Showing posts with label Other Conditions Related To HCV. Show all posts
Showing posts with label Other Conditions Related To HCV. Show all posts

Monday, February 11, 2019

Testosterone in Men With Chronic Hepatitis C Infection and After Hepatitis C Viral Clearance

Corrected Proof
Clinical Infectious Diseases, ciy965, https://doi.org/10.1093/cid/ciy965
Published: 02 February 2019
Testosterone in Men With Chronic Hepatitis C Infection and After Hepatitis C Viral Clearance
We evaluated testosterone levels and the prevalence of low testosterone in a cohort of 327 men with chronic HCV infection (human immunodeficiency virus [HIV] coinfection = 150) and in a subset of 85 men with testosterone levels obtained pre-HCV treatment and after sustained virologic response (SVR). Median follow-up was 36 months.
Full text available online:

Commentary: Healio
Low testosterone persists after HCV clearance
February 11, 2019 
Low levels of free testosterone are common among men with chronic hepatitis C infection following SVR and persist after HCV clearance, according to findings from a prospective, longitudinal cohort study.

“Previous research has shown that low total testosterone (TT), low free testosterone (FT), and elevated sex hormone-binding globulin (SHBG) are extrahepatic manifestations of chronic HCV when compared with healthy controls,” Chloe S. Chaudhury, MD, post-baccalaureate research fellow at the National Institute of Allergy and Infectious Diseases, and colleagues wrote. “There is now a need for studies to examine the effect of HCV and HCV viral clearance on long-term testosterone levels and hypogonadal status.” 

Read more:

Saturday, February 9, 2019

What are the Long-term Effects of DAA Therapy on HCV-associated Cryoglobulinemia Vasculitis?

What are the Long-term Effects of DAA Therapy on HCV-associated Cryoglobulinemia Vasculitis?
Dr. Kristine Novak
More than 95% of patients with hepatitis C virus–associated cryoglobulinemia vasculitis (HCV-CryoVas) have a full or partial response of symptoms to treatment with direct-acting antiviral (DAA) agents, researchers report in a long-term follow-up study in the February issue of Clinical Gastroenterology and Hepatology. Fewer than 5% of patients stopped therapy prematurely and fewer than 3% died. A severe form of CryoVas and peripheral neuropathy were associated with a lack of response of CryoVas to DAA therapy.
CryoVas is an immune complex–mediated systemic vasculitis that affects mainly small- and medium-sized vessels—it is observed in approximately 15% of patients with HCV infection and has an estimated 5-year mortality rate of 25%. Outcomes of patients with HCV-CryoVas associate with level of liver fibrosis and vasculitis of the kidney, central nervous system, heart, and digestive tract. Remission of vasculitis is associated with reponse to DAA therapy; a complete clinical response was reported in 90.2% of patients with HCV-CryoVas. 

Wednesday, February 6, 2019

2019 Hepatitis C - Testing, Treatment Options, Stages of fibrosis and Care

Caring for patients with chronic hepatitis C infection
Basic information about hepatitis C, published Jan 31, 2019 in: Nursing2019 - Ahead of Print, available in PDF format only.

Highlights
Who is at risk?
How HCV infection progresses
Extrahepatic complications of HCV infection
Testing for HCV
Stages of fibrosis
Treatment options
Removing treatment barriers
Promising future

Nursing. 2019 Jan 31. doi: 10.1097/01.NURSE.0000553271.39804.a4. [Epub ahead of print]
Caring for patients with chronic hepatitis C infection
Chaney, Amanda, DNP, APRN, FNP-BC, FAANP
Abstract:
Hepatitis C virus (HCV) infection is the most common chronic bloodborne infection in the US. This article discusses the pathophysiology of HCV infection, new treatment options, and nursing care and patient teaching for patients with chronic HCV infection.
Begin, here..….

For Patients On This Site
2019 February Hepatitis Newsletters: Finding Support 

Thursday, January 17, 2019

Successful hepatitis C treatment decreases the incidence of complications associated with type 2 diabetes.

Sustained virological response to hepatitis C treatment decreases the incidence of complications associated with type 2 diabetes. 
Li J, et al. Aliment Pharmacol Ther. 2019 
Li J1, Gordon SC2, Rupp LB3, Zhang T1, Trudeau S1, Holmberg SD4, Moorman AC4, Spradling PR4, Teshale EH4, Boscarino JA5, Schmidt MA6, Daida YG7, Lu M1; CHeCS Investigators.

Version of Record online: 16 January 2019

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The present analysis from a large and diverse cohort of patients with type 2 diabetes shows that successful HCV treatment reduced the risks of acute coronary syndrome, end‐stage renal disease, ischaemic stroke, and retinopathy by 39%‐66%; this effect was independent of patients’ baseline fibrosis status, and consistent in subgroup analyses restricted to patients with and without cirrhosis. Chronic HCV infection, independent of diabetic status, is known to confer an increased risk of extrahepatic complications; treatment status and outcome have been associated with improvement in some, but not all, of these conditions. The magnitude of risk reduction we observed within HCV patients with T2D supports the importance of antiviral therapy among diabetic patients to reduce risk of these extrahepatic outcomes.

Abstract
BACKGROUND:
The role of hepatitis C (HCV) eradication on the long-term complications of type 2 diabetes mellitus remains incompletely studied.

AIM: 
We investigated whether antiviral treatment impacted risk of acute coronary syndrome, end-stage renal disease, ischaemic stroke, and retinopathy among diabetic patients from the four US health systems comprising the Chronic Hepatitis Cohort Study (CHeCS).

METHODS: 
We included CHeCS HCV patients with diagnosis codes for type 2 diabetes who were on antidiabetic medications. Patients were followed until an outcome of interest, death, or last health system encounter. The effect of treatment on outcomes was estimated using the competing risk analysis (Fine-Gray subdistribution hazard ratio [sHR]), with death as a competing event.

RESULTS: 
Among 1395 HCV-infected patients with type 2 diabetes, 723 (52%) were treated with either interferon-based or direct-acting antivirals (DAAs); 539 (75% of treated) achieved sustained virological response (SVR). After propensity score adjustment to address treatment selection bias, patients with SVR demonstrated significantly decreased risk of acute coronary syndrome (sHR = 0.36; P < 0.001), end-stage renal disease (sHR = 0.46; P < 0.001), stroke (sHR = 0.34; P < 0.001), and retinopathy (sHR = 0.24; P < 0.001) compared to untreated patients. Results were consistent in subgroup analyses of DAA-treated patients and interferon-treated patients, an analysis of cirrhotic patients, as well as in sensitivity analyses considering cause-specific hazards, exclusion of patients with on-treatment retinopathy, and treatment status as a time-varying covariate.

CONCLUSION: 
Successful HCV treatment among patients with type 2 diabetes significantly reduces incidence of acute coronary syndrome, end-stage renal disease, ischaemic stroke, and retinopathy, regardless of cirrhosis. Our findings support the importance of HCV antiviral therapy among patients with type 2 diabetes to reduce the risk of these extrahepatic outcomes.

© 2019 John Wiley & Sons Ltd.

Sunday, January 6, 2019

Hepatitis C Extrahepatic Manifestations Reduced by Sustained Virologic Response

Hepatitis C Extrahepatic Manifestations Reduced by Sustained Virologic Response
JANUARY 06, 2019
Kenneth Bender, PharmD, MA
Achieving sustained virological response (SVR) with treatment of hepatitis C virus (HCV) infection was found to be associated with a reduction of extrahepatic manifestations and the corresponding mortality in a new meta-analysis.
Continue reading: https://www.mdmag.com/medical-news/hepatitis-c-extrahepatic-sustained-virologic-response

Abstract
BMJ Journal Gut
Impact of sustained virological response on the extrahepatic manifestations of chronic hepatitis C: a meta-analysis.

On This Blog
Conditions Related To HCV:
Collection of current research articles on the extrahepatic manifestations of hepatitis C.

Saturday, December 22, 2018

Hepatitis C - Impact of treatment with direct-acting antivirals on anxiety and depression

Impact of treatment with direct-acting antivirals on anxiety and depression in chronic hepatitis C 
Marta Gallach , Mercedes Vergara, Joao Pedro da Costa, Mireia Miquel, Meritxell Casas, Jordi Sanchez-Delgado, Blai Dalmau, Núria Rudi, Isabel Parra, Teresa Monllor, Meritxell Sanchez-Lloansí, Angelina Dosal, Oliver Valero, Xavier Calvet
Published: December 19, 2018 https://doi.org/10.1371/journal.pone.0208112

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Abstract
Background and aim
Treatment of hepatitis C with direct-acting antiviral agents (DAA) has few side effects. Although pivotal studies suggested that DAA were safe in patients with psychiatric diseases who could not be treated with previous antiviral therapies, their effects on anxiety and depression have not yet been analysed in clinical practice. The aim of our study was to analyse anxiety and depression in the setting of DAA treatment in a clinical practice series.

Methods
All patients starting DAA treatment between November 1, 2014 and October 31, 2015 were eligible. Patients completed the Hospital Anxiety and Depression scale at different times during treatment. The results were plotted on line graphs and evaluated using a linear regression model with repeated measures.

Results
One hundred and forty-five patients were included (11% with major psychiatric disorders; 32% on psychiatric treatment). Sustained virologic response (SVR) was achieved in 97.3% of cases. Anxiety and depression measures did not differ between time points. No differences between patients on psychiatric treatment or with advanced fibrosis or cirrhosis were found at any time point analysed.

Conclusion
DAA treatment had no impact on anxiety or depression during or after chronic hepatitis C infection treatment, even in high-risk patients with major psychiatric disorders.
Read More: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0208112

HCV patients treated with DAA undergo a marked reduction of insulin resistance

Improvement of insulin sensitivity in diabetic and non diabetic patients with chronic hepatitis C treated with direct antiviral agents 
Alessandro Gualerzi, Mattia Bellan , Carlo Smirne, Margherita Tran Minh, Cristina Rigamonti, Michela Emma Burlone, Ramona Bonometti, Sara Bianco, Azzurra Re, Serena Favretto, Giorgio Bellomo, Rosalba Minisini, Gian Piero Carnevale Schianca, Mario Pirisi
Published: December 20, 2018 https://doi.org/10.1371/journal.pone.0209216 

Full-Text Article

Abstract
Background
The increased incidence of type 2 diabetes mellitus among hepatitis C virus (HCV) infected patients is likely due to viral-induced insulin resistance (IR). Indeed, control of diabetes in these patients benefits of successful antiviral treatment; whether the same applies to subtler alterations of glucose metabolism is unknown. We aimed to fill this gap.

Methods
The study population included 82 HCV-RNA positive patients (48 males, median age 66 years, 73 with advanced fibrosis, 41 HCV-1b), attending the liver clinic of an academic hospital to receive direct antivirals. None was previously known to be diabetic. All underwent a standard oral glucose tolerance test (OGTT) before antiviral treatment and right after its conclusion.

Results
At baseline, the majority of patients had evidence of abnormal glucose metabolism (N. = 45, 55%; impaired fasting glucose 10%, impaired glucose tolerance16%, both the above 12%, 17% diabetes), while only 37 (45%) were normally glucose tolerant (NGT). At the end of treatment, HCV-RNA quantification was below the detection threshold (HCV-RNA <12 UI/ml), for all patients enrolled. A significant decrease in glucose and insulin plasma concentrations was observed, leading to a significant reduction in Homeostasis Model Assessment (HOMA)-IR (from 3.42 [2.66–5.38] to 2.80 [1.78–3.95];p<0.001) and a corresponding increase in insulin sensitivity (ISI Belfiore from 0.49 [0.26–0.75] to 0.64 [0.42–0.91];p<0.001), despite a significant reduction in insulin secretion (EFP Stumvoll from 1363 [959–1730] to 1264 [976–1588];p = 0.027). Importantly, HOMA-IR reduction occurred also in the subgroup of NGT patients (p = 0.017). The number of NGT patients increased to 53, 65% (p = 0.013) paralleled by a reduced number of those satisfying criteria for prediabetic conditions (31 (38%) vs. 17 (21%); p = 0.025).

Conclusions
Glucose metabolism parameters of HCV infected patients improve early after antiviral treatment, with benefits that are not limited to diabetics. These findings confirm how deep and widespread is the impairment of insulin pathways exerted by HCV infection.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0209216

Tuesday, November 20, 2018

Expert opinion on managing chronic HCV in patients with cardiovascular disease

Navigate this blog 
Sift through current research articles on the extrahepatic manifestations of hepatitis C, in particular an association between HCV and cardiovascular conditions.

Review
Expert opinion on managing chronic HCV in patients with cardiovascular disease
Cristina Vassalle1, Salvatore Petta2, Alessia Pepe3, Antonio Craxi2, Mark Bondin4, Patrice Cacoub

Abstract
Extrahepatic manifestations of chronic HCV infection include cardiovascular diseases and an increase in cardiovascular mortality. The pathogenic mechanisms by which HCV contributes to cardiovascular disease are not well defined, however, it is likely that systemic inflammation, and the promotion of other metabolic diseases are involved. In this Review, the evidence for HCV infection as a non-traditional risk factor for cardiovascular disease is evaluated. Furthermore, practical advice to evaluate cardiovascular disease risk and disease in chronic hepatitis C patients are included for help in daily clinical practice. Despite the advances in therapies for the treatment of HCV, there remains a need for increased awareness among specialists so that patients are more likely to obtain the treatment required to mitigate disease progression.


Conclusions
HCV has a complex role in the atherosclerotic process, although the association between HCV and CVD has not been clearly defined. In particular, the biological significance of this association remains undefined. Thus, a pathogen resident in an atherosclerotic plaque may simply represent a ‘bystander’ rather than a ‘culprit’ or a diseased vessel may simply be more vulnerable to pathogens, including HCV. In any case, it would be superficial to consider as irrelevant a hypothesis that is reinforced by multiple lines of evidence, and by the involvement of systemic inflammation and the autoimmune response, which are both critical in HCV infection and atherosclerosis.

Currently, HCV-infected patients are not generally recognized as a high priority for cardiovascular assessment and/or treatment owing to the lack of definitive conclusions on the role of HCV in CVD. In view of present available evidence, it is important that clinicians begin to consider HCV as a non-traditional risk factor for CVD. Evidence of a beneficial effect of SVR after antiviral treatment on cardiovascular risk is encouraging, especially with the introduction of new IFN-free combinations that are more effective and better tolerated than IFN-based therapies. In this context, from a pathophysiological point of view, the observation that some patients with chronic HCV infection remained free of atherosclerosis, while others develop extensive disease, represents a challenging point that merits further investigation. Thus, it remains crucial for clinicians to consider their patients as a whole, and evaluate correlated factors and diseases that place the chronic HCV infection patient at risk for HCV-related extra-hepatic complications, including CVD. Specifically, it is critical for clinicians to recognize the multilevel dimensions of HCV disease and its natural history, in the attempt to optimize treatment, apply general guidelines, avoid adverse events and improve the quality of life for each patient. In this context, the assessment of additional factors and comorbidities (for example, steatosis, diabetes) or biomarkers (for example, inflammatory, lipids) might be helpful to eventually identify subgroups of patients at higher risk of developing atherosclerosis.

It is conceivable that all patients with chronic HCV infection would benefit from a detailed assessment of their cardiovascular status, whereas patients with CVD would benefit from the screening for HCV and other HCV-related parameters. In this scenario, a close collaboration between hepatologists and cardiologists is also desirable to correctly interpret patient-specific data and make the best recommendation for each patient.

Tuesday, November 13, 2018

The incidence of diabetes, stroke and kidney disease falls after hepatitis C cure

AASLD Liver Meeting news @ infohep
The incidence of diabetes, stroke and kidney disease falls after hepatitis C cure
Keith Alcorn Published: 12 November 2018 

The incidence of some of the most serious extrahepatic health problems caused by hepatitis C declines sharply after the infection is cured by antiviral treatment, a review of people treated for hepatitis C in the Canadian province of British Columbia has found.

The findings were presented by Carmine Rossi of the British Columbia Centre for Disease Control at the 2018 AASLD Liver Meeting in San Francisco on Sunday.

Hepatitis C infection is associated with a higher incidence of chronic kidney disease, diabetes and cardiovascular disease. Although the mechanisms leading to an increased risk of these conditions in people with hepatitis C are not fully understood, liver damage caused by hepatitis C is known to disrupt glucose metabolism. Chronic hepatitis C infection affects the cardiovascular system in numerous ways and also damages the kidneys.


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Sunday, November 11, 2018

Glucose Metabolism Changes in Patients with Chronic Hepatitis C Treated with Direct Acting Antivirals

In Case You Missed It

Can J Gastroenterol Hepatol. 2018 Oct 3;2018:6095097. doi: 10.1155/2018/6095097. eCollection 2018.

Glucose Metabolism Changes in Patients with Chronic Hepatitis C Treated with Direct Acting Antivirals.
Drazilova S1, Janicko M2, Skladany L3, Kristian P4, Oltman M5, Szantova M6, Krkoska D7, Mazuchova E7, Piesecka L8, Vahalova V8, Rac M9, Schreter I4, Virag L4, Koller T10, Liptakova A11, Ondrasova M12, Jarcuska P2.

This retrospective study confirmed that the prevalence of either type 2 diabetes mellitus ( T2DM ) or impaired fasting glucose (IFG) increases in chronic hepatitis C patients with the degree of fibrosis; patients with F4 fibrosis had 27.1% prevalence of IFG and 31.8% of T2DM. The predictive factors for T2DM had besides F4 fibrosis also higher age and BMI. Significant decrease of fasting glycemia at the end of treatment and 12 weeks after that was observed in the whole cohort and in subgroups of patients with type 2 diabetes mellitus, impaired fasting glucose, Child-Pugh A cirrhotic patients, treatment experienced patients, and treatment experienced cirrhotics. Long term follow-up may further show if the achievement of SVR after DAA treatment will reduce the risk of future T2DM development similarly to SVR after interferon treatment and if the improvement of glycemic control in patients with T2DM decreases the risk of chronic complications and improves survival.

Open Access

Abstract
Background and Aims
Chronic hepatitis C is a systemic disease and type 2 diabetes mellitus (T2DM) belongs to more common extrahepatic. The aim of this study was to (i) explore the prevalence of impaired fasting glucose (IFG) and T2DM in patients with chronic hepatitis C, (ii) explore the effect of direct acting antivirals (DAA) treatment on the glycemia, and (iii) explore the factors that modulate the effect of DAA treatment on glycemia in patients with chronic hepatitis C.

Methods 
We performed a longitudinal retrospective observational study focused on the patients undergoing DAA treatment of chronic hepatitis C. Data about glycemia, history of diabetes, hepatitis C virus, treatment, and liver status, including elastography, were obtained at baseline (before treatment start), at the end of treatment and 12 weeks after the end of treatment. Patients were treated with various regimens of direct acting antivirals.

Results
We included 370 patients; 45.9% had F4 fibrosis. At baseline, the prevalence of T2DM increased with the degree of fibrosis (F0-F2 14.4%, F3 21.3%, and F4 31.8%, p=0.004). Fasting glycemia also increased with the degree of fibrosis (F0-F2 5.75±0.18 F3 5.84±0.17, and F4 6.69±0.2 mmol/L, p=0.001). We saw significant decrease of glycemia after treatment in all patients, but patients without T2DM or IFG from 6.21±0.12 to 6.08±0.15 mmol/L (p=0.002). The decrease was also visible in treatment experienced patients and patients with Child-Pugh A cirrhosis.

Conclusion
We confirmed that the prevalence of either T2DM or IFG increases in chronic hepatitis C patients with the degree of fibrosis. The predictive factors for T2DM were, besides F4, fibrosis also higher age and BMI. Significant decrease of fasting glycemia after the DAA treatment was observed in the whole cohort and in subgroups of patients with T2DM, IFG, cirrhotic, and treatment experienced patients.


30402450 PMCID:
PMC6192081 DOI: 10.1155/2018/6095097

Monday, October 29, 2018

Mavyret (glecaprevir/pibrentasvir) 8 Wks Improved Cardiovascular and Metabolic Outcomes and Stable Renal Function

Infect Dis Ther. 2018 Oct 27. doi: 10.1007/s40121-018-0218-x. [Epub ahead of print]

Pan-Genotypic Hepatitis C Treatment with Glecaprevir and Pibrentasvir for 8 Weeks Resulted in Improved Cardiovascular and Metabolic Outcomes and Stable Renal Function: A Post-Hoc Analysis of Phase 3 Clinical Trials. 
Tran TT1, Mehta D2,3, Mensa F3, Park C3, Bao Y3, Sanchez Gonzalez Y4.

First Online: 27 October 2018

Treatment with Glecaprevir and Pibrentasvir G/P for as short as 8 weeks showed improved glucose and triglyceride levels by post-treatment week 4 irrespective of treatment history and cirrhosis status. These benefits were especially pronounced in patients with elevated triglycerides, pre-diabetes and diabetes at baseline. Treatment with G/P also resulted in stable eGFR function in both during and post-treatment periods. Future studies are needed to determine whether these effects are maintained over longer periods of time.

Full-Text

Abstract
Introduction
Chronic hepatitis C (CHC) infection is associated with extrahepatic manifestations (EHMs) which can affect renal, cardiovascular and other comorbidities. The effect of CHC treatment with short-duration regimens on these EHMs is not well defined. Hence, we examined longitudinal estimated glomerular filtration rate (eGFR), triglycerides and glucose values to assess the impact of short-duration CHC therapy on renal, cardiovascular and metabolic diseases, respectively.

Methods
We conducted analyses of all patients without cirrhosis treated with glecaprevir and pibrentasvir (G/P) for 8 weeks in two phase 3 clinical trials. In addition, one phase 3 trial was carried out to explore the effects of treatment on renal EHMs in patients with advanced renal impairment at baseline. As a sensitivity analysis, we included all CHC patients treated with G/P for 8 or 12 weeks enrolled across five phase 3 trials. Adjusting for baseline demographics and clinical properties via mixed regression models enabled evaluation of changes in EHMs through end of treatment.

Results
G/P treatment for 8 weeks resulted in statistically significant declines in triglycerides (− 28.6 mg/dl) and glucose (− 11.2 mg/dl), while there was no statistically significant decline in eGFR. Biomarker improvements were greatest among patients with elevated triglycerides and elevated glucose at baseline. Similar effects were observed across all patients treated with G/P for 8 or 12 weeks.

Conclusion
Short-duration treatment with G/P resulted in stable renal function and improvements in cardiovascular and metabolic EHM markers, especially in patients with severe EHMs at baseline.

Continue reading: https://link.springer.com/article/10.1007%2Fs40121-018-0218-x

Additional Reading
HCV Advocate
Hepatitis C is NOT just a liver disease-it affects the entire body. Check out our fact sheet that lists some of the more common and uncommon extrahepatic manifestations of hepatitis C.

Navigate this blog 
Sift through current research articles on the extrahepatic manifestations of hepatitis C.

Thursday, October 25, 2018

Curing hepatitis C reduces the risk of cardiovascular events

Liz Highleyman
Published: 25 October 2018
Several studies have found that people with hepatitis C are more prone to developing cardiovascular conditions such as coronary artery disease, peripheral vascular disease, myocardial infarction and stroke; however, other studies have not seen this association.

A growing body of evidence shows that HCV treatment can help reverse this increased risk. A recent study from France, for example, found that curing hepatitis C reduces the risk of cardiovascular events in people with compensated cirrhosis. But again, some large studies from the interferon era did not see a similar benefit. 

On This Blog
A collection of current research articles on ailments related to HCV
Article directory on the extrahepatic manifestations of hepatitis C.

The following study investigated the prevalence of early signs of cardiovascular damage in patients with HCV cirrhosis. Is such damage reversible following treatment with DAAs? 

Full-text article available online @ Medscape, or purchase article, here

A Prospective Study
Aliment Pharmacol Ther. 2018 Oct;48(7):740-749. doi: 10.1111/apt.14934. Epub 2018 Aug 10.

Subclinical cardiovascular damage in patients with HCV cirrhosis before and after treatment with direct antiviral agents: a prospective study.
Novo G1, Macaione F1, Giannitrapani L2, Minissale MG2, Bonomo V1, Indovina F1, Petta S3, Soresi M2, Montalto G2, Novo S1, Craxi A3, Licata A2,3.

Abstract
BACKGROUND:
Cirrhosis is associated with morpho-functional cardiovascular alterations.

AIMS: 
To detect early features of cardiovascular damage in HCV-compensated cirrhotic patients using myocardial deformation indices and carotid arterial stiffness, and, further, to evaluate their short-term behaviour after HCV eradication with direct antiviral agents (DAAs).

METHODS: 
Thirty-nine consecutive patients with HCV cirrhosis, without previous cardiovascular events, were studied and matched for age, gender and cardiovascular risk factors to 39 controls without liver or cardiovascular disease. Patients and controls underwent a baseline echocardiographic evaluation including global longitudinal strain and ultrasound scan of carotid arteries. HCV-cirrhotics were reassessed by echocardiography and carotid ultrasound after obtaining sustained virological response (SVR) on DAAs.

RESULTS: 
HCV-cirrhotics showed at baseline a significantly reduced global longitudinal strain compared to controls -18.1 (16.3-20.5) vs -21.2 (20.4-22.3), P < 0.001. They also had a significantly higher pulse wave velocity 8.6 (7.7-9.1) m/s vs 6.6 (6.0-7.1) m/s, P = 0.0001, and β-stiffness index 12.4 (11.1-13.5) vs 8.6 (8.0-9.2) P = 0.0001. At multiple regression analysis, diabetes and HCV cirrhosis were independent predictors of global longitudinal strain. All HCV-cirrhotic patients had SVR on DAAs. Follow-up available in 32 of 39 (82%) at 9 (8-10) months showed a significant improvement of tricuspid annular plane systolic excursion (P = 0.01) and lateral E' velocity compared to baseline (P = 0.001).

CONCLUSIONS: 
HCV-cirrhotics show a significant rate of subclinical cardiac and vascular abnormalities. At a time when their survival is less linked to progression of liver disease, due to viral eradication on DAAs, cardiovascular morbidity and mortality may take a significant role.
Continue to full-text: https://www.medscape.com/viewarticle/902665
free registration required

Saturday, October 6, 2018

Epidemiology and Elimination of HCV-Related Liver Disease

In Case You Missed It

Received: 1 September 2018 / Accepted: 3 October 2018 / Published: 6 October 2018 
Viruses 2018, 10(10), 545; doi: 10.3390/v10100545

Review 
Epidemiology and Elimination of HCV-Related Liver Disease 
Pierre Pradat , Victor Virlogeux and Eric Trépo

Abstract:
Hepatitis C virus (HCV) infection, defined by active carriage of HCV RNA, affects nearly 1.0% of the worldwide population. The main risk factors include unsafe injection drug use and iatrogenic infections. Chronic HCV infection can promote liver damage, cirrhosis and hepatocellular carcinoma (HCC) in affected individuals. The advent of new second-generation, direct-acting antiviral (DAA) agents allow a virological cure in more than 90% of treated patients, and therefore prevent HCV-related complications. Recently, concerns have been raised regarding the safety of DAA-regimens in cirrhotic patients with respect to the occurrence and the recurrence of HCC. Here, we review the current available data on HCV epidemiology, the beneficial effects of therapy, and discuss the recent controversy with respect to the potential link with liver cancer. We also highlight the challenges that have to be overcome to achieve the ambitious World Health Organization objective of HCV eradication by 2030.

Read full-text article online

On This Blog
Sift through current Liver Cancer and Hepatitis C research articles

Liver Cancer After Treatment For Hepatitis C: 
Research demonstrates that while SVR markedly reduced liver-related complications and liver cancer, some long-term risk for liver cancer remained in those who were cured of Hepatitis C. But after direct-acting antiviral therapy does the risk of developing liver cancer increase? Research is saying no, check out an index of articles here..... 

Also see; HCV Newsletters & Blog Updates

Friday, September 28, 2018

Cardiovascular Risk Management and Hepatitis C: Combining Drugs

Cardiovascular Risk Management and Hepatitis C: Combining Drugs
Elise J. SmoldersPeter J. G. ter HorstSharon WoltersDavid M. Burger Elise J. Smolders

Article First Online: 27 September 2018

Abstract
Direct-acting antivirals (DAAs) are known victims (substrate) and perpetrators (cause) of drug–drug interactions (DDIs). These DAAs are used for the treatment of hepatitis C virus (HCV) infections and are highly effective drugs. Drugs used for cardiovascular risk management are frequently used by HCV-infected patients, whom also are treated with DAAs. Therefore, the aim of this review was to describe DDIs between cardiovascular drugs (CVDs) and DAAs. An extensive literature search was performed containing search terms for the marketed DAAs and CVDs (β-blocking agents, ACE inhibitors, angiotensin II antagonists, renin inhibitors, diuretics, calcium channel blockers, statins/ezetimibe, fibrates, platelet aggregation inhibitors, vitamin K antagonists, heparins, direct Xa inhibitors, nitrates, amiodarone, and digoxin). In particular, the drug labels from the European Medicines Agency and the US Food and Drug Administration were used. A main finding of this review is that CVDs are mostly victims of DDIs with DAAs. Therefore, when possible, monitoring of pharmacodynamics is recommended when coadministering these drugs with DAAs. Nevertheless, it is sometimes better to discontinue a drug on a temporary basis (statins, ezetimide). The DAAs are victims of DDIs in combination with bisoprolol, carvedilol, labetalol, verapamil, and gemfibrozil. Despite there are many DDIs predicted in this review, most of these DDIs can be managed by monitoring the efficacy and toxicity of the victim drug or by switching to another CVD/DAA.

Key Points
Drug-drug interactions (DDIs) can be of major concern in hepatitis C patients with cardiovascular issues as there are many potential DDIs.

Especially clopidogrel and ticagrelor are drugs of which the potential drug-interactions are complex and hard to manage.

With increasing number of new direct-acting antivirals (DAAs) available the number clinical relevant DDIs are decreasing.

Read full-text article online:

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Tuesday, September 25, 2018

Editorial: interferon‐free DAAs are a great boon for patients with hepatitis C and cryoglobulinaemia

Aliment Pharmacol Ther. 2018 Oct;48(7):770-771. doi: 10.1111/apt.14899.

INVITED EDITORIAL
Editorial: interferon‐free DAAs are a great boon for patients with hepatitis C and cryoglobulinaemia
M. Atsukawa, A. Tsubota
Pages: 770-771
First Published: 23 September 2018 

Chronic hepatitis C is often accompanied by various extrahepatic manifestations that affect the health‐related quality of life (HRQoL) and mortality of patients.1, 2 In particular, mixed cryoglobulinaemia (MC) and MC syndrome (MCS) are closely associated with hepatitis C virus (HCV) infection. Thus, the most rational treatment strategy for HCV‐related MC/MCS is HCV eradication. As expected, interferon (IFN)‐based treatment can alleviate MC/MCS in patients with a sustained virological response (SVR).3 However, the SVR rate is low and drug adherence is frequently reduced due to adverse events.4 MCS patients exhibit systemic complications that may attenuate the efficacy of IFN‐based treatment. Moreover, MC is a negative, independent predictor of virological response.5 Currently, IFN‐free direct‐acting antiviral (DAA) combination therapy that yields a high SVR rate with high tolerability is the standard of care for chronic hepatitis C. DAA treatment for MC patients reportedly achieved a SVR rate of 74%‐100% and reduced or resolved the symptoms in 61%‐100% of the patients with SVR.6

To our knowledge, Gragnani and colleagues were the first to conduct a prospective, case‐control study to evaluate the virological/clinical/immunological response and the HRQoL score following IFN‐free, DAA‐based treatment for cryoglobulinaemic vasculitis (CV) patients, MC patients without vasculitis, and control patients without CV/MC.7 This comparative study reconfirmed the excellent efficacy/safety profile of DAA‐based treatment even in CV/MC patients. The SVR rate (89.9%) was almost twice that (48.6%) with pegylated IFN/ribavirin treatment.5, 7 It was noteworthy that SVR persistently improved the clinical indices at a high rate in CV patients. Immunological response progressively improved in CV patients with SVR. Moreover, the HRQoL score, including physical and mental components, was lower at baseline in CV patients than in MC/control patients, while it significantly improved in CV patients with SVR. Therefore, the highly effective and safe DAA treatment is a great boon for CV patients, because it consequently reduces their physical and/or mental burden future healthcare costs.

However, the SVR rates in CV/MC patients (90.6% and 88.9%, respectively) were lower (although not significantly) than those in control patients (95.3%).7 In fact, most patients with treatment failure had cryoglobulinaemia and some exhibited severe manifestations before treatment. Such patients failed to experience clinical improvement during the post‐treatment period. These outcomes suggest the importance of early treatment for CV/MC patients before disease progression to severe stages.

DAAs are rapidly developing, and treatment options are increasing; therefore, personalised medication by regimen optimisation is possible for cryoglobulinaemic patients with various complications. For instance, sofosbuvir/ribavirin is administered to CV patients.6 However, 8%‐58% of cryoglobulinaemic patients have renal impairment.8 Sofosbuvir and ribavirin are mainly excreted in the urine; thus, both are contraindicated for, or should be carefully administered to, patients with moderate/severe renal dysfunction. Currently, the AASLD guidelines specify elbasvir/grazoprevir or glecaprevir/pibrentasvir as the first‐line treatment.9 Moreover, the EASL guidelines recommend ribavirin‐free treatment for cryoglobulinaemic patients with renal dysfunction.10 Precision medicine is required, particularly for cryoglobulinaemic patients with severe complications and refractory features.

ACKNOWLEDGEMENTS
Declaration of personal interests: M Atsukawa has served as a speaker for AbbVie, MSD and Gilead Sciences, and has received research funding from AbbVie and MSD. 

Source:
Zignego AL, et al. Aliment Pharmacol Ther. 2018

We would like to express our gratitude to Drs Atsukawa and Tsubota for their comments and the correct interpretation of the main messages that may be deduced from our study,1, 2 especially concerning the future challenges in the treatment of cryoglobulinaemic vasculitis (mixed cryoglobulinaemia syndrome, MCS), a HCV‐related disease that is often under‐estimated and not sufficiently known.3

The occurrence of MCS represents a condition that justifies careful prioritization of Interferon‐free anti‐HCV treatment. This appears to be the most effective as soon as it is carried out, whereas, when the therapy is too late and the patients have already developed severe damage (especially renal), MCS requires careful evaluation and accurate tailoring of non‐aetiological therapies (e.g, anti‐inflammatory and immunosuppressant) to be performed before, but also after, and sometimes concomitantly with anti‐viral therapy.

The complex pathogenetic cascade that underlies this lymphoproliferative disorder, and that originates from the clonal expansion of specific B‐cells (RF‐B cells), may lead to the subsequent overcoming of points of no return whose identification would be important for the assessment of a rational approach to the patients. Above all, in case of the persistence of MCS symptoms and/or signs, it would be important to distinguish the causes indicating the risk of evolution of the lymphomagenetic process (the overcoming of points of no return), from those without this risk, such as the simple occurrence of irreversible tissue damage.4

In this light, it seems conceivable that a key factor for the correct interpretation of the persistence of MCS stigmata even after viral eradication, is the evaluation of the persistence of B cell clonal expansion. Various factors have been suggested as playing a key role in inducing clonal expansion, first the important and sustained activation of the B‐cell compartment by both viral and host factors. Among the latter, special emphasis was placed on the binding of the viral E2 protein and the CD81 molecule on the surface of the B cells5 and the effect of the B‐cell‐activating factor (BAFF)/B‐lymphocyte stimulator (BLyS), especially in subjects harbouring particular genetic variants.6 Such an important and persistent B‐cell activation would cooperate to the lymphomagenetic process with B‐cell anti‐apoptotic factors including, first, the t (14; 18) translocation7 and could possibly be correlated with an exhaustion of the B cells observed during MCS.8 Consequently, it seems conceivable that the detection of persistent B cell expanded clones through sensitive methods, after HCV eradication, could help in understanding the condition that we are facing; this would be helpful in deciding the best approach to the patient (more frequent follow‐ups and/or specific therapies).

In conclusion, following the demonstration of the positive effect of viral eradication in MCS patients, the most important future challenge is the identification of markers useful in assessing the best approach to patients that maintain clinical and/or immunological MCS stigmata after SVR.

ACKNOWLEDGEMENT
The authors’ declarations of personal and financial interests are unchanged from those in the original article.2
Source:

Wednesday, September 12, 2018

Neuropsychiatric symptoms associated with hepatitis C virus (HCV)

September 12, 2018 
HCV Neuropsychiatric Symptoms Likely Linked to Virus' Effects on Brain Function
The neuropsychiatric symptoms associated with hepatitis C virus (HCV) infection are likely caused by the body's response to the virus' effects on brain function, according to a study recently published in the Journal of Viral Hepatitis. This neuro-inflammatory and systemic response is akin to that observed in patients with autoimmune diseases of the liver.

Reference 
Dirks M, Haag K, Pflugrad H, et al. 
[published online August 18, 2018]. J Viral Hepat. doi: 10.1111/jvh.12979

Abstract 
Chronic fatigue, mood alterations and cognitive impairment are frequent accessory symptoms of HCV‐infection. Fatigue and mood alterations have also been observed in autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC), but not in hepatitis B virus (HBV)‐infection, thus indicating an autoimmune response as possible cause of HCV‐infection associated encephalopathy. Data, however, are sparse. This study aims to prove that HCV patients feature similar to those with autoimmune liver disease but contrary to HBV patients regarding neuropsychiatric symptoms.

132 non‐cirrhotic patients (HCV: 46, HBV: 22, AIH: 27, PBC: 29, AIH/PBC: 8) completed questionnaires addressing the domains mentioned above. Eighty‐eight underwent a comprehensive neuropsychological assessment. Patient groups were compared among each other and to 33 healthy controls.

Fatigue, anxiety and depression scores were significantly increased, and the SF‐36 mental score significantly decreased in all patient groups compared to controls. Fatigue was significantly more pronounced in HCV than in HBV patients. HCV patients scored significantly worse than HBV patients but not AIH and PBC patients in the SF‐36. HCV, AIH and PBC but not HBV patients did significantly worse than controls in word learning. Recognition of words was impaired in HCV, AIH and PBC patients and recognition of figures in HCV patients, exclusively (p≤0.002). HCV patients did also worse than controls and HBV patients concerning alertness and working memory (p≤ 0.001).

The neuropsychiatric profiles of HCV patients are similar to those of AIH and PBC patients but differ from those of HBV patients, suggesting an autoimmune response as a possible cause for these differences.

Wednesday, August 8, 2018

Managing Neurologic Complications of Chronic HCV Infection

In case you missed it
Managing Neurologic Complications of Chronic HCV Infection
Anushka Burde, PharmD; Rebecca Hoover, PharmD, MBA, BCPS
US Pharmacist. 2018;43(1):18-22.

Abstract and Introduction
Abstract
Chronic hepatitis C virus (HCV) infection can cause a multitude of extrahepatic complications, including neurologic manifestations. These complications can lead to substantial neuropsychiatric deficits, such as fatigue, cognitive impairment, restless legs syndrome, Parkinson's disease, and peripheral neuropathy. In addition to detecting and managing these neurologic complications, pharmacists in community settings can promote HCV screening, improve medication access and adherence, and recommend preventive strategies patients can use to avoid transmission of this widespread infection.

Hepatitis C virus (HCV) infection is widespread, and about one-half of the 3.5 million HCV-infected people in the United States are likely unaware of being infected.1 Community pharmacists, as the most accessible type of healthcare practitioner, are optimally positioned to detect and manage HCV. They can help HCV-infected patients by engaging in appropriate screening, ensuring proper management of the infection, and recognizing extrahepatic symptoms, including neurologic complications.

Screening
Pharmacists in community settings should identify those patients most in need of screening. For example, the pharmacist can run a listing of baby-boomer patients (i.e., born between 1945 and 1965) at the pharmacy and can recommend one-time HCV testing irrespective of prior risk factors discussed in the American Association for the Study of Liver Diseases guidelines.1 Factors for the pharmacist to keep in mind are that about 60% of acute HCV infections in the U.S. are a result of injection-drug use and that there is a substantial risk of HCV transmission in HIV-infected men who have unprotected sex with men. The pharmacist can also identify patients for screening by checking medication histories.

The pharmacist should counsel patients to get tested for HCV infection based on the recognition of risk factors, including poor adherence to HIV medications, which can be determined by checking refill history. Patients are more likely to disclose a history of drug use to their pharmacist after developing a sense of trust and confidence. Pharmacists should put patients at ease by assuring them that their information will not be used against them, but rather will be used appropriately to refer them for HCV testing. For example, women with active HCV infection or a history of it should be advised to get their children tested as well. Pharmacists can recommend HCV testing for patients with a history of incarceration by noting that data suggest the presence of anti-HCV antibodies in about 29% of incarcerated persons in North America.1 Other risk factors, such as history of organ transplant, receipt of transfusion, and piercings and tattoos obtained at unregulated settings, should be taken into consideration regarding HCV screening.

Community pharmacies can also engage in screening practices by testing for the presence of HCV antibodies. Multiple diagnostic tests for HCV are available that combine laboratory-based and point-of-care assays. One of these, the OraQuick HCV Rapid Antibody Test, is an FDA-approved Clinical Laboratory Improvement Amendments–waived test.1 This waiver enables patients to be tested at various locations, including community pharmacies. The test is straightforward and efficient, providing results in about 20 minutes. It can test for multiple HCV genotypes, and its accuracy exceeds 98%.2

Patient Education
Pharmacists can educate patients with HCV infection on how to prevent spread of the virus, such as to avoid sharing toothbrushes or shaving equipment. Patients should also be counseled to use barrier precautions to prevent sexual transmission and to stop using illicit drugs. The use of clean needles and syringes should be encouraged, as HCV reinfection is highly likely if the risk of drug use is ongoing.3 Persons infected with HCV should be encouraged to abstain from alcohol and smoking. Patients should be counseled to enter substance-abuse treatment facilities in order to prevent progression of liver disease. The pharmacist should also mention that definitive evidence supporting the use of complementary and alternative supplements is lacking. Other clinical pearls offered by the pharmacist could include possible benefits of coffee consumption, a diet low in fat and sodium, weight loss, and vitamin D testing. The pharmacist should also recommend limiting acetaminophen use to 2 g per day in noncirrhotic HCV-infected patients and 1 g per day in those who are cirrhotic.1 The pharmacist could also recommend a daily multivitamin without iron.

Pharmacists can also ensure that patients who are susceptible to HCV infection receive appropriate, routine CDC-recommended vaccines, including those for hepatitis A and B. Pneumococcal vaccine should be administered to patients with cirrhosis.1

Treatment
Significant side effects and profound laboratory abnormalities plagued older HCV treatments, making them unfavorable options for patients.4 Interferon-based regimens, historically the standard of care, were associated with substantial side effects, such as flulike symptoms, fatigue, neuropsychiatric symptoms, and hematologic effects. Newer interferon-free, direct-acting antiviral (DAA) oral regimens introduced since 2013 have successfully achieved sustained virologic response (SVR), a marker of virologic cure. A few commonly used DAAs include ledipasvir-sofosbuvir (Harvoni), sofosbuvir-velpatasvir (Epclusa), sofosbuvir (Sovaldi), daclatasvir (Daklinza), elbasvir-grazoprevir (Zepatier), and ombitasvir-paritaprevir-ritonavir plus dasabuvir (Viekira Pak). Glecaprevir-pibrentasvir (Mavyret) and sofosbuvir-velpatasvir-voxilaprevir (Vosevi) were approved in 2017. Epclusa, Mavyret, and Vosevi are pangenotypic and may be used to treat all HCV genotypes (i.e., types 1-6). Treatment with and duration of DAAs depend on HCV genotype, presence of cirrhosis, HCV RNA level, and history of prior treatment.

Reductions in all-cause mortality, liver-related adverse outcomes such as end-stage liver disease, and hepatocellular carcinoma are the goals of treatment in HCV-infected persons. Despite the availability of successful treatments, multiple barriers must be overcome. One such barrier is lack of access to treatment, reasons for which include high medication costs, lack of insurance, geographic distance, and lack of specialist availability. A treatment-naïve genotype 1a patient will require treatment that can cost up to $54,600 to $150,000, on average.3,4 Longer duration of treatment further increases these costs. Community pharmacists can help patients by identifying patient-assistance programs and providing appropriate navigation through insurance plans to alleviate some of the cost burden.

Medication Adherence
Educating patients with HCV on the importance of medication adherence is a critical component of HCV treatment and determines virologic cure. Adherent and immunologically competent treatment-naïve patients with compensated liver disease are 95% more likely to achieve SVR with direct-acting antivirals.1,4 Several methods for checking compliance may be implemented at a community pharmacy, including pharmacy-refill assessment, pill counts, and follow-up phone calls to patients. The pharmacist should advise patients that modification of certain risk factors—such as reducing alcohol intake, weight loss (in obese patients), and cessation of cigarette smoking and marijuana use—can reduce, and may also reverse, progression of liver disease. Pharmacists are also in a key position to identify drug-drug interactions, including prescription medications for comorbidities and OTC products.

Neurologic Extrahepatic Complications
Many community pharmacists go the extra mile for their patients by screening for HCV infection and overseeing therapy upon diagnosis. However, pharmacists should understand that HCV can impact health beyond liver dysfunction. A variety of extrahepatic issues are associated with chronic hepatitis C, including diabetes and dermatologic manifestations such as porphyria cutanea tarda and lichen planus.1 Fatigue, arthralgias, renal disease, and neurologic diseases such as peripheral neuropathy are manifestations of cryoglobulinemia, a lymphoproliferative disorder that causes local deposition of immune complexes.1

An increased prevalence of neuropsychiatric symptoms in HCV-infected patients, independent of any preexisting mental disorders or high-risk behaviors, is being reported in emerging literature. HCV likely has a direct biological effect on the central nervous system. Possible mechanisms include neuroinflammation, as noted on brain imaging, and peripheral inflammation across the blood-brain barrier that is induced by elevation of proinflammatory cytokines.5

Fatigue and Cognitive Impairment: Chronic HCV infection is associated with fatigue and cognitive impairment, which contribute to reduced quality of life. More than 50% of HCV-infected patients report that fatigue is the most common symptom. The occurrence of fatigue may be difficult to predict. HCV RNA, HCV genotype, and liver histology are not associated with fatigue.6 Numerous quality-of-life measures have shown that fatigue impairs the quality of life and activity level of HCV-infected patients. Cure of HCV infection results in a reduction in fatigue, as noted in some studies.1 The community pharmacist should recognize chronic HCV as a potential cause when a patient complains of chronic fatigue, low energy levels, and pain. Abnormal circulating levels of thyroid-stimulating hormone or thyroxine have been noted in HCV-infected patients, which might result in a high prevalence of fatigue.6 Pharmacists could suggest thyroid-function testing in these patients.

Deficits in measures of attention, higher executive functions like planning, decision making, judgment, or reasoning skills, verbal learning ability, recall, and working memory have been reported in literature examining HCV-associated cognitive impairment.7 Pharmacists should refer patients to their medical provider for complaints of brain fog or neuropsychiatric symptoms such as difficulty paying attention, concentrating, failing memory, and so on. Patients should be counseled that studies have shown that successful clearance of the virus is associated with improved attention, vigilance, and working memory.

Restless Legs Syndrome (RLS): Beyond cognitive manifestations, patients with HCV may also have motor-neuron problems. HCV infection may place patients at greater risk for RLS. This condition, which is characterized by an impulse to move the legs, typically manifests in the evening and at night. Cirrhosis and use of older agents, such as interferon-alpha, for drug therapy are associated with RLS and are of particular concern.8,9 Patients complaining of sleep difficulties or those using prescription or OTC sleep aids with or without RLS treatment may benefit from further education and evaluation regarding the possible relationship between RLS and HCV infection.

Parkinson’s Disease: Most evidence supports an association between Parkinson’s disease and HCV infection, but the cause is unclear.10-12 Parkinson’s disease could be a direct consequence of HCV infection or perhaps even its treatment. The relationship could also be due to similarities in the mechanisms of the diseases. The extent of the association is unclear as well. A recent analysis of data from Medicare patients failed to find an association between HCV infection and occurrence of Parkinson’s disease.12 However, in the same way that early detection is essential for HCV treatment, early detection of Parkinson’s disease is important for maintaining quality of life. Pharmacists should be alert to complaints of movement disorders in HCV-infected patients. Asking patients about movement problems or tremors is an important first step. Parkinson’s disease may have a gradual onset, and patients may not readily recognize early signs. Community pharmacists can counsel HCV patients to self-monitor parkinsonian symptoms by looking for shaking, slowed movement, or changes in speech. Patients reporting these problems are good candidates for further assessment by a specialist or primary care provider.

Peripheral Neuropathy: Peripheral neuropathy is a common complaint presented at community pharmacies. Although most pharmacists associate neuropathy with diabetes, thyroid disorder, or renal failure, it is important to also consider HCV. Neuropathy is caused by a breakdown of sensory and motor neurons, which prevents proper signals between the central and peripheral nervous systems. Mechanisms for neuropathy in HCV are likely due to indirect factors such as inflammation and cryoglobulinemia, in which immunoglobulins precipitate and clump together.13 About 10% of HCV patients report peripheral neuropathy, which is most likely to occur in those with cryoglobulinemia.14

Patients may complain of motor problems such as weakness or sensory impairment such as numbness, burning or prickling sensation, or intense pain.4 Neuropathy presents in various forms, and it may be hard to determine the cause. Because neuropathy in HCV patients may go unrecognized, it is important to ask patients about their pain status and refer them to their primary care provider as needed. It may be useful for patients to keep a pain journal to detect triggers or determine which therapy works best. Neuropathy can be difficult to alleviate, and it may be necessary to help the prescriber select the medication and titrate as appropriate.

Interrelatedness of Extrahepatic Complications: Beyond traditional neurologic implications, it is necessary for pharmacists to appreciate that extrahepatic manifestations of HCV infection are interrelated. For example, a stroke may be caused by cardiovascular risks related to HCV infection but may result in neurologic impairment. Literature shows that HCV promotes carotid plaque formation, a well-known predictor of cardiovascular disease. Other possible contributory mechanisms are cryoglobulinemia-associated vasculitis and autoimmune antibody development. Patients who have had a cryptogenic stroke should be screened for HCV and cryoglobulins.1 Being vigilant in monitoring a patient’s response and adherence to treatment can help prevent extrahepatic issues. HCV management should be gradually geared toward primary care through collaboration with specialists, and complicated cases should always be referred to HCV specialists.

Conclusion
Community pharmacists serve a vital function in the care of patients infected with HCV. The pharmacist can play an important role in HCV management by identifying patients who should be tested for HCV, providing extensive medication and disease-state counseling, recommending and administering appropriate vaccines, determining and managing extrahepatic complications, and collaborating with providers on care.

REFERENCES

1. AASLD/IDSA HCV Guidance Panel. Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology. 2015;62:932-954.
2. OraSure Technologies, Inc. OraQuick HCV Rapid Antibody Test product information. www.orasure.com/products-infectious/products-infectious-oraquick-hcv.asp. Accessed November 3, 2017.
3. CDC. Viral hepatitis surveillance—United States, 2014. www.cdc.gov/hepatitis/statistics/2014surveillance/pdfs/2014hepsurveillancerpt.pdf. Accessed December 5, 2017.
4. Deming P. Viral hepatitis. In: DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: A Pathophysiologic Approach. 10th ed. New York, NY: McGraw-Hill Education; 2017:561-578.
5. Negro F, Forton D, Craxì A, et al. Extrahepatic morbidity and mortality of chronic hepatitis C. Gastroenterology. 2015;149:1345-1360.
6. Poynard T, Cacoub P, Ratziu V, et al. Fatigue in patients with chronic hepatitis C. J Viral Hepat. 2002;9:295-303.
7. Gess M, Forton D. Effect of hepatitis C on the central nervous system of HIV-infected individuals. J Virus Adaptation Treat. 2012;4:93-106.
8. Anderson K, Jones DE, Wilton K, Newton JL. Restless leg syndrome is a treatable cause of sleep disturbance and fatigue in primary biliary cirrhosis. Liver Int. 2013;33:239-243.
9. Tembl JI, Ferrer JM, Sevilla MT, et al. Neurologic complications associated with hepatitis C virus infection. Neurology. 1999;53:861-864.
10. Abushouk AI, El-Husseny MW, Magdy M, et al. Evidence for association between hepatitis C virus and Parkinson’s disease. Neurol Sci. 2017;38:1913-1920.
11. Pakpoor J, Noyce A, Goldacre R, et al. Viral hepatitis and Parkinson disease: a national record-linkage study. Neurology. 2017;88:1630-1633.
12. Golabi P, Otgonsuren M, Sayiner M, et al. The prevalence of Parkinson disease among patients with hepatitis C infection. Ann Hepatol. 2017;16:342-348.
13. Nemni R, Sanvito L, Quattrini A, et al. Peripheral neuropathy in hepatitis C virus infection with and without cryoglobulinaemia. J Neurol Neurosurg Psychiatry. 2003;74:1267-1271.
14. Bonetti B, Scardoni M, Monaco S, et al. Hepatitis C virus infection of peripheral nerves in type II cryoglobulinaemia. Virchows Arch. 1999;434:533.535.


Sunday, August 5, 2018

Hepatitis C-Diabetes associated w-advanced fibrosis and progression in HCV non-genotype 3 patients

In case you missed it

Dig Liver Dis. 2018 Jul 17. pii: S1590-8658(18)30814-4. doi: 10.1016/j.dld.2018.07.003. 
[Epub ahead of print]

Diabetes is associated with advanced fibrosis and fibrosis progression in non-genotype 3 chronic hepatitis C patients.

Researchers investigated if diabetes is associated with progression from the non-cirrhotic liver to cirrhosis in non-genotype 3 chronic hepatitis C (CHC) patients. In the study 976 non-genotype 3 patients with HCV were studied, out of the 976 participants, 684 did not have cirrhosis. According to ultrasound findings, 60 patients developed cirrhosis during the follow-up period. In non-genotype 3 CHC patients, diabetes was correlated with progression from the non-cirrhotic liver to cirrhosis.

Abstract
BACKGROUND:
Diabetes is a risk factor of fibrosis progression in chronic hepatitis C (CHC). However, only one longitudinal study exploring whether diabetes is associated with progression from non-cirrhotic liver to cirrhosis in CHC patients has been conducted.

AIMS: 
We investigated whether diabetes is associated with progression from non-cirrhotic liver to cirrhosis in non-genotype 3 CHC patients.

METHODS: 
A cohort consisting of 976 non-genotype 3 patients histologically proven to have CHC was studied. After excluding patients with biopsy-proven or ultrasound-identified cirrhosis, there were 684 patients without cirrhosis. All 684 patients underwent hepatocellular carcinoma surveillance using ultrasound every 6 months, with a median duration of follow-up evaluation of 102.4 months. During the follow-up period, 60 patients developed cirrhosis according to ultrasound findings.

RESULTS: 
For the subgroup of 684 patients without cirrhosis, Kaplan-Meier survival analyses showed no significantly different cumulative incidences of cirrhosis (log-rank test; P = 0.71) among the patients with diabetes as compared to those without. However, after making adjustments for age, gender, fibrosis, steatosis, sustained virological response status, and obesity using Cox's proportional hazard model, diabetes was found to be an independent predictor for cirrhosis (HR = 1.9; 95% CI = 1.05-3.43, P = 0.03).

CONCLUSIONS: 
Diabetes is associated with progression from non-cirrhotic liver to cirrhosis in non-genotype 3 CHC patients.

KEYWORDS:
Diabetes; Genotype 3; Hepatitis C virus; Liver cirrhosis; Ultrasound
PMID: 30076015 DOI: 10.1016/j.dld.2018.07.003 
Full text article requires payment 

Friday, August 3, 2018

Symptom burden and comorbid medical conditions in patients with HCV initiating direct acting antiviral therapy

A comprehensive assessment of patient reported symptom burden, medical comorbidities, and functional well being in patients initiating direct acting antiviral therapy for chronic hepatitis C: Results from a large US multi-center observational study

A comprehensive understanding of baseline symptom burden in patients with HCV is necessary to lay the groundwork for subsequent real-world investigations of potential changes in symptoms during DAA therapy and after virologic cure. We aimed to characterize patient-reported symptoms, medical conditions, and functional well-being in a large multi-center US cohort who initiated DAA therapy in clinical practices in 2016-2017. Our secondary aim was to evaluate sociodemographic/SDoH, liver-related, and other clinical features associated with these health outcomes.

Published: August 1, 2018 

Links
View full-text article online

Abstract
Background
Symptom burden, medical comorbidities, and functional well-being of patients with chronic hepatitis C virus (HCV) initiating direct acting antiviral (DAA) therapy in real-world clinical settings are not known. We characterized these patient-reported outcomes (PROs) among HCV-infected patients and explored associations with sociodemographic, liver disease, and psychiatric/substance abuse variables.

Methods and findings
PROP UP is a large US multicenter observational study that enrolled 1,600 patients with chronic HCV in 2016–2017. Data collected prior to initiating DAA therapy assessed the following PROs: number of medical comorbidities; neuropsychiatric, somatic, gastrointestinal symptoms (PROMIS surveys); overall symptom burden (Memorial Symptom Assessment Scale); and functional well-being (HCV-PRO). Candidate predictors included liver disease markers and patient-reported sociodemographic, psychiatric, and alcohol/drug use features. Predictive models were explored using a random selection of 700 participants; models were then validated with data from the remaining 900 participants. The cohort was 55% male, 39% non-white, 48% had cirrhosis (12% with advanced cirrhosis); 52% were disabled or unemployed; 63% were on public health insurance or uninsured; and over 40% had markers of psychiatric illness. The median number of medical comorbidities was 4 (range: 0–15), with sleep disorders, chronic pain, diabetes, joint pain and muscle aches being present in 20–50%. Fatigue, sleep disturbance, pain and neuropsychiatric symptoms were present in over 60% and gastrointestinal symptoms in 40–50%. In multivariable validation models, the strongest and most frequent predictors of worse PROs were disability, unemployment, and use of psychiatric medications, while liver markers generally were not.

Conclusions
This large multi-center cohort study provides a comprehensive and contemporary assessment of the symptom burden and comorbid medical conditions in patients with HCV treated in real world settings. Pain, fatigue, and sleep disturbance were common and often severe. Sociodemographic and psychiatric markers were the most robust predictors of PROs. Future research that includes a rapidly changing population of HCV-infected individuals needs to evaluate how DAA therapy affects PROs and elucidate which symptoms resolve with viral eradication.

Tuesday, May 8, 2018

Higher risk of hepatocellular carcinoma in Hispanic patients with hepatitis C cirrhosis and metabolic risk factors

Published:08 May 2018
nature.com - scientific reports

Higher risk of hepatocellular carcinoma in Hispanic patients with hepatitis C cirrhosis and metabolic risk factors
Alina Wong, An Le, Mei-Hsuan Lee, Yu-Ju Lin, Pauline Nguyen, Sam Trinh, Hansen Dang & Mindie H. Nguyen

Full-Text

In summary, this study shows that patients with CHC cirrhosis and super-imposed metabolic syndrome have increased risk of liver-related complications including both hepatic decompensation and HCC. Hispanic patients with two or more metabolic risks are at especially increased risk of developing liver-related complications. As the prevalence of obesity and metabolic syndrome increase across the world, targeted health interventions will be needed to help curb the effects of metabolic syndrome in chronic hepatitis C patients.

Abstract
The effect of metabolic syndrome on chronic liver diseases other than non-alcoholic fatty liver disease has not been fully elucidated. Our goal was to evaluate if metabolic syndrome increased the risk of liver-related complications, specifically hepatocellular carcinoma (HCC) and decompensation, in cirrhotic chronic hepatitis C (CHC) patients. We conducted a retrospective cohort study of 3503 consecutive cirrhotic CHC patients seen at Stanford University from 1997–2015. HCC developed in 238 patients (8-year incidence 21%) and hepatic decompensation in 448 patients (8-year incidence 61%). The incidence of HCC and decompensation increased with Hispanic ethnicity, diabetes, and number of metabolic risk factors. Multivariate Cox regression analysis demonstrated that, independent of HCV therapy and cure and other background risks, Hispanic ethnicity with ≥2 metabolic risk factors significantly increased the risk of HCC and hepatic decompensation. There was no interaction between Hispanic ethnicity and metabolic risk factors. All in all, metabolic risk factors significantly increase the risk of liver-related complications in cirrhotic CHC patients, especially HCC among Hispanics. As the prevalence of metabolic syndrome increases globally, targeted health interventions are needed to help curb the effects of metabolic syndrome in CHC patients.