Use of complementary and alternative medicine in patients with chronic viral hepatitis in Turkey.

INTRODUCTION: The global use of complementary and alternative medicine (CAM) is growing. The purpose of this study was to determine the prevalence of CAM use in patients in Turkey with CVH, the types of therapy, and patients' sociodemographic characteristics. METHODS: The study was designed as a questionnaire-based, cross-sectional analysis. An infectious diseases outpatient follow-up questionnaire was administered to patients at face-to-face interviews. The data obtained were analyzed using SPSS 17 software. RESULTS: This study included 588 patients, of whom 27% used CAM. No differences in sociodemographic characteristics were determined between patients using CAM and those not using it. Herbal methods were used by 63.6% of patients and cupping techniques by 25.4%. Education level was significantly correlated with herbal methods (p = 0.043). CAM use also increased in line with disease duration (p < 0.05). No difference in CAM use was determined between CHB patients using oral antiviral therapy and those not using it (p = 0.162). CONCLUSION: CAM use, particularly herbal products, is prevalent among Turkish adults with CVH. In case of use of herbal products in chronic viral hepatitis patients, toxicity and liver failure may develop as a result of herbal product-drug interactions. Physicians in the field of hepatology should, therefore, be aware of potential toxicity of CAM, especially in patients with chronic hepatitis liver diseases.

A Colocalized Hepatitis C Virus Clinic in a Primary Care Practice Improves Linkage to Care in a High Prevalence Population.

BACKGROUND: There is an urgent need to increase patient access to treatment of chronic hepatitis C virus (HCV) infection. We developed a colocalized HCV clinic integrated within a primary care practice. We report the prevalence of HCV and evaluate the impact of the integrated clinic on the HCV cascade of care. METHODS: We performed a retrospective study of patients with chronic HCV infection from 2 clinic practices, an integrated clinic practice and a similar nonintegrated clinic practice, between July 2015 and July 2016. Demographic, clinical, and HCV testing data were reviewed to estimate the prevalence of chronic HCV and to construct a cascade of care. RESULTS: A total of 8405 primary care patients were included; 4796 (57.1%) received an HCV antibody test and 390 (8.1%) were positive. A total of 310 patients with chronic HCV were included in the analysis. There were 119 patients eligible for linkage to care in the nonintegrated clinic, of which 80 (67.2%) were referred, 38 (31.9%) were linked, and 18 (15.1%) initiated treatment during the study period. Among the 70 patients eligible for linkage to care in the integrated clinic practice, 51 (72.9%) were referred, 38 (54.3%) were linked, and 16 (22.9%) initiated treatment. In a multivariable analysis, patients in the integrated clinic practice had significantly higher odds of being linked to care than patients in the nonintegrated clinic practice (adjusted odds ratio [OR] 2.5, 95% confidence interval [CI] = 1.3-4.8). CONCLUSIONS: We found a high seroprevalence of chronic HCV within our clinic population and demonstrate that a HCV clinic integrated into a primary care center increases linkage to care for patients with chronic HCV.

Integrated models of care for people who inject drugs and live with hepatitis C virus: A systematic review.

BACKGROUND: Despite the key role that people who inject drugs (PWID) play in the hepatitis C virus (HCV) epidemic, HCV treatment rates among this population have been historically low. Integrated models of HCV and substance use care have the potential to overcome some barriers to access; however, the evidence base is uncertain. This systematic review assesses the impacts of integrated HCV and substance use services on engagement in HCV care among PWID. METHODS: We searched five databases up to December 2018 to identify original quantitative studies evaluating the impacts of co-location of HCV and substance use services on engagement in the HCV cascade of care among adult PWID. We conducted a narrative synthesis, categorizing models based on patient entry point (a: HCV facility, b: substance use disorder (SUD) facility, and c: other facilities), and levels of integrated services offered (a: HCV/substance use testing only, b: HCV/substance use treatment, and c: testing/treatment + other services). RESULTS: A total of 46 articles corresponding to 44 original studies were included. Almost all studies (n = 42) were conducted in high-income countries and only six studies in the Direct-Acting Antiviral (DAA) era. Twenty-six studies discussed the integration of services at SUD facilities, one at HCV facilities, and seventeen at other facilities. Analysis of included studies indicated that overall integrated care resulted in improved engagement in HCV care (e.g., testing, treatment uptake and cure). However, the quality of evidence was predominantly low to moderate. CONCLUSIONS: Available evidence suggests that integration of HCV and substance use services may improve engagement along the continuum of HCV care among PWID. Given limitations in data quality, and very few studies conducted in the DAA era and in low- and middle-income settings, further research is urgently needed to inform strategies to optimize HCV care access and outcomes among PWID globally.

Hepatitis C virus infection in chronic kidney disease: paradigm shift in management.

Hepatitis C virus (HCV) infection in chronic kidney disease (CKD) is associated with increased liver-related morbidity and mortality rates, accelerated progression to end-stage renal disease, and risk of cardiovascular events. CKD patients with HCV infection require antiviral therapy. Pegylated interferon (peg-IFN) plus ribavirin was the standard of care for HCV-infected CKD patients before the introduction of first-generation direct-acting antiviral (DAA) oral anti-HCV agents. Peg-IFN-based treatment has a low virologic response rate and poor compliance, resulting in a high dropout rate. Recently, several clinical trials of all-DAA combination regimens have reported excellent antiviral efficacy and few adverse drug reactions in HCV-infected patients with CKD. These positive results have revolutionized the treatment of chronic HCV infection in this population. In this review, we address the impact of chronic HCV infection in CKD patients, and discuss their management using next-generation DAAs.

[Mechanism for the inhibition of proliferation and promotion of apoptosis in Huh7.5 cells by iron overload].

Objective To investigate the effect of iron overload on biological activity and apoptosis in Huh7.5 cells. Methods Huh7.5 cells were cultured in the medium supplemented with 50, 100, 200 µmol/L ferric ammonium citrate (FAC). Fluorescence microscopy was employed to determine cell iron load labeled by Phen Green FL; proliferation activity of Huh7.5 cells was evaluated by MTT assay; protein and mRNA levels of transferrin receptor (TfR1), TfR2, divalent metal transporter 1 (DMT1) and ferroportin 1 (FPN1) in Huh7.5 cells were detected by Western blotting and real-time PCR, respectively; cell reactive oxygen species (ROS) labeled by dichlorofluorescin diacetate (DCFH-DA) and cell apoptosis labeled by annexinV-FITC/PI were analyzed by flow cytometry. Results FAC treatment increased intracellular iron load in a dose-dependent manner. Compared with control group, mRNA and protein expressions of TfR1, TfR2 and DMT1 were down-regulated, while mRNA and protein expression of FPN1 was significantly up-regulated in FAC treated groups. With the increasing dose of FAC, intracellular ROS level increased significantly and cell proliferation activity decreased significantly. The cell apoptosis rate in FAC treated groups were remarkably higher than that in control group, but after antioxidant N-acetylcysteine (NAC) was added, the cell apoptosis in FAC treated group was inhibited obviously. Conclusion Iron overload can inhibit the proliferation and promote the apoptosis of Huh7.5 cells through oxidative stress.

The present and future disease burden of hepatitis C virus infections with today's treatment paradigm - volume 3.

The total number, morbidity and mortality attributed to viraemic hepatitis C virus (HCV) infections change over time making it difficult to compare reported estimates from different years. Models were developed for 15 countries to quantify and characterize the viraemic population and forecast the changes in the infected population and the corresponding disease burden from 2014 to 2030. With the exception of Iceland, Iran, Latvia and Pakistan, the total number of viraemic HCV infections is expected to decline from 2014 to 2030, but the associated morbidity and mortality are expected to increase in all countries except for Japan and South Korea. In the latter two countries, mortality due to an ageing population will drive down prevalence, morbidity and mortality. On the other hand, both countries have already experienced a rapid increase in HCV-related mortality and morbidity. HCV-related morbidity and mortality are projected to increase between 2014 and 2030 in all other countries as result of an ageing HCV-infected population. Thus, although the total number of HCV countries is expected to decline in most countries studied, the associated disease burden is expected to increase. The current treatment paradigm is inadequate if large reductions in HCV-related morbidity and mortality are to be achieved.

Statewide hepatitis C model of care for rural and remote regions.

The evolution of management of hepatitis C virus (HCV) has seen a majority of patients treated being regarded as cured. Despite this development, uptake of treatment remains low in Australia, and this is particularly true in rural and remote areas. The largest state in Australia, Western Australia (WA), covers an area of 2500 km(2). As the rural and remote population of WA is scattered in small areas rather than major centers, poor accessibility to remote areas and lack of adequate of medical and nursing resources pose major problems in providing equity of care to patients with chronic HCV. A statewide hepatitis model of care, established in 2009, has led to an increase in identification and treatment of patients living with HCV. Strategies used to facilitate these changes include telehealth, a nurse practitioner model, and general practitioner shared-care model. The statewide program will be modified to meet the changing needs of patients as all-oral treatment regimens become available, with further emphasis being placed on the role of rural and remote health professionals in identifying patients with HCV and initiating and monitoring treatment.

Addressing viral hepatitis in the opiate substitution setting: an integrated nursing model of care.

Despite the availability of effective therapies for hepatitis C virus (HCV) and B virus (HBV), only a minority of infected patients receive treatment. In the general population, morbidity and mortality associated with chronic HCV is now successfully being addressed through the use of antiviral therapy. In Australia, an estimated 41% to 68% of people who inject drugs (PWID) are HCV positive, and between 28% and 59% of users are estimated to have been exposed to HBV. Although current treatment guidelines suggest that active drug use should not preclude people from HCV treatment, uptake of therapy thus far has been low. Patient, physician, social, and logistical-related barriers contribute to the low uptake of HCV treatment among PWID. Traditional means of managing HCV infection­referral to secondary or tertiary health centers­historically has a poor track record in increasing therapy uptake among this population. The same is true for people with chronic HBV who inject drugs. Close to 50,000 Australians receive opioid substitution therapy (OST) through a range of services, including public and private clinics, thus this setting is an ideal target for identifying and treating people at risk for and already infected with HBV and HCV. Over the last 11 years, a nursing model of care initiated by a teaching hospital in Sydney, Australia that integrates viral hepatitis screening, assessment, and treatment into the OST setting has enhanced access to services among the marginalized injecting drug use population.

'Not just methadone Tracy': transformations in service-user identity following the introduction of hepatitis C treatment into Australian opiate substitution settings.

AIMS: To explore identity transformation among service users attending opiate substitution therapy (OST) clinics following the introduction of hepatitis C (HCV) care and treatment. DESIGN: An interview-based substudy of the Australian ETHOS (Enhancing Treatment for Hepatitis C in Opiate Substitution Settings) project. SETTING: Three OST clinics and one community health centre (operating a public OST) in New South Wales, Australia. Participants were interviewed at the recruitment sites. PARTICIPANTS: The sample consisted of 57 OST service users concurrently living with HCV, 16 staff, including specialist HCV clinicians, and three peer-support workers, employed on the ETHOS project. MEASUREMENTS: Semi-structured interviews. FINDINGS: Service-user participants largely welcomed the introduction of HCV treatment as a practical, clinical intervention that also intimated a more comprehensive, holistic form of care. Negative stereotypes characteristic of OST settings-of limited, routinized clinical exchanges and minimal social-care interaction-were unsettled, opening up the possibility of new relations between staff and service users. The shift in the dynamic of the clinical encounter to address health in addition to dependence appeared to catalyse transformative possibilities not only for the therapeutic alliance but also for service-user understandings of self and identity. CONCLUSION: Trial introduction of HCV care and treatment in selected Australian opiate substitution therapy (OST) clinics may have facilitated alternative, 'non-addict' identities to emerge from a clinical setting where the stigmatizing figure of 'the drug user' has traditionally prevailed.

The impact of lifetime drug use on hepatitis C treatment outcomes in insured members of an integrated health care plan.

BACKGROUND: The relation of drug use to HCV treatment outcome in an insured household population has not been previously reported. METHODS: Lifetime frequencies of marijuana use and non-medical use of stimulants, sedatives, and opioids; hallucinogens; and inhalants were retrospectively assessed in 259 privately insured members of an integrated health care plan treated for chronic hepatitis C virus infection (HCV+) with pegylated interferon alpha and ribavirin and examined with respect to rates of sustained virological response (SVR). RESULTS: The majority of patients reported chronic use of multiple illegal drugs; 61.6% reported injection drug use (IDU); 79.5% abstained from drug use during the six months prior to HCV treatment. Total frequency of individual drugs, multiple drugs, and length of abstention from drugs prior to HCV treatment were not related to impaired SVR rates. Sustained viral responses were obtained in 80.2% of patients with HCV genotype 2/3 and 45.1% of patients with genotype 1/4/6. Marijuana use during HCV treatment, reported by 8.5% of patients, was associated with higher treatment adherence (95.5% compared with 78.9%, p=0.045), but lower SVR rates (40.9% compared with 62.5%, p=0.041). In addition, drug use during HCV treatment was associated with significantly higher relapse rates, 18.8% compared with 7.7% (p=0.053). CONCLUSION: A history of chronic illegal drug use should not be considered a deterrent to HCV treatment in members of an integrated health care plan who are motivated to seek treatment and closely monitored, but drug use during HCV treatment, including marijuana use, should be discouraged.

Clinical development of monoclonal antibody-based drugs in HIV and HCV diseases.

Today there are many licensed antiviral drugs, but the emergence of drug resistant strains sometimes invalidates the effects of the current therapies used in the treatment of infectious diseases. Compared to conventional antiviral drugs, monoclonal antibodies (mAbs) used as pharmacological molecules have particular physical characteristics and modes of action, and, therefore, they should be considered as a distinct therapeutic class. Despite being historically validated, antibodies may represent a novel tool for combatting infectious diseases. The current high cost of mAbs' production, storage and administration (by injection only) and the consequent obstacles to development are outweighed by mAbs' clinical advantages. These are related to a low toxicity combined with high specificity and versatility, which allows a specific antibody to mediate various biological effects, ranging from the virus neutralization mechanisms to the modulation of immune responses.This review briefly summarizes the recent technological advances in the field of immunoglobulin research, and the current status of mAb-based drugs in clinical trials for HIV and HCV diseases. For each clinical trial the available data are reported and the emerging conceptual problems of the employed mAbs are highlighted.This overview helps to give a clear picture of the efficacy and challenges of the mAbs in the field of these two infectious diseases which have such a global impact.

Effect of soy protein supplementation in patients with chronic hepatitis C: a randomized clinical trial.

AIM: To evaluate the effects of soy supplementation on insulin resistance, fatty liver and alanine aminotransferase (ALT) levels in non-diabetic patients with chronic hepatitis C (CHC). METHODS: In a prospective, randomized and single-blinded clinical trial, we compared patients with CHC who had casein as a supplement (n = 80) (control group), with patients who consumed a soy supplement diet (n = 80) [intervention group (IG)]. Both groups received 32 g/d of protein for 12 wk. RESULTS: Patients' baseline features showed that 48.1% were overweight, 43.7% had abdominal fat accumulation, 34.7% had hepatic steatosis and 36.3% had an homeostasis model assessment index of insulin resistance (HOMA-IR) ≥ 3.0. Descriptive analysis showed that protein supplementation diet reduced hepatic steatosis in both groups; however, significant reductions in ALT levels occurred in the soy group. Multiple regression modeling indicated that in the presence of severe fibrosis (F3/F4), γ glutamyl transferase elevation and high density lipoprotein (HDL) reduction, the intervention group had 75% less chance of developing hepatic steatosis (OR= 0.25; 95% CI: 0.06-0.82) and 55% less chance of presenting with an ALT level ≥ 1.5 × the upper limit of normal (ULN) (OR = 0.45, 95% CI: 0.22-0.89). Soy treatment did not have any effect on insulin resistance (OR = 1.92; 95% CI: 0.80-4.83), which might be attributed to the fact that the HOMA-IR values at baseline in most of our patients were in the normal range. Advanced hepatic fibrosis, an ALT level > 1.5 × ULN and visceral fat were predictors of an HOMA-IR ≥ 3. The IG group had a reduced risk of an ALT level > 1.5 × ULN. An HOMA-IR ≥ 3.0 and HDL < 35 mg/dL were also risk factors for increased ALT. CONCLUSION: Soy supplementation decreased ALT levels and thus may improve liver inflammation in hepatitis C virus (HCV) patients; it also reduced hepatic steatosis in a subgroup of patients but did not change insulin resistance. It should be considered in the nutritional care of HCV patients.

Liver disease in Viet Nam: screening, surveillance, management and education: a 5-year plan and call to action.

Despite a high prevalence of liver disease in Viet Nam, there has been no nationwide approach to the disease and no systematic screening of at-risk individuals. Risk factors include chronic hepatitis B (estimated prevalence of 12%), chronic hepatitis C (at least 2% prevalence), and heavy consumption of alcohol among men. This combination of factors has resulted in liver cancer being the most common cause of cancer death in Viet Nam. There is a general lack of understanding by both the general public and health-care providers about the major risk to health that liver disease represents. We report here the initial steps taken as part of a comprehensive approach to liver disease that will ultimately include nationwide education for health-care providers, health educators, and the public; expansion of nationwide screening for hepatitis B and C followed by hepatitis B virus vaccination or treatment of chronic hepatitis B and/or hepatitis C; education about alcoholic liver disease; long-term surveillance for liver cancer; reduction of infection transmission related to medical, commercial, and personal re-use of contaminated needles, syringes, sharp instruments, razors, and inadequately sterilized medical equipment; and ongoing collection and analysis of data about the prevalence of all forms of liver disease and the results of the expanded screening, vaccination, and treatment programs. We report the beginning results of our pilot hepatitis B screening program. We believe that this comprehensive nationwide approach could substantially reduce the morbidity and mortality from liver disease and greatly lessen the burden in terms of both lives lost and health-care costs.

Diagnostic and therapeutical role of vitamin D in chronic hepatitis C virus infection.

Although initially identified as a calcium homeostatic hormone, vitamin D is now known to have pleiotropic functions, dealing with both innate and adaptative immunity. Calcitriol mediates its biological effects by binding to the vitamin D receptor (VDR), which is expressed not only by intestine, bone and kidney but also on cell membranes of T lymphocytes, B lymphocytes, dendritic cells and macrophages. Vitamin D plays a role on the degree of liver damage in patients with chronic hepatitis C (CHC): low vitamin D levels have been associated with high hepatic necroinflammatory activity and progression of liver fibrosis. Vitamin D, in CHC patients, could also affect the response to antiviral therapy: in fact, recent studies have shown a relationship between low responsiveness to IFN-based therapy and low vitamin D serum levels. Further studies are required to better assess if vitamin D could work as a reliable noninvasive marker of liver fibrosis and whether vitamin D supplementation could be given to all CHC patients together with standard antiviral treatment, in order to improve the rate of sustained virological response (SVR).

New hepatitis C therapies in clinical development.

With the current standard of care for the treatment of chronic hepatitis C, a combination of pegylated interferon alfa and ribavirin, sustained virologic response rates can be achieved in approximately 50% of patients only. - Improved understanding of the viral life cycle has led to the identification of numerous potential targets for novel, direct-acting antiviral compounds. Inhibitors of the NS3/4A protease are currently the most advanced in clinical development. Recently completed phase 3 studies of the two protease inhibitors telaprevir and boceprevir, each given in combination with standard of care, yielded sustained virologic response rates in the range of 66-75% in treatment-naive patients and 59-66% in treatment-experienced patients with HCV genotype 1 infection. Studies of second-generation protease inhibitors, with the potential advantage of improved potency, drug metabolism and pharmacokinetics profile, are already underway. - Inhibitors of the HCV NS5A protein and NS5B polymerase are potentially active across different HCV genotypes and have shown promising antiviral efficacy in early clinical studies. Other emerging mechanisms include silymarin components and inhibitors of cell proteins required for HCV replication. - While improved formulations of current HCV therapies are also being developed, future hopes lie on the combination of direct-acting antivirals with the eventual possibility of interferon-free treatment regimens.

Update of old and emerging therapies in chronic hepatitis C.

The main aim in treating hepatitis C virus (HCV) infection is to achieve a sustained virological response (SVR). It is defined as undetectable HCV-RNA in peripheral blood 24 weeks after the end of treatment. The RNA is detected by polymerase chain reaction (PCR) technique. The SVR practically reflects eradication of HCV infection and cure of the underlying HCV-induced liver disease. Treatment of HCV-induced chronic hepatitis includes one of the available Interferon-alpha (INF-alpha) in combination with Ribavirin (RBV). To achieve much better results, combination of PEG-INF with RBV is currently recommended. This regimen is quite effective in treating HCV genotype 2 and 3 but much less so in genotypes 1 and 4. At the same time it has long been observed that these combinations have sometimes severe side effects and contraindications limiting their efficacy and applicability in a significant number of chronic HCV patients. Therefore, the importance of improving existing therapies and developing new, effective, safe and tolerable drugs is well appreciated, worldwide. This review describes improvements in the current standard therapy and new emerging drugs.

Tratamiento de hepatitis crónica C en un paciente con fibrosis quística en situación de pretrasplante pulmonar / Chronic hepatitis C treatment in a cystic fibrosis patient in the pulmonary pre-transplant stage

El tratamiento estándar de la hepatitis crónica C, interferón pegilado (INF-peg) y ribavirina (RBV), puede ser inadecuado o incluso estar contraindicado en algunos pacientes debido a sus limitaciones en cuanto a eficacia y efectos adversos. En pacientes con fibrosis quística infectados por el virus de la hepatitis C (VHC) el tratamiento antiviral podría aumentar las infecciones respiratorias con el consiguiente empeoramiento de la función pulmonar. Por contra, la infección por VHC podría desestimar a estos pacientes para un necesario trasplante pulmonar. Presentamos el caso de un varón con fibrosis quística diagnosticado de infección VHC durante su evaluación previa al trasplante pulmonar. El paciente fue tratado con INF-peg y RBV. A pesar del empeoramiento en la función pulmonar y numerosas infecciones respiratorias intercurrentes, logró completar el tratamiento y obtener respuesta viral sostenida, encontrándose actualmente en lista de espera(AU)

The standard treatment of chronic hepatitis C, pegylated interferon and ribavirin (pegI/R), has many limitations in both effectiveness and secondary effects, which makes it unsuitable or even contraindicated for some patients. In hepatitis C virus-infected cystic fibrosis patients this treatment could increase respiratory infections with subsequent pulmonary function deterioration. On the contrary, hepatitis C virus (HCV) infection may make lung transplant (LT) unfeasible. We present the case of a cystic fibrosisyoung man diagnosed with HCV infection during LT assessment who was treated with pegI/R. In spite of the lung function worsening and respiratory infections, he managed to complete treatment and even sustained virological response (SVR). At present he is on LT waiting list(AU)

The use of complementary and alternative medicine by patients with chronic hepatitis C.

BACKGROUND: The use of complementary and alternative medicine (CAM) is expanding globally. However, prevalence of its use by patients with chronic hepatitis C (CHC) remains unclear. METHODS: An exploratory, descriptive study was conducted using a questionnaire and interview to describe the use of CAM by patients with CHC attending a liver clinic in the United States. RESULTS: Eighty percent (n = 120) had used CAM in the last 12 months, most often prayer for health reasons (63%), multivitamins (56%) and herbal medicine (25%). A higher level of education (p < 0.005), poorer health status (p < 0.002) and prior use of anti-viral therapy (p < 0.02) were predictors of CAM use. Participants used CAM to promote general health, but herbal medicine was used to treat CHC symptoms and prevent liver disease. CONCLUSION: Use of CAM is common among patients with CHC. Failure to acknowledge the use of CAM as a management strategy may restrict the health provider's ability to provide optimal care.