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• W4382466766 abstract "Dear Editor, Tuberculosis (TB) and hepatitis C virus (HCV) infections are both major public health problems globally. Chronic kidney disease and dialysis patients are at increased risk of acquiring both these infections when compared to the general population. HCV infection is associated with increased liver-related morbidity and mortality rates, accelerated progression to end-stage renal disease, and risk of cardiovascular events.[1] Treatment of HCV using agents such as interferons and ribavirin had historically low viremia clearance rates and has now become obsolete. Regimens with direct-acting antivirals (DAAs) have a success rate of more than 95% and are the current standard of care for treating HCV infection. Several pan-genotypic and genome-specific regimens have recently been approved for clinical use.[2] In countries with high-TB burdens, we encounter patients requiring treatment for both HCV and TB infections simultaneously. We report a case, where co-administration of antitubercular treatment (ATT) along with sofosbuvir/velpatasvir, resulted in failure of DAA regimen. The same sofosbuvir/velpatasvir combination, when administered for 12 weeks after completion of ATT, resulted in HCV viremia clearance and the patient achieved sustained viral response. A 46-year-old man came to our center for maintenance hemodialysis in March 2021. Ten years earlier, he had undergone living unrelated renal transplant elsewhere. The significant clinical events are described in Table 1.Table 1: Timeline of significant clinical eventsPan-genotypic regimen with fixed-dose sofosbuvir 400 mg and velpatasvir 100 mg for 12 weeks has demonstrated effectiveness in HCV-infected dialysis patients. The safety of sofosbuvir in the dialysis population has been established.[3] Borgia et al. demonstrated that the exposures of sofosbuvir, metabolite of sofosbuvir-GS-331007, and velpatasvir were 81%, 1719%, and 41% higher, respectively, in patients undergoing dialysis compared with HCV-infected patients with normal renal function. The increased exposure of GS-331007 was because of impaired renal clearance. These increases in exposure were not considered clinically relevant as no exposure-adverse events relationships were observed.[3] Sofosbuvir/velpatasvir is a pan-genotypic regimen and recently published KDIGO guidelines suggest fixed-dose combinations can readily be used for the management of HCV in dialysis patients. Routine testing of HCV genotype is not recommended for initiating therapy when pan-genotypic regimens are used.[2] Nabulsi et al. reported that factors such as older age, history of hepatocellular carcinoma, and availability of drugs through private insurance were the strongest predictors of treatment failure.[4] Recently, Steinbrink et al. reported DAA treatment failure in 4 postrenal transplant cases, who had received organs from HCV-infected donors. They described factors such as high pretreatment viral load, drug–drug interactions (DDIs) between famotidine and velpatasvir, viral genotype, and the development of viral resistance to DAAs could have caused the failure of DAA therapy.[5] DDI between ATT drugs and DAAs as a cause of treatment failure has not yet been reported in the literature. The clinician has to largely rely on the package insert of the drug manufacturer for potential DDIs. To our knowledge, this is the first case of DAA failure that can be attributed to DDI with anti-TB drugs. From the limited evidence available, it could be inferred that among the commonly used ATT drugs, rifampicin, rifabutin, and rifapentine could cause DDI with DAAs leading to therapy failure.[6] It should be noted that the same DAA regimen worked in this case when it was prescribed after the patient had completed ATT. To avoid such DDI in future, clinicians can follow two approaches when there is a need to treat HCV and TB coinfections. If the liver enzymes are within normal limits, treatment of HCV infection with DAAs could be postponed by some months, until the ATT regimen is completed. This situation is akin to postponing treatment with DAAs in transplant wait-listed candidates, who are anticipating surgery immediately. If the clinical condition of the patient warrants urgent initiation of treatment for HCV with DAAs, rifampicin-sparing ATT regimens should be tried. Nevertheless, pharmacokinetic studies on these classes of drugs are needed to develop and adopt co-treatment regimens for clinical use among patients coinfected with TB and HCV. Declaration of patient consent The authors certify that patient consent has been taken for participation in the study and for publication of clinical details and images. Patients understand that the names, initials would not be published, and all standard protocols will be followed to conceal their identity. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest." @default.
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• W4382466766 date "2023-01-01" @default.
• W4382466766 modified "2023-09-27" @default.
• W4382466766 title "Tuberculosis and Hepatitis C Virus Coinfection in a Renal Transplant Recipient: A Therapeutic Challenge" @default.
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• W4382466766 doi "https://doi.org/10.4103/ijot.ijot_27_23" @default.
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