January 25, 2012

Integrated Internist – Addiction Medicine – Hepatology Model for Hepatitis C Management for Individuals on Methadone Maintenance

From Journal of Viral Hepatitis

D. Martinez; R. Dimova; K. M. Marks; A. B. Beeder; M. Zeremski; M. J. Kreek; A. H. Talal

Posted: 01/24/2012; J Viral Hepat. 2012;19(1):47-54. © 2012 Blackwell Publishing

Abstract and Introduction

Despite a high prevalence of hepatitis C virus (HCV) among drug users, HCV evaluation and treatment acceptance are extremely low among these patients when referred from drug treatment facilities for HCV management. We sought to increase HCV treatment effectiveness among patients from a methadone maintenance treatment program (MMTP) by maintaining continuity of care. We developed, instituted and retrospectively assessed the effectiveness of an integrated, co-localized care model in which an internist-addiction medicine specialist from MMTP was embedded in the hepatitis clinic. Methadone maintenance treatment program patients were referred, evaluated by the internist and hepatologist in hepatitis clinic and provided HCV treatment with integration between both sites. Of 401 evaluated patients, anti-HCV antibody was detected in 257, 86% of whom were older than 40 years. Hepatitis C virus RNA levels were measured in 222 patients, 65 of whom were aviremic. Of 157 patients with detectable HCV RNA, 125 were eligible for referral to the hepatitis clinic, 76 (61%) of whom accepted and adhered with the referral. Men engaged in MMTP <36 months were significantly less likely to be seen in hepatitis clinic than men in MMTP more than 36 months (odds ratio = 7.7; 95% confidence interval 2.6–22.9) or women. We evaluated liver histology in 63 patients, and 83% had moderate to advanced liver disease. Twenty-four patients initiated treatment with 19 completing and 13 (54%) achieving sustained response. In conclusion, integrated care between the MMTP and the hepatitis clinic improves adherence with HCV evaluation and treatment compared to standard referral practices.


Five million individuals in the United States are infected with hepatitis C virus (HCV), a virus that can result in cirrhosis, end-stage liver disease and hepatocellular carcinoma. Conventional therapy, consisting of pegylated interferon (PEG-IFN) and ribavirin (RBV), results in viral eradication in roughly one-half of infected individuals.[1,2] Currently, injection drug use is the strongest risk factor for HCV acquisition with HCV seroprevalence >70% among injection drug users (DUs) older than 40 years. However, DUs have been systematically excluded from treatment for HCV owing to stigmatization, physicians' concerns regarding adherence and patients' misinformation concerning the importance of a diagnosis of HCV.[3,4] Between 2010 and 2030, the prevalence of cirrhosis is estimated to increase from 25% to 45% among chronic hepatitis C patients.[5] Simultaneously, the number of treated patients is projected to decline,[6] unless new strategies are developed to enable DUs to obtain antiviral treatment.

Despite the potential benefits of treatment, surprisingly few HCV-infected DUs are offered anti-HCV therapy, even though expert panels have endorsed HCV treatment in this population.[7,8] Active engagement in therapy for addiction has been shown to increase treatment access for various infectious diseases, such as HIV and tuberculosis, among illicit substance users.[9,10] It has also been demonstrated that the longer a patient is engaged in substance abuse treatment the greater the stability and retention in treatment for medical conditions.[11]

Traditional HCV management via referral of DUs to outpatient specialty clinics has resulted in the appearance in the clinic of less than one-third of referred patients.[12] Among DUs, therapeutic effectiveness is an issue of treatment access, acceptance and adherence rather than drug efficacy.[13] Consequently, an approach that integrates the expertise of a variety of disciplines, including specialists in addiction medicine, hepatology, infectious diseases, primary care and psychiatry, has been advocated for the treatment of HCV among DUs.[14] Adherence is likely to be further enhanced if a program offers familiarity, continuity among providers and ready access to health care professionals, as a strong relationship with medical personnel has been shown to be an important determinant of patients receiving preventative care as well as HCV and HIV treatment services.[15–17]

To address these concerns, we devised the 'internist-addiction medicine-hepatology colocalization model', an integrated, co-located program in which an internist-addiction medicine specialist (ADM) evaluated methadone-maintained patients for HCV infection in the hepatology clinic under the direction of a hepatologist (AHT). We applied our model to patients from our institution's two methadone maintenance clinics located in close proximity to our viral hepatitis clinic. A primary premise of our model was that methadone-maintained patients would be more likely to accept an HCV evaluation if continuity of care was maintained between the methadone maintenance treatment program (MMTP) and the viral hepatitis clinic by the same physician caring for patients in both venues.

Treatment Setting and Patient Selection

A total of 401 patients in our institution's two MMTP clinics between July 2006 and June 2008 with available HCV serology were eligible for inclusion. Inclusion criteria were broad, and we purposefully did not exclude active drug or alcohol use except in the case of severe incapacitation as determined by either MMTP staff psychiatrists or the internist-addiction medicine specialist as we desired to pursue HCV management in as many MMTP patients as possible. Patients were excluded if HCV serostatus was unavailable or if their active enrolment in the MMTP during the period under study could not be verified. Patients who had poorly compensated psychiatric disease as determined by MMTP staff psychiatrists were also excluded. No patients were excluded for other medical co-morbidities, such as neurological, endocrine or autoimmune conditions.

The two MMTPs are located within a one-block radius of the viral hepatitis clinic and are staffed by internists, psychiatrists, nurses and social workers. The internist-addiction medicine specialist from the MMTP, who provided comprehensive medical services including chronic disease management, was the primary care physician for the majority of patients. All MMTP patients met DSM IV[18] criteria for a diagnosis of opiate dependence and most had an additional diagnosis of dependence on alcohol, benzodiazepines or cocaine. Data were collected retrospectively through chart review. The study was conducted in accordance with a protocol approved by the Institutional Review Board and consistent with the Helsinki Declaration of 1975, as revised in 1983.

Hepatitis C virus antibody testing was performed on all individuals on admission to the MMTP and then annually in seronegative persons. Upon receipt of a positive HCV antibody test result, the patient was informed of their seropositive status, if not previously aware, provided HCV education and offered referral to the hepatitis clinic (Fig. 1). If the patient accepted referral, MMTP staff scheduled the appointment and recorded the date and time in the computerized methadone-dispensing system. During the week preceding the appointment, patients were reminded twice of their upcoming appointment. All patients who missed their initial appointments were questioned as to the reason for failure to appear. For reasons such as forgetfulness or competing priorities at the time of the initial visit, MMTP staff scheduled a second or third appointment as indicated. If a patient missed more than three appointments, they were considered noncompliant. Hepatitis C virus RNA testing was performed in the hepatitis clinic during the first 6 months of our program, and subsequently testing was performed in the MMTP to expedite the referral process. HIV antibody testing was encouraged at admission to the MMTP and repeated every six to twelve months depending upon whether or not the patient continued to engage in high-risk activities.


Figure 1. Internist-addiction medicine-hepatology colocalization model for hepatitis C evaluation and treatment among patients in the methadone maintenance treatment program. The number of patients at each step of the HCV management process is indicated. HCV, hepatitis C virus; MMTP, methadone maintenance treatment program.

In the hepatitis clinic, the patient was seen by the internist-addiction medicine specialist under the supervision of a hepatologist. All patients underwent a standard medical examination and comprehensive assessment of HCV status that included HCV RNA measurement, HCV genotyping and liver biopsy, if desired and indicated. Consistent with the 2002 NIH Consensus Conference[19] and American Association for the Study of Liver Disease guidelines,[20] patients were strongly encouraged to have histologic assessment of liver disease severity through biopsy as a surrogate marker of adherence. Histology was assessed by staff pathologists using the Scheuer 0–4 point scale.[21] In five patients, we performed FibroSURE™ (LabCorp., Research Triangle Park, NC, USA), a noninvasive test of hepatic fibrosis.

After the biopsy, patients discussed potential HCV treatment in the hepatitis clinic. Besides patient's willingness, we considered fibrosis stage and potential contraindications to PEG-IFN/RBV prior to initiating therapy. All psychiatrically unstable patients underwent psychiatric assessment prior to PEG-IFN/RBV initiation and were monitored monthly while on therapy by MMTP staff psychiatrists. Staff psychiatrists were available on a daily basis in the MMTP for patient consultation. In addition, a psychosomatic medicine fellow was present in the hepatitis clinic on the designated clinic day for consultation if requested by either the hepatologist or the internist-addiction medicine specialist.

According to standard practice, daily attendance in the MMTP is required 6 days per week. Subsequently, phased reductions in attendance can be initiated if the patient maintains abstinence from the use of illicit substances, complies with the predetermined attendance schedule and actively engages in treatment including attendance at counselling sessions with their assigned social worker. Throughout the stabilization process and treatment course, the patient must comply with random urine toxicology screening at frequent intervals.

Antiviral Therapy

Pegylated interferon α-2a 180 μg/week was injected subcutaneously. Prior to initiation of treatment, all patients participated in a teaching session with nursing staff from the viral hepatitis clinic during which the patient was instructed in interferon administration. The first dose was administered during the teaching session, and all subsequent doses were self-administered. In no case did the physicians managing the patient deem it necessary that they receive directly observed therapy. Weight-adjusted RBV was taken orally twice daily at a dose of 800–1200 mg. Hematopoietic stimulating factors were utilized as indicated for anaemia and neutropenia. All patients on PEG-IFN/RBV were seen weekly in the MMTP by the internist-addiction medicine specialist and at 6-week intervals in the liver clinic by both the hepatologist and the addiction specialist on the designated clinic day. Patients were monitored for clinical evidence of opiate withdrawal on a weekly basis by the internist-addiction medicine specialist. If a patient missed the follow-up appointment in the hepatitis clinic, they were seen in the MMTP and rescheduled to be seen in the hepatitis clinic at the first availability. Haematologic parameters and aminotransferase levels were measured weekly for the first month and at 6-week intervals thereafter. Patients had the option to have their blood drawn at either the hepatitis clinic or the MMTP. The internist-addiction medicine specialist and the hepatologist maintained a list of all HCV-seropositive patients and reviewed the status of each patient on a weekly basis either by phone or in person.

Statistical Analysis

Statistical analysis was performed using SAS (SAS Institute Inc., Cary, NC, USA) and R (R Language, version 2.10.0 http://www.r-project.org) The associations between the variables of interest were determined through chi-square tests, Fisher's exact tests, logistic regression modelling and Wald tests. Model selection was based on the Akaike information criterion (AIC). Logistic regression was used to model the probability that a patient who was referred to the liver clinic was adherent and to assess the significant factors that influenced adherence with the referral. First, simple logistic regression was used to determine the factors (gender, ethnicity, age and duration in the MMTP) for inclusion in the model. Criterion for inclusion was P ≤ 0.25. Secondly, the AIC criterion was used to select the best multiple logistic model. In addition, we modelled the probability that a patient in whom treatment was indicated actually initiated PEG-IFN/RBV. The significance level for these tests was set at 0.05, two-tailed.

Patient Characteristics

Of a total of 401 patients, 51% were Caucasian, 34% were Hispanic, 13% were African American and 66% were male (Table 1). HIV antibody testing results were available for 322 subjects, 48 of whom were positive. Of 48 HIV-positive patients, 2 were HCV seronegative, 13 were HCV seropositive but HCV RNA negative and 33 were co-infected with HCV (both HCV RNA and antibody positive).

HCV Disease Characteristics and Evaluation

Serology Hepatitis C virus antibody was obtained at a median age of 43 (33–50) years, on average 2 years after admission to the MMTP. Of 257 HCV-seropositive patients, 86% were older than 40 years, 48% were Caucasian, 35% Hispanic and 16% African American. We found higher HCV seroprevalence with increasing age. Subjects aged 40 years or older were more likely to be HCV antibody positive compared to younger people (odds ratio [OR] = 3.11; 95% CI: 2.00, 4.83, P < 0.0001). However, the association between anti-HCV positivity and age differs significantly among different ethnic groups (P = 0.049). While the likelihood of being anti-HCV positive was higher among Caucasians (OR = 3.5; 95% CI: 1.89, 6.39) and African Americans (OR = 20.7; 95% CI: 2.06, 206.64) older than 40 years, age was not associated with HCV serostatus among Hispanics (OR = 1.51; 95% CI: 0.72, 3.17). Seropositivity did not differ significantly by gender (P = 0.23). Our population was quite stable with a median duration in the MMTP of 65 months among seropositive individuals. We also found that patients who were in the MMTP for more than 36 months were 1.61 times more likely to be HCV seropositive compared to those enrolled in the MMTP for a shorter period (95% CI: 1.06, 2.46, P = 0.026).

HCV RNA Hepatitis C virus RNA was obtained from 222 (86%) HCV-seropositive patients. Of these, 65 (29%) patients were HCV RNA negative, indicating spontaneous viral eradication. Chronic HCV infection was detected in 157 (71%) patients as indicated by detectable HCV RNA. Of these, 33 patients were HIV/HCV co-infected. In 35 (14%) of seropositive patients, HCV viral quantitation was unattainable: 8 declined testing citing lack of interest, 8 had no insurance, 3 received HCV treatment elsewhere and 16 were inaccessible during the study owing to discharge/transfer from the MMTP (n = 9), death (n = 4) or incarceration (n = 3). Hepatitis C virus genotypes were obtained on 118 (75%) patients with chronic HCV infection. Hepatitis C virus genotype 1 was detected in 91 (77%) patients, followed by genotypes 2 and 3 (11% and 10%, respectively) (Table 2).

Liver Clinic Evaluation Of the 157 chronically HCV-infected patients, 125 were eligible to be seen in the clinic, 29 of whom were HIV co-infected. Seventy-six individuals adhered with the referral of whom 17 (25%) were HIV/HCV co-infected. The following patients were considered ineligible for referral: 13 received HCV care elsewhere; 12 were not evaluated owing to discharge (n = 5), transfer (n = 4), incarceration (n = 1) or death (n = 2) during the study period; and 7 were uninsured. Twenty-three patients refused hepatitis clinic referral citing lack of interest, and 26 initially accepted referral but failed to appear.

We found that patients who had been enrolled in the MMTP for more than 36 months were more likely to have been seen in liver clinic than those engaged in treatment for <36 months (OR = 3.32, 95% CI: 1.51, 7.28, P = 0.003). However, this relationship depended upon subject gender (P = 0.017). The odds of male patients engaged in MMTP for >36 months accepting and adhering to referral were significantly higher than for men enrolled in MMTP for <36 months (OR = 7.7; 95% CI 2.6–22.9). Among patients who were on methadone treatment for <36 months, men were significantly less likely to be seen in the liver clinic than women (OR = 0.167, 95% CI: 0.04, 0.69). No other demographic or disease-related factors predicted referral adherence. Of the 76 patients with chronic HCV infection evaluated in the viral hepatitis clinic, assessment of fibrosis was achieved in 63 (83%): 54 underwent liver biopsy to assess fibrosis, 4 were diagnosed with cirrhosis based upon laboratory data and/or imaging studies, and 5 preferred noninvasive blood testing to assess the degree of fibrosis. Among 58 patients with histologic assessment based upon biopsy or laboratory/imaging evidence of cirrhosis, 49 (84%) had moderate to advanced liver disease (stage ≥2) indicating the need for urgent treatment. Among patients with liver biopsy, advanced fibrosis (stage >2) differed significantly by ethnicity (P = 0.039); 58% of Caucasians and Hispanics combined had stage >2 vs 20% of African American subjects. Caucasian or Hispanic individuals were 5.5 times more likely to have fibrosis stage >2 when compared to African Americans (95% CI: 1.05, 33.33). Necroinflammatory activity was also significantly associated with fibrosis (P = 0.013 for lobular and P = 0.001 for portal inflammation). Age and gender were not associated with fibrosis.

HCV Treatment Characteristics

Of the 76 patients who underwent the evaluation process, 24 initiated treatment, including 9 individuals co-infected with HIV (Table 3). Thirty-five patients were ineligible for treatment including 2 (3%) with decompensated psychiatric disease, 6 (11%) with decompensated cirrhosis, 10 (13%) who refused a biopsy, 4 (5%) with no insurance and 2 (3%) who were treated elsewhere. Of these two patients, upon evaluation in the liver clinic, it was determined that one had successfully been treated at an outside institution and the other was treatment ineligible owing to severe thrombocytopenia. Eleven (14%) subjects with mild fibrosis postponed treatment based upon physician recommendation. Twenty-four of 41 treatment eligible patients began treatment. Of the remaining treatment eligible patients, 3 (4%) declined PEG-IFN/RBV citing fear of therapy-related side effects, 4 (5%) had unstable living conditions, 3 (4%) had relocated to different geographic areas complicating pursuit of anti-HCV treatment, 3 declined (4%) owing to co-occurring illnesses and 4 (5%) were lost to follow-up. Patients with stage 3–4 fibrosis were significantly more likely to be treated than those with stage 0–2 (OR = 11.2, 95% CI: 2.89, 43.35, P = 0.0005). Of 24 treatment initiators, 19 completed a full course of therapy with PEG-IFN/RBV. Three patients interrupted treatment owing to reasons unrelated to therapeutic success, including hepatic decompensation (n = 1), severe thrombocytopenia (n = 1) and nonadherence (n = 1). Thirteen patients (54%) achieved sustained virological response (SVR), eight of who were genotype 1 and four were co-infected with HIV. Two HIV/HCV co-infected patients currently remain on treatment.


In this investigation, we demonstrate the effectiveness of an integrated, co-localized care model for HCV utilizing a multidisciplinary approach (Fig. 1). We applied our model to patients from a large MMTP in Manhattan. Overall, HCV seroprevalence was 64% and 61% of those with chronic HCV who were eligible for referral were evaluated in the hepatitis clinic. Of those who initiated treatment, 54% successfully eradicated the virus consistent with the previous studies of HCV treatment in opiate-dependent patients.[22–26]

Despite a high prevalence of HCV infection among DUs, less than one-third of eligible individuals receive HCV therapy owing to variety of reasons at the institutional, provider and patient levels.[3] Institutional reasons often include difficulties obtaining or navigating the complexities of the referral system. In addition, many health care providers are concerned about adherence with HCV treatment by DUs, including concerns that they may be disinterested in treatment, that interferon-based therapy may potentiate psychiatric decompensation and that they might be reinfected of continued high-risk practices. Studies of HCV reinfection among successfully treated DUs, however, have shown the converse.[27,28] Using our model, we obtained an HCV evaluation in more than one-half of chronically infected individuals, markedly higher than previous clinic-based cohorts. In addition, we were able to stage the degree of fibrosis in 83% of those evaluated in the liver clinic. Factors that likely contributed to the high degree of acceptance of HCV management and adherence to an evaluation included evaluation by the same physician in both clinics, their geographical proximity and an institution-wide electronic medical record that fosters communication facilitating data access and continuity of care. The fact that these patients had a regular, stable source of medical care that originated in the MMTP and continued to the hepatitis clinic was likely crucial to the success of our program.[15,17]

Substance abuse treatment can serve as an entry point into the health care system and is possibly an essential step in preparing DUs for HCV evaluation and treatment. Well-structured MMTPs, with attributes such as access to mental health professionals and general medical staff, likely have advantages for HCV evaluation and treatment over those without such services. Consistent with the findings of prior studies,[11,29] we found that men who were engaged in the MMTP for 36 months or more were significantly more likely to appear in the hepatitis clinic than those with shorter duration of opiate substitution therapy.

Our study is limited in its retrospective, non-comparative design and its conduct at a single institution. Our goal, however, was to demonstrate the feasibility and effectiveness of an integrated, co-localized model of care. The health care services offered at our MMTP provided the requisite infrastructure to facilitate HCV evaluation and treatment among MMTP patients. Unfortunately, however, many MMTPs may not be able to offer as wide a spectrum of health care services onsite, which might impact on the ability to offer HCV management except through traditional referral based mechanisms. Our model may be utilized by community-based primary care providers or addiction medicine specialists with immediate access to experts in HCV management who can assist in navigating the complexities of treatment of the infection.

Despite our integrated, colocalized approach, a substantial number of patients did not undergo an HCV evaluation in the hepatitis clinic, with an approximate equal number refusing referral as those initially accepting referral but not appearing for their initial evaluation. Men enrolled in the MMTP for <36 months appeared to be at greatest risk for not accepting or complying with referral to the hepatitis clinic. When questioned, patients indicated that they refused HCV evaluation owing to an apparent lack of interest, reticence or a lack of education or misinformation concerning HCV. Our findings are consistent with previous data that demonstrated significant knowledge gaps among DUs.[30] Implementation of patient-oriented interventions, such as formal, structured HCV educational programs, individual case management to address patient level barriers or staff/peer accompaniment to appointments, might improve adherence with HCV evaluation and treatment and are interventions deserving of further study.

In an effort to inform patients of the severity of their infection and consistent with standard clinical practice in 2006,[20] we strongly encouraged patients to undergo a liver biopsy. On biopsy, we found that the vast majority of patients had at least moderate hepatic fibrosis, indicating the need for urgent treatment. In this model, 41% of patients who had accurate hepatic fibrosis assessment began PEG-IFN/RBV, 79% of whom completed a full course of therapy with an overall SVR rate of 54%. Notably, only one patient had treatment interrupted for issues relating to nonadherence and no patients discontinued treatment because of psychiatric decompensation.

In summary, we demonstrated that localization of addiction medicine specialists and hepatologists in a viral hepatitis clinic is both an effective and efficient model to deliver HCV evaluation and treatment to MMTP patients. This approach could be most appropriate in settings that offer pharmacologically based treatment of addiction which have ready access to expertise in the management of liver disease. As many DUs have advanced stages of hepatic fibrosis, HCV treatment is particularly urgent. Additionally, successful treatment combined with safe injection practices could decrease virus transmission even among individuals who continue to inject. Unless disenfranchised populations with the highest infection prevalence, such as DUs, have access to and accept treatment for HCV, the burden of disease will remain high.


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France: Is more frequent monitoring for liver cancer among co-infected people needed?

9 January 2012

In high-income countries such as Canada, Australia and in Western Europe, the widespread availability of potent combination therapy for HIV (commonly called ART or HAART) has greatly reduced deaths from AIDS-related infections. Furthermore, the benefit of ART is so profound that researchers in the UK recently estimated that HIV-positive people who have minimal co-existing health conditions and who are diagnosed and receive treatment early in the course of HIV disease are very likely to have near-normal life spans.

Many possible factors can affect access to and engagement in care and treatment—and thus survival; addiction is one such factor. Some HIV-positive people may not be able to seek and receive the help and support needed to break free from addiction to substances—including alcohol, street drugs and tobacco—and their associated risks. Such risks can include serious bacterial infections, overdose, cardiovascular disease, liver and kidney damage, accidents, suicide and violence.

Even among some HIV-positive people who have been able to successfully overcome their addiction, past engagement in substance use or unprotected sex may have also exposed them to co-infections such as hepatitis B virus (HBV) and hepatitis C virus (HCV). These viruses attack the liver, injuring this vital organ. Chronic hepatitis caused by these viruses degrades the liver, causing it to lose healthy tissue and have scar tissue build up. In the absence of treatment, over time the liver becomes increasingly dysfunctional and serious complications including liver failure, liver cancer and death can occur.


In high-income countries, treatment for HBV co-infection is usually one of the following combinations:

  • 3TC (lamivudine) + tenofovir (Viread)
  • tenofovir + FTC (sold as a fixed-dose combination called Truvada)

In the case of HCV mono-infection (HCV alone), a combination of the following three drugs is used:

  • ribavirin
  • interferon-alpha
  • boceprevir (Victrelis) or telaprevir (Incivik)

Note that neither boceprevir nor telaprevir are approved in Canada for the treatment of HIV-HCV co-infection.

Viral hepatitis and liver cancer

French researchers have found that while ART can greatly reduce deaths due to AIDS-related infections, complications from liver disease are increasingly taking their toll. One complication of infection with HBV or HCV is liver cancer, and researchers in France continue to study this cancer both in people with either HBV or HCV or HIV co-infection. Their most recent study results suggest that liver cancer occurs earlier and is more extensive in some co-infected people who are at high risk for liver cancer. If the French findings are confirmed, increased medical monitoring of co-infected people at high risk for liver cancer may be necessary.

Study details

The French team reviewed data collected from 2,256 participants who were being monitored as part of research on viral hepatitis. They selected 32 people from this group for further analysis. All 32 participants had cirrhosis—extensive liver damage arising from chronic infection with HBV or HCV, whereby healthy tissue is replaced by scar tissue. Additionally, all participants had liver cancer. The diagnosis of cirrhosis was made using one or more of the following methods:

  • analyzing a tiny sample of the liver
  • specialized blood tests (Fibrotest)
  • specialized ultrasound scans of the liver (Fibroscan)

The distribution of viral infections among the 32 participants was as follows:

  • HIV-HCV co-infection – 16 participants
  • HCV mono-infection – 16 participants

As people with cirrhosis are at heightened risk for the development of liver cancer, all participants underwent ultrasound scans of the liver every six months, along with medical monitoring.

On average, participants were monitored for 30 months.

All participants had tumours in their liver that arose from abnormal liver cells (primary liver cancer); none of the tumours had migrated to the liver from another part of the body.


The researchers found that co-infected people were generally younger (48 years) than mono-infected people (60 years)—a statistically significant difference. Additionally, there was a trend that approached statistical significance: Co-infected people (56%) drank more alcohol than HCV mono-infected people (20%).

In reviewing the medical records, the research team found that all mono-infected participants had previously received treatment for HCV while 67% of co-infected people received this treatment. This difference was also statistically significant. The reasons for this difference were not clear to the research team.

The researchers also found that 87% of co-infected people were taking ART; of these, 69% had low levels of HIV in their blood (less than 40 copies/ml).

Cure vs. palliative therapy

Treatment for liver cancer can vary depending on several factors, including the following:

  • the health of the liver
  • the size and number of tumours
  • whether or not the tumours have spread (metastasized) beyond the liver

In cases where doctors decide that a person does not have a good chance of recovery from cancer, palliative care—measures to minimize discomfort and complications in the short term—may be provided. In the case of the current report, when French oncologists judged that recovery was likely they choose from several options, including surgery, attacking the tumour with an electrical current (radiofrequency ablation), or surgery followed by a liver transplant.

Oncologists gave the 32 study participants either palliative or curative therapy, distributed as follows:

  • HIV-HCV co-infection – 25% received therapy with the intention to cure cancer
  • HCV mono-infection – 69% received therapy with the intention to cure cancer

This difference was statistically significant.

As cancer patients were assessed and treated outside of the study by oncologists, the research team is not certain why there was a difference in who received curative therapy. However, the researchers found that when liver cancer was diagnosed within the study, it was generally more severe (more and larger tumours) in co-infected people. Also, some co-infected participants had higher-than-normal levels of a protein called AFP (alpha-fetoprotein). Past studies have suggested that high levels of AFP are sometimes associated with liver cancer and that elevated AFP at liver cancer diagnosis may indicate a poor outcome. Thus it was possible that because liver cancer was more “advanced” when diagnosed in co-infected people, oncologists may have decided that the prospects of recovery in this group were poor.

Over an average of 30 months of monitoring, deaths due to complications from liver cancer were distributed as follows:

  • HIV-HCV co-infection – 10 out of 16 people died
  • HCV alone (mono-infection) – one out of 16 people died

International liver cancer management guidelines suggest that people with cirrhosis (who are at high risk for liver cancer) should undergo ultrasound scans of their liver and have AFP tests to help their doctors detect tumours. According to the researchers, these guidelines were followed in the French study. Therefore, the French team suggests that the worse pattern of liver cancer among co-infected people did not arise due to lack of monitoring.

The precise cause for the more rapid appearance of liver cancer among co-infected people in this study is not clear but it may be due to a weakened immune system caused by HIV infection. While most participants with HIV in the study were taking combination therapy, ART can only partially restore the immune system; residual immune dysfunction continues.

The French study had a major weakness: A relatively small number of participants (32). A larger study is necessary to confirm its findings.

If another team confirms the French results, more frequent monitoring of HIV-HCV co-infected people at high risk for liver cancer may be deemed necessary. For instance, the French team suggests that ultrasound scans and other tests could be done every three months. This shorter time span might allow technicians and doctors to detect liver cancer when it is at an early stage. This could make a difference to the prospects of surviving liver cancer for co-infected people.

—Sean R. Hosein


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  3. Hser YI, Kagihara J, Huang D, et al. Mortality among substance-using mothers in California: a 10-year prospective study. Addiction. 2012 Jan;107(1):215-22.
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  6. Bonacini M. Alcohol use among patients with HIV infection. Annals of Hepatology. 2011 Oct-Dec;10(4):502-7.
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Effect of IL28B Genotype on Early Viral Kinetics during Interferon-Free Treatment of Patients with Chronic Hepatitis C

Gastroenterology. 2012 Jan 13. [Epub ahead of print]

Chu TW, Kulkarni R, Gane EJ, Roberts SK, Stedman C, Angus PW, Ritchie B, Lu XY, Ipe D, Lopatin U, Germer S, Iglesias VA, Elston R, Smith PF, Shulman NS.


Roche, Nutley, NJ, USA.


Although IL28B genotype affects the response of patients with chronic hepatitis C (CHC) to peginterferon and ribavirin, little is known its effect on response to direct-acting antivirals in interferon-free combinations. We analyzed the effects of IL28B genotype on the viral kinetic (VK) response to an interferon-free combination of the nucleoside polymerase inhibitor mericitabine (RG7128) and hepatitis C virus (HCV) protease inhibitor danoprevir.


We performed a double-blind, dose-escalation study of patients with chronic HCV genotype 1 infection who were interferon treatment-naive or had not responded to previous therapy with peginterferon and ribavirin. Patients were sequentially assigned to 1 of 7 cohorts, then randomly assigned to groups that received up to 13 days of treatment with mericitabine (500 or 1000 mg, twice daily) plus danoprevir (100 or 200 mg, every 8 hrs or 600 or 900 mg, twice daily) or placebo. Eighty-three of 87 patients were genotyped for the IL28B single-nucleotide polymorphism rs12979860. VKs were analyzed only in patients who received 13 days of treatment, at optimal doses, using a bi-phasic model to describe first- and second-phase slopes of viral decay during therapy.


At day 14 (the end of interferon-free treatment), the mean reduction in the serum level of HCV RNA was slightly greater in patients with the CC polymorphism (5.01 log(10) IU/mL) than those without (4.59 log(10) IU/mL). Modeling revealed that patients with the CC polymorphism had slightly better early VKs, most apparent in the β-phase of viral decay. A mixed effect on the α-phase was observed, which was reduced in magnitude but prolonged in patients with CC, who also had better on-treatment response to peginterferon and ribavirin during follow up.


IL28B genotype appears to affect early VKs in patients with CHC receiving interferon-free treatment.


Treatment failure with new hepatitis C drugs

Expert Opin Pharmacother. 2012 Jan 14. [Epub ahead of print]

Soriano V, Vispo E, Poveda E, Labarga P, Barreiro P.


Hospital Carlos III, Department of Infectious Diseases , Calle Sinesio Delgado 10, Madrid 28029 , Spain +34 91 4532500 ; +34 91 7336614 ; vsoriano@dragonet.es.


Introduction: The combination of pegylated interferon-α plus ribavirin (pegIFNα-RBV) has been the only therapeutic option for patients with chronic hepatitis C virus (HCV) infection during the last decade. Unfortunately, it provides cure to less than a half of individuals infected with HCV genotype 1, which is by far the most prevalent worldwide. The recent introduction of new direct-acting antivirals (DAA) has revolutionized the hepatitis C field. The addition of any of the two recently approved HCV protease inhibitors, boceprevir or telaprevir, to pegIFNα-RBV results in the cure for two-thirds of HCV genotype 1, interferon-naive patients. Areas covered: This paper reviews new antivirals for hepatitis C and HCV treatment failures, along with HCV drug resistance and rescue therapies. Expert opinion: The application of early stopping rules may reduce the enrichment of drug-resistant viruses in patients failing first-generation HCV protease inhibitors, potentially allowing more chances of response to rescue interventions with other compounds within the same class in the near future. On the other hand, the advent of DAA belonging to distinct drug families may provide further opportunities for clearing definitively HCV in patients currently failing first-generation HCV protease inhibitors. Thus, hepatitis C has entered a new era that hopefully will end with its eradication. In the meantime, a wise use of DAA is warranted, including adequate selection of candidates for therapy, close monitoring of drug adherence, proper management of side effects and early application of stopping rules.


Hepatitis Health Action Alert: Stop the Attacks on Prevention and Public Health Fund


Posted on January 23, 2012 on The Hepatitis B Foundation blog

Action Alert! The Hepatitis Community Responds to Health Care Reform. Tell Congress Not To Cut The Prevention and Public Health Fund

The Prevention and Public Health Fund is under attack in Congress once again. Some leaders in the House of Representatives would like to make drastic cuts to the Fund as part of negotiations on a long-term deal on the payroll tax cut and Medicare payments rates to medical providers.

The Prevention and Public Health Fund, part of the Affordable Care Act, provides money each year for vital prevention and public health services. The fund will grow each year until it eventually provides $2 billion/year.

This fund is extremely important to the nation’s fight against the viral hepatitis epidemic. Later this year, the Department of Health and Human Services is expected to allocate $10 million from the Fund for viral hepatitis screening, testing, and education programs. This initiative will greatly help efforts to identify the millions of Americans who have chronic hepatitis B or C and link them to care and treatment.

Please take a few minutes to call Congress in support of this lifesaving program!

What YOU can DO:

Please call your U.S. House Representative and two U.S. Senators immediately. We are hearing directly from Congressional staff that phone calls are the most effective form of communication.

Call the Capitol Switchboard toll-free at 1-888-876-6242 and ask to be connected to your United States Representative. When you reach your Representative’s office, tell whoever answers the phone that you are a constituent and that you would like to speak to the staff person who handles health care issues. Whether you speak to the staff person live or leave a voicemail, tell him/her:

“My name is _______________ and I live in (city/state). I am calling in strong support of the Prevention and Public Health Fund, which is an important part of the Affordable Care Act. This Fund is a great opportunity to provide badly needed funding for viral hepatitis prevention, testing, and screening programs and must be preserved. I urge Representative_____________ to oppose any efforts to cut the Fund as part of the payroll tax/Medicare physician reimbursement negotiations.”

After you speak to your Representative’s office, call the Capitol Switchboard again and deliver the same message to the health care staff person in your two U.S. Senators’ office.

Thank you for taking the time to make a difference! Please spread the word.

Get involved with Hepatitis Health Action!

  • Join Hepatitis Health Action’s Facebook group: http://tinyurl.com/hephealthfacebook where you can participate in discussions with other advocates and share your ideas and strategies.

Hepatitis Health Action is a campaign led by viral hepatitis advocates working to make sure that health care reform addresses hepatitis B and C.