Had Hepatitis C Virus Research Articles

Circulating Galectin-3: A Prognostic Biomarker in Hepatocellular Carcinoma

ABSTRACT Introduction Galectin-3 plays critical roles in the adhesion, proliferation, and differentiation of tumor cells. Recent data have suggested that galectin-3 plays a role in the development of hepatocellular carcinoma (HCC); however, its prognostic value has not been validated. The aim of our study was to evaluate the clinical and prognostic value of galectin-3 in patients with HCC. Methods We prospectively enrolled and collected clinicopathologic data and serum samples from 767 patients with HCC between 2001 and 2014 at The University of Texas MD Anderson Cancer Center. Two hundred patients without HCC were also enrolled and had data collected. The Kaplan-Meier method was used to estimate overall survival (OS) distributions. Results The median OS in this cohort was 14.2 months (95% CI, 12–16.1). At the time of analysis, the 1-year OS rate was 45% (95% CI, 0.4–0.51) among patients with high galectin-3 levels and 59% (95% CI, 0.54–0.63) among patients with low galectin-3 levels. OS was significantly inferior in patients with high galectin-3 levels than in patients with lower galectin-3 levels (median OS: 10.12 vs. 16.49 months; p = 0.0022). Additionally, the multivariate model showed a significant association between high galectin-3 level and poor OS (hazard ratio [HR] = 1.249; 95% CI, 1.005–1.554). Comparison between low (n = 464 patients) and high (n = 302 patients) galectin-3 levels showed that mean serum galectin-3 levels were significantly higher in patients with HCC who had hepatitis C virus (HCV) infection (p = 0.0001), higher Child-Pugh score (CPS) (p = 0.0009), and higher Cancer of the Liver Italian Program (CLIP) score (p = 0.0015). Conclusion Our study shows that serum galectin-3 level is a valid prognostic biomarker candidate.

Advancing Diagnosis of Current Hepatitis C Virus Infection: A Key to Hepatitis C Elimination in the United States.

More than 2 million adults have hepatitis C virus (HCV) infection in the United States, and new infections continue to increase. Without treatment, HCV infection can lead to advanced liver disease and death. Treatment is recommended for nearly everyone with hepatitis C, resulting in a cure in >95% of people treated and raising the possibility of hepatitis C elimination. Testing is the first step to accessing life-saving treatment. The Centers for Disease Control and Prevention recommends hepatitis C screening for all adults, all pregnant persons, and anyone with risk; yet about one-third of people with hepatitis C remain unaware of their infection. Testing begins with a hepatitis C antibody test, followed, when reactive, by a nucleic acid test to detect HCV RNA. This antibody-first, 2-step testing strategy misses early infections and can result in incomplete diagnoses. Advancements in hepatitis C diagnostics and the US regulatory landscape have created an opportunity to include viral-first testing strategies and improve hepatitis C diagnosis. This journal supplement features 8 articles detailing challenges and opportunities for improving hepatitis C diagnostics in support of advancing hepatitis C elimination in the United States.

Prevalence and prediction of hepatocellular carcinoma in alcohol-associated liver disease: a retrospective study of 136 571 patients with chronic liver diseases

Background and aimsTo explore the incidence of alcohol-related hepatocellular carcinoma (HCC), evaluate possible synergisms between alcohol and well-known risk factors associated with HCC and establish a nomogram to predict alcohol-associated...

Hepatitis C Virus Clearance Cascade - United States, 2013-2022.

Approximately 2.4 million adults were estimated to have hepatitis C virus (HCV) infection in the United States during 2013-2016 (1). Untreated, hepatitis C can lead to advanced liver disease, liver cancer, and death (2). The Viral Hepatitis National Strategic Plan for the United States calls for ≥80% of persons with hepatitis C to achieve viral clearance by 2030 (3). Characterizing the steps that follow a person's progression from testing to viral clearance and subsequent infection (clearance cascade) is critical for monitoring progress toward national elimination goals. Following CDC guidance (4), a simplified national laboratory results-based HCV five-step clearance cascade was developed using longitudinal data from a large national commercial laboratory throughout the decade since highly effective hepatitis C treatments became available. During January 1, 2013-December 31, 2021, a total of 1,719,493 persons were identified as ever having been infected with HCV. During January 1, 2013-December 31, 2022, 88% of those ever infected were classified as having received viral testing; among those who received viral testing, 69% were classified as having initial infection; among those with initial infection, 34% were classified as cured or cleared (treatment-induced or spontaneous); and among those persons, 7% were categorized as having persistent infection or reinfection. Among the 1.0 million persons with evidence of initial infection, approximately one third had evidence of viral clearance (cured or cleared). This simplified national HCV clearance cascade identifies substantial gaps in cure nearly a decade since highly effective direct-acting antiviral (DAA) agents became available and will facilitate the process of monitoring progress toward national elimination goals. It is essential that increased access to diagnosis, treatment, and prevention services for persons with hepatitis C be addressed to prevent progression of disease and ongoing transmission and achieve national hepatitis C elimination goals.

Association of TGF-β1 Polymorphism and TGF-β1 Levels With Chronic Hepatitis C and Cirrhosis: A Systematic Review and Meta-Analysis.

Despite the extensive research conducted on the relationship between transforming growth factor-beta 1 (TGF-β1) polymorphisms and levels and the onset and development of liver disease, there are still certain gaps that need to be addressed. To address these gaps and provide a comprehensive overview of the current knowledge, this review aimed to identify relevant published research on TGF-β1/TGF-β1 polymorphism, TGF-β1/TGF-β1 levels, and their associations with cirrhosis and hepatitis C. The synthesis of available data was performed to further enhance our understanding in this area. Adopting the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a search strategy was implemented across several online databases to search for relevant articles as per the defined selection criterion. Eight studies were selected after the completion of the search strategy. Of the eight studies, five revealed a considerably high level of TGF-β1 in patients who had hepatitis C virus (HCV) and liver cirrhosis caused by hepatocellular carcinoma (HCC). The forest plot analysis showed a statistically significant impact of TGF-β1polymorphism and levels on the incidence of hepatic cirrhosis and hepatitis C, with an odds ratio (OR) of 0.65 and a risk ratio (RR) of 0.76. The heterogeneity test showed a high level of heterogeneity at 94% and 95% for OR and RR, respectively, but the overall effect was significant with P< 0.01 for both measures.According to the results obtained, the authors concluded that TGF-β1 polymorphism and its associated levels should be taken into account while developing preventive and therapeutic approaches for hepatic cirrhosis and hepatitis C.

Evaluation of the Cherokee Nation Hepatitis C Virus Elimination Program - Cherokee Nation, Oklahoma, 2015-2020.

Approximately 2.4 million persons in the United States have hepatitis C virus (HCV) infection, and 66,700 acute HCV infection cases were estimated for 2020 (1,2). American Indian or Alaska Native (AI/AN) persons are disproportionately affected by HCV infection and experienced the highest rates of acute HCV infection (2.1 cases per 100,000 persons) and HCV-associated mortality (10.17 per 100,000 persons) in the United States during 2020 (1). During 2015, Cherokee Nation Health Services (CNHS) in Oklahoma implemented an HCV elimination program, which includes universal HCV screening, primary HCV workforce expansion, and harm reduction services (3). To assess progress 5 years after program initiation, CNHS analyzed deidentified health record data. During November 1, 2015-October 31, 2020, a total of 1,423 persons received a diagnosis of HCV infection. Among these persons, 1,227 (86.2%) were linked to HCV care, and 871 (61.2%) initiated HCV treatment; 702 (49.3%) returned for their 12-week post treatment completion visit, at which time 698 (49.1%) had achieved laboratory-confirmed sustained virologic response (SVR), defined as undetectable HCV RNA at ≥12 weeks after completion of treatment (SVR12). Although CNHS has linked the majority of persons diagnosed with HCV infection to care, and those who returned for the SVR12 visit had high cure rates (99.4%), treatment initiation was lower than expected. Future activities should prioritize addressing gaps in treatment initiation after linkage to care and confirmation of hepatitis C cure with SVR12 testing.

Vital Signs: Hepatitis C Treatment Among Insured Adults - United States, 2019-2020.

IntroductionOver 2 million adults in the United States have hepatitis C virus (HCV) infection, and it contributes to approximately 14,000 deaths a year. Eight to 12 weeks of highly effective direct-acting antiviral (DAA) treatment, which can cure ≥95% of cases, is recommended for persons with hepatitis C.MethodsData from HealthVerity, an administrative claims and encounters database, were used to construct a cohort of adults aged 18–69 years with HCV infection diagnosed during January 30, 2019–October 31, 2020, who were continuously enrolled in insurance for ≥60 days before and ≥360 days after diagnosis (47,687). Multivariable logistic regression was used to assess the association between initiation of DAA treatment and sex, age, race, payor, and Medicaid restriction status; adjusted odds ratios (aORs) and 95% CIs were calculated.ResultsThe prevalence of DAA treatment initiation within 360 days of the first positive HCV RNA test result among Medicaid, Medicare, and private insurance recipients was 23%, 28%, and 35%, respectively; among those treated, 75%, 77%, and 84%, respectively, initiated treatment within 180 days of diagnosis. Adjusted odds of treatment initiation were lower among those with Medicaid (aOR = 0.54; 95% CI = 0.51–0.57) and Medicare (aOR = 0.62; 95% CI = 0.56–0.68) than among those with private insurance. After adjusting for insurance type, treatment initiation was lowest among adults aged 18–29 and 30–39 years with Medicaid or private insurance, compared with those aged 50–59 years. Among Medicaid recipients, lower odds of treatment initiation were found among persons in states with Medicaid treatment restrictions (aOR = 0.77; 95% CI = 0.74–0.81) than among those in states without restrictions, and among persons whose race was coded as Black or African American (Black) (aOR = 0.93; 95% CI = 0.88–0.99) or other race (aOR = 0.73; 95% CI = 0.62–0.88) than those whose race was coded as White.Conclusions and Implications for Public Health PracticeFew insured persons with diagnosed hepatitis C receive timely DAA treatment, and disparities in treatment exist. Unrestricted access to timely DAA treatment is critical to reducing viral hepatitis–related mortality, disparities, and transmission. Treatment saves lives, prevents transmission, and is cost saving.

Sofosbuvir-based therapy for late pregnant women and infants with severe chronic hepatitis C: A case series study.

Data on sofosbuvir-based therapy for pregnant women and infants with severe chronic hepatitis C (CHC) are lacking. Two late pregnant women and one female infant with severe CHC were enrolled for treatment. Pregnant Women 1 and 2 and Infant 3 were 30, 33, and 1.2 years old, respectively; the gestational ages of pregnant Women 1 and 2 were 31 and 26 weeks, respectively. Notably, pregnant Women 1 and 2 and Infant 3 had hepatitis C virus (HCV) RNA levels of 139 000, 198 000, and 8 450 000 IU/ml; alanine aminotransferase levels of 420, 781, and 220 U/L; and received sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, and sofosbuvir/ledipasvir for 12 weeks, respectively. All three patients were safely cured with favorable tolerance, and two newborns were both breastfeeding and were consistently negative for the anti-HCV antibody during the 1-year follow-up after birth. Additionally, two newborns and Infant 3 had normal growth parameters during the follow-up year one. In conclusion, this case series study found that sofosbuvir-based therapy for pregnant women and infants with severe CHC is safe and effective. The data may fill the gap and provide evidence of the use of sofosbuvir-based therapy as a reference when similar severe CHC situations are encountered during clinical practice.

Outcome of Treatment in Children With Chronic Viral Hepatitis C: A Single Centre Study.

ObjectiveTo review the efficacy of the combination of pegylated interferon-α 2b and ribavirin, and sofosbuvir and ribavirin in achieving sustained viral response (SVR) in chronic hepatitis C genotypes 1 and 3 in children.MethodsA retrospective descriptive study was performed for children under 15 years of age treated for chronic hepatitis C at Pakistan Kidney and Liver Institute and Research Centre, Lahore, between 2018 and 2019. Demographic data and clinical information were collected. In addition, treatment outcome was assessed by SVR, defined as the absence of detectable viral RNA in blood after 24 weeks of initiation of treatment.ResultsA total of 30 children aged 15 years and below were included in this study. Sixteen of 30 children were males, and 14 were females. Of these 30 patients, four had hepatitis C virus (HCV) genotype 1, and 26 children had HCV genotype 3. The children with genotype 1 (a+b) were given the combination of ribavirin and pegylated interferon alfa-2b (Peg-IFN-α-2b). The remaining with HCV genotype 3 were given the combination of ribavirin and sofosbuvir for 24 weeks. Overall, 27 out of 30 (90%) children attained SVR at six months (100% children with genotype 1 and 88.4% children with genotype 3).ConclusionThe combined therapy of ribavirin and sofosbuvir or Peg-IFN-α-2b and ribavirin is highly effective in treating chronic HCV infection in children.

Intravenous Drug Use: a Significant Risk Factor for Serratia Bacteremia.

Background:Serratia is an opportunistic pathogen known to cause an array of infectious presentations. Aside from case reports, intravenous (IV) drug use has not been adequately quantified as a major risk factor for Serratia infection.Methods:A retrospective cohort study of 103 adult patients admitted to four community hospitals in Ohio from January 2014 to December 2018 with a positive blood culture for Serratia species. A complete data set of 103 patients was analyzed for demographics, comorbidities, initial diagnosis, treatment, and outcomes. Outcomes were recurrence of infection, in hospital mortality, 90-day mortality, length of hospital stay (LOS), complications (endocarditis, osteomyelitis, abscess), and evaluation for resistance to third-generation cephalosporins and extended-spectrum beta-lactamase (ESBL) activity. Descriptive statistics were performed using frequencies for discrete variables and median [interquartile range (IQR)] for continuous variables.Results:Serratia marcescens was the predominate species 94 (91%). Demographics were White 88 (85%) and male 63 (62%); 42 (42%) were IV drug users. IV drug users were younger than non-IV drug users with a median (IQR) age of 40 [33–50] versus 71 years [41–72] and likely to have hepatitis C virus (HCV) infection 37 (88%) versus 3 (5%), p < 0.0001. Culture and susceptibility analysis revealed 36% of isolates with possible or confirmed ESBL production. The most common complications were endocarditis (12%) and osteomyelitis (10%). In-hospital mortality was 2%, 90-day mortality (2%), with 90-day readmission (21%). The median (IQR) LOS is 7 [3.25–14.75].Conclusion:This is the largest study to our knowledge evaluating non-nosocomial Serratia bacteremia. Our study shows that a high proportion of patients hospitalized with a positive Serratia culture are IV drug users and have HCV co-infection. There is significant ceftriaxone resistance and ESBL activity noted in our population. Based on this, we suggest empiric treatment with cefepime or consider carbapenem therapy for Serratia bloodstream isolates pending full susceptibility data. Focus should be on proper antibiotic treatment as the readmission rate and LOS are high.

HÉRNIA INCISIONAL PRECOCE APÓS TRANSPLANTE HEPÁTICO: FATORES DE RISCO E RESULTADOS DO REPARO CIRÚRGICO

Liver transplantation is a complex and valuable therapy. However, complications that burden postoperative quality of life, such as incisional hernia, are to be better elucidated, such as risk factors and prophylactic measures. This study aimed to define the rate of incisional hernia in patients who underwent liver transplantation in a population in southern Brazil and to assess the related risk factors in order to establish measures for prior optimization and specific prophylactic care in the future. Patients undergoing adult Liver transplantation from January 2004 to November 2020 were retrospectively analyzed, assessing demographic features, surgical outcomes, and predisposing factors. Among 261 liver transplantation patients included, incisional hernia was diagnosed in 71 (27.2%). Of the 71 incisional hernia patients, 28 (39.4%) developed IH during the first post-transplant. Majority of the patients were male (52/71, 73.2%); of the 71 patients, 52 had hepatitis C virus (HCV) and 33 (46.5%) had hepatocellular carcinoma (HCC). Male gender (p=0.044), diabetes mellitus (p=0.008), and acute cellular rejection (p<0.001) were risk factors for IH. In all, 28 (39.4%) patients were submitted for hernia repair with mesh, with a recurrence rate of 17.8%. Incisional hernia after liver transplantation is a relatively common problem associated with male gender, diabetes, and acute cellular rejection. This is a problem that should not be trivialized in view of the complexity of liver transplantation, as it can lead to a reduction in quality of life as well as jeopardize late liver transplantation results and lead to incarceration and strangulation.

Economic Considerations in Using HCV and HIV Positive Donors for Kidney Transplant

End Stage Renal Disease is becoming more prevalent in the United States of America, with demand for kidney transplant exceeding the available organ supply. A novel method to increase the donor pool has been to consider transplanting organs from deceased patients who have had Hepatitis C Virus (HCV) or Human Immunodeficiency Virus (HIV) infections. Transplants with HCV infected kidneys are becoming more prevalent, due to increased organ supply due to increased mortality from injection opioid use. Similarly, deceased donor transplants using kidneys infected with HIV have become more common following the passage of the “HIV Organ Policy Equity (HOPE) Act” in 2013. These novel transplant strategies present distinct socioeconomic impacts which differ from those of prior transplant practices. Here, we have reviewed the costs and benefits of receiving a kidney transplant from deceased donors infected with HIV or HCV, compared to receiving a non-viremic kidney transplant.

Global burden of atherosclerotic cardiovascular disease in people with hepatitis C virus infection: a systematic review, meta-analysis, and modelling study

SummaryBackgroundMore than 70 million people worldwide are estimated to have hepatitis C virus (HCV) infection. Emerging evidence indicates an association between HCV and atherosclerotic cardiovascular disease. We aimed to determine the association between HCV and cardiovascular disease, and estimate the national, regional, and global burden of cardiovascular disease attributable to HCV.MethodsFor this systematic review and meta-analysis, we searched MEDLINE, Embase, Ovid Global Health, and Web of Science databases from inception to May 9, 2018, without language restrictions, for longitudinal studies that evaluated the risk ratio (RR) of cardiovascular disease in people with HCV compared with those without HCV. Two investigators independently reviewed and extracted data from published reports. The main outcome was cardiovascular disease, defined as hospital admission with, or mortality from, acute myocardial infarction or stroke. We calculated the pooled RR of cardiovascular disease associated with HCV using a random-effects model. Additionally, we calculated the population attributable fraction and disability-adjusted life-years (DALYs) from HCV-associated cardiovascular disease at the national, regional, and global level. We also used age-stratified and sex-stratified HCV prevalence estimates and cardiovascular DALYs for 100 countries to estimate country-level burden associated with HCV. This study is registered with PROSPERO, number CRD42018091857.FindingsOur search identified 16 639 records, of which 36 studies were included for analysis, including 341 739 people with HCV. The pooled RR for cardiovascular disease was 1·28 (95% CI 1·18–1·39). Globally, 1·5 million (95% CI 0·9–2·1) DALYs per year were lost due to HCV-associated cardiovascular disease. Low-income and middle-income countries had the highest disease burden with south Asian, eastern European, north African, and Middle Eastern regions accounting for two-thirds of all HCV-associated cardiovascular DALYs.InterpretationHCV infection is associated with an increased risk of cardiovascular disease. The global burden of cardiovascular disease associated with HCV infection was responsible for 1·5 million DALYs, with the highest burden in low-income and middle-income countries.FundingBritish Heart Foundation and Wellcome Trust.

Long-term Liver-related Outcomes of Patients With Chronic Liver Diseases in Australia

Chronic liver disease is a major health burden that produces significant liver-related morbidity and mortality. We aimed to evaluate liver-related outcomes of patients with different causes of chronic liver disease in Australia. We collected data from 10,933 patients with chronic liver disease assessed by Hepascore (a serum fibrosis model) in Western Australia from 2004 through 2015. We obtained records of liver-related death, transplantation, decompensation, and hepatocellular carcinoma from WA Data Linkage Unit databases. Competing risk analysis was used to calculate the cumulative risk of each clinical endpoint, and risks for clinical endpoints were compared among all causes of chronic liver disease. In our final cohort for analysis, 5566 patients had hepatitis C virus (HCV) infection, 1989 had HBV infection, 119 were infected with HBV and HCV, 955 had alcohol-associated liver disease, 1597 had non-alcoholic fatty liver disease (NAFLD), 123 had alcohol-associated liver disease and metabolic risk factors, 561 had autoimmune liver disease without overlap syndrome, and 23 autoimmune overlap syndrome. Significant differences among chronic liver diseases were observed in risk of all-cause death (P <.001), liver-related death (P < .001), liver transplantation (P < .001), and decompensation (P < .001) but not hepatocellular carcinoma (P=.095). Patients with alcohol-associated liver disease had the highest 5-year cumulative risk of liver-related death (17.1%) and the second-highest 5-year cumulative risk of decompensation (29.2%). Multivariate analysis found patients with alcohol-associated liver disease had significantly higher risks of liver-related death and decompensation than patients with HCV infection with hazard ratios (HRs) of 2.39 (95% CI, 1.88-3.03) and 3.42 (95% CI, 2.74-4.27), respectively. Patients with NAFLD had a significantly lower risk of liver related death and decompensation than patients with HCV infection, with HRs of 0.67 (95% CI, 0.48-0.95) and 0.70 (95% CI, 0.52-0.94) respectively. In an analysis of patients in Western Australia, we found patients with alcohol-associated liver disease to have significantly higher risk of decompensation and liver-related death than patients with HCV infection, whereas patients with NAFLD have significantly lower risks of either outcome.

Refractory Helicobacter pylori gastritis: The hidden predictors of resistance.

Failure of Helicobacter pylori eradication is documented in 20% of patients. Some patients show a negative faecal antigen test (FAT) with persistent symptoms after therapy. The aim of this study was to detect occult H. pylori infection in patients with persistent symptoms despite FAT negativity following therapy. A total of 200 symptomatic patients presenting with dyspepsia and positive FAT were treated with H. pylori triple therapy for 2 weeks. Refractory patients received levofloxacin-based salvage therapy. Upper gastrointestinal endoscopy was performed for patients with persistent symptoms despite negative FAT after salvage therapy. Gastric biopsies were exposed to rapid urease test and RFLP-PCR for clarithromycin resistance in domain V of 23S rRNA (2142/2143 point mutations) as well as culture and antimicrobial susceptibility testing (AST). A total of 136 patients responded to classic triple therapy with negative FAT, and 15 patients showed persistent symptoms with positive FAT and received salvage therapy. The remaining 49 patients showed persistent symptoms despite negative FAT, therefore gastric biopsies with rapid urease test were performed. Clarithromycin resistance was confirmed in 12/49 patients (24.5%). Cultures were most commonly susceptible to norfloxacin (n=18), moxifloxacin (n=13), doxycycline (n=11) and amikacin (n=8). Non-responders with negative FAT had moderate or severe fatty liver disease (26.5% and 32.7%, respectively), 40.9% had hepatitis C virus (HCV) infection, and they had significantly higher HOMA-IR and HbA1c. Diabetes mellitus, HCV and non-alcoholic fatty liver disease predispose to refractory H. pylori requiring culture and AST.

Hearts and Lungs from Hepatitis C Virus–Infected Donors Were Safely Transplanted into HCV-Negative Recipients

The opioid epidemic has produced a growing number of potentially transplantable organs from donors who had hepatitis C virus (HCV) infection. At the

Influence of Sorafenib on Host Immunity in Patients with Liver Cirrhosis With Advanced Hepatocellular Carcinoma Stratified by Etiology.

We previously reported that sorafenib induces Th1 [interferon-γ (IFNγ)-positive interleukin 4 (IL4)-negative] dominance which prevents tumor cells from escaping the host immune system in patients with liver cirrhosis (LC) and advanced hepatocellular carcinoma (aHCC). However, in that study we did not assess the influence of sorafenib on host immunity according to the etiology of LC. Therefore, this study was retrospectively performed to evaluate the impact of sorafenib therapy for aHCC on host immunity in patients stratified according to the etiology of LC: Patients and Methods: A total of 116 adult Japanese patients with LC and aHCC received sorafenib therapy at our hospital. Blood samples were collected before and after treatment for 4 weeks. Twenty-two patients had hepatitis B virus (HBV)-related LC, 62 patients had hepatitis C virus (HCV)-related LC, 22 patients had alcoholic LC, and 10 patients had LC without these causative factors. In patients receiving sorafenib at a dose of 400 mg/day, patients in Child-Pugh class A, and patients with stage IVA aHCC, Th2 (IFNγ-negative/IL4-positive) cells decreased significantly after treatment, although there was no significant impact on the tumor response. In addition, Th2 cells decreased significantly in patients with HCV-related LC after treatment, while there were no significant changes in the other groups. Sorafenib might prevent tumor cells from escaping the host immune system in patients with aHCC and HCV-related LC, although it does not seem to do so in those with LC of other etiologies.

Using telehealth to improve access to hepatitis C treatment in the direct-acting antiviral therapy era

Introduction One-third of the Australian population lives outside major cities and this group has worse health outcomes. Telehealth is becoming an accepted way to improve patient access to specialist healthcare. Over 200,000 Australian’s have hepatitis C virus (HCV) and new treatments are very effective and well tolerated. We aim to demonstrate that HCV treatment utilising telehealth support for care delivery has cure rates similar to onsite care in clinical trials. We also report length of consultation and calculate reductions in travel and carbon output. Methods Patient demographic, clinical, and treatment outcome data were collected prospectively from hospital software and analysed retrospectively. This was an audit of all patients treated for HCV in one year from a single tertiary hospital that included telehealth in their care delivery. Results Sustained virological response was achieved in 51/52 (98%) patients with completed treatment courses, and 51/58 (88%) of those who had a planned telehealth consultation as part of their management. A median of 634 km of patient travel was saved per telehealth consultation. Discussion We found that a telehealth-supported outreach programme for patients in regional Australia with HCV produced similar outcomes to clinical trials. There was a considerable saving in time and cost for the patients and significant environmental benefit through the reduction in carbon footprint associated with travel to distant specialist health services. We conclude that telehealth facilitated outreach is a feasible and effective way to access HCV treatment and cure in regional Australia.

Bone Mineral Density Declines Twice as Quickly Among HIV-Infected Women Compared With Men.

Initial declines in bone mineral density (BMD) after antiretroviral therapy initiation in HIV are well described, but data on long-term changes and risk factors for decline, particularly among women, are limited. HIV-infected men and women in the Modena Metabolic Clinic underwent dual-energy X-ray absorptiometry (DXA) scans every 6-12 months for up to 10 years (median 4.6 years). Mixed effect regression models in combined and sex-stratified models determined annual rates of decline and clinical factors associated with BMD. Models included demographics, HIV-specific factors, and bone-specific factors; a final model added a sex × time interaction term. A total of 839 women and 1759 men contributed ≥2 DXA scans. The majority (82%) were 50 years and younger; 76% had HIV-1 RNA <50 copies per milliliter at baseline; 15% of women were postmenopausal and 7% of men had hypogonadism; and 30% and 27%, respectively, had hepatitis C virus (HCV) coinfection. The adjusted slopes in BMD among women and men were significantly different at both the femoral neck (women -0.00897 versus men -0.00422 g/cm per year; P < 0.001) and L-spine (women -0.0127 versus men -0.00763 g/cm per year; P < 0.001). Modifiable risks associated with BMD decline included antiretroviral therapy exposure (greater decline with tenofovir disoproxil fumarate and less decline with integrase strand transfer inhibitor therapy), HCV, physical activity, and vitamin D insufficiency. Among HIV-infected individuals, bone density at the femoral neck, a significant predictor of fracture risk, declined twice as quickly among women compared with men. Female sex was independently associated with both lower femoral neck and lumbar BMD over time in adjusted models.

Glecaprevir–Pibrentasvir for 8 or 12 Weeks in HCV Genotype 1 or 3 Infection

BackgroundGlecaprevir and pibrentasvir are direct-acting antiviral agents with pangenotypic activity and a high barrier to resistance. We evaluated the efficacy and safety of 8-week and 12-week courses of treatment with 300 mg of glecaprevir plus 120 mg of pibrentasvir in patients without cirrhosis who had hepatitis C virus (HCV) genotype 1 or 3 infection.MethodsWe conducted two phase 3, randomized, open-label, multicenter trials. Patients with genotype 1 infection were randomly assigned in a 1:1 ratio to receive once-daily glecaprevir–pibrentasvir for either 8 or 12 weeks. Patients with genotype 3 infection were randomly assigned in a 2:1 ratio to receive 12 weeks of treatment with either glecaprevir–pibrentasvir or sofosbuvir–daclatasvir. Additional patients with genotype 3 infection were subsequently enrolled and nonrandomly assigned to receive 8 weeks of treatment with glecaprevir–pibrentasvir. The primary end point was the rate of sustained virologic response 12 weeks after the end of treatment.ResultsIn total, 1208 patients were treated. The rate of sustained virologic response at 12 weeks among genotype 1–infected patients was 99.1% (95% confidence interval [CI], 98 to 100) in the 8-week group and 99.7% (95% CI, 99 to 100) in the 12-week group. Genotype 3–infected patients who were treated for 12 weeks had a rate of sustained virologic response at 12 weeks of 95% (95% CI, 93 to 98; 222 of 233 patients) with glecaprevir–pibrentasvir and 97% (95% CI, 93 to 99.9; 111 of 115) with sofosbuvir–daclatasvir; 8 weeks of treatment with glecaprevir–pibrentasvir yielded a rate of 95% (95% CI, 91 to 98; 149 of 157 patients). Adverse events led to discontinuation of treatment in no more than 1% of patients in any treatment group.ConclusionsOnce-daily treatment with glecaprevir–pibrentasvir for either 8 weeks or 12 weeks achieved high rates of sustained virologic response among patients with HCV genotype 1 or 3 infection who did not have cirrhosis. (Funded by AbbVie; ENDURANCE-1 and ENDURANCE-3 ClinicalTrials.gov numbers, NCT02604017 and NCT02640157.)