‘12m people infected with hepatitis in Pakistan’

Bureau report
Friday, September 06, 2013
From Print Edition

PESHAWAR: The prevalence of Hepatitis B stands at 2.6 percent and that of Hepatitis C at 4.8 percent, while currently there are 12 million people infected with the disease in the country.

Associate Professor of Medicine at the Lady Reading Hospital Dr Javed Iqbal Farooqi and Chairman Association of Pakistani Physicians of North America (APPNA) Hepatitis Initiatives Dr Maqbool Arshad expressed these views while speaking at a one-day symposium on “Hepatitis Epidemic and Control Strategy in Khyber Pakhtunkhwa” at a hotel.

The speakers said the main reasons for the spread of hepatitis are frequent use of therapeutic injections, re-use of syringes, blood transfusions with unscreened blood, inappropriate sterilisation practices and weak hospital waste management.

The Khyber Medical University had organised the event in collaboration with the Department of Health and APPNA with main objective of raising awareness about treatment and prevention of hepatitis.

Provincial Minister for Health Shaukat Ali Yousafzai was chief guest on the occasion, while acting KMU Vice-chancellor Prof Dr Shad Mohammad, Dr Fakhar-e-Alam, secretary for health, Prof Dr Mukhtiar Zaman, director research KMU, and central PTI leader Azam Khan Swati also spoke on the occasion.

The speakers said the spread of hepatitis could easily be checked by raising awareness among people on large scale.

About causes of spread of hepatitis B & C, the speakers said use of used syringes, unsafe sexual relations, unscreened blood transfusions, shaving with contaminated razor, tattooing, contaminated instruments of footpath dentists, unsafe intravenous infusions, wastes in hospital wards and improper blood sample collection are among major factors contributing to spread of the disease. By adopting simple preventive measures, we can control the spread of the disease, they added.

Addressing the symposium Shaukat Ali Yousafzai said awareness among general public can reduce the burden of hepatitis on society. The government of Khyber Pakhtunkhwa is committed to adopting all possible measures to contain hepatitis from the province, he said.

Source

Interferon-Free Regimen for HCV Genotype 1 Infection: Closer Still

August 14, 2013

Atif Zaman, MD, MPH reviewing Zeuzem S et al. N Engl J Med 2013 Aug 15.

Despite promising findings, including higher response rates with inclusion of ribavirin in a triple-therapy regimen, response rates are still too low in this group to forgo interferon. Atif Zaman, MD, MPH

Interferon-free regimens should be available soon for hepatitis C virus (HCV) genotype 2 infection and probably genotype 3 infection. For now, the next-generation regimen for genotype 1 infection will be shorter and more tolerable but will still include interferon.

To continue the search for an effective, interferon-free regimen for HCV genotype 1 infection, researchers conducted an industry-funded, multicenter, randomized, open-label, phase IIb study in 362 treatment-naive patients. Patients received faldaprevir (120 mg once daily) plus deleobuvir (600 mg 2 or 3 times daily) with or without ribavirin (1000–1200 mg daily) for 16, 28, or 40 weeks. The primary endpoint was sustained virologic response at 12 weeks posttreatment (SVR12).

SVR12 did not differ by treatment duration (16 weeks, 59%; 28 weeks, 59%; 40 weeks, 52%) or by deleobuvir dose (69% for twice daily and 59% for three times daily). SVR12 was higher in ribavirin users versus nonusers (59% vs. 39%, P=0.03). SVR12 rates were numerically higher in patients with genotype 1b versus 1a (range across treatment groups, 56% to 85% vs. 11% to 47%) and in patients with IL28B genotype CC versus non-CC (range across treatment groups, 58% to 84% vs. 33% to 64%). Of 75 patients with virologic breakthrough, 73 had resistant HCV variant strains. Discontinuation rates ranged from 5% to 25% across treatment groups; the most common adverse events were rash, photosensitivity, nausea, vomiting, and diarrhea.

Comment

We are getting closer to an interferon-free regimen for genotype 1 hepatitis C virus infection, but we are not there yet. Ribavirin will likely still be needed as a part of the regimen. Also, multiple interferon-free regimens might be required, with choice of regimen based on predictors of response such as genotype 1 subtype and IL28B status. Finally, until their sustained virologic response rates approach 80%, interferon-free regimens will likely only be an option for patients for whom interferon-based regimens are intolerable or contraindicated.

Citation(s):

Zeuzem S et al. Faldaprevir and deleobuvir for HCV genotype 1 infection. N Engl J Med 2013 Aug 15; 369:630. (http://dx.doi.org/10.1056/NEJMoa1213557)

Source

Study helps characterize HCV exacerbation course, outcomes

By: SHARON WORCESTER,  Oncology Report Digital Network

09/01/13

Most patients who experience an acute exacerbation of chronic hepatitis C achieve a sustained viral response after treatment with pegylated interferon and ribavirin, a long-term case-control follow-up study shows.

Of 82 consecutive patients who had an acute exacerbation of chronic hepatitis C virus (HCV) between January 2005 and June 2010, 32 were treated with peg-IFN and ribavirin, and 26 of those (81.2%) achieved a sustained viral response (SVR); of 82 control subjects with HCV who did not experience an acute exacerbation, 38 were treated with peg-IFN and ribavirin, and 23 of those (60.5%) achieved an SVR, Dr. Evangelista Sagnelli of Second University of Naples, Italy, and her colleagues reported online April 15 ahead of print in Clinical Gastroenterology and Hepatology.

The case patients, who were a mean age of 50 years, were anti-HCV/HCV RNA positive, hepatitis B surface antigen (HBsAG)/anti-HIV–negative patients who were naive to anti-HCV therapy. HCV genotype 1 was detected in 43.9% of cases, and genotype 2 was detected in 46.4% of cases.

The patients, who were followed for a median of 36 months after a 2-month observation period, were matched to 82 controls based on age, sex, and disease genotype. The controls, who were followed for 32 months, were HBsAG-negative patients who never showed signs of symptomatic acute exacerbation; they had steady alanine aminotransferase (ALT) values at four checks per year over the prior 5 years. They also were anti-HCV therapy-naive.

More case patients than control patients carried the interleukin-28B CC genotype (40.2% vs. 24.4%).

"In several determinations over the years before reactivation, these 82 patients had been HCV RNA positive with normal or moderately increased serum alanine aminotransferase levels, suggesting an indolent, slowly progressing course of chronic hepatitis C," the investigators said.

They had a mean aspartate aminotransferase (AST) serum value of 672 IU/dL, a mean ALT serum value of 1063 IU/dL, and a total bilirubin level of 15.87 mg/dL, the investigators said (Clinical Gastroenterology and Hepatology 2013 [doi:10.1016/j.chg.2013.03.025]).

In 43.5% of cases, ALT increased steadily to at least twice the baseline value, but more than half of these (56.5%) experienced a return to baseline values prior to the acute exacerbation, they noted.

A comparison of biopsy specimens showed increasing fibrosis in 78.3% of 23 cases, compared with 38.7% of 31 controls with biopsies available. Fibrosis scores remained stationary in 21.7% of the case patients, and in 58.1% in the control group. Only one patient in the control group (3.2%) improved.

Additionally, histologic activity index (HAI) scores deteriorated by at least 2 points in 60.9% of cases, compared with 9.7% of controls.

"An improvement in the HAI of at least 2 scores was found only in 4 (12.9%) in the control group patients, whereas 9 patients (39.1%) in the case group and 24 patients (77.5%) in the control group remained stationary," the investigators said.

This study, which was designed to better characterize the clinical presentation and course of symptomatic acute exacerbation of chronic hepatitis C, as well as outcomes and response to antiviral therapy, improves "the scanty knowledge" on these topics, they said.

The findings demonstrate marked variability in the clinical presentation, with ALT levels ranging from 6- to 43-fold the normal values, and serum bilirubin increases ranging from 2 to 22 mg/dL.

The investigators also observed that although the clinical course of acute exacerbations was usually characterized by a single flare, in some cases more than one flare occurred, and that acute exacerbations can occur at any age; in this study they occurred in patients ranging in age from 24 to 87 years.

Furthermore, the observation that nearly half of the study patient with an acute exacerbation showed HCV genotype 2 confirms the association between exacerbation and genotype 2 demonstrated in previous studies, they said.

"The reasons for this association remain unknown and warrant further investigation," they said, noting that exacerbations in the current study were also common among those with HCV genotype 1, but were rare in other HCV genotypes.

The unexpectedly higher prevalence of genotype IL-28-B CC in the case patients in this study "may suggest a greater likelihood of developing acute exacerbation of chronic hepatitis C for patients with the genotype," they said, noting that this observation also deserves additional study.

"Most probably acute exacerbation of chronic hepatitis C is a consequence of a reactivation of cell-mediated immune reaction to clear HCV infection, in some ways in line with the well-known propensity of IL-28-B CC genotype to undergo a spontaneous or treatment-induced clearance of HCV infection," they said.

Another observation in this study is that acute HCV exacerbation frequently causes deterioration both in fibrosis and necroinflammation – a finding that underscores "the profound implications of acute exacerbation of chronic hepatitis C on the progression to cirrhosis and risk of hepatocellular carcinoma," they said.

"In conclusion ... acute exacerbation of chronic hepatitis is responsible for an unfavorable outcome in patients with chronic hepatitis. However, the majority of patients with acute exacerbation of chronic hepatitis C obtained an SVR, most probably because of the high frequency of HCV genotype 2 and IL-28-B CC genotypes in the case group, and possibly because the reactivation of a cell-mediated immune response may favor HCV clearance," they said, adding that "the more rapid progression to cirrhosis and the risk of hepatocellular carcinoma strongly warrant the early initiation of anti-HCV therapy for acute exacerbation of chronic hepatitis C patients."

In this study, such patients showed "an impressive rate of SVR to peg-IFN + ribavirin," they said.

This study was supported by grants from PRIN 2008, MIUR, Rome, Italy, "Ottimizzazione Della Diagnosi Eziologica dell’epatite Acuta C E Studio dei Fattori Viro-Immunologici di Guarigione, di Cronicizzazione E di Risposta Alla Terapia Con Interferone," and Tegione Campania "Progetti per il miglioramento della qualita dell’assistenza, diagnosi e terapia del paziente afetto da AIDS nei settori: immunologia, coinfezioni, informazione e prevenzione," 2008. The authors reported having no disclosures.

Source

Smart syringe turns red to tell you it's been used

By Holden Frith, for CNN

updated 11:17 AM EDT, Tue September 3, 2013 | Filed under: Innovations

The ABC Syringe turns dark red after use, warning doctors and patients that it may be contaminated

Editor's note: Every two years, the prestigious INDEX: Awards seek out designers working on innovative solutions to global challenges. In this special CNN series, we profile a selection of the nominees.

(CNN) -- Of the four to five billion injections given each year in India, at least 2.5 billion are unsafe, according to one study. In some cases, that means they are administered using unsterilized second-hand syringes that could be contaminated with a blood-borne disease such as hepatitis or HIV.

A simple change to the way syringes are made could dramatically reduce those figures and save thousand of lives each year, according to David Swann of Huddersfield University, in England. His design for a new kind of syringe that changes color after it has been used was nominated for an INDEX: Award.

"1.3 million people (globally) a year die from unsafe injection practices," Swann says, quoting WHO figures. "It accounts for over 30% of hepatitis A and B cases and 5% of HIV cases."

He explained that in India it is common for scavengers to hunt through landfill sites looking for old syringes that they can clean up and sell to clinics.

"When you compare a sterile syringe just out of its packaging with a syringe that's been washed, how do you determine the difference?" he said. "We conceived an intelligent ink that, if exposed to air by taking it out of the package or if the package is breached that would activate it and turn it red."

The ABC Syringe is impregnated with an ink that's sensitive to carbon dioxide and then sealed in a protective atmosphere so that it remains transparent until it is ready for use. After the seal is broken, the shell of the syringe starts to turn a dark red, alerting both doctors to the risk that the syringe may already have been used.

Swann's intention is that the introduction of the ABC syringe should be accompanied by a public information campaign so that patients would also associate a red syringe with danger and would be able to insist on sterile equipment.

"We had to be really quite clever in looking at technologies that cost next to nothing, and modified-air packaging is one of those technologies," Swann said. "It only adds 1% to the retail price, so on a two-and-a-half pence (four cents) syringe it becomes quite an interesting proposition."

According to Swann's calculations, if the ABC syringe is used for 5% of injections administered in India, after five years it will have prevented more than 700,000 infections and saved $130 million in medical costs.

Denis Maire, who works for the World Health Organization's health systems and innovation taskforce, said the ABC Syringe could help to make injections safer.

"Anything that can contribute to decrease the reuse of syringes is worth considering and cost is certainly a major factor," he said. "The great advantage of this concept is that not only health care workers but also patients can have a visual appreciation on the safety status of the device. In my view this could be a good deterrent for practitioners to reuse."

However, he noted that it would be possible for unscrupulous doctors to override the visual warning if their patients did not know the meaning of the color change. He also said that the one-minute delay before the syringe turned red may not be long enough.

"How would you distinguish good and bad syringes if the injections are not practised inside this lap of time?" he said. "It could create confusion and render the concept ineffective."

Ravi Naidoo, a member of the INDEX Award jury and the managing director of Design Indaba, an agency that aims to put creative ideas into practice, said that working with the international medical community would help to turn the prototype into a viable product.

"This innovation speaks to the endless possibilities of design, creativity and innovation in addressing real-world issues," he said. "In addition to being cost-effective, which will ensure the accessibility of the solution, it also allows patients to take charge of a critical issue — great example of empowerment through smart design."

Source

Study Examines Ways to Restore Immunity to Chronic Hepatitis C Infection

Released: 9/3/2013 11:25 AM EDT
Source Newsroom: Nationwide Children's Hospital

Newswise — The hepatitis C virus hijacks the body’s immune system, leaving T cells unable to function. A new study in animal models suggests that blocking a protein that helps the virus thrive could restore immune function, allowing the body to fight infection. The work, led by teams at The Research Institute at Nationwide Children’s Hospital and Emory University, was published online Aug. 26 in the Proceedings of the National Academy of Sciences.

Previous studies show that antibody treatments that inhibit the protein, called programmed cell death 1 (PD-1), can shrink tumors in humans. This new work suggests that anti-PD-1 antibodies might be equally effective in treating hepatitis C and other persistent human viral infections, says Christopher Walker, PhD, a senior author on the study and director of the Center for Vaccines and Immunity at Nationwide Children’s.

PD-1 is a regulatory protein that helps keep the immune system in check. Normally, PD-1 acts as a switch to turn off immune responses when an infection is under control. Some viruses such as HCV manipulate the PD-1 off switch so that T cells lose their ability to fight the infection, a condition scientists call “T-cell exhaustion.” The result is life-long persistence of HCV in the liver, which increases the risk of cirrhosis, liver cancer and other serious diseases.

The researchers treated animal models with persistent HCV infection with repeated doses of an anti-PD-1 antibody. Although the responses were mixed, one animal did show a dramatic increase in HCV-specific T cell activity in the liver and a sharp decrease in viral load. A closer examination of the data found that the animal had more HCV-specific T cells in the liver before therapy, which could mean that therapeutic success hinges on the amount of HCV-specific T cells in the liver before treatment.

“Our supposition is that these T cells remained in the liver for years at levels too low to detect before treatment, and had the capacity to expand after treatment,” Dr. Walker says. “The animal that responded to therapy had a broad, strong response during the early acute phase of infection. This suggests that one predictor of response to an anti-PD-1 antibody is the quality of the T-cell response when the initial infection occurs.”

Another interesting finding was the impact of the antibody on CD4+ T cells, helper cells that promote the development of killer T cells called CD8+, which target and destroy virus-infected liver cells. One hallmark of chronic HCV is the collapse of CD4+ cells.

“We have no information on whether PD-1 signaling is a primary mechanism for silencing helper cells, so recovery of the CD4+ helper cell response in this instance provides some indirect evidence that PD-1 signaling also impairs the helper cells,” Dr. Walker says.

Because much of the research focus on HCV is now directed at developing antiviral therapies, it’s likely that these new findings may have a greater impact on treatments for chronic hepatitis B (HBV), rather than the virus studied in this experiment, Dr. Walker says.

“Chronic hepatitis B is an even larger public health problem than HCV and direct-acting drugs control but do not eliminate the virus,” he says. “Immune reconstitution is the holy grail for HBV.”

Toward that end, Dr. Walker’s team plans to explore the insight this new study provides into why anti- PD-1 antibody therapy sometimes succeeds and sometimes fails. Specifically, they want to know what role the quality of T-cell immunity before treatment plays in therapeutic response.

“There is wide variation in the strength of T-cell immunity when people are first infected with the virus, ranging from very strong and sustained to none,” notes Dr. Walker, who also is a professor of pediatrics and molecular virology, immunology, and medical genetics at The Ohio State University.

“Those with very strong sustained responses tend to clear the virus. Anything less, and the virus persists,” Dr. Walker says. “This study suggests that if your T-cell response to the initial infection is good, but not enough to clear the virus, then you may respond to PD-1 blockade years later. If your initial acute phase T cell response is limited and weak, there is less opportunity for PD-1 blockade to work.”

Source

Maternal transmission cause of HCV in children

Provided by Healio

Indolfi G. J Pediatr. 2013;doi:10.1016/j.jpeds.2013.06.077.

September 4, 2013

Mother-to-child transmission is the leading causes of hepatitis C virus infection in children, according to recent findings published in The Journal of Pediatrics.

“Mother-to-child transmission of HCV is defined as transmission occurring during pregnancy or in the perinatal period from the HCV-infected mother to the fetus or to the child,” according to background information in the study. “The exact timing and the ultimate mechanism of mother-to-child transmission of HCV infection are unknown. Among children acquiring infections from the mother, only a few have been found to be HCV-RNA positive in the first days of life.”

Transmission of HCV is more likely to occur if the mothers had a history of IV drug use, were coinfected with HIV, and had higher liver disease activity as defined by the presence of elevated aminotransferase levels. The major risk factors for perinatal transmission of HCV were shown to be dependent on peripheral blood mononuclear cell (PBMC) infection with HCV.

“HCV-infected maternal PBMCs can be the carrier of the virus inside the child, serving as a Trojan horse for HCV entry,” researchers wrote. “Once inside the child, the efficiency of transmission is dependent on the infection of newborn target cells that in turn is related to the persistence of maternal-infected cells in fetal/neonatal blood.”

However, because transmission is not completely understood, no effective prevention intervention is currently available.

”Perinatal transmission of HCV is a complex and almost unexplained phenomenon,” Giuseppe Infoldi, MD, of Meyer Children’s University Hospital of Florence, told Infectious Diseases in Children. “Further research and attention by clinicians is needed in the future for the leading route of acquisition of HCV infection in children.”

Disclosure: The researchers report no relevant financial disclosures.

Giuseppe Indolfi, MD, can be reached at Meyere Children’s University Hospital of Florence, Viale Pieraccini 34, I-50139, Florence, Italy; email: g.indolfi@meyer.it

Source

10 Tips to Help Adjust Your Attitude for HCV

August 15, 2013

They say attitude is everything. They are right. Having a good attitude can help you get the job you want, find the love of your life and even fight chronic disease. Even though every authority on Hepatitis C highlights a positive outlook as the most important thing you can do for your health, many are left in the dark as to how to do this.

By Nicole Cutler L.Ac.

The messages we tell ourselves not only dictate our mood and behavior but can also have a powerful impact on physical health. As such, anyone struggling with a Hepatitis C diagnosis, symptoms or treatment will benefit from an attitude adjustment.

Medical experts agree that thoughts can lead physical health along their route. “It’s clear that stressors produce abnormal changes in the immune system,” said Ronald Glaser, director of Ohio State University’s Institute for Behavioral Medicine Research. Glaser and his wife, Janice Kiecolt-Glaser, a clinical psychologist also at Ohio State, studied the mind-body connection and found that chronic stress and psychological stress can impede wounds from healing, may impair the effectiveness of vaccines and can weaken the immune system of caregivers. A pioneer in the field, cardiologist and associate professor of medicine at Harvard Medical School, Herbert Benson says, “Mind-body medicine is now scientifically proven.”

Continue reading this entire article …….

Worldwide death rate for AIDS cut by 21% since 2006

By Dawn Denmar

Aug 31, 2013 in Health

Recent studies show the global death rate for AIDS has fallen by 21 percent since 2006, but AIDS-related mortality and disabilities from HIV are rising in 22 percent of the 182 countries reporting AIDS due to low prevalence or late arrival of the virus.

The Global Burden of Disease, Injuries and Risk Factors Study 2010 found that worldwide AIDS/HIV peaked in 2006 and has been slowly declining at an average annual rate of just over 4 percent since. The decline is due to decreased incidence of the virus in some areas, together with more common use of anti-retroviral medications.

World Health Organization statistics on HIV/AIDS show that since the disease was first recognized, nearly 70 million people have been infected with the HIV virus, with 35 million deaths. Sub-Saharan Africa accounts for 69 percent of the total people living with HIV and globally. It is estimated that 0.8 percent of adults from 15 to 49 years of age are living with HIV.

The disease burden is measured by DALYS, which are standardized calculations based on the sum of years of life with the virus and the years of life lost due to premature mortality, together with the percentage of deaths and proportion of global death and disabilities.

Findings show that in 2010 HIV/AIDS was the leading cause of DALYS for men and women in the 30 to 44 age group. It is also the highest cause of DALYS for 21 countries globally.

HIV is the top cause of death in southern and East African countries, including South Africa and Somalia. It is the worst health problem in a number of West African countries and number two in Nigeria, Cameroon and Ghana. It is the number one cause for DALYS lost in a number of Caribbean countries including Jamaica, Belize and Suriname and the largest cause of death and disability in Thailand. In Russia it is the fourth largest cause of DALYS lost, but the size of the country means it contributes more to the total figures of global disease, giving Russia its place in the top ten worst affected countries.

Countries that have seen the largest drop in AIDS burden are either high-income countries that put control measures into place at an early stage, or low income countries that have initiated good anti-retroviral programs.

Eight countries have reduced DALYS lost by more than 80 percent including Spain, France and Rwanda.

There are only eight countries in the world that have not yet recorded cases of AIDS, typically these are small Pacific nations.

Although the declining rates of AIDS and HIV conveyed by the report indicate an overall promising situation, this should not be a cause for complacence. The report highlights a number of trends but it is clear that the virus is still very much a global problem with country, and often city-specific, needs that have to be addressed at localized levels.

Source

Third International Symposium on Hepatitis Care in Substance Users, Munich, Germany

[Event Date: 2013-09-05]
[Expiry Date: 2013-09-05]

The Third International Symposium on Hepatitis Care in Substance Users (INHSU) will be held from 5 to 6 September 2013 in Munich, Germany.

Hepatitis C is caused by the virus (HCV) which is most prevalent among injecting drug users. This high-risk group acts as a virus reservoir and threatens to be responsible for the future burden of HCV-induced disease.

This event will bring together experts from various disciplines in health and social care. It will promote novel intervention strategies for hepatitis in substance users by taking a cross-sectional approach to pathogenic, diagnostic and therapeutic research.

For further information, please visit:
http://www.inhsu.com/about-inhsu.html

Category: Events
Data Source Provider: Arud Centres for Addiction Medicine
Document Reference: Based on an event announcement
Subject Index: Healthcare delivery/services; Medicine, Health

RCN: 35995

Source

Factors Associated With Guideline-based Hepatitis C Virus (HCV) Treatment Initiation in HIV/HCV-coinfected Patients

HIV Medicine

Role of Comorbidities and Physicians' Perceptions

M Winnock, F Bani-Sadr, E Pambrun, M-A Loko, P Carrieri, D Neau, P Morlat, B Marchou, F Dabis and D Salmon

HIV Medicine. 2013;14(7):430-436.

Abstract and Introduction

Abstract

Objectives Many HIV-infected patients with chronic hepatitis C virus (HCV) infection do not receive treatment for HCV infection, often because of contraindications or poor adherence to anti-HIV therapy. The aim of this study was to identify factors influencing guideline-based HCV treatment initiation in a large cohort of HIV/HCV-coinfected patients.

Methods Between 2005 and 2011, 194 (40.5%) of 479 coinfected patients not previously treated for HCV infection started this treatment based on current recommendations, i.e. a Metavir score > F1 for liver fibrosis; HCV genotype 2 or 3 infection; or HCV genotype 1 or 4 infection and low HCV viral load (< 800 000 IU/mL), whatever the fibrosis score. Clinical and biological data were compared between patients who started HCV therapy during follow-up and those who did not.

Results In multivariate analyses, good adherence to treatment for HIV infection, as judged by the patient's physician, was associated with HCV treatment initiation [odds ratio (OR) 2.37; 95% confidence interval (CI) 1.17–4.81; P = 0.017], whereas patients with children (OR 0.53; 95% CI 0.30–0.91; P = 0.022) and those with cardiovascular disease or respiratory distress (OR 0.10; 95% CI 0.01–0.78; P = 0.03) were less likely to be treated.

Conclusions Adherence to treatment for HIV infection, as judged by the patient's physician, appears to have a major influence on the decision to begin treatment for HCV infection in coinfected patients. This calls for specific therapeutic education and adherence support in order to ensure timely anti-HCV therapy in this population.

Introduction

Compared with isolated hepatitis C virus (HCV) infection, concurrent infection by HIV and HCV results in more rapid progression towards cirrhosis and liver failure.^{[1, 2]} In the last decade, chronic liver disease, mainly resulting from HCV infection, has become one of the leading causes of morbidity and mortality in HIV-infected patients.^[3] In the first published trials of anti-HCV therapy in this setting, the pegylated interferon alpha (peg-interferon) and ribavirin combination was less effective in HIV-coinfected patients. Sustained virological response (SVR) rates ranged from 14 to 38% among patients with HCV genotype 1 infection and from 44 to 73% among those with genotype 2 or 3 infection.^{[4, 5]} However, markedly higher SVR rates among coinfected patients, reaching more than 50%, have been observed in clinical practice in the last few years.^[6] Furthermore, SVR has been found to have major benefits in HIV/HCV-coinfected patients, with slower progression of fibrosis, less frequent severe liver toxicity of antiretroviral therapy, and a reduction in liver-related complications and mortality.^{[1, 7]} Under-treatment of chronic HCV infection in HIV-infected patients remains frequent, however, for several reasons, including contraindications, patient refusal and poor adherence.^{[6, 8, 9]} The French Expert Group recommendations for medical management of HIV infection advised the use of peg-interferon plus ribavirin combination therapy for patients with stage ≥ F2 fibrosis and, whatever the fibrosis score, for patients with a high likelihood of achieving an SVR, i.e. patients infected with genotype 2 or 3 and those infected with genotype 1 or 4 who have a low viral load (< 800 000 IU/mL).^[10] The aim of this study was to identify factors associated with guideline-based HCV treatment initiation in a large cohort of HIV/HCV-coinfected patients.

Methods

This study involved HIV/HCV-coinfected patients enrolled in the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) CO13 HEPAVIH cohort, a French prospective hospital-based cohort of HIV/HCV-coinfected adults, created in 2005 and involving 17 hospital units, of which 16 were academic hospitals.^[11]

The outcome variable was the initiation of HCV treatment, defined as the first prescription of peg-interferon and ribavirin to an HCV-treatment-naïve patient during follow-up (between 2005 and 2011). In a first analysis, clinical and biological data were compared between patients with an indication for HCV therapy and who started treatment during follow-up (patients with ≥ F2 fibrosis, patients infected with genotype 2 or 3, and patients infected with genotype 1 or 4 who had a low viral load (< 800 000 IU/mL), whatever the fibrosis score), and patients who remained HCV-treatment-naïve. The second analysis was restricted to patients with a formal indication for HCV therapy, i.e. a fibrosis score ≥ F2 regardless of the HCV genotype.

Liver fibrosis was assessed by liver histology or noninvasive methods [transient elastometry (TE) or FibroTest (BioPredictive, Paris, France)]. The results of liver biopsy (LB), when available, were documented and graded with the Metavir system. Liver fibrosis was systematically assessed with noninvasive methods [FibroTest and/or FibroScan (Echosens, Paris, France)]. FibroScan cut-offs used for conversion to the Metavir score were as follows: F0–F1, < 7.1 kPa; F2, 7.1–9.5 kPa; F3, 9.5–12.5 kPa, and F4, ≥ 12.5 kPa.^[12] Only liver stiffness measurements based on 10 successful acquisitions with a success rate of at least > 60% and an interquartile range of < 30% were considered reliable.

The following data were collected at enrolment, during follow-up, and at HCV treatment initiation: age, sex, risk categories for HIV and HCV infection, alcohol consumption and smoking, active drug use (yes/no), duration of HIV infection, use of highly active antiretroviral therapy (HAART) and duration of antiretroviral therapy, duration of HCV infection (from the date of the first transfusion, first narcotic injection, or first positive HCV serology in subjects infected through sexual contact and who did not develop acute hepatitis), liver enzyme activities, CD4 lymphocyte counts (absolute number and percentage) at baseline and at initiation of antiretroviral therapy, plasma HIV RNA and HCV RNA load, and the HCV genotype.

The self-administered patient questionnaire used at baseline included items on socio-demographic characteristics (secondary school certificate, parenthood, living alone/with a partner, employment, and housing conditions), psychiatric disorders (depressive symptoms) and use of antidepressant drugs. Items on patients' beliefs about the effectiveness and toxicity of HCV treatment, measured on a four-point visual analogue scale, were also included.^[13]

Depressive symptoms were assessed with the Center for Epidemiological Studies Depression Questionnaire (CES-D), which provides a global depression score ranging from 0 to 60, with gender-specific cut-off values (17 for men and 23 for women).^{[14, 15]} Score values above these cut-offs were taken to indicate the presence of depressive symptoms.

A section of the self-administered questionnaire, based on the Symptoms Distress Module proposed by Justice et al., collected data on the occurrence of 39 treatment-related symptoms (defined here as self-reported side effects) over the previous 4 weeks, and the discomfort they caused.^[14]

A self-administered questionnaire was provided to the physician for each one of his/her patients which allowed the collection of data on the physicians' experience with HIV and the physicians' perceptions about their patients in terms of adherence to HIV treatment, depression, and alcohol use at enrolment and at scheduled annual visits.

Among patients potentially eligible for HCV treatment, we compared clinical, biological and psychosocial data between patients who initiated HCV therapy during cohort follow-up and patients who did not begin this treatment. Explanatory variables were collected at the HCV treatment initiation visit for patients who had initiated treatment, and at the last follow-up visit for HCV-treatment-naïve patients. Continuous variables were expressed as medians (range), and categorical variables as frequencies and percentages. The χ² test or Fisher's exact test was used to compare qualitative variables, and the Mann–Whitney–Wilcoxon test was used for quantitative variables. Logistic regression models were used to identify associations between the outcome variable and explanatory variables. Factors with P-values < 0.20 in univariate analyses were included in a multivariate model. The Hosmer–Lemeshow backward procedure was used to select factors associated with HCV treatment initiation. All statistical tests were two-sided, with a type I error of 5%.

Results

Among 1048 chronically HCV/HIV-coinfected patients included in the HEPAVIH cohort, 347 patients (33.1%) had already received HCV treatment before enrolment in the cohort (before 2005) and were excluded from this study. Compared with all remaining patients, these previously treated patients were significantly older [median age 46 (range 31–81) years vs. 44 (range 18–70) years for remaining patients; P = 0.0023], had a longer duration of antiretroviral therapy [median 125 (range 1–255) months vs. 110 (range 1–244) months, respectively; P = 0.0001], had a lower prevalence of alcohol consumption [never or former (as opposed to current) drinkers, 28% vs. 20%, respectively; P = 0.0062], had a more frequent liver fibrosis score ≥ F2 (66% vs. 47%, respectively; P < 0.0001), and had more frequent cirrhosis (35% vs. 19%, respectively; P < 0.0001).

Among the 479 patients with an indication for HCV therapy at enrolment in the cohort, 194 (40.5%) initiated this treatment during follow-up. Table 1 shows the last clinical and biological data obtained before HCV treatment initiation in patients who started HCV therapy (n = 194) and in patients who did not start HCV therapy (n = 285).

Table 1.  Last clinical and biological data before guideline-based hepatitis C virus (HCV) treatment initiation in HIV/HCV-coinfected patients (indications: ≥ F2 fibrosis, genotype 2 or 3 infection, and genotype 1 or 4 infection with low viral load (< 800 000 IU/mL)

	HCV treatment initiation		P value
No	Yes
Number (total = 479)	285	194
Age (years)	48 (21–75)	45 (23–62)	<0.0001
Male gender	192 (67)	145 (75)	0.08
European origin	176 (69)	127 (72)	0.72
High-school certificate (yes)	60 (28)	54 (36)	0.10
Living with a partner	117 (49)	85 (50)	0.91
Having children	88 (37)	46 (27)	0.03
Employment (yes)	108 (45)	87 (51)	0.27
Home owner or tenant (yes)	187 (79)	131 (77)	0.58
Alcohol consumption			0.03
None or formerly	107 (43)	91 (52)
≤50 g daily for men or ≤30 g daily for women	132 (53)	71 (41)
>50 g daily for men or >30 g daily for women	11 (4)	13 (7)
Duration of HIV infection (years)	21 (2–29)	18 (1–29)	<10-4
AIDS	92 (32)	55 (31)	0.70
Lipodystrophy (yes)	118 (52)	91 (53)	0.84
CD4 count nadir (cells/μL)	138 (1–1258)	144 (0–918)	0.12
Absolute CD4 count (cells/μL)	490 (6–2574)	444 (63–1363)	0.16
CD4 count <150 cells/μL	21 (7)	4 (2)	0.01
Patients with <50 HIV RNA copies/ml	211 (76)	143 (78)	0.58
Ongoing antiretroviral treatment*	263 (92)	179 (92)	0.18
Duration of antiretroviral treatment (months)*	146 (0–268)	122 (0–232)	<10-4
Good adherence to HIV therapy, as perceived by physician (yes)	181 (78)	130 (84)	0.04
Duration of HCV infection (years)	27 (2–40)	24 (1–38)	<10-4
HCV infection through injecting drug use	212 (84)	139 (80)	0.36
History of decompensated cirrhosis, hepatocarcinoma or transplantation (%)	10 (4)	7 (4)	0.95
Metavir score > F1	180 (68)	147 (77)	0.04
HCV viral load (IU/ml), log10	5.9 (2.1–7.7)	6.0 (3.1–7.8)	0.07
HCV genotype			0.01
1	128 (45)	106 (55)
2	16 (6)	10 (5)
3	66 (23)	51 (26)
4	75 (26)	27 (14)
ALT (× normal upper limit)	1.2 (0.1–27.7)	1.4 (0,3–9,9)	0.005
Platelet count (cells/μL)	192 (23–589)	183 (32–458)	0.59
Prothrombin time <70%	10 (4)	11 (6)	0.22
Patients with negative perceptions of HCV treatment side effects (severe vs. moderate or none)	67 (49)	47 (41)	0.47
Patients with negative perceptions of HCV treatment efficacy (none or low vs. high)	52 (38)	48 (42)	0.85
Type 2 diabetes	10 (4)	12 (6)	0.17
Cardiovascular disease or respiratory distress	21 (7)	8 (4)	0.14
History of multiple treatments for depression, as reported by physician	53 (19)	29 (15)	0.30
Depression: patient's self perception	152 (64)	106 (62)	0.68
Follow-up in hospital units having enrolled more than 25 patients	225 (79)	149 (77)	0.58

Results are shown as median (range) or number (%).

ALT, alanine aminotransferase.

*Zero in patients not receiving antiretroviral therapy.

In univariate analyses, the following factors were significantly related to HCV treatment initiation: age, male sex, less alcohol consumption (current vs. former or none), childless status, shorter durations of HIV infection and antiretroviral therapy, a higher current CD4 cell count (≥ 150vs. < 150 cells/μL), a shorter duration of HCV infection, a higher alanine aminotransferase (ALT) level, and better adherence to HIV treatment, as perceived by the physician.

No association was observed between HCV treatment and ethnicity, living alone/with a partner, employment status, home ownership/rental, HCV infection through injecting drug use, AIDS status, ongoing antiretroviral treatment, lipodystrophy, a history of decompensated cirrhosis, hepatocarcinoma and/or transplantation, type 2 diabetes, a history of multiple treatments for depression (as reported by the physician), depressive symptoms or negative perceptions about HCV treatment efficacy or side effects and the hospital unit in which the patients were followed up.

Other factors such as a higher level of education (P = 0.098), a higher CD4 cell nadir (P = 0.099) and no history of cardiovascular disease or respiratory distress (P = 0.15) tended to be associated with HCV treatment initiation.

The liver fibrosis score, HCV genotype and HCV viral load (the parameters used to select the study population) were not included in the multivariate model.

In multivariate analysis (Table 2), good adherence to antiretroviral treatment, as perceived by the physician [odds ratio (OR) 2.37; 95% confidence interval (CI) 1.17-4.81; P = 0.017], remained associated with HCV treatment initiation, whereas parenthood (OR 0.53; 95% CI 0.30-0.91; P = 0.022) and a history of cardiovascular disease or respiratory distress (OR 0.10; 95% CI 0.01-0.78; P = 0.03) were associated with the absence of HCV treatment.

Table 2.  Correlates of hepatitis C virus (HCV) treatment initiation in HIV/HCV-coinfected patients with an indication for HCV therapy* (n = 479)

Univariate analyses		Multivariate analysis
OR (95% CI)	P value	OR (95% CI)	P value
Male gender	1.43 (0.95–2.15)	0.08
High-school certificate (yes)	1.46 (0.93–2.28)	0.098
Having children	0.63 (0.41–0.97)	0.036	0.53 (0.30–0.91)	0.022
Alcohol consumption: current vs. past or never (%)	0.67 (0.46–0.99)	0.045
CD4 count <150 vs. ≥150 cells/μL	3.73 (1.26–11.1)	0.017
ALT (× normal upper limit)	1.08 (0.98–1.20)	0.13
Good adherence, as perceived by the physician (yes)	1.50 (0.87–2.55)	0.14	2.37 (1.17–4.81)	0.017
Cardiovascular disease or respiratory distress	0.54 (0.23–1.25)	0.15	0.10 (0.01–0.78)	0.03

ALT, alanine aminotransferase.

*Patients with ≥ F2 fibrosis, patients infected with genotype 2 or 3, and patients infected with genotype 1 or 4 and with low viral load (< 800 000 IU/mL).

As adherence to HIV treatment was associated with HCV treatment initiation, we examined whether certain patient characteristics were associated with good adherence. Patients with good adherence to HIV treatment, as perceived by the physician, had lower alcohol consumption [current (as opposed to former or none), 32% vs. 51% for patients with poor perceived adherence; P = 0.0013] and fewer depressive symptoms (60% vs. 75%, respectively; P = 0.02), were more likely to own or rent their home (80% vs. 67%, respectively; P = 0.03), were less likely to have contracted HCV through injecting drug use (81% vs. 91%, respectively; P = 0.048) and had a higher CD4 cell nadir [median 156 (range 64–266) cells/μL vs. 98 (range 30–184) cells/μL, respectively; P = 0.002] than patients with poor perceived adherence. HIV viral load did not differ between the two groups.

We then restricted the analysis to the 339 patients with a formal indication for HCV therapy (fibrosis score ≥ F2 whatever the HCV genotype), of whom 147 patients (43.3%) received this treatment. In multivariate analysis, only good perceived adherence to HIV treatment remained associated with HCV treatment initiation (OR 2.40; 95% CI 1.08-5.32; P = 0.031).

Discussion

We analysed factors associated with HCV treatment initiation between 2005 and 2011 in a large cohort of HIV/HCV-coinfected patients (n = 1048) managed in 17 French hospital units. One-third of the patients (n = 347) had been treated for HCV infection before their enrolment in the cohort (before 2005). Among the remaining, treatment-naïve patients, 194 (40.5%) of those with an indication for HCV therapy, as defined in French guidelines (see Methods), started treatment with peg-interferon plus ribavirin during cohort follow-up.^[16] [European guidelines for HCV therapy are similar to French guidelines, except that they include a lower HCV viral load threshold (< 400 000–500 000 IU/mL) for patients with genotype 1 infection, and do not deal with HCV genotype 4 infection [16]].

Patients with good adherence to HIV treatment (as perceived by their physician), patients who were childless, and patients with no history of cardiovascular disease or respiratory distress were more likely to be treated. When the analysis was restricted to the 339 patients with a formal indication for HCV treatment (fibrosis score ≥ F2), the only factor associated with HCV treatment initiation was good perceived adherence to HIV treatment.

Good adherence is critical for the efficacy of both anti-HIV and anti-HCV therapy.^{[17, 18]} High levels of adherence are required to obtain sustained HIV suppression and long-term immunological and clinical benefits. The optimal level of adherence may differ according to the antiretroviral class, and should be better than 95% for nonboosted or boosted protease inhibitor (PI) regiments and at least 80% for nonnucleoside reverse transcriptase inhibitor (NNRTI) regimens.^{[18, 19]} Good adherence to HCV therapy is also required to achieve a sustained viral response, with a 'golden rule' of 80/80/80 (continued prescription of at least 80% of the interferon dose and 80% of the ribavirin dose for at least 80% of the planned treatment period).^[17] Patients who take > 80% of their peg-interferon alpha-2b plus ribavirin dosage for the entire treatment period have higher SVR rates.^{[17, 20]} Adherence tends to be better for peg-interferon than for ribavirin, but decreases over time for both medications. Self-reported adherence is usually higher than that assessed by electronic measures, and the degree of discrepancy increases as treatment progresses.^[21]

In our study, 16% of patients did not receive HCV treatment because their physician considered their adherence to HIV treatment to be poor. In other studies, poor adherence or patient refusal was the reason for noninitiation of HCV treatment in 18% to 22% of patients.^{[8, 9]} Specific interventions should be able to reduce this figure.

Social determinants may have a bearing on an individual's decision to begin anti-HCV treatment. In our study, parenthood was the only such factor associated with a lower rate of HCV therapy. Living with a partner was not a barrier to HCV therapy, but there was a trend in univariate analysis towards a higher rate of HCV treatment initiation in men (P = 0.08). The long duration of HCV therapy and side effects such as asthenia and depressive symptoms probably explain this barrier to HCV treatment in mothers. Newly available anti-HCV drugs with better efficacy, possibly allowing shorter treatment, may help to overcome this barrier. Housing status was not directly associated with HCV treatment initiation in our study, but patients who did not either own or rent their home were more likely to be considered as having poor adherence to HIV therapy by their physicians. Social interventions may help to ensure timely HCV treatment in this population.

Barriers to HCV treatment are more frequent in HIV/HCV-coinfected patients than in patients with isolated HCV infection, and mainly involve severe psychiatric disorders and ongoing alcohol use.^[6] We found that cardiovascular disease and respiratory distress were also barriers to HCV treatment initiation. Patients with a history of multiple treatments for depression were less likely to be treated when treated and nontreated patients were compared, whatever the indication (OR 0.39; 95% CI 0.17-0.88; P = 0.02) (data not shown).

Interestingly, despite the lower efficacy and poorer tolerability of HCV treatment in HIV/HCV-coinfected patients, we found no association between patients' negative perceptions of side effects or efficacy and treatment initiation. This could be a result of the fact that most patients (68%) had a formal indication for HCV treatment (Metavir score ≥ F2).

The main strength of our study is its large size: we enrolled 1048 HIV/HCV-coinfected patients managed in 17 hospital units throughout France, all with lengthy follow-up. This population was therefore probably adequately represented in the sample. The most important limitation of this study is probably our inability to determine the main reasons why physicians decided not to start HCV therapy. The number of different reasons cited by physicians for nontreatment has fallen over the years. HCV treatment is deemed less questionable: the lack of liver biopsy no longer seems to be a major barrier, and the number of contraindications to HCV treatment has also decreased.^[6] However, the numerous side effects associated with either peg-interferon or ribavirin, such as asthenia or depression, and/or the increase in the number of pills, which may result in poor adherence to therapy and therefore poor efficacy, could remain the reasons why physicians defer HCV treatment in some patients.

The second limitation of our study is that adherence to HIV therapy was only evaluated through the physician's personal perception and not by more objective methods such as self-reporting, pharmacy refill data or pill counting. However, in our study, perceived poor adherence to HIV therapy was associated with well-known factors such as alcohol consumption, homelessness, a history of injecting drug use, and depressive symptoms.^{[22, 23]} The nadir CD4 cell count was also lower in patients with poorer adherence, reflecting a delay in linkage to care. In contrast, the rates of undetectable plasma HIV and CD4 cell counts were similar between patients who started HCV therapy and those who did not, maybe reflecting a hint of a discrepancy between the physician's personal perception and actual antiretroviral therapy adherence. Therefore, we presume that the physician's perception about adherence may be more related to perceived tolerability and potential risk of HCV treatment interruption. Developing expertise in HCV treatment and effective strategies for managing the side effects often encountered during HCV treatment might help to change physicians' personal perception of patients' poor adherence and help them to overcome the challenges of HCV therapy.

In conclusion, adherence to HIV therapy, as perceived by the patient's physician, seems to play a key role in the decision to prescribe treatment for HCV infection to HCV/HIV-coinfected patients. As a high level of adherence is required for new HCV PIs, which carry a higher risk of inducing resistance [24] and are possibly more toxic, developing the physician's expertise in HCV treatment, therapeutic education and adherence support might help to enable timely HCV treatment in patients with poor adherence to HIV therapy.

References

1. Bani-Sadr F, Lapidus N, Bedossa P et al. Progression of fibrosis in HIV and hepatitis C virus-coinfected patients treated with interferon plus ribavirin-based therapy: analysis of risk factors. Clin Infect Dis 2008; 46: 768–774.

2. Loko MA, Bani-Sadr F, Winnock M et al. Impact of HAART exposure and associated lipodystrophy on advanced liver fibrosis in HIV/HCV-coinfected patients. J Viral Hepat 2011; 18: e307–e314.

3. Salmon-Ceron D, Rosenthal E, Lewden C et al. Emerging role of hepatocellular carcinoma among liver-related causes of deaths in HIV-infected patients: the French national Mortalite 2005 study. J Hepatol 2009; 50: 736–745.

4. Carrat F, Bani-Sadr F, Pol S et al. Pegylated interferon alfa-2b vs standard interferon alfa-2b, plus ribavirin, for chronic hepatitis C in HIV-infected patients: a randomized controlled trial. JAMA 2004; 292: 2839–2848.

5. Torriani FJ, Rodriguez-Torres M, Rockstroh JK et al. Peginterferon Alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med 2004; 351: 438–450.

6. Cacoub P, Halfon P, Rosenthal E et al. Care of hepatitis C virus infection in human immunodeficiency virus-infected patients: modifications in three consecutive large surveys between 2004 and 2009. J Hepatol 2010; 53: 230–237.

7. Macias J, Berenguer J, Japon MA et al. Fast fibrosis progression between repeated liver biopsies in patients coinfected with human immunodeficiency virus/hepatitis C virus. Hepatology 2009; 50: 1056–1063.

8. Angeli E, Mainini A, Meraviglia P et al. Eligibility and feasibility of the treatment of chronic hepatitis C in a Cohort of Italian HIV-positive patients at a single HIV reference center. AIDS Patient Care STDS 2011; 25: 295–301.

9. Reiberger T, Obermeier M, Payer BA et al. Considerable under-treatment of chronic HCV infection in HIV patients despite acceptable sustained virological response rates in a real-life setting. Antivir Ther 2011; 16: 815–824.

10. Rapport du Groupe. d'Experts 2008 sur la prise en charge médicale des patients infectées par le VIH, sous la direction du Pr Patrick Yeni 2008:254–285.

11. Loko MA, Salmon D, Carrieri P et al. The French national prospective cohort of patients co-infected with HIV and HCV (ANRS CO13 HEPAVIH): early findings, 2006-2010. BMC Infect Dis 2010; 10: 303.

12. Castera L, Vergniol J, Foucher J et al. Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology 2005; 128: 343–350.

13. Fuhrer RRF. La version française de l'échelle CES-D. Description and translation of the autoevaluation scale (in French). Psychiatrie et Psychobiologie 1989; 4: 163–166.

14. Justice AC, Holmes W, Gifford AL et al. Development and validation of a self-completed HIV symptom index. J Clin Epidemiol 2001; 54 (Suppl 1): S77–S90.

15. Bohn MJ, Babor TF, Kranzler HR. The Alcohol Use Disorders Identification Test (AUDIT): validation of a screening instrument for use in medical settings. J Stud Alcohol 1995; 56: 423–432.

16. Rockstroh JK, Bhagani S, Benhamou Y et al. European AIDS Clinical Society (EACS) guidelines for the clinical management and treatment of chronic hepatitis B and C coinfection in HIV-infected adults. HIV Med 2008; 9: 82–88.

17. McHutchison JG, Manns M, Patel K et al. Adherence to combination therapy enhances sustained response in genotype-1-infected patients with chronic hepatitis C. Gastroenterology 2002; 123: 1061–1069.

18. Maggiolo F, Ravasio L, Ripamonti D et al. Similar adherence rates favor different virologic outcomes for patients treated with nonnucleoside analogues or protease inhibitors. Clin Infect Dis 2005; 40: 158–163.

19. Glass TR, Rotger M, Telenti A et al. Determinants of sustained viral suppression in HIV-infected patients with self-reported poor adherence to antiretroviral therapy. PLoS ONE 2012; 7: e29186.

20. Wagner G, Chan Osilla K, Garnett J et al. Patient characteristics associated with HCV treatment adherence, treatment completion, and sustained virologic response in HIV coinfected patients. AIDS Res Treat 2011; 2011: 903480.

21. Smith SR, Wahed AS, Kelley SS, Conjeevaram HS, Robuck PR, Fried MW. Assessing the validity of self-reported medication adherence in hepatitis C treatment. Ann Pharmacother 2007; 41: 1116–1123.

22. Starace F, Ammassari A, Trotta MP et al. Depression is a risk factor for suboptimal adherence to highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2002; 31 (Suppl 3): S136–S139.

23. Lazo M, Gange SJ, Wilson TE et al. Patterns and predictors of changes in adherence to highly active antiretroviral therapy: longitudinal study of men and women. Clin Infect Dis 2007; 45: 1377–1385.

24. Weiss JJ, Alcorn MC, Rabkin JG, Dieterich DT. The critical role of medication adherence in the success of boceprevir and telaprevir in clinical practice. J Hepatol 2012; 56: 503–504.

Source

Hepatitis C: A Focus on Dietary Supplements

Provided by NIH - National Center for Complementary and Alternative Medicine (NCCAM)

Get The Facts

Introduction

Hepatitis C is a liver disease caused by a virus. It is usually chronic (long-lasting), but most people do not have any symptoms until the virus causes liver damage, which can take 10 or more years to happen. Without medical treatment, chronic hepatitis C can eventually cause liver cancer or liver failure. Conventional medical treatments are available for chronic hepatitis C. Some people with hepatitis C also try complementary health approaches, especially dietary supplements. This fact sheet provides basic information on hepatitis C, summarizes scientific research on selected supplements, and suggests sources for additional information.

Key Points

• Are Dietary Supplements for Hepatitis C Safe?
  • Colloidal silver is not safe; it can cause irreversible side effects.
  • Data on the safety of other supplements is limited. However, some can have side effects or may interact in harmful ways with medications, and some may be unsafe for people with certain health problems.
  • If you have hepatitis C, check with your health care provider before using any dietary supplement to make sure that it is safe for you and compatible with any medical treatment that you are receiving for hepatitis C or any other health problem.
• Are Dietary Supplements for Hepatitis C Effective?
  • No dietary supplement has been shown to be effective for hepatitis C or its complications.
  • The results of research supported by the National Center for Complementary and Alternative Medicine (NCCAM) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) have shown that silymarin, the active extract of milk thistle and the most popular complementary health product taken by people with liver disease, was no more effective than placebo in people with hepatitis C.
  • Research on other dietary supplements for hepatitis C, such as zinc, licorice root (or its extract glycyrrhizin), S-adenosyl-L-methionine (SAMe), and lactoferrin, is in its early stages, and no firm conclusions can be reached about the potential effectiveness of these supplements.

Keep in Mind

• It is important not to replace conventional medical therapy for hepatitis C with dietary supplements or other approaches that have not been shown to be effective.
• Tell all your health care providers about any complementary health approaches you use. Give them a full picture of what you do to manage your health. This will help ensure coordinated and safe care.

About Hepatitis C

Hepatitis C, a contagious liver disease, is caused by the hepatitis C virus. People can get hepatitis C through contact with blood from a person who is already infected or, less commonly, through having sex with an infected person. The infection usually becomes chronic. Chronic hepatitis C often is treated with drugs that can eliminate the virus. This may slow or stop liver damage, but the drugs may cause side effects, and for some people, treatment is ineffective. An estimated 3.2 million Americans have chronic hepatitis C. To learn more about hepatitis C, visit the NIDDK Web site.

Use of Herbal Supplements and Other Complementary Approaches for Hepatitis C

Several herbal supplements have been studied for hepatitis C, and substantial numbers of people with hepatitis C have tried herbal supplements. For example, a survey of 1,145 participants in the HALT-C (Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis) trial, a study supported by the National Institutes of Health (NIH), found that 23 percent of the participants were using herbal products. Although participants reported using many different herbal products, silymarin (milk thistle) was by far the most common. Another study, which surveyed 120 adults with hepatitis C, found that many used a variety of complementary health approaches, including multivitamins, herbal remedies, massage, deep breathing exercises, meditation, progressive relaxation, and yoga.

What the Science Says

No dietary supplement has been shown to be effective for hepatitis C. This section summarizes what is known about the safety and effectiveness of milk thistle and some of the other dietary supplements studied for hepatitis C.

• Milk thistle (scientific name Silybum marianum) is a plant from the aster family. Silymarin is an active component of milk thistle believed to be responsible for the herb’s health-related properties. Milk thistle has been used in Europe for treating liver disease and jaundice since the 16th century. In the United States, silymarin is the most popular dietary supplement taken by people with liver disease. However, two rigorously designed studies of silymarin in people with hepatitis C did not show any benefit.
  • A 2012 controlled clinical trial, cofunded by NCCAM and NIDDK, showed that two higher-than-usual doses of silymarin were no better than placebo in reducing the high blood levels of an enzyme that indicates liver damage. In the study, 154 people who had not responded to standard antiviral treatment for chronic hepatitis C were randomly assigned to receive 420 mg of silymarin, 700 mg of silymarin, or placebo three times per day for 24 weeks. At the end of the treatment period, blood levels of the enzyme were similar in all three groups.
  • Results of the HALT-C study mentioned above suggested that silymarin use by hepatitis C patients was associated with fewer and milder symptoms of liver disease and somewhat better quality of life, but there was no change in virus activity or liver inflammation. The researchers emphasized that this was a retrospective study (one that examined the medical and lifestyle histories of the participants). Its finding of improved quality of life in patients taking silymarin was not confirmed in the more rigorous 2012 study described above.

Safety. Available evidence from clinical trials in people with liver disease suggests that milk thistle is generally well-tolerated. Side effects can include a laxative effect, nausea, diarrhea, abdominal bloating and pain, and occasional allergic reactions. In NIH-funded studies of silymarin in people with hepatitis C that were completed in 2010 and 2012, the frequency of side effects was similar in people taking silymarin and those taking placebos. However, these studies were not large enough to show with certainty that silymarin is safe for people with chronic hepatitis C.

Other supplements have been studied for hepatitis C, but overall, no benefits have been clearly demonstrated. These supplements include the following:

• Probiotics are live microorganisms that are intended to have a health benefit when consumed. Research hasn’t produced any clear evidence that probiotics are helpful in people with hepatitis C. Most people can use probiotics without experiencing any side effects—or with only mild gastrointestinal side effects such as intestinal gas—but there have been some case reports of serious adverse effects in people with underlying serious health conditions.
• Preliminary studies, most of which were conducted outside the United States, have examined the use of zinc for hepatitis C. Zinc supplements might help to correct zinc deficiencies associated with hepatitis C or reduce some symptoms, but the evidence for these possible benefits is limited. Zinc is generally considered to be safe when used appropriately, but it can be toxic if taken in excessive amounts.
• A few preliminary studies have looked at the effects of combining supplements such as lactoferrin, SAMe, or zinc with conventional drug therapy for hepatitis C. The evidence is not sufficient to draw clear conclusions about benefit or safety.
• Glycyrrhizin—a compound found in licorice root—has been tested in a few clinical trials in hepatitis C patients, but there is currently not enough evidence to determine if it is helpful. In large amounts, glycyrrhizin or licorice can be dangerous in people with a history of hypertension (high blood pressure), kidney failure, or cardiovascular diseases.
• Preliminary studies have examined the potential of the following products for treating chronic hepatitis C: TJ-108 (a mixture of herbs used in Japanese Kampo medicine), schisandra, oxymatrine (an extract from the sophora root), and thymus extract. The limited research on these products has not produced convincing evidence that they are helpful for hepatitis C.
• Colloidal silver has been suggested as a treatment for hepatitis C, but there is currently no research to support its use for this purpose. Colloidal silver is known to cause serious side effects, including a permanent bluish discoloration of the skin called argyria (for more information, see the NCCAM fact sheet Colloidal Silver.

NCCAM-Funded Research

NCCAM-supported research includes projects studying:

• Herbal combinations for boosting antioxidant activity to treat liver disease
• Potential drugs for treating hepatitis C derived from rare and endangered plants.

If You Are Considering Taking a Dietary Supplement for Hepatitis C

• Do not use any complementary health approach to replace conventional treatments for hepatitis C or as a reason to postpone seeing your health care provider about any medical problem.
• Be aware that dietary supplements may have side effects or interact with conventional medical treatments. To learn more about using supplements, see the NCCAM fact sheet Using Dietary Supplements Wisely.
• If you are pregnant or nursing a child, or if you are considering giving a child a dietary supplement, it is especially important to consult your (or your child’s) health care provider. Supplements can act like drugs, and many have not been tested in pregnant women, nursing mothers, or children.
• Tell all your health care providers about any complementary health approaches you use. Give them a full picture of what you do to manage your health. This will help ensure coordinated and safe care. For tips about talking with your health care providers about complementary health approaches, see NCCAM's Time to Talk campaign.

Key References

• Azzam HS, Goertz C, Fritts M, et al. Natural products and chronic hepatitis C virus. Liver International. 2007;27(1):17–25.
• Dhiman RK, Chawla YK. Herbal medicines for liver diseases. Digestive Diseases and Sciences. 2005;50(10):1807–1812.
• Filipowicz M, Bernsmeier C, Terracciano L, et al. S-adenosyl-methionine and betaine improve early virological response in chronic hepatitis C patients with previous nonresponse. PLoS ONE. 2010;5(11):e15492.
• Fried MW, Navarro VJ, Afdhal N, et al. Effect of silymarin (milk thistle) on liver disease in patients with chronic hepatitis C unsuccessfully treated with interferon therapy: a randomized controlled trial. JAMA. 2012;308(3):274–282.
• Ghany MG, Strader DB, Thomas DL, et al. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009;49(4):1335–1374.
• Grüngreiff K, Reinhold D. Zinc: a complementary factor in the treatment of chronic hepatitis C? Molecular Medicine Reports. 2010;3(3):371–375.
• Hawke RL, Schrieber SJ, Soule TA, et al. Silymarin ascending multiple oral dosing phase I study in noncirrhotic patients with chronic hepatitis C. Journal of Clinical Pharmacology. 2010;50(4):434–449.
• Kaito M, Iwasa M, Fujita N, et al. Effect of lactoferrin in patients with chronic hepatitis C: combination therapy with interferon and ribavirin. Journal of Gastroenterology and Hepatology. 2007;22(11):1894–1897.
• Richmond JA, Bailey DE, Patel K, et al. The use of complementary and alternative medicine by patients with chronic hepatitis C. Complementary Therapies in Clinical Practice. 2010;16(3):124–131.
• Seeff LB, Curto TM, Szabo G, et al. Herbal product use by persons enrolled in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial. Hepatology. 2008;47(2):605–612.
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See All References

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Acknowledgments

NCCAM thanks Leslie Curtis, M.A., and her colleagues at NIDDK, and Catherine Meyers, M.D., and John (Jack) Killen, Jr., M.D., NCCAM, for their contributions to the 2013 update of this publication.

This publication is not copyrighted and is in the public domain. Duplication is encouraged.

NCCAM has provided this material for your information. It is not intended to substitute for the medical expertise and advice of your primary health care provider. We encourage you to discuss any decisions about treatment or care with your health care provider. The mention of any product, service, or therapy is not an endorsement by NCCAM.

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NCCAM Pub No.: D422

Date Created: October 2008

Last Updated: May 2013

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