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

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.

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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.

Full Text
Online
PDF

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.

Full Text : https://www.wjgnet.com/1948-5182/full/v10/i2/329.htm

Friday, March 2, 2018

Monday, February 12, 2018

Is global elimination of HCV realistic?

Liver International 
Is global elimination of HCV realistic?
Vincenza Calvaruso, Salvatore Petta, Craxì A
DOI: 10.1111/liv.13668

First published: 10 February 2018

Online:

Abstract
The elimination of hepatitis C virus (HCV) has been made possible through the availability of new antiviral drugs which may now be administered to all patients with HCV infection, even those with decompensated cirrhosis. The goal of the World Health Organization (WHO) is to reduce the incidence of chronic hepatitis infection from the current 6-10 million to 0.9 million cases of chronic infections by 2030, and annual deaths from 1.4 million to fewer than 0.5 million. Achieving these targets will require full implementation of epidemiological knowledge of HCV infection, screening and testing practices and strategies to link HCV patients to care. This review will focus on the current state of knowledge in the epidemiology of HCV and what can be done to increase patient awareness and reduce the barriers to treatment. Furthermore, we will discuss the role of HCV clearance on the control of HCV-related outcomes

Monday, February 5, 2018

Managing the Fruits of HCV Cure: How Much Care do the Cured Need?

In case you missed it

The following article appeared in the January/February print edition of HCV NEXT, provided online at Healio

Editorial
Managing the Fruits of HCV Cure: How Much Care do the Cured Need?

The feature by Eric Lawitz, MD, very nicely encapsulates the revolutionary changes occurring within hepatitis C therapy over the past few years. As he explains, this extraordinary newfound ability to cure almost all patients with chronic HCV raises many questions about clinical outcomes.

We’ve felt strongly for years that it was unjust to deny therapy to patients who didn’t have “sufficiently advanced scarring of the liver to warrant treatment” — a cost-based position that was anathema to most clinicians and patients. Today, there’s a wealth of literature showing fibrosis progression stabilizes or reverses after achieving SVR. Even patients with cirrhosis may have regression of cirrhosis after SVR. But an additional dimension of HCV infection about which our knowledge has dramatically expanded is the potential for extrahepatic morbidity and mortality associated with HCV infection, and the opportunity to ameliorate or prevent such outcomes by effecting virologic cure — problems such as diabetes, atherosclerosis, renal disease, cryoglobulinemia, lymphoma and others.

Monday, January 29, 2018

Impact of hepatitis C virus infection on long-term mortality after acute myocardial infarction

BMJ Open. 2018 Jan 26;8(1):e017412. doi: 10.1136/bmjopen-2017-017412.

Impact of hepatitis C virus infection on long-term mortality after acute myocardial infarction: a nationwide population-based, propensity-matched cohort study in Taiwan.
Kuo SH1, Hung WT1, Tang PL1, Huang WC1,2,3, Yang JS2, Lin HC1, Mar GY1, Chang HT1, Liu CP1,3.

Myocardial infarction , commonly known as a heart attack, occurs when blood flow decreases or stops to a part of the heart, causing damage to the heart muscle. 

Abstract
INTRODUCTION:
The influence of hepatitis C virus (HCV) infection on long-term outcomes of patients with acute myocardial infarction (AMI) is unclear. Therefore, this study aimed to analyse the impact of HCV infection on 12-year mortality rates after AMI using data from the Taiwan National Health Insurance Research Database (NHIRD).

METHODS:
NHIRD data for approximately 23 000 000 patients between January 2000 and December 2012 were analysed. A total of 186 112 cases of first AMI admission were identified. A total of 4659 patients with HCV infection not receiving interferon therapy were enrolled and divided into those with (n=107) or without (n=4552) cirrhosis. Using one-to-one matching, 4552 matched controls were included in the final analysis.

RESULTS:
The 12-year mortality rate was significantly higher in patients with AMI with HCV infection and cirrhosis than in those with HCV infection but without cirrhosis (P<0.0001) or controls (P<0.0001). Patients with HCV infection but without cirrhosis had significantly higher long-term mortality rates than the matched controls (P<0.0001). The HR for mortality was higher in patients with HCV infection (HR 1.12; 95% CI 1.06 to 1.18). HCV influenced outcomes among the subgroups of patients who were male (HR 1.15) and those who had hypertension (HR 1.14).

CONCLUSIONS:
HCV infection influenced the 12-year mortality rates of patients with AMI, especially those who were male and those who had hypertension. Cirrhosis further increased the long-term mortality rates of patients with AMI with HCV infection.

Link
View full text article online: http://bmjopen.bmj.com/content/8/1/e017412

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Wednesday, January 24, 2018

Treating Insulin Resistance in Hepatitis C-Infected Patients With Diabetes

Treating Insulin Resistance in Hepatitis C-Infected Patients With Diabetes
Elizabeth Kukielka, PharmD
Publish Date: Wednesday, January 24, 2018
Both insulin resistance (IR) and type 2 diabetes mellitus (T2DM) are more prevalent in patients with chronic hepatitis C virus (HCV) infection compared with the general population. 
As this is one of the first studies to demonstrate the benefit of treating HCV-positive patients who also have IR with both standard HCV therapy and metformin to achieve SVR, more studies are needed to confirm the results and help determine a standard regimen for patients with HCV and IR, researchers noted.

Full Text

Thursday, January 18, 2018

Editorial: direct-acting antivirals significantly improve quality of life in patients with HCV

INVITED EDITORIALS

Editorial: direct-acting antivirals significantly improve quality of life in patients with hepatitis C virus infection 
Authors S. Sanagapalli, M. Danta

First published: 17 January 2018
DOI: 10.1111/apt.14467

Abstract
Linked Content
This article is linked to Younossi et al and Younossi papers. To view these articles visit https://doi.org/10.1111/apt.14423 and https://doi.org/10.1111/apt.14481.

The effect of direct-acting antiviral chronic Hepatitis C (HCV) therapies on patients’ quality of life has been a topic of minor attention compared with their impressive effects on virological endpoints. Yet, therapeutic benefits on quality of life are important to patients, and knowledge regarding such benefits may be an important tool in improving compliance in real-world scenarios.[1] For this reason, Younossi and colleagues are to be commended for their study, which describes clinically significant improvements in almost all measured physical and mental health-related quality of life outcomes following therapy with sofosbuvir and velpatasvir with or without voxilaprevir.[2] This replicates findings from other direct-acting antiviral regimens, but also confirms our own observations from clinical experience using these drugs.

Comparison with quality of life data from the interferon era may help us to tease out the mechanisms behind these findings. First, impairments in both mental and physical aspects of quality of life have long been described in chronic HCV, with or without cirrhosis, using the SF-36, one of the four instruments used in this study.[3] Second, very similar improvements in quality of life parameters were described 24 weeks after completion of interferon-based therapy, with the benefit confined only to those with sustained virological response.[4] More recent data comparing interferon-containing to interferon-free regimens clearly demonstrates that while both regimens result in equivalent improvements in quality of life (in responders) post therapy, the interferon-containing treatments are associated with significant worsening of quality of life during therapy. In contrast, quality of life seems to be improved early during interferon-free therapy and improves further following completion of successful treatment.[5, 6] Taken cumulatively we can infer that virological clearance plays a key role in improvement of quality of life, but cannot be the only factor, since improvement continues long after the virus has completely cleared from the serum.

What might such other factors be? The authors propose that improvement of liver function may play a role, though this still fails to explain the persistent improvement in benefit in non-cirrhotics post therapy. On the other hand, cerebral inflammation due to chronic HCV may explain some of the findings. Magnetic resonance spectroscopy and positron emission tomography scanning have demonstrated significant metabolic abnormalities in the brains of noncirrhotics with HCV, implying a low-grade inflammatory state, with the microglial cells being a focus of activation.[7, 8] In a small study, Byrnes and colleagues demonstrated that successful treatment with pegylated interferon and ribavirin led to normalisation of these central nervous system metabolic changes. Crucially, however, normalisation occurred gradually and improvement in metabolic abnormalities continued until 12 weeks post therapy, implying that the neuroinflammatory process may take time to settle after HCV therapy.[9] While the underlying mechanisms for improved quality of life are of interest, this study adds to the weight of evidence for the overall benefits of direct-acting antiviral therapies for HCV.
http://onlinelibrary.wiley.com/doi/10.1111/apt.14467/full

Editorial: direct-acting antivirals significantly improve quality of life in patients with hepatitis C virus infection—Author's reply
Z. M. Younossi

First published: 17 January 2018
DOI: 10.1111/apt.14481

Abstract
Linked Content
This article is linked to Younossi et al and Sanagapalli and Danta papers. To view these articles visit https://doi.org/10.1111/apt.14423 and https://doi.org/10.1111/apt.14467.

We appreciate the Editorial comments by Drs. Sanagapalli and Danta about our recent study reporting patient-reported outcomes in patients with hepatitis C virus infection who were treated with sofosbuvir (SOF), velpatasvir (VEL) with or without voxilaprevir (VOX).[1, 2] We agree with their comments and would like to emphasise the importance of these findings in the context of the “comprehensive benefit” of HCV cure.

To fully understand the comprehensive benefit of HCV treatment, we believe it is important to assess the comprehensive impact of HCV infection including all the pertinent clinical consequences (hepatic and extrahepatic manifestations of HCV infection), the impact on patient-reported outcomes (health-related quality of life or HRQL) and the economic burden of HCV (resource utilisation and cost of illness).[3] Similarly, the benefit of anti-HCV treatment must be assessed in this comprehensive manner.[3] The most clinically relevant endpoint of HCV treatment is achieving sustained virologic response (SVR), a surrogate of improving survival by reducing the hepatic and extrahepatic complications.[3] Another important endpoint of HCV treatment should be its positive impact on patient-reported outcomes, a surrogate of HCV patients' experience.[4] Finally, we must assess the impact of anti-HCV treatment on important economic outcomes (resource utilisation, cost of illness, cost-effectiveness of treatment) must also be assessed.[5] Although the total impact of HCV infection has been well established,[3, 6] the comprehensive benefit of “HCV cure” has only recently been recognised.[1-6] In this context, our study provides additional evidence that the new regimen of SOF/VEL+/-VOX not only has superior clinical outcomes (high SVR) but also improves patient-reported outcomes during treatment and after SVR.[2]

In their Editorial, the authors have reflected about the mechanism of patient-reported outcome improvement post-SVR-12; we agree that this improvement is partly related to viral eradication. It is plausible that the additional patient-reported benefits of SVR may be related to the amelioration of the inflammatory environment of chronic hepatitis, which takes longer to resolve. This “inflammatory milieu” of HCV infection may exert its influence on the brain or the periphery of the infected patients. In fact, HCV has been associated with a number of extrahepatic manifestations such as neuropsychiatric diseases, chronic fatigue and others.[7, 8] In this context, neurocognition, fatigue and their changes after SVR may be differentially affected which in turn can influence changes in patient-reported outcome scores.[7, 8] In fact, the impact of SVR on fatigue has been recently substantiated and the data have shown that while most patients with HCV improve fatigue scores post-SVR, some do not improve.[9] Furthermore, these subjects who continue to report disabling fatigue post-SVR seem to have significant comorbidities such as depression, anxiety, type 2 diabetes.[9] Nevertheless, in the majority of HCV subjects with SVR, fatigue continues to improve and seems to maximise by post-treatment week 48.[10]

In summary, we believe that the initial patient-reported outcome improvements are due to viral eradication. The subsequent improvement may be due to a number of post-SVR changes including improvement of the inflammatory milieu and its impact of HCV on the brain and other extrahepatic targets. In contrast, patients with HCV who continue to show residual patient-reported outcome impairments post-SVR seem to have other comorbidities, which will require other treatment modalities to optimise their well-being. In this context, we believe that patient-reported outcomes must be a routine part of assessment of any chronic liver disease. These assessments will complement the clinical outcomes and provide evidence for the comprehensive impact of treatment on the patients and the society.

Friday, December 29, 2017

Direct medical costs associated with the extrahepatic manifestations of Hep C

In Case You Missed It

Direct medical costs associated with the extrahepatic manifestations of Hep C
January's issue of the Alimentary Pharmacology & Therapeutics examines the direct medical costs associated with the extrahepatic manifestations of hepatitis C virus infection.

Volume 47, Issue 1
January 2018
Pages 123–128

The economic impact of extrahepatic manifestations of hepatitis C virus (HCV) infection remains unknown for France. Dr Cacoub and colleagues from France estimated the prevalence of extrahepatic manifestations of HCV and the direct medical costs associated with them.

Estimates of 13 extrahepatic manifestations prevalence were obtained from a retrospective data analysis of HCV-infected patients in a specialized center, and the baseline prevalence in the general French population, and an international systematic review.

The impact of achieving HCV cure after anti-viral therapy was applied to the French healthcare costs. Using the first approach, the team found increased prevalence rates in HCV patients compared to the general population were observed for most extrahepatic manifestations.

The researchers observed that the mean per-patient-per-year cost of these manifestations in the tertiary centre was 3296 €. In France, HCV-extrahepatic manifestations amounted to a total cost of 215 million € per year.

Using a systematic review, the team found that the mean per-patient-per-year cost was estimated to be 1117 €. The estimated total cost reduction in France associated with HCV cure was 13.9 million € for diabetes, 8.6 million € for cryoglobulinemia vasculitis, 6.7 million € for myocardial infarction, 2.4 million € for end-stage renal disease and 1.4 million € for stroke.

Dr Cacoub's team concludes, "Extrahepatic manifestations of HCV infection substantially add to the overall economic burden of the disease in France." "HCV cure after anti-viral therapy is expected to significantly reduce the total costs of managing these manifestations in France."
Aliment Pharmacol Ther 2017: 47(1): 123–128
22 December 2017

Direct medical costs associated with the extrahepatic manifestations of hepatitis C virus infection in France
P. Cacoub, M. Vautier, A. C. Desbois, D. Saadoun, Z. Younossi
First published: 18 October 2017

Introduction
Patients chronically infected by the hepatitis C virus (HCV) are at risk of developing major liver complications.[1] Up to two-thirds of HCV-infected patients also experienced extrahepatic manifestations that include HCV-related autoimmune and/or lymphoproliferative disorders, and cardiovascular, renal, metabolic and central nervous system diseases.[2-7] The link between extrahepatic manifestations and HCV infection has been demonstrated for many years for lymphoproliferative disorders (mixed cryoglobulinemia, lymphoma), whereas it became more recently evident for cardiovascular, renal and metabolic diseases.[4, 5] Nevertheless, HCV infection showed higher morbidity and mortality rates for extra-hepatic complications, while viral eradication reduced the rate of extra-hepatic complications and deaths.[3, 5]

New oral, interferon-free direct-acting anti-virals (DAA) offer opportunities to cure most patients.[1] Sofosbuvir plus ledipasvir has been shown to improve patient-reported outcomes after achieving sustained virological response (SVR).[8-10] As new all-oral interferon-free DAA regimens for HCV are approved, their effectiveness in a real-world setting and their economic impact on health systems and society require further assessment. Previous analyses have typically focused on the hepatic complications of HCV infection and have not considered the burden of extra-hepatic manifestations.[8, 11] There is a need to accurately characterise the burden of extrahepatic manifestations in HCV-infected patients, and the impact of achieving a SVR on the costs of managing these manifestations outside the United States.[12] The objective of this study was to estimate the annual direct medical costs associated with the extrahepatic manifestations of HCV infection in France.


Recommended Reading
Extrahepatic manifestations of HCV & Treatment

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

Tuesday, December 12, 2017

Impact of HCV eradication on insulin resistance (IR), and the control of type 2 diabetes.

What We Know
Achieving Sustained Virologic Response (SVR) in patients treated with direct-acting antivirals (DAAs) is associated with the reversal of fibrosis, reduces the risk of liver transplant, liver cancer, and risk of other complications of chronic liver disease, including extrahepatic manifestations of HCV. The hepatitis C virus is associated with various extrahepatic manifesations, some of these include systemic manifestations such as thyroid disease, cardiovascular disease, renal disease, eye disease (sicca syndrome), skin disease (PCT, vasculitis, and lichen planus), lymphomas, and type II diabetes mellitus. As for the latter, previous research has demonstrated a significant association between hepatitis C - type 2 diabetes - and insulin resistance.

The Stats
According to The World Health Organization (WHO) people infected with HCV are at risk for liver related complications, worldwide around 399 000 people die each year from hepatitis C, mostly from cirrhosis and hepatocellular carcinoma.

Extrahepatic Consequences of HCV
However, because these estimates do not included extrahepatic consequences of HCV infection the risks of morbidity and mortality are underestimated, according to a systematic review investigating the relationship between HCV infection and glucose abnormalities; Diabetes mellitus, insulin resistance and hepatitis C virus infection: A contemporary review, published in World J Gastroenterol.

New In The Journals
Learn more about the impact of HCV eradication on insulin resistance (IR), and the control of type 2 diabetes by viewing this collection of recent articles.

Journal of Medical Virology
Volume 90, Issue 2 February 2018 Pages 320–327
RESEARCH ARTICLE
Authors Alessia Ciancio, Roberta Bosio, Simona Bo, Marianna Pellegrini, Marco Sacco, Edoardo Vogliotti, Giulia Fassio, Andrea G. F. Bianco Mauthe Degerfeld, Monica Gallo, Chiara Giordanino, Lodovico Terzi di Bergamo, Davide Ribaldone, Elisabetta Bugianesi, Antonina Smedile, Mario Rizzetto, Giorgio Maria Saracco
First published: 14 November 2017
Full publication history DOI: 10.1002/jmv.24954
Abstract
Many studies showed insulin resistance amelioration in HCV-patients achieving Sustained Virologic Response (SVR) but results on glycemic control in diabetic patients are unclear. This study aimed to assess fasting glucose (FG) and glycated hemoglobin (HbA1c) values before and after therapy with direct-acting antivirals (DAAs) in HCV-patients with type 2 diabetes mellitus (T2DM). Of the 122 consecutively recruited patients with chronic hepatitis C and T2DM, 110 patients were treated with DAAs and 12 remained untreated. Clinical, biochemical, virological, and metabolic features were collected both at baseline and at 12 weeks after the end of therapy (EOT) or after a comparable period of time in untreated patients. A total of 101 patients obtained a SVR (Group 1), while nine were relapsers. Group 2 (21 patients) was composed by the nine relapsers and the 12 untreated patients. A significant reduction of mean FG (134.3 ± 41.32 mg/dL vs 152.4 ± 56.40 mg/dL, P = 0.002) and HbA1c values (46.51 ± 16.15 mmoL/moL vs 52.15 ± 15.43 mmoL/moL, P <  0.001) was found in Group 1 but not in Group 2 (140.6 ± 47.87 mg/dL vs. 145.31 ± 30.18 mg/dL, P = 0.707, and 55.31 ± 20.58 mmoL/moL vs. 53.38 ± 9.49 mmoL/moL, P = 0.780). In Group 1, 20.7% of patients could reduce or suspend their antidiabetic therapy compared to none in Group 2 (P = 0.03), despite the significant weight increase observed in Group 1. SVR induced a significant amelioration of glycemic control in diabetic HCV-patients, despite a significant weight increase; larger prospective studies are needed to verify whether these results are maintained over the long-term.
View Full Text Article: Downloaded and shared by @HenryEChang on Twitter

Journal of Gastroenterology and Hepatology
Luigi E Adinolfi,Riccardo Nevola,Barbara Guerrera,Giovanni D’Alterio,Aldo Marrone,Mauro Giordano, Luca Rinaldi
Accepted manuscript online: 11 December 2017
DOI: 10.1111/jgh.14067
Abstract Background and Aim
Chronic hepatitis C (HCV), particularly genotype 1, is associated with insulin resistance (IR) and diabetes. We evaluated the impact of HCV clearance by all-oral direct-acting antiviral (DAAs) treatments on IR and glycemic control.

Methods
Included in this prospective case-control study were 133 consecutive HCV-genotype 1 patients with advance liver fibrosis (F3-F4) without type 2 diabetes. Sixty-eight treated with DAAs and 65 untreated. Liver fibrosis was assessed by transient elastography. Pre-, end- and 3 months post-treatment withdrawal IR homeostasis was assessed by HOMA-IR, QUICKI and HOMA-B.

Results
At baseline, treated and untreated patients showed similar liver fibrosis levels, HOMA-IR was 4.90±4.62 and 4.64±5.62, respectively. HOMA-IR correlated with HCV RNA levels. At the end of treatment, all patients cleared HCV RNA, regardless of liver fibrosis and BMI, a reduction in HOMA-IR at 2.42±1.85 was showed (p<0.001), in addition, increased insulin sensitivity, decreased insulin secretion, reduction of serum glucose and insulin levels were observed. Data were confirmed 3 months after treatment withdrawal in the 65 patients who cleared HCV. No variation occurred in untreated patients. Overall, 76.5% of SVR patients showed IR improvements, of which 41.2% normalized IR. Improvement of IR was strict associated with HCV clearance, however, patients with the highest levels of fibrosis remain associated with some degree of IR.

Conclusions
The data underline a role of HCV in development of IR and that viral eradication reverses IR and improves glycemic control and this could prevent IR-related clinical manifestations and complications.
Subscription required to view full text article

Diabetes Care
Diabetes Care 2017 Sep - Justine Hum,1 Janice H. Jou,1 Pamela K. Green,2 Kristin Berry,2 James Lundblad,3 Barbara D. Hettinger,3 Michael Chang,1 and George N. Ioannou2,4 1Division of Gastroenterology, Portland Veterans Affairs Medical Center, Portland, OR 2Health Services Research and Development, Veterans Affairs Puget Sound Healthcare System, Seattle, WA 3Division of Endocrinology, Portland Veterans Affairs Medical Center, Portland, OR 4Division of Gastroenterology, Veterans Affairs Puget Sound Healthcare System and University of Washington, Seattle, WA

Hepatitis C virus (HCV) infection is associated with diabetes and may worsen glycemic control in patients with diabetes. We aimed to investigate whether eradication of HCV infection with direct-acting antiviral (DAA) agents is associated with improved glycemic control in patients with diabetes.

In summary, glycemic control improves in patients with diabetes after DAA-induced SVR. Patients not only have an improvement in HbA1c level after achieving SVR, they are also less likely to require insulin. These endocrine benefits of SVR provide additional justification for considering antiviral treatment in all patients with diabetes. ....hepatitis C virus (HCV) infection is associated with a higher prevalence of type 2 diabetes mellitus (T2DM) . In addition, HCV proteins increase the release of proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-α, which then upregulate gluconeogenesis and enhance lipid accumulation in the liver

Future studies are needed to confirm our findings, to determine how durable the SVR-induced improvement in glycemic control is over time, and to assess the long-term effect on complications of diabetes such as nephropathy, neuropathy, and cardiovascular disease.
View Full Text Article: Available at NATAP

Medpage Today
Commentary: Improvement in Glycemic Control of Type 2 Diabetes After Successful Treatment of Hepatitis C Virus
Researchers at the VA health system—the largest provider of integrated hepatitis C care in the country—recently tested the role of viral eradication on the control of type 2 diabetes
By Kristin Bundy
Researchers at the VA health system—the largest provider of integrated hepatitis C care in the country—recently tested the role of viral eradication on the control of type 2 diabetes (T2D). Previous data demonstrated that the risk of developing T2D is about 4 times higher in people infected with the hepatitis C virus (HCV) than those without. Investigators wanted to know: Could HCV suppression lead to better control of T2D?
Continue reading: Available at Medpage Today

Nature - Scientific Reports
Yun Soo Hong, Yoosoo Chang, Seungho Ryu, Miguel Cainzos-Achirica, Min-Jung Kwon, Yiyi Zhang, Yuni Choi, Jiin Ahn, Sanjay Rampal, Di Zhao, Roberto Pastor-Barriuso, Mariana Lazo, Hocheol Shin, Juhee Cho & Eliseo Guallar
doi:10.1038/s41598-017-04206-6
Published online:04 2017
In conclusion, in this large study of men and women at low risk of diabetes, we found that serologic evidence of HBV and HCV infection was associated with the prevalence of diabetes. In addition, HBV infection was associated with the risk of incident diabetes in prospective analyses, but we could not reliably evaluate the prospective association between HCV infection and diabetes due to the small number of infected participants. Our studies add to the growing body of evidence suggesting that diabetes is an additional metabolic complication of HBV and HCV infection.

On This Blog