nederlands tijdschrift voor geneeskunde. 2016;:A9166
Abstract
The porphyrias are a clinically and genetically heterogeneous group of relatively rare metabolic diseases that result from disorders in the biosynthesis of haeme. Porphyria cutanea tarda (PCT) is the most common type, accounting for 80-90% of all porphyrias, and is essentially an acquired disease, although PCT can also occur on a familial basis. We describe a 71-year-old female and a 62-year-old male patient, both of whom had several risk factors for developing PCT, ranging from iron overload due to a mutation in the hereditary haemochromatosis protein (HFE) gene, alcohol use, smoking, and exogenous oestrogen, to persistent hepatitis C infection. The clinical relevance of the several diagnostic modalities is important in PCT. Diagnostic evaluation is important in order to confirm the diagnosis, but also to evaluate the treatment response in the context of long-term follow-up in the prevention of late complications of PCT, i.e. hepatocellular carcinoma.
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9.
Treatment of chronic hepatitis C with direct-acting antivirals: The role of resistance.
Jiménez-Pérez, M, González-Grande, R, España Contreras, P, Pinazo Martínez, I, de la Cruz Lombardo, J, Olmedo Martín, R
World journal of gastroenterology. 2016;(29):6573-81
Abstract
The use of direct-acting antivirals (DAAs) to treat chronic hepatitis C has resulted in a significant increase in rates of sustained viral response (around 90%-95%) as compared with the standard treatment of peginterferon/ribavirin. Despite this, however, the rates of therapeutic failure in daily clinical practice range from 10%-15%. Most of these cases are due to the presence of resistant viral variants, resulting from mutations produced by substitutions of amino acids in the viral target protein that reduce viral sensitivity to DAAs, thus limiting the efficacy of these drugs. The high genetic diversity of hepatitis C virus has resulted in the existence of resistance-associated variants (RAVs), sometimes even before starting treatment with DAAs, though generally at low levels. These pre-existing RAVs do not appear to impact on the sustained viral response, whereas those that appear after DAA therapy could well be determinant in virological failure with future treatments. As well as the presence of RAVs, virological failure to treatment with DAAs is generally associated with other factors related with a poor response, such as the degree of fibrosis, the response to previous therapy, the viral load or the viral genotype. Nonetheless, viral breakthrough and relapse can still occur in the absence of detectable RAVs and after the use of highly effective DAAs, so that the true clinical impact of the presence of RAVs in therapeutic failure remains to be determined.
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10.
Directly acting antivirals against hepatitis C virus: mechanisms of action and impact of resistant associated variants.
Premoli, C, Aghemo, A
Minerva gastroenterologica e dietologica. 2016;(1):76-87
Abstract
Hepatitis C virus (HCV) drug development has resulted in interferon-free (IFN) regimens of direct-acting antivirals (DAAs). The new therapies are highly effective achieving 90-95% of sustained virologic response (SVR) rates among all genotypes with minimal treatment-related side effects. They opened a new scenario in HCV treatment representing a treatment option for patients who were ineligible to IFN-based regimens as those with decompensated liver disease, autoimmune disorders and psychiatric disturbs. However, numerous research and clinical questions remain. In particular, drug resistance is an upcoming clinical issue in HCV treatment. The aim of this review is to provide an overview of the different DAAs approved or in clinical development and their mechanism of actions. For each class of agents the resistance profile will be examined according to the available in vitro and in vivo data discussing the clinical implications. Resistance-associated variants (RAVs) are driven by the selection of mutations at different virologic targets. The most clinically relevant NS3/4A protease substitutions are detected at positions V36, Q80, T54, R155 and A156. S282T is the most frequent NS5B polymerase aminoacids substitutions. M28, Q30, L31 and Y39 mutations are involved in NS5A proteins associated resistance. The baseline RAVs seems not to affect the SVR rates. Thus, their detection by sequencing analysis should not to be recommended. Conversely, RAVs testing after DAAs failure is of clinical practice concern in order to select the most appropriate retreatment combination.