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

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 

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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.


Saturday, April 14, 2018

Hepatitis C Symptoms Can Persist After Cure Cryoglobulins observed 2 years after sustained virologic response

Meeting Coverage > EASL
Hepatitis C Symptoms Can Persist After Cure Cryoglobulins observed 2 years after sustained virologic response
by Ed Susman, Contributing Writer, MedPage Today April 13, 2018

PARIS – Long after hepatitis C virus has been eradicated by direct acting antiviral therapy, manifestations of the disease persist and can relapse with potentially deadly consequences, researchers suggested here.

Despite having achieved a sustained virologic response to therapy, 10% of symptomatic cryoglobulinemic vasculitis still had relapses of symptoms of their disease, said Martin Bonacci, MD, a hepatologist at the Liver and Digestive Diseases Networking Biomedical Research Centre in Barcelona.

"Clinical and particularly immunological response improves significantly over time after hepatitis C virus cure in symptomatic and asymptomatic patients," Bonacci said in his presentation at the International Liver Congress, sponsored by the European Association for the Study of the Liver. "However, 2 years after hepatitis C virus elimination cryoglobulinemia may persist and clinical relapse may occur in a small proportion of patients, suggesting that a longer monitoring of these patients is still warranted."
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Coverage: International Liver Congress

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Thursday, April 12, 2018

The Benefits of Hepatitis C Virus Cure via DAAs: Every Rose Has Thorns

In case you missed it

The Benefits of Hepatitis C Virus Cure: Every Rose Has Thorns
D. Salmon; M. U. Mondelli; M. Maticic; J. E. Arends

J Viral Hepat. 2018;25(4):320-328.

The advent of DAAs has revolutionized the treatment of HCV infection, enabling a cure for most patients. This will result in declining mortality rates due to HCC and to fewer extrahepatic manifestations. However, it will require early treatment of HCV at an individual and population level, with broad access to DAAs. To achieve the collective targets, a radical change is needed, with highly motivated national policies to improve screening and access to care, particularly in high–risk populations.

Abstract
To examine mid–term benefits on hepatic complications, extrahepatic clinical syndromes and quality of life associated with HCV cure; to review the few safety issues linked to oral direct–acting antivirals (DAAs); and to discuss the potential population benefits of reducing the burden of HCV infection. DAAs cure HCV infection in more than 95% of patients. The halting of liver inflammation and fibrosis progression translates into both hepatic and extrahepatic benefits and reduces the need for liver transplantation. A reduction in the frequency of extrahepatic manifestations such as mixed cryoglobulinaemia and vasculitis and improvements in quality of life and fatigue have also been described. A few safety issues linked to DAAs such as the potential recurrence of aggressive HCC, the flares of hepatitis B virus in patients with overt or occult HBV infection are been discussed. Curing HCV infection also has a high potential to reduce the burden of HCV infection at the population level. With widespread scaling up of HCV treatment, several modeling studies suggest that major reductions in HCV prevalence and incidence are possible, and that elimination of viral hepatitis is an achievable target by 2030.

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Wednesday, April 11, 2018

The link between hepatitis C virus and diabetes mellitus: Improvement in insulin resistance after HCV eradication

 https://aasldpubs.onlinelibrary.wiley.com/toc/20462484/11/3
Updates published in Clinical Liver Disease (CLD)
Clinical Liver Disease (CLD) is a digital educational resource published on behalf of the American Association for the Study of Liver Diseases (AASLD).

Radiology in Liver Disease
The link between hepatitis C virus and diabetes mellitus: Improvement in insulin resistance after eradication of hepatitis C virus
Justine Hum M.D. Janice H. Jou M.D., M.H.S.
Pages: 73-76
First Published:6 April 2018
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Abstract
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References

Controversies in HCV Management
Hepatitis C: Who should treat hepatitis C virus? The role of the primary care provider
Tram T. Tran M.D.
Pages: 66-68
First Published:6 April 2018
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Abstract
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Saturday, April 7, 2018

HCV Screening: Important for Rheumatology Patients

HCV Screening: Important for Rheumatology Patients
Cassandra Calabrese, DO, shares her experiences
by Cassandra Calabrese, DO
April 07, 2018
I spent this past week seeing hepatitis C virus (HCV) patients with our hepatologists. Being a rheumatologist, I was looking forward to seeing extrahepatic manifestations of HCV that we read about in textbooks -- cryoglobulinemic vasculitis, sicca syndrome, porphyria cutanea tarda, and many others. I suppose I should not be surprised that the week passed without seeing a single one of these.

While a wide array of extrahepatic manifestations, including may rheumatologic ones, will occur in 40%-70% of chronic HCV patients, the advent of direct-acting antivirals (DAA) has changed HCV outcomes, such that I do not think we will be seeing these cases much longer...

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Other Conditions That May Be Related To HCV

Thursday, March 8, 2018

Neurological manifestation in chronic hepatitis C: Peripheral neuropathy

Research Article
Neurological manifestations in chronic hepatitis C patients receiving care in a reference hospital in sub-Saharan Africa: A cross-sectional study
N. Y. Mapoure , M. N. Budzi, S. A. F. B. Eloumou, A. Malongue, C. Okalla, H. N. Luma

Published: March 7, 2018
https://doi.org/10.1371/journal.pone.0192406

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Abstract Background
Chronic hepatitis C infection is a major public health concern, with a high burden in Sub-Saharan Africa. There is growing evidence that chronic hepatitis C virus (HCV) infection causes neurological complications. This study aimed at assessing the prevalence and factors associated with neurological manifestations in chronic hepatitis C patients.

Methods
Through a cross-sectional design, a semi-structured questionnaire was used to collect data from consecutive chronic HCV infected patients attending the outpatient gastroenterology unit of the Douala General Hospital (DGH). Data collection was by interview, patient record review (including HCV RNA quantification, HCV genotyping and the assessment of liver fibrosis and necroinflammatory activity), clinical examination complemented by 3 tools; Neuropathic pain diagnostic questionnaire, Brief peripheral neuropathy screen and mini mental state examination score. Data were analysed using Statistical package for social sciences version 20 for windows.

Results
Of the 121 chronic hepatitis C patients (51.2% males) recruited, 54.5% (95% Confidence interval: 46.3%, 62.8%) had at least one neurological manifestation, with peripheral nervous system manifestations being more common (50.4%). Age ≥ 55 years (Adjusted Odds Ratio: 4.82, 95%CI: 1.02–18.81, p = 0.02), longer duration of illness (AOR: 1.012, 95%CI: 1.00–1.02, p = 0.01) and high viral load (AOR: 3.40, 95% CI: 1.20–9.64, p = 0.02) were significantly associated with neurological manifestations. Peripheral neuropathy was the most common neurological manifestation (49.6%), presenting mainly as sensory neuropathy (47.9%). Age ≥ 55 years (AOR: 6.25, 95%CI: 1.33–29.08, p = 0.02) and longer duration of illness (AOR: 1.01, 1.00–1.02, p = 0.01) were significantly associated with peripheral neuropathy.

Conclusion
Over half of the patients with chronic hepatitis C attending the DGH have a neurological manifestation, mainly presenting as sensory peripheral neuropathy. Routine screening of chronic hepatitis C patients for peripheral neuropathy is therefore necessary, with prime focus on those with older age and longer duration of illness.

Continue reading: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0192406

Recommended Reading
October 24, 2017
In the past, peripheral neuropathy was believed to be confined to people only infected with hepatitis C-related cryoglobulinemia, but now it is known that peripheral neuropathy may occur even in the absence of cryoglobulinemia.

Of Interest In The Media
Mar 12, 2018

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Tuesday, March 6, 2018

Hepatitis C Virus Eradication by Direct Antiviral Agents Improves Carotid Atherosclerosis in patients with Severe Liver Fibrosis

In case you missed it

J Hepatol. 2018 Mar 2. pii: S0168-8278(18)30132-6. doi: 10.1016/j.jhep.2018.02.015. [Epub ahead of print]

Article in Press
Hepatitis C Virus Eradication by Direct Antiviral Agents Improves Carotid Atherosclerosis in patients with Severe Liver Fibrosis
Salvatore Petta, Luigi Elio Adinolfi, Anna Ludovica Fracanzani, Francesca Rini, Rosalia Caldarella, Vincenza Calvaruso, Calogero Cammà, Marcello Ciaccio, Vito Di Marco, Stefania Grimaudo, Anna Licata, Aldo Marrone, Riccardo Nevola, Rosaria Maria Pipitone, Antonio Pinto, Luca Rinaldi, Daniele Torres, Antonino Tuttolomondo, Luca Valenti, Silvia Fargion, Antonio Craxì

DOI: https://doi.org/10.1016/j.jhep.2018.02.015

Atherosclerosis is a condition in which the arteries become narrow as a result of gradual plaque accumulation. Cholesterol plaque may slowly build up in the carotid artery wall, over decades. The growing plaque may eventually narrow the carotid artery, known as stenosis, and can lead to a stroke.

Highlights

•HCV eradication by direct antiviral agents improves carotid atherosclerosis.
•Atherosclerosis improvement is confirmed after stratification for cardiovascular risk factors.
•Atherosclerosis improvement is observed in patients with and without cirrhosis.

Abstract
Background and Aim
Recent studies suggest an association between HCV infection and cardiovascular damage, including carotid atherosclerosis, with a possible effect of HCV clearance on cardiovascular outcomes. We aimed to examine whether HCV eradication by direct antiviral agents (DAA) improves carotid atherosclerosis in HCV-infected patients with advanced fibrosis/compensated cirrhosis.

Materials and Methods
One hundred eighty-two consecutive HCV patients with advanced fibrosis or compensated cirrhosis were evaluated by virological, anthropometric and metabolic measurements. All patients underwent DAA-based antiviral therapy according to AISF/EASL guidelines. Intima-media thickness (IMT), carotid thickening (IMT≥1 mm) and carotid plaques, defined as focal thickening of ≥ 1.5 mm at the level of common carotid, were evaluated by ultrasonography (US) at baseline and 9-12 months after the end of therapy.

Results
Fifty-six percent of patients were males, mean age was 63.1±10.4 years and 65.9% had compensated cirrhosis. One patient out of five had diabetes, 14.3% were obese, 41.8% had arterial hypertension and 35.2% were smokers. Mean IMT was 0.94±0.29 mm, 42.9% had IMT≥1 mm, and 42.9% had carotid plaques. All patients achieved a 12-weeks sustained virological response. IMT significantly decreased from baseline to follow-up (0.94±0.29 mm vs. 0.81±0.27, p<0.001). Consistently, a significant reduction in the prevalence of patients with carotid thickening from baseline to follow-up was observed (42.8% vs. 17%, p<0.001), while no changes were reported for carotid plaques (42.8% vs. 47.8%, p=0.34). These results were confirmed in sub-groups of patients stratified for cardiovascular risk factors and liver disease severity.

Conclusion
HCV eradication by DAA improves carotid atherosclerosis in patients with severe fibrosis without or with additional metabolic risk factors. The impact of this improvement in the atherosclerotic burden in terms of reduction of major cardiovascular outcomes is worth investigating in the long term.

Lay of Summary
Hepatitis C Virus (HCV) eradication by direct antiviral agents improves carotid atherosclerosis in patients with advanced fibrosis/compensated cirrhosis

The improvement in intima-media thickness and carotid thickening was confirmed after stratification for severity of liver disease and cardiovascular risk factors

HCV eradication by DAA also lead to improvement in glucose homeostasis and increase in cholesterol levels

Of Interest:
HCV eradication with DAAs improves carotid thickening
March 6, 2018
Hepatitis C eradication by direct-acting antivirals improved carotid atherosclerosis in patients with severe fibrosis regardless of the presence of additional metabolic…

Evolving Recognition of Chronic Hepatitis C Infection as a Modifiable Risk Factor for cardiovascular disease (CVD)
Increasingly, data have amassed exploring whether HCV infection acts as an independent risk factor for cardiovascular diseases. However, the results are conflicting and have led to some ambiguity.

Risk of Cardiovascular Disease (CVD) Due to Chronic Hepatitis C Infection: A Review
The current data support the assertion that CHC infection increases the risk of subclinical and likely clinical CVD, through a multifactorial cascade which may include direct and indirect immune and inflammatory effects, metabolic derangements and possibly direct cardiotropism exhibited by the HCV virus. There is an urgent need for translational research to delineate these proposed mechanisms for the apparent association between HCV and CVD. Additionally, more prospective cohort studies conducted in different patient populations are needed to confirm the findings of HCV infection and increased subclinical and clinical CVD. Furthermore, larger, well-designed therapeutic studies are critical to establish whether CHC truly increases CVD risk and to evaluate if HCV treatment can attenuate or even eliminate that increased CVD risk. The promise of large-scale HCV therapy ushered in by the highly efficacious and well tolerated DAAs has arrived, and therefore understanding the relationship between HCV and CVD and how this relationship is affected by HCV eradication with treatment has substantial public health implications.

Hepatitis C Virus Infection and Cardiovascular Disease Risk
A strong association between HCV infection and immune-related disorders, such as cryoglobulinemia, and metabolic alterations, such as insulin resistance, has been demonstrated. More recent evidence suggests HCV infection is linked to an increased risk for cardiovascular disorders. Whether a relationship between HCV infection and cardiovascular disease exists may have important implications for HCV treatment.

Infectious Disease Advisor spoke with David E. Bernstein, MD, from the Hofstra-Northwell School of Medicine, and Vincent Lo Re, MD, MSc, from the Perelman School of Medicine at the University of Pennsylvania, regarding the link between HCV infection and cardiovascular disease.
Continue reading....

Monday, March 5, 2018

Outcomes - HCV psoriatic patients using Pegylated Interferon plus Ribavirin compared to new Direct-Acting Antiviral agents

World J Hepatol. Feb 27, 2018; 10(2): 329-336
Published online Feb 27, 2018. doi: 10.4254/wjh.v10.i2.329

Outcomes assessment of hepatitis C virus-positive psoriatic patients treated using pegylated interferon in combination with ribavirin compared to new Direct-Acting Antiviral agents
Giovanni Damiani, Chiara Franchi, Paolo Pigatto, Andrea Altomare, Alessia Pacifico, Stephen Petrou, Sebastiano Leone, Maria Caterina Pace, Marco Fiore

Core tip: Psoriasis is a chronic inflammatory disease affecting approximately the 2% of population in Europe and North America. The hepatitis C virus (HCV) infection affects approximately the 3% of the world population with an estimated prevalence of 5 million people in the United States. Up to 0.06% of people in the United States suffer from both psoriasis and HCV. Psoriatic patients with HCV are excluded by randomized controlled clinical trials. Therefore, no data is currently available concerning the concomitant administration of biological disease modifying drugs and the new Direct-Acting Antiviral agents (DAAs) medications approved for the treatment of HCV infection. The aim of this study is to evaluate the outcomes in biological treatment and quality of life of psoriatic patients with HCV infection treated with DAAs compared to the previous standard therapy of Pegylated Interferon plus Ribavirin.

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AIM
To evaluate the outcomes in biological treatment and quality of life of psoriatic patients with chronic hepatitis C (CHC) treated with new Direct-Acting Antiviral agents (DAAs) compared to pegylated interferon-2α plus ribavirin (P/R) therapy.

METHODS
This is a retrospective study involving psoriatic patients in biological therapy who underwent anti-hepatitis C virus (HCV) treatment at the Department of Dermatology Galeazzi Orthopaedic Institute Milan, Italy from January 2010 to November 2017. The patients were divided into two groups: patients that underwent therapy with DAAs and patients that underwent HCV treatment with P/R. Patients were assessed by a dermatologist for psoriasis symptoms, collecting Psoriasis Area Severity Index (PASI) scores and the Dermatology Quality of Life Index (DLQI). PASI and DLQI scores were evaluated 24 wk after the end of HCV treatment and were assumed as an outcome of the progression of psoriasis. Switching to a different bDMARD was considered as an inadequate response to biological therapy. The dropout of HCV therapy and sustained virological response (SVR) were considered as outcomes of HCV therapy.

RESULTS
Fifty-nine psoriatic patients in biological therapy underwent antiviral therapy for CHC. Of this, 27 patients were treated with DAAs and 32 with P/R. After 24 wk post treatment, the DLQI and the PASI scores were significantly lower (P < 0.001 and P < 0.005, respectively) in the DAAs group compared with P/R group. None of the patients in the DAAs group (0/27) compared to 8 patients of the P/R group (8/32) needed a shift in biological treatment.

CONCLUSION
DAAs seem to be more effective and safe than P/R in HCV-positive psoriatic patients on biological treatment. Fewer dermatological adverse events may be due to interferon-free therapy.

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