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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.
Efficacy and safety of elbasvir/grazoprevir in participants with hepatitis C virus genotype 1, 4, or 6 infection from the Asia-Pacific region and Russia: Final results from the randomized C-CORAL study.
Wei, L, Jia, JD, Wang, FS, Niu, JQ, Zhao, XM, Mu, S, Liang, LW, Wang, Z, Hwang, P, Robertson, MN, et al
Journal of gastroenterology and hepatology. 2019;(1):12-21
Abstract
BACKGROUND AND AIM Although treatment with direct-acting antivirals has dramatically improved morbidity and mortality attributable to chronic hepatitis C virus infection, universal access to these medicines has been slow in the Asia-Pacific region and Russia. This study evaluated efficacy and safety of elbasvir/grazoprevir in participants with hepatitis C virus infection from Asia-Pacific countries and Russia (C-CORAL). METHODS C-CORAL was a phase 3, randomized, placebo-controlled study (NCT02251990). Treatment-naive, HIV-negative, cirrhotic and non-cirrhotic participants with chronic hepatitis C genotype 1, 4, or 6 infection were randomized to elbasvir 50 mg/grazoprevir 100 mg once daily for 12 weeks (immediate-treatment group) or placebo followed by deferred treatment with elbasvir/grazoprevir (deferred-treatment group). The primary efficacy outcome was sustained virologic response at 12 weeks, and the primary safety outcome was a comparison between the immediate-treatment group and placebo phase of the deferred-treatment group. RESULTS A total of 489 participants were randomized (immediate-treatment group, n = 366; deferred-treatment group, n = 123). Sustained virologic response at 12 weeks in the combined immediate/deferred-treatment groups was 94.4% (459/486; 95% confidence interval = 92.4-96.5%). Sustained virologic response at 12 weeks was 98.2% in participants with genotype 1b, 91.9% with genotype 1a, and 66.7% with genotype 6 infection. Similar rates of adverse events and drug-related adverse events were seen in the immediate-treatment group versus placebo phase of the deferred-treatment group (51.0% vs 50.4% and 21.4% vs 21.1%). CONCLUSIONS Elbasvir/grazoprevir for 12 weeks represents an effective and well-tolerated treatment option for treatment-naive people with genotype 1 infection from Asia-Pacific countries and Russia.
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Real-world effectiveness and safety of sofosbuvir plus daclatasvir with or without ribavirin for genotype 2 chronic hepatitis C in Taiwan.
Cheng, PN, Chiu, YC, Chien, SC, Chiu, HC
Journal of the Formosan Medical Association = Taiwan yi zhi. 2019;(5):907-913
Abstract
BACKGROUND AND PURPOSE Sofosbuvir (SOF) and daclatasvir (DCV) treatment achieves excellent efficacy and safety in treating chronic hepatitis C (CHC) with various genotypes. Real world experience of SOF/DCV regimen to treat genotype 2 CHC was scanty in Asia. This study aimed to evaluate the effectiveness and safety of SOF/DCV with or without ribavirin to treat genotype 2 CHC patients in real world practice in Taiwan. METHODS Patients with genotype 2 CHC treated with 12-week of SOF/DCV or SOF/DCV/ribavirin were enrolled prospectively. Effectiveness was evaluated by sustained virological response (SVR) which was defined as undetectable hepatitis C virus (HCV) RNA at post-treatment week 12. Adverse events were recorded for safety analysis. RESULTS In total of 32 patients were enrolled from October 2016 to June 2017. All were infected with genotype 2 HCV. Sixteen patients (50%) exhibited cirrhosis including 6 patients with decompensation. Regimens of SOF/DCV and SOF/DCV/ribavirin were used to treat 14 and 18 patients, respectively. SVR was achieved in all 31 patients (100%) who completed follow-up. Significantly higher levels of cholesterol (p = 0.013) and higher low density lipoprotein-cholesterol (p = 0.015) were exhibited after successful viral clearance. SOF/DCV/ribavirin regimen resulted in more adverse events, significantly higher bilirubin levels, and decline of hemoglobin during treatment than SOF/DCV regimen. Four patients with chronic kidney disease maintained renal function during treatment. Overall, SOF/DCV or SOF/DCV/ribavirin treatment was well tolerated. CONCLUSION SOF/DCV with or without ribavirin is highly effective and safe for patients with genotype 2 HCV infection in real-world experience in Taiwan.
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Anatomical and Functional Retinal Complications of Combined Sofosbuvir and Ribavirin Therapy in Patients With Chronic Hepatitis C Virus.
Elgouhary, SM, Said-Ahmed, KE, Mowafy, MA
Ophthalmic surgery, lasers & imaging retina. 2019;(1):39-41
Abstract
BACKGROUND AND OBJECTIVE To evaluate the anatomical and functional retinal complications of combined sofosbuvir and ribavirin therapy in patients with chronic hepatitis C virus (HCV). PATIENTS AND METHODS Three hundred patients with chronic HCV were recruited for this prospective, observational study from the National Liver Institute of Menoufia University from November 2015 to September 2017. Ophthalmic examination and follow-up were performed in the outpatient clinic of the Ophthalmology Department at Menoufia University. All patients received the same regimen (sofosbuvir and ribavirin) for 6 months. Patients were followed up during the period of treatment (6 months) and for 6 months after treatment completion. Complete ophthalmic examination, fundus fluorescein angiography (FFA) (to detect retinal ischemia), optical coherence tomography (OCT) (to detect retinal nerve fiber layer [RNFL] thickness and central macular thickening), and electroretinogram (ERG) (to detect rod and cone functions) tests were performed before and after treatment completion. RESULTS The mean age of the patients was 46.17 years ± 11.38 years (range: 20 years to 60 years). The study included 138 men (46%) and 162 women (54%). During follow-up, there were no signs of retinopathy or optic nerve affection. There were also no signs of retinal ischemia (by FFA), RNFL affection, macular edema (by OCT), or rod or cone affection (by ERG). CONCLUSION Combined treatment (sofosbuvir and ribavirin) may be safe without causing anatomical or functional retinal complications. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:39-42.].
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Impact of the Uridine⁻Cytidine Kinase Like-1 Protein and IL28B rs12979860 and rs8099917 SNPs on the Development of Hepatocellular Carcinoma in Cirrhotic Chronic Hepatitis C Patients-A Pilot Study.
Buivydiene, A, Liakina, V, Kashuba, E, Norkuniene, J, Jokubauskiene, S, Gineikiene, E, Valantinas, J
Medicina (Kaunas, Lithuania). 2018;(5)
Abstract
Background and objectives: The hepatitis C virus (HCV) is the major causative agent of hepatocellular carcinoma (HCC) in the western world. The efficacy of surveillance programs for early detection of HCC is not satisfactory: many tumors are diagnosed at the late, incurable stages. Therefore, there is a need in reliable prognostic markers for the proper follow-up of HCV-positive patients. The aim of the present study was to assess the prognostic value of the uridine⁻cytidine kinase-like protein 1 (UCKL-1), a putative oncoprotein, together with genetically determined polymorphisms in the interleukin 28B (IL28B) gene (rs12979860, rs8099917) in the development of HCC in HCV-positive cirrhotic patients. Materials and Methods: We included 32 HCV cirrhotic patients, 21 (65.6%) of whom had HCC. The expression of UCKL-1 was assessed in liver tissue sections, using immunohistochemistry. For IL28B rs12979860 and rs8099917 genotype analysis, the corresponding genomic regions were amplified by polymerase chain reaction (PCR) with appropriate primers. Results: We have found that UCKL-1 expression was significantly increased in HCC (p = 0.003). The presence of rs8099917 TT single-nucleotide polymorphism (SNP) elevated the chances of HCC manifestation more than sevenfold (OR = 7.3, p = 0.0273). The presence of rs12979860 CC SNP also heightened HCC chances more than sevenfold (OR = 7.5, p = 0.0765). Moreover, in the HCC group, a combination of IL28B rs12979860 non-TT and rs8099917 TT genotypes was observed more often, compared with the non-HCC group. Other combinations of IL28B rs12979860 and rs8099917 SNIPs were associated with a reduced risk of HCC development, approximately at the same extent. Conclusions: The presence of IL28B rs8099917 TT and rs12979860 CC SNPs, but not the intensity of UCKL-1 expression, is strongly associated with increased chances of HCC development in HCV-positive cirrhotic patients.
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8.
Efficacy of vitamin D supplementation in combination with conventional antiviral therapy in patients with chronic hepatitis C infection: a meta-analysis of randomised controlled trials.
Kim, HB, Myung, SK, Lee, YJ, Park, BJ, ,
Journal of human nutrition and dietetics : the official journal of the British Dietetic Association. 2018;(2):168-177
Abstract
BACKGROUND Although a contributory role of vitamin D levels for the development of chronic hepatitis C has been suggested, the efficacy of vitamin D supplementation in combination with conventional antiviral therapy consisting of pegylated interferon-α (Peg-IFN-α) injection and oral ribavirin (RBV) remains unclear. We investigated its efficacy in the treatment of chronic hepatitis C via a meta-analysis of randomised controlled trials. METHODS We searched PubMed, EMBASE, the Cochrane Library, ClinicalTrials.gov and the bibliographies of relevant articles to locate additional publications in September 2016. Three evaluators independently reviewed and selected eligible studies based on predetermined selection criteria. RESULTS Of 522 articles meeting our initial criteria, a total of seven open-label, randomised controlled trials involving 548 participants, were included in the final analysis. Vitamin D supplementation in combination with Peg-IFN-α injection and oral RBV significantly increased the rate of viral response for hepatitis C at 24 weeks after treatment in a random-effects meta-analysis (relative risk = 1.30; 95% confidence interval = 1.04-1.62; I2 = 75.9%). Also, its significant efficacy was observed in patients with hepatitis C virus genotype 1, which is known to be refractory to antiviral therapy. CONCLUSIONS In summary, we observed that additional use of vitamin D has a positive effect on sustained viral response rates of patients with chronic hepatitis C infection. However, we cannot establish the efficacy because of substantial heterogeneity, a small sample size and a low methodological quality.
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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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10.
Circulating visfatin level is associated with hepatocellular carcinoma in chronic hepatitis B or C virus infection.
Tsai, IT, Wang, CP, Yu, TH, Lu, YC, Lin, CW, Lu, LF, Wu, CC, Chung, FM, Lee, YJ, Hung, WC, et al
Cytokine. 2017;:54-59
Abstract
Adipocytokines play an important role in adipose tissue homeostasis, especially in obesity-associated disorders such as non-alcoholic fatty liver and their complications including hepatocellular carcinoma (HCC). Although visfatin is an adipocytokine highly expressed in visceral fat that has been demonstrated to play a critical role in the progression of human malignancies, little is known about the role of visfatin in HCC associated with chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infection. In this study, we investigated whether plasma visfatin levels were altered in patients with HCC and the association between plasma visfatin levels and pretreatment hematologic profiles. Plasma visfatin levels were measured by enzyme-linked immunosorbent assays in 193 patients with different stages of HBV or HCV infection, and 92 healthy control subjects. The patients with HCC and chronic HCV or HBV infection had higher levels of visfatin than patients with HBV, HCV, and cirrhosis. In multivariate logistic regression analysis, levels of alpha-fetoprotein (AFP) (OR: 1.13, p=0.003), and plasma visfatin (OR: 1.17, p=0.046) were independently associated with HCC. Multiple stepwise regression analysis showed that plasma visfatin level was positively associated with age, aspartate aminotransferase to platelet ratio index (APRI), and AFP. Trend analyses confirmed that plasma visfatin concentration was associated with AFP>8ng/mL, cirrhosis, HCC, tumor size>5cm, and Barcelona Clinic Liver Cancer-C stage. These results suggested that the plasma visfatin level is associated with the presence of HCC, and that a higher plasma visfatin level may be important in the pathogenesis of HCC. Visfatin may act as both a protective and pro-inflammatory factor. Plasma visfatin concentration may serve as an additional tool to identify patients with more advanced necroinflammation.