Untreated Hepatitis C Virus Infection Research Articles

Innovating the Model for Student Pharmacists to Increase Access to Hepatitis C Testing (Project IMPACT)

BackgroundPrevious initiatives have described the feasibility of conducting point-of-care testing (POCT) for hepatitis C virus (HCV) within community pharmacies. Limited research has been conducted to evaluate the role of student pharmacists and technicians in providing these services. ObjectiveDescribe the implementation of a student pharmacist–run HCV POCT initiative within an independent community pharmacy and evaluate the linkage to care process. Practice descriptionOne specialty and 3 community pharmacies managed by one independent pharmacy chain. Practice innovationPharmacy students screened participants for HCV and referred those with a reactive result or reporting untreated HCV to a partnering medical facility for confirmatory testing. Individuals with confirmed HCV had the option to receive their prescriptions, along with monthly telephonic monitoring services from the independent pharmacy’s specialty pharmacy. Evaluation methodsResearchers evaluated the number of participants who screened reactive or reported current HCV infection, successful referrals to medical care, and prescriptions dispensed by the specialty pharmacy for HCV treatment. ResultsFrom September 2020 to September 2022, 236 individuals were screened for HCV at the pharmacy, of whom 11 screened reactive (4.7%) and 4 participants reported untreated HCV infection. In total, 15 participants were referred to care and 4 of these participants (26.7%) were successfully linked. One participant received prescriptions and telephonic monitoring for HCV treatment from the specialty pharmacy as a direct result of Project IMPACT (Innovating the Model for Student Pharmacists to Increase Access to Hepatitis C Testing). Practice implications and conclusionsProject IMPACT demonstrated that community pharmacies can increase access to HCV screenings by using student pharmacists and technicians. Potential strategies to improve the linkage to care process include enhancing the quality of patient education and implementing telehealth services.

Association of Treated and Untreated Chronic Hepatitis C With the Incidence of Active Tuberculosis Disease: A Population-Based Cohort Study.

Hepatitis C virus (HCV) infection causes dysregulation and suppression of immune pathways involved in the control of tuberculosis (TB) infection. However, data on the role of chronic hepatitis C as a risk factor for active TB are lacking. We sought to evaluate the association between HCV infection and the development of active TB. We conducted a cohort study in Georgia among adults tested for HCV antibodies (January 2015-September 2020) and followed longitudinally for the development of newly diagnosed active TB. Data were obtained from the Georgian national programs of hepatitis C and TB. The exposures of interest were untreated and treated HCV infection. A Cox proportional hazards model was used to calculate adjusted hazard ratios (aHRs). A total of 1 828 808 adults were included (median follow-up time: 26 months; IQR: 13-39 months). Active TB was diagnosed in 3163 (0.17%) individuals after a median of 6 months follow-up (IQR: 1-18 months). The incidence rate per 100 000 person-years was 296 among persons with untreated HCV infection, 109 among those with treated HCV infection, and 65 among HCV-negative persons. In multivariable analysis, both untreated (aHR = 2.9; 95% CI: 2.4-3.4) and treated (aHR = 1.6; 95% CI: 1.4-2.0) HCV infections were associated with a higher hazard of active TB, compared with HCV-negative persons. Adults with HCV infection, particularly untreated individuals, were at higher risk of developing active TB disease. Screening for latent TB infection and active TB disease should be part of clinical evaluation of people with HCV infection, especially in high-TB-burden areas.

Association between breast cancer and hepatitis C: A joint study of hospitalized patients and nationwide cohorts

Whether hepatitis C virus (HCV) infection is associated with breast cancer risk remains elusive, and we aimed to elucidate it. A nationwide population-based cohort study of the Taiwan National Health Insurance Research Database (TNHIRD) was conducted. Additionally, breast cancer risk factors, and HCV core expression were surveyed in breast cancer patients of a tertiary care center. Three TNHIRD cohorts (1:4:4, propensity score-matched, 2003-2012), including HCV-treated (3646 HCV-infected females with interferon-based therapy ≥6 months), HCV-untreated (n=14,584) and HCV-uninfected (n=14,584) cohorts, were enrolled. The HCV-untreated cohort had the highest 9-year breast cancer cumulative incidence (2.017%; 95% confidence interval [CI]: 1.382%-2.846%), while the HCV-treated (1.073%; 0.414%-2.356%), and HCV-uninfected (1.453%; 0.785%-2.486%) cohorts showed no difference. Untreated HCV infection (hazard ratio [HR]: 1.701; 95% CI: 1.205%-2.400), urban residency (1.658, 1.183-2.323), and baseline cardiovascular events (1.920; 1.005-3.668) were associated with incident breast cancers. The interaction analysis showed that particularly among patients <49 years, HCV infection was associated with breast cancer development (2.193; 1.097-4.384). Of 12,170 hospitalized breast cancer patients, 4.90% were HCV Ab-positive. HCV Ab-positive patients were older (60.92+/-10.82 vs 53.91+/-11.38 years, P < 0.0001) and had a higher body mass index (25.39+/-5.1 vs 24.5+/-4.3 kg/m2, P = 0.007), rates of diabetes (30.60 vs 19.98%, P < 0.0001), hypertension (46.9 vs 30.39%, P < 0.0001), dyslipidemia (25.52 vs 20.28%, P = 0.031), and hyperuricemia (11.38 vs 5.52%, P < 0.0001) than their counterparts. No HCV core-positive cells were demonstrated in breast cancer tissues. Conclusions: Untreated HCV infection, urbanization, and cardiovascular events were potential risk factors for breast cancer. The HCV-associated risk was most prominent among patients <49 years, might not be associated with in situ HCV core-related oncogenesis but with metabolic alterations, and was reversed by anti-HCV therapy.

Diagnostic Dilemma of Aspergillus Meningitis in Patients With Hepatitis C Virus Co-Infection: A Case Series

Aspergillus meningitis can occur in immunocompromised and immunocompetent patients. The diagnostic yield is only 39% in immunocompromised patients and 69% in immunocompetent patients. Diagnosis can be challenging, as repeated cerebrospinal fluid (CSF) cultures can be negative. Even with multiple cultures, the diagnostic yield is meager, sometimes requiring a tissue diagnosis. However, prompt recognition and treatment initiation are crucial to minimize morbidity. We present two cases of patients with a history of intravenous drug use disorder (IVDU) co-infected with hepatitis C virus (HCV) and Aspergillus . Two young Caucasian patients with untreated HCV infection and a history of IVDU, presented with fevers and headaches. Their imaging and multiple CSF samples showing pleocytosis with negative fungal cultures led to a diagnostic dilemma. Due to progressive decline and to ascertain a definitive diagnosis, a brain biopsy resulted in a tissue diagnosis of fungal meningitis secondary to Aspergillus , with hyphae and granulomas, in both individuals. In the workup of chronic meningitis, Aspergillus infection should be strongly considered in patients with IVDU and HCV co-infection. In patients with chronic meningitis lacking definitive diagnosis from spinal fluid, tissue sampling should be pursued as soon as possible to ensure rapid treatment and prevent disability. HCV is associated with a reduction in cellular immunity; our two cases support that HCV and a history of IVDU carry risks of immunosuppression, warranting early and expedited workup for chronic fungal meningitis. J Neurol Res. 2022;12(1):25-29 doi: https://doi.org/10.14740/jnr706

The oral microbiome of treated and untreated chronic HCV infection: A preliminary study.

Chronic hepatitis C virus (HCV) infection is a debilitating disease that is lately treated using direct-acting antivirals (DAAs). Changes in the oral microbiome were detected in other liver diseases; however, oral microbiome was never investigated in patients having chronic HCV infection, whether pre- or post-treatment. This case-control preliminary study enrolled three equal groups: Group (I): untreated HCV patients; group (II): HCV patients who achieved viral clearance after DAA administration; and group (III): healthy controls. For each participant, a buccal swab was harvested and its 16S rRNA was sequenced. The oral microbiome of chronic HCV patients had a significantly distinct bacterial community compared to healthy controls, characterized by high diversity and abundance of certain pathogenic species. These changes resemble that of oral lichen planus patients. After treatment by DAAs, the oral microbiome shifted to a community with partial similarity to both the diseased and the healthy ones. Chronic HCV is associated with dysbiotic oral microbiome having abundant pathogenic bacteria. With HCV clearance by DAAs, the oral microbiome shifts to approach the healthy composition.

A Case Report on Treatment of Nonhealing Leg Ulcer: Do Not Forget the Underlying Disease.

Prevalence of nonhealing ulcers of lower extremities has increased over years causing heavy health, social, and economic burdens. Chronic ulcers are difficult to treat since they require tailored multistep treatment and patient compliance. To treat chronic wounds successfully, clinicians must keep in mind the ulcer etiology as well as the underlying diseases. Several factors may be involved in the pathogenesis of chronic skin ulcers. Leukocytoclastic vasculitis belongs to the group of immune vascular diseases and may be an extrahepatic manifestation of hepatitis C virus (HCV) infection. We describe the case of a patient with a nonhealing vasculitic leg ulcer and chronic HCV infection successfully treated with the combination of advanced dermal substitute and direct-acting antiviral therapy. An 81-year-old female presented to our unit with a 6-month history of a leg ulcer that developed from an exudating skin nodule. At presentation, the lesion was large,caused a severe pain and was unresponsive to analgesics. Skin biopsy showed leukocytoclastic vasculitis. She had a history of old untreated HCV infection, hypertension, type 2 diabetes mellitus, chronic venous insufficiency and tibial arteriopathy. The application of porcine-derived dermal substitute achieved only initial improvement. Therefore, direct-acting antiviral therapy was started, and when HCV RNA became undetectable in blood, pain disappeared and skin ulcer improved up to healing. In conclusion vasculitic leg ulcers can be caused by HCV infection. In such cases, even the use of innovative skin therapy, may obtain only initial and partial improvement, and eradication of HCV viremiais essential to obtain wound healing.

Relation between levels of toll-like receptors 3 and 7 and clinical profile of Child-Pugh B cirrhotic patients.

Aim of the studyGrowing data show that toll-like receptors (TLRs) have considerable roles in the pathogenesis of many liver diseases. We aimed to study the relation between TLR3 and TLR7 levels and clinical manifestations of liver decompensation among hepatitis C virus (HCV)-infected Child-Pugh B patients.Material and methodsThis study included 60 adult patients with Child-Pugh B liver cirrhosis on top of untreated HCV infection. We performed a two-step clustering algorithm depending on TLR-3 gene expression, TLR-7 gene expression, and other influential patients’ characteristics.ResultsPatients were optimally divided into 2 clusters, each cluster containing 30 patients. The average silhouette score of the clustering algorithm was 0.52, indicating a good clustering power of the model. Patients in cluster 1 showed lower relative expression of TLR3 (0.188 vs. 0.29). The same was true of TLR7 (0.20 vs. 0.31). All patients within cluster 1 had lower limb edema and 93% of them had ascites. On the other hand, no one within cluster 2 had ascites or lower limb edema. The mean platelet count was lower in patients within cluster 1 (74,000 vs. 100,000 cell/mm3). The mean international normalized ratio (INR) level was higher in cluster 1 (1.61 vs. 1.3). The mean Model for End-Stage Liver Disease (MELD) score was higher in cluster 1 (15 vs. 10).ConclusionsFrom these results, we can suggest that lower TLR3 and TLR7 can lead to worse clinical manifestations among patients with HCV-related liver cirrhosis. A deeper exploration of this point can open the door for new approaches for managing decompensated cirrhosis.

Daclatasvir Plus Sofosbuvir With and Without Ribavirin for Previously Treated or Untreated Chronic HCV Infection Genotype 1, 2 and 4 in Togo

Background: Daclatasvir (DCV) is a potent, pangenotypic nonstructural protein 5A inhibitor with demonstrated antiviral efficacy when combined with sofosbuvir (SOF) with or without ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection. We are using SOF-DCV combination for large scale treatment. Objectives: The aim of the current study was designed to investigate the efficacy and safety of sofosbuvir/daclatasvir, with or without ribavirin for previously treated or untreated in treatment of HCV genotype 1, 2 and 4, as well as their effect on the liver fibrosis. Methods: One hundred twenty-seven patients with chronic HCV infection were categorized into 2 groups. The group 1 comprised treatment naïve patients, with total serum bilirubin ≤ 1.2mg/10-1L, serum albumin ≥ 3,5g/10-1L, ALAT ≥ 3N, ASAT≤ 2N and platelets count 150 x 109 /L. The group 2 included Peg-INF-alpha or sofosbuvir treatment-experienced patients or patients having at least 2 of the following characteristics: total bilirubin ≤ 1.2mg/10-1L, serum albumin ≥ 3,5g/10-1L, ALAT ≥ 3N, ASAT ≤ 2N and platelets count 150 x 109 /L. The first group was treated with sofosbuvir/daclatasvir for 12 weeks except sofosbuvir treatment experienced patients, who were treated with sofosbuvir/daclatasvir + ribavirin for 24 weeks, with generic medications: DCV 60 mg plus SOF 400 mg ± ribavirin (RBV) within the treatment of hepatitis C virus infection. Efficacy and safety were assessed, and baseline factors associated with sustained virological response at post-treatment week 12 (SVR12) were explored. Results: Sustained virological response (SVR12), was 95,8% in group 1 and 93,8% in group 2. Such high efficacy was accompanied with tolerable adverse effects as well as with significant improvement in liver fibrosis. Conclusion: SOF plus DCV with or without ribavirin achieved high efficacy and safety in HCV genotypes 1,2 and 4 patients. Their effect was accompanied with attenuation of liver fibrosis. Further wider-scale studies are needed to evaluate the actual role of IL 18 polymorphism in treatment response with Sofosbuvir/Daclatasvir.

Cost-effectiveness of Universal and Targeted Hepatitis C Virus Screening in the United States

Between 2 and 3.5 million people live with chronic hepatitis C virus (HCV) infection in the US, most of whom (approximately 75%) are not aware of their disease. Despite the availability of effective HCV treatment in the early stages of infection, HCV will result in thousands of deaths in the next decade in the US. To investigate the cost-effectiveness of universal screening for all US adults aged 18 years or older for HCV in the US and of targeted screening of people who inject drugs. This simulated economic evaluation used cohort analyses in a Markov model to perform a 10 000-participant Monte Carlo microsimulation trail to evaluate the cost-effectiveness of HCV screening programs, and compared screening programs targeting people who inject drugs with universal screening of US adults age 18 years or older. Data were analyzed in December 2019. Cost per quality-adjusted life-year (QALY). Cost per QALY gained. In a 10 000 Monte Carlo microsimulation trail that compared a baseline of individuals aged 40 years (men and women) and people who inject drugs in the US, screening and treatment for HCV were estimated to increase total costs by $10 457 per person and increase QALYs by 0.23 (approximately 3 months), providing an incremental cost-effectiveness ratio of $45 465 per QALY. Also, universal screening and treatment for HCV are estimated to increase total costs by $2845 per person and increase QALYs by 0.01, providing an incremental cost-effectiveness ratio of $291 277 per QALY. The findings of this study suggest that HCV screening for people who inject drugs may be a cost-effective intervention to combat HCV infection in the US, which could potentially decrease the risk of untreated HCV infection and liver-related mortality.

Thyroid dysfunction in Egyptian patients with hepatitis C virus: prevalence and possible triggering

BackgroundThe contribution of chronic hepatitis C virus (HCV) infection per se in thyroid autoimmunity and dysfunction remains controversial. We investigate the prevalence of thyroid disorders and the possible association between thyroid dysfunction and different factors in a cohort of HCV-untreated patients.Patients and methodsA total 1050 patients with untreated HCV infection were enrolled in this study. Thyroid function tests, antiperoxidase (TPO-Ab), antithyroglobulin, thyroid ultrasound, real-time PCR to assess HCV RNA viral load, and fibroscan to determine degree of hepatic fibrosis were done.ResultsThyroid dysfunction was found in 17.1% of patients: 11.5% hypothyroidism and 5.6% hyperthyroidism. Subclinical hypothyroidism, overt hypothyroidism, subclinical hyperthyroidism, and overt hyperthyroidism were detected in 8.6, 2.8, 3.3, and 2.3% of patients, respectively. Thyroid ultrasound showed abnormality in 10.2% of patients. TPO-Ab and antithyroglobulin were positive in 5.1 and 6.4% of patients, respectively. TPO-Ab was more frequently positive in hyperthyroid patients compared with euthyroid (P<0.001) and hypothyroid (P<0.001) patients. Positive TPO-Ab was only significantly associated with thyroid state (P<0.001) and duration of HCV infection (P=0.02).ConclusionThe prevalence of thyroid dysfunction is 17.1% among patients with HCV infection. Furthermore, thyroid disorder is related mainly to thyroid autoimmunity independent of age, sex, or level of viremia.

Hepatitis C Treatment Differences in Elderly Patients: Single-Center Retrospective Study.

Background: Clinical studies evaluating direct-acting antivirals (DAAs) for hepatitis C virus (HCV) treatment show sustained virological response at 12 weeks (SVR12) rates >90%. However, there are few elderly patients included in these studies; thus, generalizability of high success rates to patients >70 years old cannot be assumed. Objective: To identify treatment differences between elderly and nonelderly patients. Methods: This is a retrospective cohort study of all patients who were treated with DAAs between June 2014 and September 2016 at our institution. Patients were divided into 2 groups: elderly, age ≥70 years at the time of initiation of DAAs, and nonelderly, <70 years. The primary outcome was achievement of SVR12. Results: Among the 551 patients, 60 with age range 70 to 86 years comprised the elderly group. SVR12 rates were significantly lower in the elderly population, especially in those with liver cirrhosis. SVR12 was achieved in 81% of the elderly group as compared with 95% in the nonelderly group. Among cirrhotic patients, 69.4% in the elderly group, and 94.1% in the nonelderly group achieved SVR12. Binary logistic regression modeling showed age >70 years to be the strongest predictor of treatment failure (odds ratio = 3.4), along with diagnosis of cirrhosis (odds ratio = 2.4), when corrected for gender, race, prior treatment experience, genotype, and presence of hepatocellular carcinoma. Conclusion and Relevance: Lower SVR12 was seen in elderly cirrhotic patients (69.4%), who are at higher risk of complications related to advanced liver disease and untreated HCV infection, highlighting the need to treat patients before cirrhosis develops.

The seroprevalence of untreated chronic hepatitis C virus (HCV) infection and associated risk factors in male Irish prisoners: a cross-sectional study, 2017.

IntroductionData on chronic hepatitis C (HCV) infection prevalence in European prisons are incomplete and impact the public health opportunity that incarceration provides.AimsWe aimed to estimate the seroprevalence of untreated chronic HCV infection and to identify associated risk factors in an Irish male prison.MethodsWe conducted a cross-sectional study involving a researcher-administered questionnaire, review of medical records and HCV serology.ResultsOf 422 prisoners (78.0% of the study population) who participated in the study, 298 (70.6%) completed the questionnaire and 403 (95.5%) were tested for HCV antibodies. Of those tested, 92 (22.8%) were HCV antibody-positive, and of those, 53 (57.6%) were HCV RNA-positive, 23 (25.0%) had spontaneous clearance, 16 (17.4%) had a sustained viral response, 10 (11.0%) were co-infected with HIV and six (6.0%) with HBV. The untreated chronic HCV seroprevalence estimate was 13.1% and the seroprevalence of HCV among prisoners with a history of injecting drug use (IDU) was 79.7%. Risk factors significantly associated with past HCV infection were IDU (p < 0.0001), having received a prison tattoo (p < 0.0001) or a non-sterile community tattoo (p < 0.0001), sharing needles and other drug-taking paraphernalia (p < 0.0001). Small numbers of prisoners had a history of sharing razors (n=10; 3.4%) and toothbrushes (n=3; 1.0%) while incarcerated. On multivariable analysis, history of receiving a non-sterile community tattoo was the only significant risk factor associated with HCV acquisition (after IDU was removed from the model) (p = 0.005, β = 0.468).ConclusionThe level of untreated chronic HCV infection in Irish prisons is high, with IDU the main associated risk.

Comparison of prevention, screening and treatment of hepatitis C in Iran, Egypt and Georgia

Hepatitis C virus (HCV) infection represents one of the major public health challenges worldwide. HCV is a blood-borne pathogen associated with a high rate of mortality and imposes a dramatic societal and economic burden on health systems. Untreated chronic HCV infection can progress to liver cirrhosis and cancer. Lessons can be learned from countries such as Egypt and Georgia that are considered to be ‘on-track’ for the World Health Organization HCV elimination targets, as well as countries such as Iran that are ‘working towards elimination’. This article compares HCV-related policies and strategies in Iran, Egypt and Georgia to identify programme strengths and limitations that could inform policy and decision makers in Iran. Controlling and eliminating HCV remain a serious public health challenge. The rising HCV incidence could generate a dramatic economic burden in the coming years. Therefore, Iran requires a strategic plan to fight HCV. Adequate cultural and social infrastructures are needed. Centres specifically devoted to the diagnosis and management of this infection should be used for screening and delivery of inexpensive and high-quality testing. Quick initiation of treatment should take place at lower costs to facilitate access to treatment.

Cost-effectiveness analysis of strategies to manage the disease burden of hepatitis C virus in Switzerland.

A previous analysis of hepatitis C virus (HCV)-related healthcare costs in Switzerland found that the annual healthcare costs of untreated HCV infection (excluding antiviral treatment) could increase by more than 25 million Swiss francs (CHF) between 2013 and 2030. Since that publication, highly efficacious direct-acting antiviral therapies (DAAs) have become available, making HCV elimination a possibility. This analysis quantifies the clinical and economic burden of HCV intervention strategies over the next 15 years. A model was developed to estimate the future clinical and economic burden of HCV infection if patients are diagnosed and treated according to a historical paradigm (historical base case), or at higher levels without treatment reimbursement restrictions (Scenario 1). The infected population was tracked by age- and sex-defined cohorts, and associated direct medical costs (healthcare, screening, diagnostics and treatment) and quality-adjusted life years (QALYs) were calculated. Direct cost savings and the incremental cost-effectiveness ratio (ICER) were calculated to assess the economic impact of each scenario. Additionally, we generated a net-zero cost scenario (Scenario 2), assuming the same treatment paradigm as Scenario 1 but at the treatment price that would break even by 2031. In the historical base case, annual direct costs are projected to decrease from 150 million (95% UI: 132&ndash;170 million) CHF in 2016 to 90 million (95% UI: 65&ndash;111 million) CHF in 2031. Cumulative direct costs are projected to reach 1.7 billion (95% UI: 1.2&ndash;2.0 billion) CHF by 2031. In Scenario 1, annual direct costs first increased to 175 million CHF by 2018, before declining to 44 million CHF by 2031. Cumulative direct costs in this scenario are projected to reach 1.8 billion CHF by 2031. For Scenario 2, the treatment price needed to achieve break-even by 2031 considering only direct costs would be 27,900 CHF per patient. By 2031, Scenarios 1 and 2 would gain 58,300 QALYs. In both scenarios, the ICER drops below the cost-effectiveness threshold of 78,000 CHF in 2018. Over the 15-year span, the ICER was determined to be 2,200 CHF for Scenario 1. Increasing the number of patients treated and treating all fibrosis stages is cost-effective compared to the historical base case and could achieve break-even by 2031 at a price of 27,900 CHF.

Liver transplantation for hepatitis C virus (HCV) non-viremic recipients with HCV viremic donors.

In the context of organ shortage, the opioid epidemic, and effective direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV), more HCV-infected donor organs may be used for liver transplantation. Current data regarding outcomes after donor-derived HCV in previously non-viremic liver transplant recipients are limited. Clinical data for adult liver transplant recipients with donor-derived HCV infection from March 2017 to January 2018 at our institution were extracted from the medical record. Ten patients received livers from donors known to be infected with HCV based on positive nucleic acid testing. Seven had a prior diagnosis of HCV and were treated before liver transplantation. All recipients were non-viremic at the time of transplantation. All 10 recipients derived hepatitis C infection from their donor and achieved sustained virologic response at 12weeks posttreatment with DAA-based regimens, with a median time from transplant to treatment initiation of 43days (IQR 20-59). There have been no instances of graft loss or death, with median follow-up of 380days (IQR 263-434) posttransplant. Transplantation of HCV-viremic livers into non-viremic recipients results in acceptable short-term outcomes. Such strategies may be used to expand the donor pool and increase access to liver transplantation.

Lower Cure Rates of Hepatitis C Treatment in Elderly Patients (aged 70 Years and Above) With Cirrhosis: Single Center Comparative Analysis

Introduction: Although Hepatitis C virus (HCV) infection can affect all age groups, the highest prevalence is estimated to be in those born between the years of 1945-1965. Elderly patients may be on more medications, potentially causing decreased efficacy of HCV therapy, increased drug interactions, or higher rates of adverse effects. Clinical studies evaluating Direct Acting Antivirals (DAAs) show Sustained Virologic Response (SVR12) rates in excess of 90%, however, there are very few elderly patients included in these studies thus generalizability of high success rates to patients over the age of 70 cannot be assumed. As this “baby-boomer” population is approaching age 70 and above, unique barriers to HCV cure that elderly patients face should be evaluated. Methods: This is a retrospective cohort study evaluating all patients who were treated and completed DAAs between June 2014 and September 2016 at our center. Patients were divided into two groups: Elderly: those age 70 and above at the time of initiation of DAA. Non-Elderly: those age less than 70. Patients were treated with standard of care therapy and were evaluated every 2-4 weeks while on therapy. Primary outcome: achievement of SVR12. Results: A total of 588 patients were treated for HCV during the study duration: 62 elderly patients (11%) were identified with age range (70-86) who completed HCV therapy. SVR12 data was available in 61 patients. 526 patients were included in non-elderly group. SVR12 data was available in 386 patients Fibrosis/cirrhosis was assessed with various non-invasive and non-invasive methods. SVR12 rates were significantly lower in elderly population, especially in those with liver cirrhosis. 52% (33/63) of patients reported an AE, with the most common being fatigue, however, none discontinued DAA. Direct Logistic Regression model which included Race, Age above 70, Gender, Presence of cirrhosis, Prior treatment expreience, and Baseline RNA, was stasitically significant, and Age above 70 was the strongest predictor of treatment failure (odds ratio 7.95) when controlled for other variable. Conclusion: Overall SVR12 rate in elderly patients was lower than that of the non-elderly population at TUH. Age above 70 was shown to be an independant risk factor for treatment failure. Lower SVR12 was seen in elderly cirrhotics, who are at higher risk of complications related to advanced liver disease and untreated HCV infection, highlighting the need to treat patients before cirrhosis develops<./p>970_A Figure 1 No Caption available.970_B Figure 2 No Caption available.970_C Figure 3. Logistic Regression Predicting likelihood of treatment failure

Acquired factor VIII inhibitor associated with chronic untreated hepatitis C

Acquired inhibitors of coagulation are antibodies that either inhibit the activity or increase the clearance of a clotting factor. A hemorrhagic diathesis is a common clinical manifestation in affected patients. Acquired factor VIII inhibitor – or acquired hemophilia A – is a rare disorder and presents similarly to hemophilia A, though patients are less likely to develop hemarthroses. This inhibition is most commonly due to autoantibodies against coagulation factor VIII. These autoantibodies often occur in pregnancy, autoimmune disorders, solid tumors, and lymphoproliferative syndromes. Several drugs, including penicillins, phenytoin, and sulfa drugs, have also been associated with antibodies to factor VIII. Chronic infection with the hepatitis C virus (HCV), in addition to various degrees of liver inflammation and fibrosis, can have extrahepatic manifestations, especially autoimmune disorders. The most common hematological complications of HCV infection are thrombocytopenia, cryoglobulinemia, and anti-cardiolipin antibodies. A few cases of factor VIII inhibitors occurring in HCV patients have been reported, with a higher incidence after prolonged treatment with interferon-α. Here, we present a case of a patient with chronic untreated HCV infection developing acquired factor VIII deficiency.

Adiponectin levels and insulin resistance among patients with chronic hepatitis C

Chronic hepatitis C virus (HCV) infection is associated with insulin resistance (IR), rapid disease progression, and decreased virological response to antiviral treatment. In addition, obesity is a risk factor for chronic hepatitis C evolution and is associated with IR. As adiponectin is an adipokine that is associated with obesity and IR, this study aimed to investigate serum levels of adiponectin among patients with HCV infection and IR. Thirty-three patients with untreated HCV infection underwent testing of serum adiponectin levels (capture ELISA) and were compared to 30 healthy subjects with similar body mass indexes (BMI). Data were also obtained for several homeostatic model assessment (HOMA) indexes: HOMA-IR, HOMA-β, and HOMA-adiponectin. Patients with HCV infection had higher adiponectin levels, which predominantly were observed among women. Hyperadiponectinemia was not associated with high BMI. Patients with HCV infection had higher HOMA-IR and HOMA-β values, although no difference was observed for HOMA-adiponectin. Patients with HCV infection and overweight/obese status had higher HOMA-IR values, although no association was observed for adiponectin levels. Hyperadiponectinemia and IR were not influenced by HCV load or liver fibrosis. The predictors of IR were BMI, glycemia, and serum levels of insulin and non-high-density lipoprotein cholesterol, but not adiponectin levels. Thus, patients with chronic hepatitis C have significant metabolic alterations (hyperadiponectinemia and high HOMA-IR values) that are independent of HCV viremia and liver fibrosis. Among these patients, HOMA-IR but not HOMA-adiponectin was appropriate for diagnosing IR.

Impact of ledipasvir/sofosbuvir on the work productivity of genotype 1 chronic hepatitis C patients in Asia.

Chronic, untreated hepatitis C virus (HCV) infection is associated with a poor clinical prognosis and a detrimental impact on patients' lives, including on work productivity. To estimate the value of productivity losses due to genotype 1 (GT1) HCV infection in Hong Kong, Singapore, South Korea and Taiwan and to estimate the potential productivity gains associated with treating patients with ledipasvir/sofosbuvir (LDV/SOF) therapy, an economic model was developed with a time horizon of 1year. Hepatitis C virus patients entered the model at 12weeks post-treatment, having achieved or not achieved sustained virological response (SVR). Absenteeism and presenteeism rates were taken from a pooled analysis of data from the ION 1-3 studies. These rates were converted into hours of lost productivity, multiplied by the average wage and applied to the total employed, adult GT1 population in each country. Results were compared assuming no treatment, and assuming all patients were treated with LDV/SOF. Total productivity losses due to untreated HCV were: $11.3 million, $17.1m, $146.0m and $349.1m in Hong Kong, Singapore, South Korea and Taiwan. LDV/SOF treatment resulted in economic gains of $4.5m, $6.8m, $58.7m and $138m, respectively. These gains were due to reduced presenteeism. The results were sensitive to changes in the prevalence of HCV and the average wage. In conclusion, productivity losses due to untreated HCV infection represent a substantial economic burden. By instituting universal HCV treatment with LDV/SOF (or other therapies with high SVR rates), productivity gains can be achieved.

The Current Status of Renal Transplant Recipients with Hepatitis C: A Single Center Experience

Renal transplantation (RTx) may result in the development of liver disorder/hepatic cancer or hepatitis C virus (HCV)- related membranoproliferative glomerulonephritis, which may lead to graft loss, in renal failure patients with previously untreated HCV infection. Long-term survival is longer in HCV antibody-positive renal transplant recipients than in HCV antibody-negative/-positive dialysis patients, whereas renal graft survival and patient survival are lower in HCV antibody-positive renal transplant recipients than in HCV antibody-negative patients; thus, HCV treatment should be administered to HCV antibodypositive renal transplant recipients. Interferon/ribavirin (IFN/Rib) therapy is one of the current HCV treatments in Japan. In renal failure patients including those undergoing hemodialysis, Rib is contraindicated because of possible kidney function problems; IFN monotherapy is indicated for these patients. However, in clinical practice, IFN monotherapy is not performed adequately because of efficacy problems or adverse reactions to IFN, leading to the presence of many HCV carriers and patients with previous HCV infection among hemodialysis patients in the RTx waiting list. The sustained virological response in patients receiving IFN therapy after RTx is low. Many patients discontinue the therapy and some develop graft loss because of IFN-related acute rejection. Therefore, dialysis patients with HCV infection who are scheduled for RTx should first receive IFN therapy. In Japan, daclatasvir/ asunaprevir combination therapy was introduced as an IFN-free antiviral therapy in September 2015. However, its safety in dialysis patients has not been established, and these patients still require IFN therapy. We report the current state of renal transplant recipients with HCV at our hospital.