Hepatitis C -Can We Really Accomplish Widespread Screening?

A pessimist sees the difficulty in every opportunity; an optimist sees the opportunity in every difficulty.  -Winston Churchill

The aforementioned quote leads a recent editorial (Lutchman G, Kim WR, Hepatology 2015; 1455-8) which discusses the challenges of widespread Hepatitis C virus (HCV) screening and avoiding late diagnosis/missed opportunity for timely treatment.  The associated article (Moorman AC et al. Hepatology 2015; 1479-84) reviewed a large cohort of 14,717 patients with HCV and noted that 17% (n=1056) had a ‘late diagnosis’ which resulted in high rates of hospitalization and mortality.  Late diagnosis was defined as having cirrhosis at time of diagnosis or hepatic decompensation within 12 months of initial diagnosis.

The editorialists note that the related article presents data from 2006-11 which models ‘real-life’ practice settings.  Late diagnosis was more common in African-Americans and in patients with Medicare insurance.

With regard to widespread screening, pessimists argue that “we do not have coherent strategies and resources” to implement.

  • there are too few health care providers who are qualified and interested
  • the ‘treat-all” strategy is too expensive.  “For example, in the first 3 months after the release of sofosbuvir, a large commercial health insurance carrier announced that it had spent over $100 million on hepatitis C prescriptions…cause[d] a substantial drop in its stock price”
  • “while prioritizing treatment to patients who are at risk of future problems seems the optimal solution to deliver the most benefits at the lowest costs, the problems lies in the identification of those patients.”

Optimists see the opportunity for early intervention and improved outcomes.

Bottomline: While more effective treatment is available, there are still many questions, especially who should receive treatment and how to identify those most in need.  If/when costs of therapy are reduced, some of the difficult questions will resolve.

Related blog posts:

Briefly noted:

  • “Adding Pegylated Interferon to Entecavir for Hepatitis e Antigen-Positive Chronic Hepatitis B: A Multicenter Randomized Trial (ARES Study)” Brouwer WP et al. Hepatology 2015; 1512-22). “Peg-IFN add-on therapy may facilitate the discontinuation of nucleus(t)ice analogs.”
  • “The Impact of Phlebotomy in Nonalcoholic Fatty Liver Disease: A prospective, randomized, controlled trial.” Adams LA et al. Hepatology 2015; 1555-64).  “Reduction in ferritin by phlebotomy does not improve liver enzymes, hepatic fat, or IR in subjects with NAFLD”
  • “Nonalcoholic Steatohepatitis is the Second Leading Etiology of Liver Disease Among Adults Awaiting Liver Transplantation in the United States.” Wong RJ et al. Gastroenterol 2015; 148: 547-55.
Chattahoochee River

Chattahoochee River

Clinical Science Year in Review in Pediatric GI – NASPGHAN 2014

For many participants at NASPGHAN, the “year in review” presentations are a highlight.  This year was no exception.

This blog entry has abbreviated/summarized this presentation. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.

William Balistreri –Clinical Science Year in Review 

Lay press remains excellent source of information.

Benefit of microbiome. (from NPR) Now there is elephant poop coffee -$645/lb ($70/cup).  Link: No. 1 Most Expensive Coffee Comes From Elephant’s No. 2 : The ... Collecting elephant poop is probably a less ideal job than what most of us have.  As for coffee, “make mine de-crap.”

Elephant Microbiome Collector

Topic of the year: Hepatitis C

  • 25 years since identification of Hepatitis C in 1989
  • Now approaching cure (Related blog post: Wiping out Hepatitis C | gutsandgrowth). All-oral highly effective regimen –newest regimen as easy as one pill per day for 8-12 weeks. Direct-acting antivirals (DAAs). Moving past 1st generation of DAAs: telaprevir/boceprevir with interferon/ribavirin.(refs = Pawlotsky, Gastroenterology 146:1176, 2014 and Schmidt, Clinical Gastroent Hepatol 12:728, 2014)
  • New drugs for HCV –just in time –increasing risk of HCV complications. Ann Intern Med 2014; 160: 293.
  • Goal –SVR –sustained virological response
  • Reviewed large number of articles: Sofosbuvir, Simeprevir, Sofosbuvir/Ledipasvir (Harvoni).  3-D regimen: ABT-450, ABT-267, ABT-333 –will be approved in coming weeks (Related blog post:Have You Heard of Harvoni? | gutsandgrowth)
    • Gane, NEJM 368:34, 2013
    • Zeuzem, NEJM 370:1993,2014
    • Kowdley, N Engl J Med 370:1879, 2014
    • Lawitz, Lancet 383:515, 2014
    • Feld, New England Journal of Medicine, 370:1594, 2014
  • Mild side effects with newer drug therapies
  • Awaiting pediatric studies.
  • Costly $1000/pill –“if dog swallows it,” may have to look for it in the stool
  • Stay updated with recommendations: www.hcvguidelines.org  (AASLD/IDSA)

Hepatitis B –success of vaccination.

  • Preventing perinatal transmission with HBIG/vaccine. JAMA 2013; 310: 974. Those born after 1984, with much lower HCC. Ann Intern Med 2014; 160: 828; Hepatology 2014; 60: 448
  • Give antivirals (eg. telbivudine) for HBeAg-positive mothers prior to delivery. (Related blog post: Hepatology Update -Summer 2014 | gutsandgrowth) Greenup, Journ of Hepatology 61:502, 2014 AND Zhang, Hepatology 60:468, 2014
  • Antiviral therapy lowers the risk of HCC. Hepatology 2014; 147: 143 (Wu et al).
  • Make sure children with IBD are being screened for hepatitis B. ~13% may not be immune. Moses, Am J Gastro 107:133, 2012

Trend of the Year: Social Media

  • Genome sequencing –tremendous advance. Families may push for this option on their own.
  • Magnets –banned. Social media allowed this problem to be quickly identified. (Related blog post: Buckyball Recall –It’s Official | gutsandgrowth)
  • Social media allows family to share information and get answers. Internet blogging allows families to reach out to scientists.
    • Schumacher, Pediatrics 133:e1345, 2014
    • Enns, Genetics in Medicine, March 2014
  • BiliCam –can take picture with mobile phones.

Biliary Atresia

Threat of the Year: Obesity along with NAFLD

  •  NAFLD can have significant liver histologic abnormalities even with normal ALT levels. J Pediatr 2014; 164: 707.
  • Clinical burden of NAFLD is not restricted to liver-related morbidity or mortality Armstrong, HEPATOLOGY 59:1174, 2014. Also, concern for obstructive sleep apnea and cardiovascular disease.  Sundaram, J Pediatr 164:699, 2014. Pacifico, HEPATOLOGY 59:461, 2014
  • Elastography is promising tool. Xanthakos, J Peds 164:186, 2014
  • Current treatment –lifestyle changes. Snacking contributes to fatty liver. Sleep curtailment is associated with obesity. Spaeth. SLEEP 36:981, 2013, Taveras, Pediatrics 133:1013, 2014, Mitchell, Pediat 131:e1428, 2013
  • Increased antibiotics in early life associated with obesity due to alteration of microbiome. Bailey, JAMA Pediatrics, Sept 29, 2014
  • Suggestion for future: “Diet Water.”

Diet Water.jpg

For those who want to learn more from Dr. Balistreri directly, I would recommend the Aspen Conference:

Aspen Meeting

Related link: Dr. Balistreri’s Review of the Growth and Development of the Pediatric Gastroenterology Specialty.

 

Wrongful Conviction: HCV Acquitted of Causing Diabetes & a Word on Ebola

First about Ebola –here’s the Ebola recommendation from the NEJM editors regarding quarantine:

An excerpt:

The governors of a number of states, including New York and New Jersey, recently imposed 21-day quarantines on health care workers returning to the United States from regions of the world where they may have cared for patients with Ebola virus disease. We understand their motivation for this policy — to protect the citizens of their states from contracting this often-fatal illness. This approach, however, is not scientifically based, is unfair and unwise, and will impede essential efforts to stop these awful outbreaks of Ebola disease at their source, which is the only satisfactory goal…We should be honoring, not quarantining, health care workers who put their lives at risk not only to save people suffering from Ebola virus disease in West Africa but also to help achieve source control, bringing the world closer to stopping the spread of this killer epidemic.

Take-home message: Read the entire editorial why quarantine is not the right approach for asymptomatic returning health care workers.

Direct Ebola Risk to Health Care Workers

Direct Ebola Risk to Health Care Workers

Now in followup to yesterday’s post about HCV and diabetes:

Even Perry Mason would have had a difficult time proving hepatitis C virus (HCV) did not cause diabetes until a recent publication (Hepatology 2014; 60: 1139-49, editorial 1121-23).

In this study using population-based data from the U.S. National Health and Nutrition Examination Survey (NHANES) with 15,128 adult participants, the authors show that the prevalence of diabetes and prediabetes did not differ by HCV status.  The authors used standardized definitions for diabetes and prediabetes and adjusted for major confounders.  The authors did note a relationship between elevated alanine aminotransferase (ALT) with diabetes regardless of HCV status.  In their cohort, 56.7% had normal glucose, 32.8% had prediabetes, 3.2% had undiagnosed diabetes, and 7.3% had diagnosed diabetes.  The mean age progressively increased in these groups: 40.8 years, 51.9 years, 58.9 years, and 59.2 years respectively.

Among those with diabetes, 10.5% were HCV RNA-negative and 12.0% were HCV RNA-positive –unadjusted for ALT values; the unadjusted HCV antibody status was nearly identical at 10.5% and 10.2% respectively. After adjustment, the OR for being HCV RNA-positive was 1.06 (P=0.53) with confidence limits of 0.59-1.90.

In examining the evidence, the editorial and the discussion review previous evidence of a significant association between HCV infection, insulin resistance, and diabetes.  The odds ratio for this association (HCV and diabetes) was estimated to be about 1.7.  The problems with this association were the following:

  • Much of the work was reported from tertiary care centers
  • Advanced liver disease (of any type) is a well-established risk factor for type 2 diabetes (T2DM)
  • Many studies may have included patients with nonalcoholic fatty liver disease which is another risk factor for diabetes
  • These studies did not control for ALT values

Bottomline (from editorial): This study “calls one to reconsider the dogma on the role of IR [insulin resistance] in the pathogenesis of HCV infection and its association with T2DM.” If there is an association, it is much smaller than previous estimates.

Related blog post: Treating HCV Helps Diabetics | gutsandgrowth

Telaprevir-Based HCV Therapy is Expensive Too

With the arrival of newer expensive hepatitis C virus (HCV) therapies, there has been an effort to prove that the costs are within reason.  One study (Hepatology 2014; 60: 1187-95) looking at this issue examines the cost of a sustained virological response (SVR) with the previous best therapy: Telaprevir-Based Triple Therapy.

Design: Records from 147 patients who received telaprevir-based triple therapy in 2011 were reviewed.

According to the authors (supported by Gilead Sciences), median cost of care was $83,721 per patient and the median cost per SVR was $189,338.  The costs of two of the drugs, telaprevir and pegylated interferon, accounted for 85% of the total costs.  Other costs included adverse management (8%), ribavirin (4%), professional fees (2%), and laboratory fees (1%).

The main reason besides pharmaceutical prices for the high costs were the SVR rate of 44%.

Bottomline: If a patient requires HCV therapy, the newer, more effective, expensive agents are likely to compare favorably with the less new, less effective, expensive medications.

Related blog posts:

Also noted: Hepatology 2014; 60: 1211-21.  “WELCOME” Study tested whether 15-18 months of docosahexaenoic acid (DHA) plus eicosapentaenoic acid (EPA) decreased liver fat and histology in nonalcoholic fatty liver disease (NAFLD). n=101, with 51 in treatment group. Findings the DHA+EPA had a “trend toward improvement in liver fat” percentage but no improvement in fibrosis.

Have You Heard of Harvoni?

The U.S. Food and Drug Administration on 10/10/14 approved Harvoni (ledipasvir and sofosbuvir) to treat chronic hepatitis C virus (HCV) genotype 1 infection.

“Harvoni is the first combination pill approved to treat chronic HCV genotype 1 infection. It is also the first approved regimen that does not require administration with interferon or ribavirin, two FDA-approved drugs also used to treat HCV infection.”

Full FDA press release –includes data supporting approval.

Related blog postThe Future is Now (for Hepatitis C) | gutsandgrowth