Tuesday, October 31, 2017

HCV treatment in patients with decompensated liver disease

CLD Updates
Clinical Liver Disease (CLD) is a digital educational resource published on behalf of the American Association for the Study of Liver Diseases (AASLD). CLD publishes easy to read reviews on relevant topics for clinicians diagnosing and managing patients with liver disease. Each article is accompanied by a podcast audio version, and a video interview with the author to help emphasize the key teaching points for a clinical audience.

Volume 10 Issue 4 Issue Publication: October 2017

HCV treatment in patients with decompensated liver disease
Authors Elizabeth C. Verna First Published: 31 October 2017Vol: 10 
Pages: 83–86DOI: 10.1002/cld.663
Abstract
Full Text (HTML)
PDF (189.7KB)
PDF (189.7KB)
References
Watch a video presentation of this article

Controversies in hepatitis C therapy: Reactivation of hepatitis B virus
Authors Sarah R. Lieber, Michael W. Fried
First Published: 31 October 2017 Vol: 10, Pages: 87–92 DOI: 10.1002/cld.665

VA's Updated - Chronic Hepatitis C Virus Infection:Treatment Considerations

Shared by @HenryEChang via Twitter

Chronic Hepatitis C Virus (HCV) Infection: Treatment Considerations from the Department of Veterans Affairs National Hepatitis C Resource Center and the HIV, Hepatitis, and Related Conditions Program in the Office of Specialty Care Services

This revision ( October 18 , 2017 ) incorporates updates to treatment regimens for chronic hepatitis C virus (HCV) infection, genotype s 1 -4, including re-treatment of patients who previously failed direct -acting antiviral therapy. A new table (Table 4) , “HCV Direct -Acting Antiviral Agents by Drug Class ” has been added. The section on “ Interpretation of Resistance -Associated Substitutions” has been revised , as have tables showing drug- drug interaction s to provide clinicians with guidance on the concomitant use of HCV drugs and other drugs, including HIV antiretroviral agents ( Table 23 and Table 24 ). The Panel continues to recommend that HIV/HCV-coinfected patients receive the same HCV antiviral regimen s as HCV - monoinfected patients unless ledipasvir/sofosbuvir is being considered, in which case a 12 -week regimen should be used (instead of an 8 -week regimen) . The previous revision included HBV testing and monitoring recommendations prior to starting HCV DAA , which can be found in Appendix D.

View: Updated Treatment considerations 

Living With HCV Or Chronic Liver Disease? Updated Videos From Advocate Karen Hoyt

Sometimes it's nice to have a place to call your own, a place that feels very much like home. Karen Hoyt has created such a place some six years ago, a safe haven with a candid look at liver disease from a patients prospective, called: I Help C.

Karen shares her own journey living with cirrhosis and liver cancer, to the emotional ups and downs of her lifesaving liver transplant. If you haven't found Karen yet, she is a master at providing patient-friendly diet and lifestyle tips for liver disease patients, filling a much needed void for people living with the hepatitis C virus (HCV) and fatty liver disease.

While we have effective drugs to cure HCV, in little as twelve to eight weeks, across all six HCV genotypes, including treatment options for people with severe liver damage, such as compensated cirrhosis, not everyone - was or is - diagnosed with HCV before serious liver damage occurs. According to a study published in Clinical Infectious Diseases and presented at CROI 2015, a substantial number of baby boomers are living with advanced liver disease. In data collected between 2010-2013, researchers reported in 2013, close to half of people born during 1945-1965 had severe fibrosis or cirrhosis. In addition, in a prospective study presented at this months Liver Meeting, close to half of people with hepatitis C, who achieved SVR (cure), were found to have fatty liver disease. The article was recently published over at Medscape.

Karen's Been Busy 
A series of  new videos is now available on Karen's YouTube channel. You'll find each video informative; from haircare tips to serious topics such as ascites, hepatic encephalopathy and other liver-related complications. Not that haircare isn't a serious topic, nuff said!

To help guide you through a well-balanced diet, which is essential to help fight or curtail liver damage, Karen published: The Liver Loving Diet. The book is a labor of love, a huge undertaking for someone dealing with Hepatic Encephalopathy (HE), a serious disorder that can happen without warning if you have advanced liver disease, causing confusion, brain fatigue (brain fog) and problems with hand movements, making concentration and typing difficult. Get to know Karen better by reading an excerpt from her book: Emergency Room Diagnosis with Liver Cirrhosis.

In this uncertain world, there are few people who help others without expecting something in return. In her own modest way, with an open heart, Karen is determined to improve the lives of people struggling with liver disease, an act of kindness that does not go unnoticed.

MSF Issue Brief: Not even close - Reasons underlying the continued lack of access to HCV treatment are discussed

MSF Issue Brief: Not even close

https://reliefweb.int/report/world/msf-issue-brief-not-even-close
Worldwide, an estimated 71 million people have chronic hepatitis C virus (HCV) infection, 72 per cent of whom live in low- and middle-income countries. HCV is a blood-borne virus that can lead to cirrhosis, liver failure and liver cancer, as well as a range of systemic health problems. In 2015, more people were newly infected with HCV than were treated for it (1.75 million versus 1.1 million), and more than 490,000 people died from HCV-related complications. Estimates indicate that only 2.1 million people had been treated with newer sofosbuvir-based treatment regimens as of the end of 2016, leaving 68.9 million people waiting for access to safer, more tolerable and more effective direct-acting antivirals (DAAs) to treat their HCV.

This issue brief provides information on currently available HCV diagnostics and treatments, including pricing and registration information from manufacturers of DAAs. Reasons underlying the continued lack of access to HCV treatment are discussed, including delayed scale-up by governments, intellectual property barriers, regulatory challenges and high prices.

Download PDF (988.16 KB)
Report - https://reliefweb.int/report/world/msf-issue-brief-not-even-close

World Hepatitis summit
MSF secures generic hepatitis C treatment at $120 compared to $147,000 launch price tag
Close to 3 million people access hepatitis C cure

MSF secures generic hepatitis C treatment at $120 compared to $147,000 launch price tag

MSF secures generic hepatitis C treatment at $120 compared to $147,000 launch price tag
Report from Médecins Sans Frontières

Tuesday, October 31, 2017 — Dramatic price drops should allow countries to provide treatment for millions of people

Reading Material: Not Even Close: This issue brief provides information on currently available HCV diagnostics and treatments, including pricing and registration information from manufacturers of DAAs www.msfaccess.org/hep-c-not-even-close

Geneva/Sao Paolo, 31 October 2017—On the eve of the World Hepatitis Summit in Sao Paolo, the international medical humanitarian organization Médecins Sans Frontières (MSF) today announced that it had secured deals for generic hepatitis C medicines for as low as US$1.40 per day, or $120 per 12-week treatment course for the two key medicines sofosbuvir and daclatasvir.

In the US, pharmaceutical corporation Gilead launched sofosbuvir at $1,000 per pill in 2013, and Bristol-Myers Squibb (BMS) launched daclatasvir at $750 per pill in 2015, leading to the original price tag of $147,000 for a person’s 12-week combination treatment course. The corporations have also been charging exorbitant prices in many developing countries, paralyzing the launch of national treatment programs and causing treatment rationing in many countries around the world.

“What good is a breakthrough medicine that people cannot afford?” asked Jessica Burry, Pharmacist for MSF’s Access Campaign. “Pharmaceutical corporations price hepatitis C medicines far out of reach for people paying out of pocket around the world, and also for many governments struggling to provide treatment in the public sectors; but the prices for generic versions keep coming down. Governments must use every tool in their toolbox to fight for access to lower-priced generics so they can scale up treatment for the millions of people who need it; they should follow the lead of countries like Malaysia and issue compulsory licenses when patents block people’s access to this life-saving treatment.”

In 2015, MSF started procuring sofosbuvir and daclatasvir from Gilead and BMS through their ‘access programs’ at a price of $1,400 to $1,800 per 12-week treatment. Today, MSF pays a fraction of that, at $120, sourced from quality-assured generic manufacturers.

An estimated 71 million people have chronic hepatitis C infection worldwide, 72 per cent of whom live in low- and middle-income countries. Direct-acting antiviral medicines (DAAs) represent a treatment breakthrough for people with hepatitis C, with cure rates of up to 95%, and with far fewer side effects than previous treatments. Yet access to DAAs has remained limited because pharmaceutical corporations charge unaffordable prices, leading many countries to reserve treatment only for people with the most advanced stages of the disease. By the end of 2016, three years after sofosbuvir was launched, only an estimated 2.1 million people globally had been treated with the medicines, leaving 69 million people still without access.

These high prices have also put a major strain on health systems in wealthy countries, in particular those enacting universal health care. Treatment is being rationed in countries such as Australia, Canada, Italy and the US, in addition to developing countries, and is a stark reminder of the early days of HIV treatment.

“Almost two decades ago, MSF and others worked hard to get access to generics and bring down prices for HIV medicines,” said Mickael Le Paih of MSF in Cambodia, where MSF treats people living with hepatitis C. “History is repeating itself with hepatitis C—the medicines we need are again too expensive, but we are finding ways to make treatment affordable so that our patients can be cured.”

MSF treats people with hepatitis C in 11 countries. Since 2015, MSF has provided DAA treatment to nearly 5,000 people with hepatitis C. Of those who have completed treatment to date, the overall cure rate – measured by ‘sustained viral response’ – is 94.9 per cent.

Reading Material: Not Even Close: This issue brief provides information on currently available HCV diagnostics and treatments, including pricing and registration information from manufacturers of DAAs

Close to 3 million people access hepatitis C cure

Close to 3 million people access hepatitis C cure

World Hepatitis Summit 2017 calls for accelerated action to eliminate viral hepatitis

31 October 2017 | São Paulo, Brazil - On the eve of the World Hepatitis Summit in Brazil, WHO reports increasing global momentum in the response to viral hepatitis. A record 3 million people were able to obtain treatment for hepatitis C over the past two years, and 2.8 million more people embarked on lifelong treatment for hepatitis B in 2016.

"We have seen a nearly 5-fold increase in the number of countries developing national plans to eliminate life-threatening viral hepatitis over the last 5 years," says Dr Gottfried Hirnschall, Director of WHO's Department of HIV and Global Hepatitis Programme. "These results bring hope that the elimination of hepatitis can and will become a reality."

Hosted by the Government of Brazil, the World Hepatitis Summit 2017 is being co-organized by WHO and the World Hepatitis Alliance. The Summit aims to encourage more countries to take decisive action to tackle hepatitis, which still causes more than 1.3 million deaths every year and affects more than 325 million people.

"We cannot lose sight of the fact that last year 194 governments committed to eliminating viral hepatitis by 2030. For sure we are still a long way from this goal but that doesn’t mean it’s some unattainable dream. It’s eminently achievable. It just requires immediate action," says Charles Gore, President of World Hepatitis Alliance. "The World Hepatitis Summit 2017 is all about how to turn WHO’s global strategy into concrete actions and inspire people to leave with a ‘can do’ attitude."

"Brazil is honored to host the World Hepatitis Summit 2017 – and welcomes this extraordinary team of experts, researchers, managers and civil society representatives to discuss the global health problem posed by viral hepatitis," says Dr Adele Schwartz Benzaken, Director of the Brazilian Ministry of Health’s Department of Surveillance, Prevention and Control of STIs, HIV/AIDS and Viral Hepatitis."Brazil is committed to taking recent advances in its response to hepatitis forward – on the road to elimination."
Progress in treatment and cure

Many countries are demonstrating strong political leadership, facilitating dramatic price reductions in hepatitis medicines, including through the use of generic medicines—which allow better access for more people within a short time.

In 2016, 1.76 million people were newly treated for hepatitis C , a significant increase on the 1.1 million people who were treated in 2015. The 2.8 million additional people starting lifelong treatment for hepatitis B in 2016 was a marked increase from the 1.7 million people starting it in 2015. But these milestones represent only initial steps – access to treatment must be increased globally if the 80% treatment target is to be reached by 2030.

However, funding remains a major constraint: most countries lack adequate financial resources to fund key hepatitis services.
Diagnosis challenge

To achieve rapid scale-up of treatment, countries need urgently to increase uptake of testing and diagnosis for hepatitis B and C. As of 2015, an estimated 1 in 10 people living with hepatitis B, and 1 in 5 people living with hepatitis C, were aware of their infection. Countries need to improve policies, and programmes to increase awareness and subsequent diagnosis.
Prevention gaps

Countries need to provide a full range of hepatitis prevention services that are accessible to different population groups, particularly those at greater risk.

Largely due to increases in the uptake of hepatitis B vaccine, hepatitis B infection rates in children under 5 fell to 1.3% in 2015, from 4.7% in the pre-vaccine era.

However, the delivery of other prevention services, such as birth-dose vaccination for hepatitis B, harm reduction services for people who inject drugs, and infection control in many health services, remains low. This has led to continuing rates of new infections, including 1.75 million new hepatitis C cases every year.
Need for innovation

Innovation in many aspects of the hepatitis response must continue. New tools required include a functional cure for hepatitis B infection and the development of more effective point-of-care diagnostic tools for both hepatitis B and C.

"We cannot meet the ambitious hepatitis elimination targets without innovation in prevention interventions and approaches, and implementing them to scale,” said Dr Ren Minghui Assistant Director-General for Communicable Diseases, WHO. “The great successes of hepatitis B vaccination programmes in many countries need to be replicated and sustained globally in the context of moving forward to universal health coverage."
Implementation of elimination strategy

The World Hepatitis Summit 2017 will be attended by over 900 delegates from more than 100 countries, including Ministers of Health, national programme managers, and representatives from organizations of people affected by viral hepatitis. The Summit will review progress and renew commitments by global partners to achieve the elimination of viral hepatitis by 2030 – a target reflected in WHO's elimination strategy and the UN Sustainable Development Goals.

Monday, October 30, 2017

Fatty Liver Common After Direct-Acting Antivirals for Hep C

Medscape Conference Coverage: The Liver Meeting 2017: American Association for the Study of Liver Diseases (AASLD)

Fatty Liver Common After Direct-Acting Antivirals for Hep C
Damian McNamara
October 30, 2017

WASHINGTON, DC — Evidence of steatosis is found in almost half the patients with hepatitis C who achieved a sustained virologic response after treatment with direct-acting antivirals, results from a prospective study show.

"Fatty liver is very common now that hepatitis C is being treated effectively," said Mazen Noureddin, MD, from Cedars-Sinai Medical Center in Los Angeles.

American and European guidelines state that a patient can be discharged from care in the absence of cirrhosis and elevated liver enzymes, but "we wanted to see what happens after direct-acting antiviral treatment," he said.

Steatosis was "very prevalent" in the study population, "although liver enzymes were normal," Dr Noureddin reported here at The Liver Meeting 2017.

Monitoring people for steatosis after a sustained virologic response is not common practice, he told Medscape Medical News, but these findings suggest that long-term monitoring is warranted.

Long-term Monitoring Needed
In their study, Dr Noureddin and his colleagues compared transient elastography findings (FibroScan, Echosens) in 101 patients — 49 men and 52 women — before and after they were treated with direct-acting antivirals. After each participant achieved a sustained virologic response, the researchers used the controlled attenuation parameter (CAP) to assess liver fat.

Mean age of the participants was 60 years and mean body mass index (BMI) was 28 kg/m². In addition, 36% of the patients were white, 25% were Hispanic, and 90% had diabetes. The hepatitis C infection was genotype 1 in 86% of the patients, genotype 2 in 13%, and genotype 4 in 1%. People with genotype 3 infection were excluded from the analysis because the etiology of hepatic steatosis is different in this population.

Decreases were significant in alanine transaminase (ALT) and aspartate transaminase (AST) levels and fibrosis scores from baseline to the achievement of sustained virologic response (P < .05).
In the study cohort, 48% of the patients showed evidence of steatosis after treatment, 6% of whom had advanced fibrosis. None of the 52% of patients without steatosis showed evidence of advanced fibrosis, defined as a score of at least 11 kPa.

For patients with steatosis, weight did not change during the study period. However, there were significant differences between these patients and those without steatosis.

Table. Mean Values After Patients Achieved a Sustained Virologic Response

ParameterPatients With SteatosisPatients Without SteatosisP Value
BMI29 m/kg²26 m/kg²<.05
Glucose level108 mg/dL96 mg/dL<.05
ALT level20 mg/dL15 mg/dL<.05
CAP score297 dB/m214 dB/m<.05
Fibrosis score7.0 kPa5.3 kPa<.05

"We need more follow-up," said Dr Noureddin. "We looked at patients 8 weeks after treatment. Next, we want to follow patients longitudinally to see if more patients with a fatty liver also develop fibrosis."

The study showed that even after achieving a cure for hepatitis C, approximately 50% of those patients demonstrated evidence of NAFLD.
"This is one of the most important studies presented at this meeting," said Naim Alkhouri, MD, from the Texas Liver Institute in San Antonio.

"The treatment of chronic hepatitis C infection has been revolutionized by the introduction of highly effective direct-acting antivirals, with cure rates of 95% or higher," he told Medscape Medical News. "However, the study showed that even after achieving a cure for hepatitis C, approximately 50% of those patients demonstrated evidence of NAFLD, which may increase their risk for liver cirrhosis and liver cancer."

"The use of FibroScan with CAP to assess for the presence of NAFLD and fibrosis progression should be considered in patients who are cured from hepatitis C infection," Dr Alkhouri said.

Dr Noureddin is a speaker and advisor for EchoSense. Dr Alkhouri has disclosed no relevant financial relationships.

The Liver Meeting 2017: American Association for the Study of Liver Diseases (AASLD): Abstract 2155. Presented October 23, 2017.

Follow Medscape Gastroenterology on Twitter @MedscapeGastro and Damian McNamara @MedReporter

https://www.medscape.com/viewarticle/887760#vp_1

Modeling cost-effectiveness and health gains of a “universal” versus “prioritized” hepatitis C virus treatment policy in a real-life cohort

In Case You Missed It

Hepatology 2017

Modeling cost-effectiveness and health gains of a “universal” versus “prioritized” hepatitis C virus treatment policy in a real-life cohort
Loreta A. Kondili, Federica Romano, Francesca Romana Rolli, Matteo Ruggeri, Stefano Rosato, Maurizia Rossana Brunetto, Anna Linda Zignego, Alessia Ciancio, Alfredo Di Leo, Giovanni Raimondo,

First published: Full publication history
DOI: 10.1002/hep.29399

Full-Text
View Online

Abstract
We evaluated the cost-effectiveness of two alternative direct-acting antiviral (DAA) treatment policies in a real-life cohort of hepatitis C virus–infected patients: policy 1, “universal,” treat all patients, regardless of fibrosis stage; policy 2, treat only “prioritized” patients, delay treatment of the remaining patients until reaching stage F3. A liver disease progression Markov model, which used a lifetime horizon and health care system perspective, was applied to the PITER cohort (representative of Italian hepatitis C virus–infected patients in care). Specifically, 8,125 patients naive to DAA treatment, without clinical, sociodemographic, or insurance restrictions, were used to evaluate the policies’ cost-effectiveness. The patients’ age and fibrosis stage, assumed DAA treatment cost of €15,000/patient, and the Italian liver disease costs were used to evaluate quality-adjusted life-years (QALY) and incremental cost-effectiveness ratios (ICER) of policy 1 versus policy 2. To generalize the results, a European scenario analysis was performed, resampling the study population, using the mean European country-specific health states costs and mean treatment cost of €30,000. For the Italian base-case analysis, the cost-effective ICER obtained using policy 1 was €8,775/QALY. ICERs remained cost-effective in 94%-97% of the 10,000 probabilistic simulations. For the European treatment scenario the ICER obtained using policy 1 was €19,541.75/QALY. ICER was sensitive to variations in DAA costs, in the utility value of patients in fibrosis stages F0-F3 post–sustained virological response, and in the transition probabilities from F0 to F3. The ICERs decrease with decreasing DAA prices, becoming cost-saving for the base price (€15,000) discounts of at least 75% applied in patients with F0-F2 fibrosis.

Conclusion: Extending hepatitis C virus treatment to patients in any fibrosis stage improves health outcomes and is cost-effective; cost-effectiveness significantly increases when lowering treatment prices in early fibrosis stages. (Hepatology 2017)

HCV Cirrhosis - Liver-related morbidity and mortality with and without sustained virologic response

Liver-related morbidity and mortality in patients with chronic hepatitis C and cirrhosis with and without sustained virologic response
Sofie Hallager,1 Steen Ladelund,2 Peer Brehm Christensen,3 Mette Kjær,4,5 Birgit Thorup Roege,6 Karin Elmegaard Grønbæk,7 Erika Belard,8 Toke S Barfod,9 Lone Galmstrup Madsen,10 Jan Gerstoft,11 Britta Tarp,12 Henrik Bygum Krarup,13 Nina Weis,1,5

Accepted for publication 5 July 2017
Published 24 October 2017 Volume 2017:9 Pages 501—516
DOI https://doi.org/10.2147/CLEP.S132072

Full-Text

Background: Chronic hepatitis C (CHC) causes liver cirrhosis in 5%–20% of patients, leading to increased morbidity and mortality. This study aimed to estimate liver-related morbidity and mortality among patients with CHC and cirrhosis in Denmark with and without antiviral treatment and sustained virologic response (SVR). Furthermore we aimed to estimate the rate of hepatocellular carcinoma (HCC) and decompensation associated with certain prognostic factors.

Materials and methods: Patients with CHC and cirrhosis registered in the Danish Database for Hepatitis B and C were eligible. Cirrhosis was based on liver biopsy, transient elastography, and clinical cirrhosis. Data were extracted from nationwide registries. The study period was from 2002 until 2013.

Results: Of 1,038 patients included, 716 (69%) were male and the median age was 52 years. Median follow-up was 3.8 years, 360 patients died, and 233 of 519 treated patients achieved SVR. Alcohol overuse and hepatitis C virus genotype 3 were associated with an increased incidence rate (IR) of HCC, whereas diabetes and alcohol overuse were associated with increased IRs of decompensation. Achieving SVR reduced all-cause mortality (adjusted mortality rate ratio 0.68 [95% CI 0.43–1.09]) and liver-related mortality (mortality rate ratio 0.6 [95% CI 0.36–1]), as well as liver-related morbidity with adjusted IR ratios of 0.37 (95% CI 0.22–0.62) for HCC and 0.31 (95% CI 0.17–0.57) for decompensation. The IRs of HCC and decompensation remained elevated in patients with alcohol overuse after SVR.

Conclusion: Alcohol overuse, hepatitis C genotype 3, and diabetes were associated with liver-related morbidity in patients with CHC and cirrhosis. SVR markedly reduced liver-related morbidity and mortality; however, special attention to patients with alcohol overuse should continue after SVR.

Saturday, October 28, 2017

Alcoholic liver disease confers a worse prognosis than HCV and non-alcoholic fatty liver disease among patients with cirrhosis

Alcoholic liver disease confers a worse prognosis than HCV infection and non-alcoholic fatty liver disease among patients with cirrhosis: An observational study
Astrid Marot, Jean Henrion, Jean-François Knebel, Christophe Moreno, Pierre Deltenre
Published: October 27, 2017 https://doi.org/10.1371/journal.pone.0186715

In conclusion, patients with cirrhosis related to alcoholic liver disease (ALD) have a lower incidence of HCC but die more frequently from decompensation of cirrhosis than patients with cirrhosis related to chronic HCV infection or non-alcoholic fatty liver disease (NAFLD). Cirrhosis related to ALD should be considered as a condition associated with a poor outcome. This population should deserve specific patient care focused on the management of complications related to liver failure. The impact of HCC surveillance on mortality remains to be established in ALD patients.

Full-Text

Abstract
Background
Cirrhosis is a heterogeneous clinical condition that includes patients at wide-ranging stages of severity. The role of the underlying liver disease on patient prognosis remains unclear.

Aim
To assess the impact of the underlying liver disease on the occurrence of hepatocellular carcinoma (HCC) and death.

Methods
Data related to the occurrence of HCC and death were collected during a 21-year period among patients with cirrhosis related to alcoholic liver disease (ALD) (n = 529), chronic hepatitis C virus (HCV) infection (n = 145) or non-alcoholic fatty liver disease (NAFLD) (n = 78).

Results
At inclusion, ALD patients were younger than HCV and NAFLD patients (56 vs. 67 vs. 63 years; p<0.001) and had worse liver function (percent of patients with Child-Pugh stages B or C: 48% vs. 8% vs. 17%; p<0.001). During follow-up, 85 patients developed HCC and 379 died. The 10-year cumulative incidence rate of HCC was lower in ALD patients than in HCV and NAFLD patients (8.4% vs. 22.0% vs. 23.7%; p<0.001). The 10-year cumulative incidence rates of mortality were not statistically different between ALD, HCV and NAFLD patients (58.1% vs. 47.7% vs. 49.9%; p = 0.078). Alcohol abstinence and viral eradication were associated with reduced mortality among ALD and HCV patients, respectively. In multivariate analyses, ALD was associated with a reduced risk of HCC (0.39; 95% CI, 0.20–0.76; p = 0.005) but with a higher risk of mortality (1.53; 95% CI, 1.20–1.95; p<0.001). ALD patients died more frequently from decompensation of cirrhosis.

Conclusion
Despite a lower incidence of HCC, patients with ALD-related cirrhosis have a worse outcome than those with chronic HCV infection or NAFLD-related cirrhosis.

Friday, October 27, 2017

A new study shows that liver cancer in Asia is linked to herbal remedies

A new study shows that liver cancer in Asia is linked to herbal remedies Researchers have uncovered widespread evidence of a link between traditional Chinese herbal remedies and liver cancer across Asia, a study said Wednesday.

The findings suggest stronger measures are needed to prevent people from consuming chemicals called aristolochic acids (AA), which are derived from the woody vines of the Aristolochia plant family, said the report in the journal Science Translational Medicine.

The acids can be found in some traditional Chinese medicines that are given during childbirth, to prevent parasites and promote healing.
Read the article.....

Full Text Article
Science Translational Medicine

Aristolochic acids and their derivatives are widely implicated in liver cancers in Taiwan and throughout Asia
Alvin W. T. Ng1,2,3,*, Song Ling Poon4,*, Mi Ni Huang1,2, Jing Quan Lim4,5, Arnoud Boot1,2, Willie Yu1,2, Yuka Suzuki1,2, Saranya Thangaraju4, Cedric C. Y. Ng4, Patrick Tan2,6,7,8, See-Tong Pang9, Hao-Yi Huang10, Ming-Chin Yu11, Po-Huang Lee12, Sen-Yung Hsieh10,†, Alex Y. Chang13,†, Bin T. Teh2,4,7,14,† and Steven G. Rozen
Science Translational Medicine  18 Oct 2017:Vol. 9, Issue 412, eaan6446
DOI: 10.1126/scitranslmed.aan6446

The dark side of an herbal medicine
Aristolochic acid, an herbal compound found in many traditional medicines, had been previously linked to kidney failure, as well as cancers of the urinary tract. Because of these known toxicities, herbs containing this compound have been restricted or banned in some countries, but it is still available on the internet and in alternate formulations. By analyzing numerous samples from Taiwan and other countries in Asia and elsewhere, Ng et al. demonstrated the effects of aristolochic acid in hepatocellular carcinoma, a much more common tumor type. The authors showed that the use of this drug remains widespread in Asia and particularly in Taiwan, and that it appears to increase the risk of multiple different cancer types.

Abstract
Many traditional pharmacopeias include Aristolochia and related plants, which contain nephrotoxins and mutagens in the form of aristolochic acids and similar compounds (collectively, AA). AA is implicated in multiple cancer types, sometimes with very high mutational burdens, especially in upper tract urothelial cancers (UTUCs). AA-associated kidney failure and UTUCs are prevalent in Taiwan, but AA’s role in hepatocellular carcinomas (HCCs) there remains unexplored. Therefore, we sequenced the whole exomes of 98 HCCs from two hospitals in Taiwan and found that 78% showed the distinctive mutational signature of AA exposure, accounting for most of the nonsilent mutations in known cancer driver genes. We then searched for the AA signature in 1400 HCCs from diverse geographic regions. Consistent with exposure through known herbal medicines, 47% of Chinese HCCs showed the signature, albeit with lower mutation loads than in Taiwan. In addition, 29% of HCCs from Southeast Asia showed the signature. The AA signature was also detected in 13 and 2.7% of HCCs from Korea and Japan as well as in 4.8 and 1.7% of HCCs from North America and Europe, respectively, excluding one U.S. hospital where 22% of 87 “Asian” HCCs had the signature. Thus, AA exposure is geographically widespread. Asia, especially Taiwan, appears to be much more extensively affected, which is consistent with other evidence of patterns of AA exposure. We propose that additional measures aimed at primary prevention through avoidance of AA exposure and investigation of possible approaches to secondary prevention are warranted.
Full Text Article - http://stm.sciencemag.org/content/9/412/eaan6446.full

Why the VA is so Successful Tackling HCV

Why the VA is so Successful Tackling HCV
by Pippa Wysong
Contributing Writer, MedPage Today

VA experts tell how they get high-risk patients engaged, nationally
The U.S. Department of Veterans Affairs (VA) is a leader in its ability to reach hepatitis C virus (HCV)-infected patients and engage them in care. Here, the secrets to its success are laid bare.

According to a recent paper in the Annals of Internal Medicine, the VA is the country's largest care-provider for HCV-infected patients and is well on its way to eliminating the disease in its population.

As of July 2017, a total of 51,000 veterans remain potentially eligible for treatment, a significant drop from more than 168,000 only 3 years ago. The number of people infected is decreasing by an estimated 30,000 per year...
Read the article at... MedPage Today

Expert Critique
Michelle Long
Assistant Professor of Medicine, Department of Medicine, Section of Gastroenterology
Boston University School of MedicineBoston, MA
With the success of direct-acting antiviral (DAA) medication for the treatment of hepatitis C virus (HCV), the challenges now are in linking patients with hepatitis C to care. The U.S. Department of Veterans Affairs (VA) has been very successful in treating patients infected with HCV, and the number of people infected within the VA care system is decreasing by about 30,000 people per year. The VA is well suited to treat HCV since it has a single integrated, electronic health record and a large case registry to link patients to care. Using these systems, the VA is able to screen high-risk populations and monitor disease incidence and prevalence. Patients who were eligible for screening were reached via letters or phone calls or through partnerships with shelters. The VA also has utilized care-delivery teams that personalize care delivery to different clinical settings and allowed outreach to patients in remote locations. The VA also was able to place DAA medications on the formulary, which lowered costs and allowed better access to medications.

Safety and efficacy of ledipasvir/sofosbuvir on hepatitis C eradication in hepatitis C virus/human immunodeficiency virus co-infected patients

World J Hepatol. Oct 28, 2017; 9(30): 1190-1196
Published online Oct 28, 2017. doi: 10.4254/wjh.v9.i30.1190

Safety and efficacy of ledipasvir/sofosbuvir on hepatitis C eradication in hepatitis C virus/human immunodeficiency virus co-infected patients
Xiaoping He, Lynne Hopkins, George Everett, Willie M Carter, Cynthia SchroppDyce, Khalid Abusaada, Vincent Hsu

Core tip: This is a retrospective study to evaluate the safety and efficacy of ledipasvir/sofosbuvir on hepatitis C eradication in patients with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection in an urban HIV clinic. It demonstrated the high rates of SVR12 of ledipasvir/sofosbuvir on HCV eradication in patients co-infected with HCV and HIV, regardless of HCV baseline levels, HCV treatment history or cirrhosis condition. The oral combination of ledipasvir/sofosbuvir represents a safe and well tolerated HCV treatment option that does not require modification for many of the common HIV antiretroviral therapy (ART). Occasional HIV virologic rebound occurred but later resolved without the need to change ART.

Full-Text

Abstract
AIM
To evaluate the safety and efficacy of ledipasvir/sofosbuvir on hepatitis C eradication in patients with hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infection in an urban HIV clinic.

METHODS
A retrospective cohort study of 40 subjects co-infected with HIV-1 and HCV treated with the fixed-dose combination of ledipasvir and sofosbuvir for 12 wk from 2014 to 2016. All patients included were receiving antiretroviral therapy (ART) with HIV RNA values of 100 copies/mL or fewer regardless of baseline HCV RNA level. The primary end point was a sustained virologic response of HCV at 12 wk (SVR12) after the end of therapy.

RESULTS
Of the 40 patients enrolled, 55% were black, 22.5% had been previously treated for HCV, and 25% had cirrhosis. The patients were on a wide range of ART. Overall, 39 patients (97.5%) had a SVR 12 after the end of therapy, including rates of 97.1% in patients with HCV genotype 1a and 100% in those with HCV genotype 1b. One patient with HCV genotype 3a was included and achieved SVR12. Rates of SVR12 were similar regardless of previous treatment or the presence of compensated cirrhosis. Only 1 patient experienced relapse at week 12 following treatment and deep sequencing didn’t reveal any resistance associated mutation in the NS5A or NS5B region. Interestingly, 7 (17.5%) patients who were adherent to ART experienced HIV viral breakthrough which resolved after continuing the same ART regimen. Two (5%) patients experienced HIV-1 virologic rebound due to noncompliance with HIV therapy, which resolved after resuming the same ART regimen. No severe adverse events were observed and no patient discontinued treatment because of adverse events. The most common adverse events included headache (12.5%), fatigue (10%), and diarrhea (2.5%).

CONCLUSION
This retrospective study demonstrated the high rates of SVR12 of ledipasvir/sofosbuvir on HCV eradication in patients co-infected with HCV and HIV, regardless of HCV baseline levels, HCV treatment history or cirrhosis condition. The oral combination of ledipasvir/sofosbuvir represents a safe and well tolerated HCV treatment option that does not require modification for many of the common HIV ART. Occasional HIV virologic rebound occurred but later resolved without the need to change ART.

Endocarditis - SPECIAL REPORT: London doctors’ simple strategy may stem a deadly toll

SPECIAL REPORT
London doctors’ simple strategy may stem a deadly toll
By Randy Richmond, The London Free Press
Friday, October 27, 2017 11:30:42 EDT AM

At University Hospital, Koivu started to notice more and more endocarditis deaths. When she asked her dying patients what they were using, almost all those who injected drugs said they were using HydromorphContin capsules.

To inject the drug, you first have to crush the capsules in a tiny container, usually a little pan called a cooker – the kind seen in movies and on television used to melt crack cocaine or crystal meth.

Cooking doesn’t dissolve the capsules, so you have to crush them as best as you can in a bit of water.

Then you place a tiny filter, sometimes called a sponge, over the hydro-laced mixture and draw liquid up with your needle.

Koivu theorized that when people drew up the crushed capsules in a syringe, even through a properly used filter, some particles were being drawn up as well.
Those particles scratch the heart valves...

Read the article here......

Of Interest
HIV and Hepatitis C Are No Longer the Most Serious Infectious Threats to People Who Inject Drugs
For whatever reason, endocarditis and other invasive bacterial infections are not nearly as feared as HIV and HCV, despite the fact that the former are far more immediately life threatening and way more difficult to treat.

Liver Meeting 2017: Diabetes Medications Have Different Effects on the Liver

Conference Coverage from
The Liver Meeting 2017: American Association for the Study of Liver Diseases (AASLD)

Diabetes Medications Have Different Effects on the Liver
Damian McNamara
October 26, 2017


WASHINGTON, DC — For people with advanced liver fibrosis due to nonalcoholic fatty liver disease (NAFLD) who also have type 2 diabetes, outcomes are better with metformin than with sulfonylureas, results from a large international trial show.

"The patients who use metformin can see a long-term benefit," Eduardo Vilar-Gomez, MD, from the Indiana University School of Medicine in Indianapolis, said here at The Liver Meeting 2017.
With metformin, survival improves and the risk for hepatic decompensation and hepatocellular carcinoma decreases.

"The bad news is that taking sulfonylureas can increase mortality and increase hepatic decompensation, in particular, in those taking sulfonylurea monotherapy," he told Medscape Medical News.

Therefore, clinicians should to "try to identify patients with higher rates of decompensation and avoid administration of sulfonylureas," he advised.

Read the article at Medscape......

Thursday, October 26, 2017

Liver Meeting 2017: I'm A HCV Patient - Show Me What I Need To Know!

Hi folks, because this blog has always been about you, the patient, I put together a quick overview of the Liver Meeting, using easy to follow video clips, and future learning activities.

Update: Released Online December 7, 2017 - AASLD Symposium
Breaking News On HCV Regimens: An Interactive Case-based Symposium
Watch experts Fred Poordad, MD; Robert S. Brown, Jr., MD, and MPH; Kris V. Kowdley, MD, discuss the following topics:

1. Breaking News and Introduction
2. CASE 1: GT1a Treatment-Naïve Patient with Early-Stage Disease
3. CASE 2: GT3 Treatment-Experienced Patient
4. CASE 3: GT1b Patient with Renal Disease Who Previously Failed NS5A Therapy
5. Q&A

Quick Review 
Jump over to Practice Point, sit back and watch 5 minute video clips reviewing each day of the meeting. The good doctor, Mark Sulkowski, will discuss SVR results, toxicity/adverse events, drug interactions, and HCV management. Although, a free registration is required, its worth the time you'll save looking elsewhere for cure rates that either correlate with your own stage of disease or genotype.

Clinical Clips Each Day Of The Meeting - ‘What you need to know in 5-minutes’
Hosted by Mark Sulkowski, MD

I have summarized each video, followed with a link to a few study results (slides), commentary and media coverage.

Day 1
October 21  - Summary
1 - Treatment: Access in the US, active or recent drug use.
2 - Liver transplant patients HCV genotype 1-4.
3 - Treatment with glecaprevir + pibrentasvir, impact of treatment on renal, cardiovascular and metabolic comorbidities. What happens after a patient is cured. SVR, cohort of persons in clinical trials followed for up to 2.5 years; extreme low rates of liver-related events.
Watch Video Clip (LINK)

Access to treatment in the United States - Medicaid and Medicare
Abstract 561 -  Disparate Access Based on Insurance Status to Highly Effective Direct Acting Antivirals (DAA) for Hepatitis C Virus Treatment in the Post-DAA Era Persists: Alarmingly Impaired Access in Medicaid Recipients

Liver transplant patients HCV genotype 1-4
Abstract  - Sofosbuvir/Velpatasvir for 12 Weeks in Genotype 1-4 HCV-Infected Liver Transplant Recipients


Of Interest - HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C
October 22 - Summary
1 - Mavyret (glecaprevir/pibrentasvir) for genotype 3 patients treated for 8 and 12 weeks with and without cirrhosis; SVR and relapse rates.
2 - Mavyret in patients with genotype 1-6.
3 - Harvoni (Ledipasvir/Sofosbuvir) genotype 1 with kidney disease.
4 - Quality of life in patients achieving SVR in a long-term study.
5 - VA study, does cure matter, reduce in liver cancer, improved survival.
6 - Risk calculator, can you predict which person after SVR will develop liver cancer, calculator will soon be on VA hepatitis website.
Watch Video Clip (LINK)

Commentary 
Maviret cures most people with HCV genotype 3 and those with cirrhosis
Steven Flamm of Northwestern Feinberg School of Medicine in Chicago and colleagues performed an integrated analysis of efficacy and safety data from phase 2 and 3 clinical trials of glecaprevir/pibrentasvir for previously untreated people with HCV genotype 3, either without cirrhosis or with compensated cirrhosis.
http://www.aidsmap.com/iMavireti-cures-most-people-with-HCV-genotype-3-and-those-with-cirrhosis/page/3183352/

(Slides) Mavyret (glecaprevir/pibrentasvir) for genotype 3 patients treated for 8 and 12 weeks
Efficacy and Safety of Glecaprevir/Pibrentasvir for 8 or 12 Weeks in Treatment-naïve Patients with Chronic HCV Genotype 3: An Integrated Phase 2/3 Analysis
Conference Coverage - NATAP

(Slides)Mavyret in patients with genotype 1-6
Efficacy, Safety, and Pharmacokinetics of Glecaprevir/Pibrentasvir in Adults With Chronic Genotype 1-6 Hepatitis C Virus Infection and Compensated Cirrhosis: An Integrated Analysis
Conference Coverage - NATAP 

(Slides) Harvoni (Ledipasvir/Sofosbuvir) genotype 1 with kidney disease 
Safety and Efficacy of Treatment With Once-Daily Ledipasvir/Sofosbuvir (90/400 mg) for 12 Weeks in Genotype 1 HCV-Infected Patients With Severe Renal Impairment 
Conference Coverage - NATAP  

Abstract 64. Significant and Sustained Improvement of Health-Related Quality of Life (HRQL) Scores in Patients with Hepatitis C (HCV) and Sustained Virologic Response (SVR)

Hepatitis C cure leads to improved quality of life
CommentaryQuality of life in patients achieving SVR in a long-term study.
Liz Highleyman
Cirrhosis, depression, anxiety and fatigue were independent predictors of lower health-related quality of life scores in a multivariate analysis. However, after adjusting for baseline levels, people with cirrhosis, depression, fatigue, insomnia and type 2 diabetes saw larger gains, suggesting that people with co-morbidities may experience the largest improvements after achieving SVR, Younossi said.
Read the article - http://www.infohep.org/Hepatitis-C-cure-leads-to-improved-quality-of-life/page/3182893/

(Slides) VA study, does cure matter, reduce in liver cancer, improved survival
Impact of Sustained Virologic Response with Direct-Acting Antiviral Treatment on Mortality and Hepatocellular Carcinoma - significantly lower mortality, HCC 60% to 84% -
Conference Coverage - NATAP 

AASLD Press Release

The Liver Meeting® - Direct‐Acting Antiviral Therapy Cuts Liver Cancer Risk By 71%

Reuters Health
Direct-acting Antivirals Cut Risk of Liver Cancer
"Our results, I think, are very definitive as far observational studies go, in that we did show that the eradication of hepatitis C with DAAs was associated with a 71% reduction in hepatocellular cancer risk," Dr. Ioannou told Reuters Health. "Eradicating hepatitis C will have a tremendous benefit in reducing liver cancer in individuals and in the entire population," he added in the news release. "Physicians and patients should not be withholding antiviral treatment for fear of inducing liver cancer. On the contrary, physicians should be treating hepatitis C specifically to reduce the risk of liver cancer."

Of Interest
Vets with HCV Might Settle Cancer Controversy
VA experience seems to rule out possible cancer-causing effect of new drugs
In the largest cohort analyzed to date -- some 62,000 patients in the VA system -- there is no evidence that therapy with newer agents that act directly against the virus (DAAs) increases the risk of hepatocellular carcinoma (HCC), according to George Ioannou, BMBCh, of the Veterans Affairs Puget Sound Health Care System in Seattle.
Read the article -  https://www.medpagetoday.com/meetingcoverage/aasld/68717

Day 3
October 23  - Summary
1 - Treatment as prevention in high risk populations, active drug use, risk for HCV infection.
2 - Opioid agonist treatment for acute, first infection or re-infection.  
Watch Video Clip (LINK)

Treatment as prevention in high risk populations - testing.
Conference Coverage - NATAP

Low reinfection
(Slides) - HEPATITIS C VIRUS REINFECTION AND INJECTING RISK BEHAVIOR FOLLOWING ELBASVIR/GRAZOPREVIR TREATMENT IN PARTICIPANTS ON OPIATE AGONIST THERAPY: C-EDGE CO-STAR PART B
Conference Coverage - NATAP

Opioid agonist treatment for acute, first infection or re-infection 
Conference Coverage - NATAP

AASLD Press Release
The Liver Meeting® 2017 - Screening for Hepatitis C Improves Opioid Abuse Treatment Outcomes
Hepatitis C virus, commonly called HCV, is a liver disease that ultimately can cause cirrhosis (scarring of the liver), liver cancer and liver failure. HCV is mainly contracted when a person comes in contact with an infected person’s blood. One of the most common ways to contract HCV is through needle sharing to inject drugs – thus making HCV an additional concern for those working to combat the opioid epidemic.

Commentary
Hepatitis C testing linked to reduced opioid use among people who inject drugs
"Patients diagnosed with HCV reduced their non-prescription drug use, including benzodiazepines and cocaine, in the year following diagnosis," the researchers concluded. "This highlights the importance of screening individuals in OST for HCV, as this alone may have a positive impact on their drug use activity."

Journal Of Hepatology - Shared by Henry E. Chang on twitter
Should we treat acute hepatitis C? A decision and cost-effectiveness analysis
It is not standard practice to treat patients with acute hepatitis C virus (HCV) infection. However, as the incidence of HCV in the United States continues to rise, it may be time to re-evaluate acute HCV management in the era of direct-acting antiviral agents (DAAs).

Day 4
October 24  - Summary
1 - The development of new drugs to treat HCV ends.
2 - Getting difficult people linked to care. 
3 - Treatment adherence, Mavyret
4 - SVR rates in patients who were Non adherent (defined at less than 80%) vs adherent, more than 80%. How many pills can you miss? What were the SVR rates in both groups?
Watch Video Clip (LINK)

Linkage to care
(Slides) - Randomized Controlled Trial of Cash Incentives or Peer Mentors to Improve HCV Linkage and Treatment Among HIV/HCV Coinfected Persons Who Inject Drugs: The CHAMPS Study 
Conference Coverage - NATAP

Treatment adherence Mavyret
(Slides) - Adherence to Pangenotypic Glecaprevir/Pibrentasvir Treatment and SVR12 in HCV-infected Patients: An Integrated Analysis of the Phase 2/3 Clinical Trial Program

(Slides) - C-BREEZE-2: Efficacy and Safety of a Two-Drug Direct-Acting Antiviral Agent Regimen Ruzasvir 180 mg and Uprifosbuvir 450 mg for 12 Weeks in Adults With Chronic Hepatitis C Virus Genotype 1, 2, 3, 4, 5, or 6 

Commentary
New three-drug HCV regimen shows nearly 100% response in 6, 8 weeks
Zeuzem and colleagues presented findings for a three-drug combination called JNJ-4178 that includes the NS5B inhibitor AL-335 (Achillion) at 800 mg, the NS5A inhibitor odalasvir (Achillion) at 25 mg, and Olysio (simeprevir, Janssen) at 75 mg once daily. Researchers followed eligible participants for 24 weeks after the end of treatment.

(Slides) - Evaluation of the efficacy and tolerability of JNJ-4178 (AL-335, odalasvir, and simeprevir) in hepatitis C virus-infected patients without cirrhosis: The Phase IIb OMEGA-1 study 

The presentation was summed up nicely, noting that as the HCV pipeline ends, the task at hand is now testing, access to care and treatment.  

Testing
Implementation of Hepatitis C Elimination
John Ward, MD, CDC


(LINK) - Coverage At NATAP
ID Week San Diego CA October 4-8, 2017

Access To Care 
State of Hepatitis C Medicaid Access
This week, National Viral Hepatitis Roundtable (NVHR) together with The Center for Health Law & Policy Innovation of Harvard Law School (CHLPI) launched Hepatitis C: State of Medicaid, an in-depth evaluation of treatment access in each state’s Medicaid program, while highlighting successes in access expansion as well as ongoing challenges. Over half of Medicaid programs received a “D” or an “F” for imposing discriminatory restrictions on hepatitis C cures.
View an Interactive Map - Click on your state to find out - State of Hepatitis C Medicaid Access - read your states full report, this includes: Liver damage restrictions, Sobriety restrictions, Prescriber restrictions with recommendations, and download the full report: 2017 NATIONAL SUMMARY REPORT.

Some state Medicaid programs continue to restrict access to hepatitis C drugs
By Ed Silverman @Pharmalot
October 23, 2017
Over the past three years, state Medicaid programs have done a much better job of disclosing information about access to expensive hepatitis C medicines and fewer are restricting treatment to patients, according to a new analysis.

Opioid Epidemic
One of the most dramatic medical success stories in recent years has been the introduction of new drugs that eradicate hepatitis C virus (HCV). But it's a different story among HCV patients with substance use disorders. This population typically does not have easy access to conventional health care so it is difficult to screen, diagnose and treat these individuals.
Read the article - Solving the hepatitis C epidemic among people with substance abuse disorders

Surgeon General: We will conquer HCV, opioids ‘one bite at a time’
During a session focused on the connection between the hepatitis and opioid epidemics at The Liver Meeting 2017, Jerome M. Adams, MD, MPH, Surgeon General of the U.S., advised physicians in attendance that hepatitis C elimination will require nontraditional partnerships and innovative strategies for education, prevention and screening.

“I want to ask you all a question that I hope all of you know the answer to,” Adams said to the audience. “How do you eat an elephant? One bite at a time. If you take one bite at a time, if you help all of our partners see which part of that elephant they can take a bite of, we will be able to consume that elephant that is the opioid epidemic.”
Read article available online at Healio

HCV Advocate
UNDER THE UMBRELLA Hepatitis C Statistics and Information: The Elephant in the Room
Matthew Zielske
Statistics are used in the fight to end the hepatitis C epidemic and the opioid crisis; stats show the way certain things have been, most likely are right now and will reasonably end up if nothing is done. Besides laying a foundation for understanding a certain event or situation, statistics and information are neatly packaged inside national ad campaigns and marketing materials. They make their way from the boardrooms of government agencies, private and nonprofit organizations and pharmaceutical companies, to our televisions and smartphones.
Read the article here  (LINK)

HCV In The Older Patient 
(Slides) - Safety and Efficacy of 12 Weeks of Elbasvir (EBR)/Grazoprevir (GZR) in Hepatitis C Virus (HCV) GT1- and GT4-Infected Participants 65 Years and Older: An Integrated Analysis of Twelve Clinical Trials
Conference Coverage - NATAP

ABSTRACT FINAL ID: 1577 - Does age matter? Direct-acting antiviral therapy for hepatitis C in a real-life cohort of elderly patients: pretreatment drug-drug interactions, tolerability and efficacy of current treatment regimens.

Great Article - Published in Infectious Diseases Clinics


Hepatitis C is the most common bloodborne virus in the U.S. More people die every year from hep C than all 60 reportable infectious diseases combined, including HIV. Historically, hepatitis C virus infection (HCV) was considered a baby boomer disease; a legacy that we hoped would die with us. However, we got that wrong. Today’s opioid crisis is causing a new wave of HCV infections, and is threatening our youth.
Read the article - https://www.hepmag.com/article/hepatitis-c-threatening-youth

Save The Date - Advances in Chronic Hepatitis C: Management and Treatment
Next week, ViralEd will slowly launch a series of video modules with comprehensive coverage of the meeting, hosted by a panel of leading HCV experts. On Nov 3rd: Advances in Chronic Hepatitis C: Management and Treatment, will be available for your viewing pleasure.
Begin here - http://www.viraled.com/modules/info/aasld_2017_comp_review.html

Video - Review Of HCV Treatment Data
VIDEO: Expert reviews promising treatment data from The Liver Meeting 2017
WASHINGTON, D.C. — In this exclusive video from The Liver Meeting 2017, Kris V. Kowdley, MD, FAASLD, of the Swedish Medical Center, Liver Care Network, Seattle, highlights some of the ground-breaking presentations from the meeting.

Fatty Liver
Fatty Liver Common After Direct-Acting Antivirals for Hep C
Medscape Conference Coverage: The Liver Meeting 2017: American Association for the Study of Liver Diseases (AASLD)
Damian McNamara
October 30, 2017
WASHINGTON, DC — Evidence of steatosis is found in almost half the patients with hepatitis C who achieved a sustained virologic response after treatment with direct-acting antivirals, results from a prospective study show.

Helpful Links
December 1, 2017

HCV Guidance Updates
New Treatment-Naïve & Treatment-Experienced
The following pages include guidance for management of treatment-naive patients.
Genotype 1
Genotype 2
Genotype 3
Genotype 4
Genotype 5 or 6

The following pages include guidance for management of treatment-experienced patients.
Genotype 1
Genotype 2
Genotype 3
Genotype 4
Genotype 5 or 6

Stay current with all guideline updates, "click here."

On This Blog
Get started by clicking on this (LINK) for patient-friendly coverage of the meeting, or click on the following topics:

Fibrosis
Fatty Liver
Herbal and dietary supplements

I hope this collection of links will help make the rest of your journey a little easier.
Tina

The importance of addressing poor nutrition in patients with liver failure

The importance of addressing poor nutrition in patients with liver failure
Poor nutrition is common in patients with liver failure, or cirrhosis, and it can lead to muscle wasting, weakness, fatigue, and worse outcomes before and after patients undergo liver transplantation. A new review published in Liver Transplantation addresses aspects of nutrition in transplant candidates with cirrhosis and emphasizes the need to screen all patients to identify those with poor nutritional status, especially those suffering from muscle wasting.

"Muscle wasting is frequently overlooked in liver transplant candidates as nutritional assessment is not routinely carried out as part of clinical practice, and an accurate assessment can be complicated by obesity or fluid retention," said the review's senior author, Aldo J. Montano-Loza, MD, MSc, PhD, of the University of Alberta. "Muscle wasting is one of the major features of undernutrition in cirrhosis, and currently, high resolution image-based techniques such as computed tomography constitute the best way to evaluate body composition in these patients."

According to Dr. Montano-Loza and his colleagues, ensuring adequate caloric and protein intake forms the foundation of therapy for undernutrition in liver transplant candidates, and patients should avoid fasting for longer than six hours. Studies have demonstrated potential for additional therapies--such as consuming branched-chain amino acids or fish oil supplements and taking hormone replacement therapy; however, their potential benefits need to be confirmed in randomized controlled trials.

"Physical activity is also an important aspect of therapy," said Dr. Montano-Loza. "Therefore, supervised mobilization should be encouraged and physiotherapy should be consulted liberally when patients are in the hospital to minimize total bed rest and muscle atrophy."

He noted that for cirrhosis patients who do not have access to dieticians and exercise specialists, it's especially important that their clinicians are aware of guideline recommendations for both diet and physical activity.

Additional Information
Full Citation: "Nutrition and the Transplant Candidate." Vera Mazurak, Puneeta Tandon, and Aldo Montano-Loza. Liver Transplantation; Published Online: October 26, 2017 (DOI: 10.1002/lt.24848).
URL Upon Publication: http://doi.wiley.com/10.1002/lt.24848

http://newsroom.wiley.com/press-release/liver-transplantation/importance-addressing-poor-nutrition-patients-liver-failure

Primary Care Screening for Fatty Liver Disease Debated

Medscape Conference Coverage from

Primary Care Screening for Fatty Liver Disease Debated
Damian McNamara
October 23, 2017

"We are well aware that more than 50% of patients with fatty livers have normal ATL values," he pointed out. And interoperator variability and "poor predictive ability for diagnosis of fibrosis and steatosis" limit the utility of ultrasonography, which is also commonly used to evaluate patients for liver disease. Liver biopsies are more accurate, but they are invasive, he added.

For their study, Dr Hassanein and his colleagues implemented a 16-week transient elastography screening program at a primary care clinic in Chula Vista, California. They offered screening to 1298 consecutive patients, and ended up with 958 evaluable scans.

Operators used a hand-held FibroScan probe, from Echosens, to assess liver stiffness, an indication of fibrosis, and a controlled attenuation parameter (CAP) score to detect steatosis.

Read the article (LINK)

Wednesday, October 25, 2017

Sustained virological response halts fibrosis progression: A long-term follow-up study of people with chronic hepatitis C infection

PLOS ONE

Sustained virological response halts fibrosis progression: A long-term follow-up study of people with chronic hepatitis C infection
Swee Lin G. Chen Yi Mei , Alexander J. Thompson, Britt Christensen, Georgina Cunningham, Lucy McDonald, Sally Bell, David Iser, Tin Nguyen, Paul V. Desmond
Published: October 24, 2017 https://doi.org/10.1371/journal.pone.0185609

Full-Text
Download PDF
View Online

Abstract
Background/Aims
Long-term follow-up studies validating the clinical benefit of sustained virological response (SVR) in people with chronic hepatitis C (CHC) infection are lacking. Our aim was to identify rates and predictors of liver fibrosis progression in a large, well characterized cohort of CHC patients in whom paired liver fibrosis assessments were performed more than 10 years apart.

Methods
CHC patients who had undergone a baseline liver biopsy pre-2004 and a follow up liver fibrosis assessment more than 10 years later (biopsy or liver stiffness measurement (LSM) using transient elastography [FibroScan]) were identified. Subjects who had undergone a baseline liver biopsy but had no follow up fibrosis assessment were recalled for LSM. Fibrosis was categorised as mild-moderate (METAVIR F0-2 / LSM result of ≤ 9.5 kPa) or advanced (METAVIR F3-4/ LSM >9.5 kPa). The primary objective was to assess the association between SVR and the rate of liver fibrosis progression over at least 10 years, defined as an increase from mild-moderate fibrosis at baseline liver biopsy (METAVIR F0-2) to advanced fibrosis at follow-up liver fibrosis assessment.

Results
131 subjects were included in this analysis: 69% male, 82% Caucasian, 60% G1 HCV, 25% G3 HCV. The median age at F/U fibrosis staging was 57 (IQR 54–62) years with median estimated duration of infection 33-years (IQR 29–38). At F/U, liver fibrosis assessment was performed by LSM in 86% and liver biopsy in 14%. The median period between fibrosis assessments was 14-years (IQR 12–17). 109 (83%) participants had received interferon-based antiviral therapy. 40% attained SVR. At F/U, there was a significant increase in the proportion of subjects with advanced liver fibrosis: 27% at baseline vs. 46% at F/U (p = 0.002). The prevalence of advanced fibrosis did not change among subjects who attained SVR, 30% at B/L vs 25% at F/U (p = 0.343). However, advanced fibrosis became more common at F/U among subjects with persistent viremia: 10% at B/L vs 31% at F/U (p = 0.0001). SVR was independently associated with protection from liver fibrosis progression after adjustment for other variables including baseline ALT (p = 0.011), duration of HCV infection and mode of acquisition.

Conclusion
HCV eradication is associated with lower rates of liver fibrosis progression. The data support early treatment to prevent long-term liver complications of HCV infection.

HCV in the Older Patient - Natural history, extrahepatic disorders, safety and efficacy of treatment regimens

Infectious Diseases Clinics
December 2017
Volume 31, Issue 4, Pages 827–838
Download PDF

Hepatitis C Virus Infection in the Older Patient

Hepatitis C virus (HCV) is the most common blood-borne infection in the United States and is of concern in older adults. HCV infection is associated with not only hepatic but also extrahepatic comorbidities common to the aging patient including diabetes, kidney and cardiovascular diseases, and neurocognitive impairment. The effect of direct-acting antiviral agents to treat HCV on these outcomes is limited. This article summarizes the literature regarding the epidemiology and natural history of HCV infection; the impact of age on clinical outcomes in HCV-infected persons; and current knowledge regarding safety and efficacy of HCV treatment regimens in the older patient.


Introduction
Hepatitis C virus (HCV) infection is the most common blood-borne infection in the United States and is of concern in older adults. Although the rate of new HCV infections has declined over the last two decades because of implementation of HCV screening of donated blood and harm-reduction programs, the proportion of HCV-infected patients that are of older age and that have had infection for a prolonged duration of time has increased. The growing burden of older HCV-infected patients poses challenges for clinicians who care for these patients and for the health care system because of the increased use of health care resources to treat the long-term sequelae of HCV-associated liver disease including cirrhosis, hepatocellular carcinoma (HCC), and liver transplantation.

Before the advent of all oral direct-acting antiviral (DAA) agents, HCV treatment was associated with poor response and increased adverse side effects with some studies showing worse outcomes in the older patient. Since the introduction of DAA agents in 2011 to treat HCV infection, clinicians are now able to successfully treat the growing number of HCV-infected patients of older age. However, information regarding the effect of HCV treatment on short- and long-term clinical outcomes in the older HCV-infected patient is limited.

This article summarizes the literature regarding the epidemiology, natural history, and clinical course of HCV infection; the impact of age on clinical outcomes in persons with HCV infection; and current knowledge regarding the safety and efficacy of newer HCV treatment regimens in the older HCV-infected patient.

Epidemiology and screening of hepatitis C virus infection in the United States
An estimated 4.1 million persons in the United States (or 1.6% of the US population) have been exposed to HCV.1 About 70% of these persons were born between 1945 and 1964, and most were infected between 1970 and 1990 when the incidence of new HCV infections peaked.2 Since the identification of HCV as the main cause of non-A/non-B chronic hepatitis in 1989, HCV incidence has declined because of the implementation of donor blood screening and increased availability of harm-reduction programs for persons who inject drugs. However, recent data suggest that there may be an emerging epidemic of HCV infection among young nonurban persons mainly of white race; prescription opioid use has been implicated as a factor.3

In 2012, the US Centers for Disease Control and Prevention revised their recommendations to include one-time HCV serologic testing of all adults born from 1945 through 1965 regardless of HCV risk status.4 The prevalence of HCV antibodies in persons born between 1945 and 1964 (also known as the Baby Boomer cohort in the United States) has been estimated to be about 3.5%, which is more than double the reported HCV prevalence in the US population. The revised recommendations were based on findings from the Chronic Hepatitis Cohort Study of 4689 HCV-infected persons who completed a survey regarding the reason for their HCV testing.5 That study found that less than 25% of the HCV-infected persons had an identifiable risk factor for HCV infection; rather, 78% were born during the period between 1945 and 1965. With implementation of this new recommendation, an increase in incident HCV infections is expected.

Recent studies6, 7 have also suggested that older patients in long-term care facilities should be targeted for HCV screening and confirmatory HCV RNA screening, and that there should be a shared commitment by all health care facilities to adhere to basic infection control procedures. These studies have largely been borne out of reports of viral hepatitis outbreaks resulting from lapses in infection control practices, particularly in ambulatory care settings. A systematic review and meta-analysis of HCV infection prevalence in long-term care facilities found a pooled prevalence of 3.3% (95% confidence interval, 1.5%–7.2%) compared with the 0.9% to 1.0% prevalence reported in noninstitutionalized elders (generally defined as older than 65 years of age).6 In that study, it was unclear if adults were previously infected or were exposed to HCV in the long-term care setting.

Another case-control study7 examined the association of health care exposures with acute hepatitis B and C from 2006 to 2008 in 71 (mostly acute hepatitis B infection) cases who were 55 years and older and found that 37% of new infections were likely attributable to injections of parenteral medications and 8% to hemodialysis. There is concern that as the Baby Boomer cohort of HCV-infected persons seeks more health care in ambulatory settings and residency in long-term care facilities, there could be a growing reservoir of infected persons who could serve as a source of transmission. Therefore, studies advocate for greater adherence to HCV screening recommendations (particularly in institutionalized settings), basic infection control precautions, and safe injection practices.

Natural history and clinical course of hepatitis C virus infection and the impact of age
Studies estimate that between 55% and 75% of newly infected persons develop chronic HCV infection as determined by detectable HCV RNA in the blood.8 Patients of older age at time of infection and impaired immune system are at increased risk of developing chronic HCV infection.8
A large proportion of chronically HCV-infected persons in the United States are now about 50 to 70 years old and have lived with HCV infection for about 25 to 45 years.9

The increased duration of HCV infection has been accompanied by an increased incidence of liver disease and related sequelae. Over the natural course of HCV infection, it is expected that at least one-third of HCV-infected persons progress to advanced fibrosis and cirrhosis, and among those with cirrhosis, about 3% to 5% per year develop decompensated cirrhosis (ie, ascites, hepatic encephalopathy, esophageal varices) and/or HCC (Fig. 1).10



Because several decades can elapse from incident HCV infection until the peak prevalence of cirrhosis, it has been estimated that the proportion of liver-related deaths and patients diagnosed with HCV-related cirrhosis and HCC is fast approaching its peak.11 This increase is largely driven by the burden of HCV in the Baby Boomer cohort and will be associated with increased health care use and hospitalizations for end-stage liver disease and the subsequent need for liver transplantation.12

Because the clinical sequelae of HCV disease is expected to increase in the older patient, some studies have specifically examined the association of older age (defined as 65 years or older) with clinical outcomes in HCV-infected persons. One retrospective cohort study13 of 161,744 HCV-infected patients in the US Veterans Health Administration Hepatitis C Clinical Case Registry compared HCV-infected veterans aged greater than 65 with those aged 20 to 49 years. They found that even after adjusting for several metabolic factors, including diabetes and obesity, age greater than or equal to 65 years remained associated with a 1.14, 2.44, and 2.09 greater risk of cirrhosis, HCC, and death from all causes, respectively. Longer duration of HCV infection is likely a primary reason for the increased risk in older HCV-infected persons. Prolonged duration of HCV infection has been shown to predict faster progression to cirrhosis14 and has been associated with increased risk of HCC.15

However, studies suggest that age-related mechanisms may also play a role. In one study of patients who acquired HCV infection during transfusion, the median time to development of cirrhosis was reported to decrease from 33 years in patients who acquired the infection between the ages of 21 and 30 years to 16 years in patients who acquired the infection when they were 40 years or older.16 Another study of patients who acquired HCV infection during transfusion found that the mean time to development of HCC was 15 years in persons 50 years or older compared with 32 years in those infected when they were under 50 years of age.15 Although Poynard and colleagues14 established that duration of HCV infection predicted faster progression to cirrhosis, they also demonstrated that in those older than 50 years at the time of infection, the progression of fibrosis was substantially greater when compared with those less than 50 years at the time of infection. Finally, recurrent HCV infection after liver transplantation is nearly universal among patients with HCV viremia at the time of transplant, and in this context, older donor age has consistently been associated with accelerated graft loss.17 These studies indicate that older age independent of duration of HCV infection may also play a role in the progression of HCV-associated liver disease.

Aging-related mechanisms that have been postulated to increase the risk of liver disease outcomes in the setting of HCV infection include a greater vulnerability to environmental factors, such as oxidative stress, with increasing age; reduction in the rate of hepatic flow; reduced mitochondrial capacity; impaired immunity; and increased carcinogenic potential caused by a reduced ability to repair DNA.18, 19 There are also limited data that HCV infection may be associated with increased markers of immune-senescence, which has been shown to occur in the setting of human immunodeficiency virus (HIV) infection and is thought to play a role in the earlier onset of aging-related comorbidities in HIV infection. HCV infection itself might be associated with loss of early differentiated T cells and progressive accumulation of chronically activated, late-differentiated senescent T cells. One small study20 comparing HCV-infected individuals with healthy control subjects, all of whom were less than 54 years of age, found that the CD4 and CD8 T cells from HCV-infected individuals showed a significant increase in the T-cell immunosenescent phenotype that is more commonly associated with advancing age. Whether or not this increase is associated with the premature onset of not only liver but also nonliver clinical outcomes related to aging in HCV-infected persons is unclear.21

Hepatitis C virus infection and extrahepatic clinical outcomes
HCV infection is also associated with extrahepatic disorders (Box 1), likely because in addition to being a hepatotropic virus, it is also lymphotropic leading to immune-system dysregulation. Thus, a variety of autoimmune disorders have been associated with HCV infection including systemic disorders, such as mixed cryoglobulinemia and less commonly arthritis, sicca syndrome, and porphyria cutanea tarda, or organ-specific disorders, such as glomerulonephritis, diabetes, or thyroiditis. Apart from diabetes, these disorders are thought to be uncommon, so few studies have been able to adequately examine the effect of age on these disorders in the HCV-infected patient.


By contrast, HCV infection is a chronic inflammatory process leading to not only hepatic inflammation but also persistent systemic inflammation, which has been associated with extrahepatic outcomes that are also common with aging including extrahepatic malignancies, cardiometabolic complications, and neurocognitive disturbances. The complex interplay between aging outcomes and HCV-induced immune dysregulation and systemic inflammation could partly explain why some but not all studies show an association of HCV infection with these outcomes.

Hepatitis C Virus Infection and Malignancy
Few studies have examined the association of HCV infection with non-HCC malignancy in the older patient. A recent registry-based case-control study22 using the Surveillance, Epidemiology, and End Results Medicare database in US adults aged greater than or equal to 65 years from 1993 to 2011 found that as expected, HCV infection was strongly associated with cancers of the liver compared with those without HCV infection. However, HCV infection was also associated with higher odds of intrahepatic (adjusted odds ratio [aOR], 3.40) and extrahepatic (aOR, 1.90) bile duct cancer, pancreatic cancer (aOR, 1.23), anal cancer (aOR, 1.97), nonmelanoma nonepithelial skin cancer (aOR, 1.53), myelodysplastic syndrome (aOR, 1.56), and diffuse large B-cell lymphoma (aOR, 1.57).

The increased risk for non-HCC cancers could indicate that HCV infection directly promotes oncogenesis. As a lymphotropic virus, HCV infection is thought to trigger B-cell proliferation and thus, has been associated with a greater risk of lymphoproliferative disorders, such as B-cell lymphoma.23, 24 Alternatively, the increased risk for non-HCC cancers could also be explained as confounding by shared risk factors. Such risk factors as high-risk sexual behaviors and injection drug use could explain the association with anal cancer and skin cancer, but were not accounted for in the analysis. These findings suggest that in addition to HCC, providers should be vigilant to the fact that HCV-infected patients who are 65 years or older could have an increased risk of non-HCC malignancies compared with HCV-uninfected patients who are 65 years or older.

Hepatitis C Virus Infection and Diabetes
An association between HCV infection and diabetes mellitus (DM) has been demonstrated in several studies.32, 33, 34, 35 In one longitudinal study, the development of DM was found to be 11 times more common in HCV-infected than HCV-uninfected persons.36 In persons older than 39 years of age, HCV infection increased the risk of DM by almost four times.37 Although a direct effect of HCV on the hepatocyte insulin-signaling cascade38, 39, 40 and pancreatic β-cell function41 has been postulated as a cause of insulin resistance, the cause of DM is invariably multifactorial. In older HCV-infected persons, DM onset may be a result of the direct effects of HCV and increasing visceral adiposity that occurs with older age.

Hepatitis C Virus Infection and Cardiovascular Disease

Similarly, there is growing evidence that HCV infection is associated with an increased risk of cardiovascular disease (CVD) and heart failure.42 The mechanisms by which HCV infection might be associated with CVD include an HCV-induced proinflammatory state43 and possible direct effects of the virus on the myocardium and endothelium.44 HCV infection is also associated with a higher prevalence of DM, a well-known risk factor for CVD. However, low-density lipoprotein (LDL) cholesterol and total cholesterol are reported to be lower in HCV-infected persons compared with those without HCV infection.45 Lower circulating levels of LDL cholesterol are commonly observed in primates and humans in response to infection and inflammation, but other changes in LDL cholesterol metabolism (ie, increased small LDL particle size) may occur that could promote atherogenesis.46 There may also be direct effects of HCV infection that lower LDL levels by lowering very low density lipoprotein (VLDL) secretion independent of liver fibrosis severity,47 which could potentially decrease the risk of CVD. The contribution of aging to lipid levels and thus CVD in the setting of direct effects of HCV infection and HCV-associated systemic inflammation add some uncertainty as to whether HCV infection is associated with an increased risk of CVD compared with those without HCV infection.

Hepatitis C Virus and Neuropsychological and Neurocognitive Effects
Up to 30% of HCV-infected persons report neuropsychological disorders, not limited to depression, and up to two-thirds complain of fatigue; the older HCV-infected patient may be at particular risk.48 Although the presence of depressive symptoms might be related to the psychological burden of chronic HCV infection, some studies suggest that HCV infection directly affects the central nervous system (CNS) through alterations in serotoninergic and dopaminergic neurotransmission, with resultant depressive symptoms.49 This mechanism might also explain other CNS symptoms seen in HCV infection, such as fatigue, although a causal link has not been established.50, 51

HCV infection is also associated with increased cognitive impairment when compared with those without HCV infection.52 Between 33% and 50% of all HCV-infected persons report some degree of impaired neurocognition.53, 54 Whether this impairment is directly attributable to HCV infection, advancing age, progressive liver disease, and/or other comorbid conditions is often difficult to elucidate. Studies have demonstrated HCV RNA in brain tissue and cerebrospinal fluid suggesting active HCV replication in the CNS.55 There is also a growing body of evidence that HCV directly affects the brain and nerves independently of hepatic-mediated processes.56, 57

Hepatitis C virus treatment in the older patient with hepatitis C virus infection
Because patients between the ages of 50 and 70 will constitute a large proportion of the patients being treated in the next decade, understanding the impact of age on HCV treatment outcomes in the era of all-oral DAA regimens is important. Before the advent of DAA agents, some58, 59 but not all studies13, 60 found that HCV-infected patients that were of older age had worse sustained virologic response (SVR) rates than those that were of younger age. Some attributed the worse response to the more frequent treatment discontinuation and/or dose reductions in the older patient resulting from treatment with an interferon-based regimen plus ribavirin, which are often accompanied by adverse effects including cytopenia, flu-like symptoms, and CNS effects.

Few studies have examined the association of older age with SVR rates using all oral DAA regimens partly because elderly patients are often excluded from clinical trials. A recent study of four open-label phase 3 clinical trials was able to examine the safety and efficacy of ledipasvir/sofosbuvir for the treatment of genotype 1 HCV in subjects 65 years or older.61 Of the 2293 subjects in the four trials, 264 (12%) were greater than or equal to 65 years of age (and 24 of those were ≥75). That study found little difference in SVR rates (97% in those <65 years vs 98% in those ≥65 years) despite subjects greater than 65 years being more likely to have cirrhosis. Furthermore, there was little difference by age in the proportion reporting at least one adverse effect (78% in those <65 years vs 80% in those ≥65 years).

The most common adverse effects were fatigue and headache in both groups, but in subjects who were also on ribavirin, the rate of study drug modification or interruption was double in the older group (6% in those <65 years vs 13% in those ≥65 years). That study suggests that age is not a barrier to achieving SVR in patients taking ledipasvir/sofosbuvir, but ribavirin-free regimens should be considered for the treatment of elderly patients. If ribavirin must be used, then close monitoring is needed for the development of anemia.

Furthermore, because sofosbuvir and ribavirin are renally eliminated, safe and effective doses of sofosbuvir in those with an estimated glomerular filtration rate less than 30 mL/min have not been established. In the HCV-infected patient with severely compromised renal function, other HCV regimens, such as grazoprevir plus elbasvir, have been shown to be safe and effective.

Another cohort-based retrospective study62 of 17,487 HCV-infected patients grouped into six age categories (<55 years, 55–59, 60–64, 65–69, 70–74, and ≥75 years) in the Veterans Affairs Healthcare System who started an all-oral HCV regimen between 2014 and 2015 also found that DAAs were associated with high SVR rates (from 90% to 94%) even in the oldest age cohort (≥75 years) and that advanced age was not a negative predictor for SVR. Although the SVR rates were lower in those with cirrhosis compared with those without cirrhosis, the SVR rates were similar between age groups among those with cirrhosis. Similarly, SVR rates were lower in treatment-experienced patients compared with treatment-naive patients but similar between age groups among those who were treatment-experienced.

Another question of tremendous interest to clinicians is whether HCV treatment will be associated with improvement in long-term outcomes, especially in the older patient. A study of US veterans13 before the advent of DAA therapy found that successful HCV treatment is associated with significant reductions in HCC and overall mortality. That study found mortality benefit in all age categories including those 65 to 85 years. The same group also reported in another publication63 that although achievement of SVR was associated with decreased HCC risk, the annual risk of HCC among those who cleared the virus was not negligible ranging from 0.1% to 1.55% (overall 0.33%) with the highest residual risk in those diagnosed with cirrhosis followed by those who achieved SVR after age 65 irrespective of cirrhosis. They concluded that there remains a risk of HCC post-SVR, and the risk may be greater in those with cirrhosis or in the elderly, supporting HCV treatment before the development of cirrhosis and continued surveillance even after SVR in those who already developed cirrhosis.

Finally, whether HCV treatment improves long-term nonliver disease outcomes is unclear. A recent small study of HIV/HCV-coinfected persons demonstrated that even after SVR, older patients treated with DAA agents did not experience any change in neuropsychological assessments.64 By contrast, a small study from the interferon era of 34 HCV-infected adults with a median age less than 40 years found that successful HCV eradication can lead to improvements in cognitive function, at least for individuals with mild deficits.65 These apparently contradictory findings from the pre- and post-DAA area may reflect how older patients with more advanced neurocognitive deficits who may not have been candidates for treatment are now being treated more readily. Additional studies examining the impact of HCV cure in the era of DAA agents on long-term outcomes are needed.

Summary
Understanding the impact of older age and HCV infection on liver and nonliver outcomes is critical. The advent of potent all-oral DAA agents for HCV infection has ushered in a new era where declines in HCV-associated liver disease are tangible; yet whether there will be an effect on longer-term outcomes in other organ tissues besides the liver is unclear and needs study. Examination of limited published studies of the safety and efficacy of DAAs in the older HCV-infected patient suggests that age should not be a barrier to treatment. Given that the proportion of older patients with HCV is increasing, clinical trials of DAA agents should include older HCV-infected patients.
References

Full-Text Article
Download PDF