November 6, 2014

Watchful waiting: role of disease progression on uncertainty and depressive symptoms in patients with chronic Hepatitis C

Journal of Viral Hepatitis

Volume 21, Issue 10, pages 727–733, October 2014

Original Article

J. P. Colagreco1,*, D. E. Bailey2, J. J. Fitzpatrick3, C. M. Musil3, N. H. Afdhal1 and M. Lai1

Article first published online: 7 NOV 2013

DOI: 10.1111/jvh.12207

© 2013 John Wiley & Sons Ltd


Background and Aims: New therapies for HCV are rapidly emerging and providers are advising select patients to defer treatment and elect ‘watchful waiting’. During the watchful waiting period, patients have been shown to have high rates of illness uncertainty and depression. We sought to answer the question of whether reassuring histological data (showing minimal fibrosis or no fibrosis progression over time) is associated with less illness uncertainty and depressive symptoms.

Methods: This was a single-centre outpatient prospective cohort study to determine whether stage of fibrosis, fibrosis progression and reasons for treatment deferral were related to illness uncertainty and depressive symptoms in patients following watchful waiting.

Results: Illness uncertainty was significantly related to depressive symptoms (r = 0.49, P < 0.01). More than half of the participants (54%) had moderate levels of uncertainty. About 40% of the participants were at risk for clinical depression (21.7% at mild to moderate risk and 18.5% at high risk). Treatment naïve subjects had lower mean scores on both the CES-D (depressive symptoms measure) and the MUIS-A (illness uncertainty measure) total score, MUIS-A Ambiguity subscale and MUIS-A Inconsistency subscale than subjects who failed treatment or were interferon intolerant or ineligible. Surprisingly, liver fibrosis stage and progression were not significantly associated with overall illness uncertainty or depressive symptoms.

Conclusion: Patients with chronic hepatitis C on watchful waiting are at high risk for significant illness uncertainty and depressive symptoms. Reassuring histological data does not seem to correlate with less uncertainty or depressive symptoms.


AASLD: HCV Not Main Attraction Anymore


Published: Nov 6, 2014

By Michael Smith, North American Correspondent, MedPage Today

As the therapeutic picture for hepatitis C begins to settle down, the volume of abstracts on the topic is plateauing at the annual meeting of the American Association for the Study of Liver Diseases (AASLD).

That's not to say that new HCV therapies won't get a lot of play, according to Gary Davis, MD, president of MedLogician Consulting of Ponte Vedra Beach, Fla., and secretary of the liver association.

But, he told MedPage Today in advance of the meeting, "there's a big shift toward fatty liver disease ... that reflects what people are seeing in the clinics."

Over the past several years, direct-acting HCV medications have stolen the show, with a host of new drugs and drug combinations working through the clinical trials process.

Now, with many of those drugs approved and others in the home stretch, meeting participants will be getting mature data, he said.

For instance, the meeting will get an update on the research that underpinned the recent approval of Gilead's ledipasvir/sofosbuvir combination, trade-named Harvoni.

And, Davis said, they can look forward to seeing the data that AbbVie is using to support its multidrug combination -- dubbed 3D -- which is now under review at the FDA.

"It's going to be pretty exciting to see where that's at," he said.

Gilead famously unleashed a firestorm of debate when it priced sofosbuvir (Sovaldi) at $1 a pill and Davis said participants might take all the drug-makers to task over pricing of HCV drugs.

"I'm anxious to hear the audience questions on this, what with the whole controversy over pricing," he said.

The picture in fatty liver disease is less clear than in HCV, but the condition is increasingly prevalent and researchers are now turning their attention to it, looking at the basic mechanisms as well as drug therapy.

It's a "hot area," he said.

Among the hot topics this year:

  • The role of bariatric surgery in non-alcoholic steatohepatitis.
  • Prednisone and pentoxifylline in alcoholic hepatitis
  • Combinations of direct-acting HCV agents post-transplant.
  • A recombinant enzyme in liposomal acid lipase deficiency.

Davis also said that there is increased interest in possible curative options for hepatitis B, an area of research that has been "stuck in the mud for years." HBV is tricky to cure, because the virus integrates itself into host cells and -- rather like HIV -- therapy has aimed at suppressing the virus rather than getting rid of it.

But several new compounds in the early stages of investigation aim to change that and the "HBV people are quite excited about it," Davis said.

As well, he said, participants will get results from a major trial of terlipressin, a drug for hepatorenal syndrome that is approved in several countries but not the U.S.

An initial report from the so-called REVERSE study -- of terlipressin plus albumin versus albumin alone -- will attract considerable interest, Davis said, since improvement in renal function in patients with the syndrome is correlated with improved survival.


Maintenance Opioid Agonists Protect Against HCV in Injection Drug Users

Judith I. Tsui, MD, MPH1,2; Jennifer L. Evans, MS3; Paula J. Lum, MD, MPH4; Judith A. Hahn, PhD3,4; Kimberly Page, PhD, MPH5

[+-] Author Affiliations

1Clinical Addiction Research and Education Unit, Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts
2Department of Medicine, Boston Medical Center, Boston, Massachusetts
3Department of Epidemiology and Biostatistics, University of California, San Francisco
4Department of Medicine, University of California, San Francisco
5Division of Epidemiology, Biostatistics and Preventive Medicine, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque

JAMA Intern Med. Published online October 27, 2014. doi:10.1001/jamainternmed.2014.5416


Importance Injection drug use is the primary mode of transmission for hepatitis C virus (HCV) infection. Prior studies suggest opioid agonist therapy may reduce the incidence of HCV infection among injection drug users; however, little is known about the effects of this therapy in younger users.

Objective To evaluate whether opioid agonist therapy was associated with a lower incidence of HCV infection in a cohort of young adult injection drug users.

Design, Setting, and Participants Observational cohort study conducted from January 3, 2000, through August 21, 2013, with quarterly interviews and blood sampling. We recruited young adult (younger than 30 years) injection drug users who were negative for anti-HCV antibody and/or HCV RNA.

Exposures Substance use treatment within the past 3 months, including non–opioid agonist forms of treatment, opioid agonist (methadone hydrochloride or buprenorphine hydrochloride) detoxification or maintenance therapy, or no treatment.

Main Outcomes and Measures Incident HCV infection documented with a new positive result for HCV RNA and/or HCV antibodies. Cumulative incidence rates (95% CI) of HCV infection were calculated assuming a Poisson distribution. Cox proportional hazards regression models were fit adjusting for age, sex, race, years of injection drug use, homelessness, and incarceration.

Results Baseline characteristics of the sample (n = 552) included median age of 23 (interquartile range, 20-26) years; 31.9% female; 73.1% white; 39.7% who did not graduate from high school; and 69.2% who were homeless. During the observation period of 680 person-years, 171 incident cases of HCV infection occurred (incidence rate, 25.1 [95% CI, 21.6-29.2] per 100 person-years). The rate ratio was significantly lower for participants who reported recent maintenance opioid agonist therapy (0.31 [95% CI, 0.14-0.65]; P = .001) but not for those who reported recent non–opioid agonist forms of treatment (0.63 [95% CI, 0.37-1.08]; P = .09) or opioid agonist detoxification (1.45 [95% CI, 0.80-2.69]; P = .23). After adjustment for other covariates, maintenance opioid agonist therapy was associated with lower relative hazards for acquiring HCV infection over time (adjusted hazard ratio, 0.39 [95% CI, 0.18-0.87]; P = .02).

Conclusions and Relevance In this cohort of young adult injection drug users, recent maintenance opioid agonist therapy was associated with a lower incidence of HCV infection. Maintenance treatment with methadone or buprenorphine for opioid use disorders may be an important strategy to prevent the spread of HCV infection among young injection drug users.