Risk of Late Relapse or Reinfection with Hepatitis C Virus After Achieving a Sustained Virological Response: A Systematic Review and Meta-analysis

Background. 

Treatment for hepatitis C virus (HCV) can lead to sustained virological response (SVR) in over 90% of people. Subsequent recurrence of HCV, either from late relapse or reinfection, reverses the beneficial effects of SVR.

Methods. 

A search identified studies analysing HCV recurrence post-SVR. The recurrence rate for each study was calculated using events/person years of follow-up (PYFU). Results were pooled using a random-effects model and used to calculate 5-year recurrence risk. Three patient groups were analysed: (1) Mono-HCV infected “low-risk” patients; (2) Mono-HCV infected “high-risk” patients (injecting drug users or prisoners); (3) human immunodeficiency virus (HIV)/HCV coinfected patients. Recurrence was defined as confirmed HCV RNA detectability post-SVR.

Results. 

In the 43 studies of HCV mono-infected “low-risk” patients (n = 7969) the pooled recurrence rate was 1.85/1000 PYFU (95% confidence interval [CI], .71–3.35; I² = 73%) leading to a summary 5-year recurrence risk of 0.95% (95% CI, .35%–1.69%). For the 14 studies of HCV monoinfected “high-risk” patients (n = 771) the pooled recurrence rate was 22.32/1000 PYFU (95% CI, 13.07–33.46; I² = 27%) leading to a summary 5-year risk of 10.67% (95% CI, 6.38%–15.66%). For the 4 studies of HIV/HCV coinfected patients the pooled recurrence rate was 32.02/1000 PYFU (95% CI, .00–123.49; I² = 96%) leading to a summary 5-year risk of 15.02% (95% CI, .00%–48.26%). The higher pooled estimates of recurrence in the high-risk and coinfected cohorts were driven by an increase in reinfection rather than late relapse.

Conclusions. 

SVR appears durable in the majority of patients at 5 years post-treatment. The large difference in 5 year event rate by risk group is driven mainly by an increased reinfection risk.

Below:  Summary 5-year risk (95% confidence interval) of recurrence post-sustained virological response (SVR), by risk group. Presented are the pooled estimates for the 5-year risk of recurrence after achieving an SVR. Also shown are the number of studies that were included to derive each estimate. Abbreviations: HCV, hepatitis C virus; HIV, human immunodeficiency virus.

Full article at:   http://goo.gl/7iLF2K

By:  Bryony Simmons,1 Jawaad Saleem,1 Andrew Hill,2 Richard D. Riley,3 and Graham S. Cooke1

¹Division of Medicine, Imperial College London

²Pharmacology and Therapeutics, Liverpool University

³Research Institute of Primary Care and Health Sciences, Keele University, Staffordshire, United Kingdom

Correspondence: B. Simmons, St Mary's Campus, Imperial College London, Norfolk Place, London W2 1PG, UK (Email:ku.ca.lairepmi.inmula@31snommis.ynoyrb).

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Cascade of Care for Hepatitis C Virus Infection within the US Veterans Health Administration

OBJECTIVES:

We measured the quality of HCV care using a cascade of HCV care model.

METHODS:

We estimated the number of patients diagnosed with chronic HCV, linked to HCV care, treated with HCV antivirals, and having achieved a sustained virologic response (SVR) in the electronic medical record data from the Veterans Health Administration's Corporate Data Warehouse and the HCV Clinical Case Registry in 2013.

RESULTS:

Of the estimated 233 898 patients with chronic HCV, 

• 77% (181 168) were diagnosed, 
• 69% (160 794) were linked to HCV care, 
• 17% (39 388) were treated with HCV antivirals, and 
• 7% (15 983) had achieved SVR.

CONCLUSIONS:

This Cascade of HCV Care provides a clinically relevant model to measure the quality of HCV care within a health care system and to compare HCV care across health systems.

Purchase full article at:   http://goo.gl/3RmCVj

By:  Maier MM1, Ross DB1, Chartier M1, Belperio PS1, Backus LI1.

• 1Marissa M. Maier is with the VA Portland Health Care System, Veterans Health Administration (VHA), Portland, OR, and the Office of Public Health/HIV, Hepatitis, and Public Health Pathogens Programs, VHA, Washington, DC. David B. Ross is with the VA Washington DC Health Care System, and the Office of Public Health/HIV, Hepatitis, and Public Health Pathogens Programs, VHA, Washington, DC. Maggie Chartier is with the VA San Francisco Health Care System, VHA, San Francisco, CA, and the Office of Public Health/HIV, Hepatitis, and Public Health Pathogens Programs, VHA, Washington, DC. Pamela S. Belperio is with the VA Greater Los Angeles Health Care System, VHA, Los Angeles, CA, and the Office of Public Health/Population Health, VHA, Washington, DC. Lisa I. Backus is with the VA Palo Alto Health Care System, VHA, Palo Alto, CA, and the Office of Public Health/Population Health, VHA, Washington, DC. 
• Am J Public Health. 2016 Feb;106(2):353-8. doi: 10.2105/AJPH.2015.302927. Epub 2015 Nov 12.

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Hepatitis C Reinfection Following Sustained Virological Response - Seven-Year Follow-Up of Patients Infected Through Injecting Drug Use

BACKGROUND AND AIMS:

On-going risk behaviour can lead to hepatitis C virus (HCV) reinfection following successful treatment. We aimed to assess the incidence of persistent HCV reinfection in a population of people who inject drugs (PWID) who had achieved sustained virological response (SVR) seven years earlier.

METHODS:

In 2004-2006 we conducted a multicentre treatment trial comprising HCV genotype 2 or 3 patients in Sweden, Norway and Denmark (NORTH-C). Six months of abstinence from injecting drug use (IDU) was required before treatment. All Norwegian patients who had obtained SVR (n=161) were eligible for participation in this long-term follow-up study assessing virological and behavioural characteristics.

RESULTS:

Follow-up data were available in 138 of 161 (86%) individuals. Persistent reinfection was identified in 10 of 94 (11%) individuals with a history of IDU prior to treatment (incidence rate 1.7/100 person-years (PY); 95% CI 0.8-3.1) and in 10 of 37 (27%) individuals who had relapsed to IDU after treatment (incidence rate 4.9/100 PY; 95% CI 2.3-8.9). Although relapse to IDU perfectly predicted reinfection, no baseline factor was associated with reinfection. Relapse to IDU was associated with age < 30 years (vs. ⩾ 40 years) at treatment (adjusted odds ratio [aOR] 7.03; 95% CI 1.78-27.8) and low education level (aOR 4.10; 95% CI 1.56-10.8).

CONCLUSIONS:

Over time, persistent HCV reinfection was common among individuals who had relapsed to IDU after treatment. Reinfection should be systematically addressed and prevented when providing HCV care for PWID.

Purchase full article at:   http://goo.gl/fKlhz0

By:  Midgard H1, Bjøro B2, Mæland A3, Konopski Z4, Kileng H5, Damås JK6, Paulsen J7, Heggelund L8, Sandvei PK9, Ringstad JO9, Karlsen LN10, Stene-Johansen K11, Pettersson JH11, Dorenberg DH11, Dalgard O12.

• 1Department of Infectious Diseases, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway. Electronic address: havardmi@medisin.uio.no.
• 2Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway.
• 3Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway.
• 4Department of Gastroenterology, Oslo University Hospital, Oslo, Norway.
• 5Section of Gastroenterology, University Hospital of North Norway, Tromsø, Norway.
• 6Centre of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Department of Infectious Diseases, St. Olav's Hospital, Trondheim, Norway.
• 7Section of Gastroenterology, Telemark Hospital Trust, Skien, Norway.
• 8Section of Infectious Diseases, Vestre Viken Hospital Trust, Drammen, Norway.
• 9Department of Medicine, Østfold Hospital Trust, Grålum, Norway.
• 10Department of Medicine, Stavanger University Hospital, Stavanger, Norway.
• 11Department of Virology, The Norwegian Institute for Public Health, Oslo, Norway.
• 12Department of Infectious Diseases, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway. 

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The Impact of Direct-Acting Antivirals in the Hepatitis C-Sustained Viral Response in HIV-Infected Patients with Ongoing Barriers to Care

Background. Access to hepatitis C virus (HCV) medications for human immunodeficiency virus (HIV)-infected patients with ongoing barriers to care is restricted by healthcare payers in the absence of HCV treatment outcomes data in the era of direct-acting antivirals (DAA).

Methods. Retrospective analysis of HCV treatment outcomes using interferon (IFN)-free DAA regimens and an inclusive treatment protocol in an urban HIV clinic where ongoing barriers to care (drug or alcohol use, psychiatric disease, and/or unstable housing) are common. Then, using logistic regression analysis, we compared the proportion of HIV-infected patients who achieved HCV sustained viral response (SVR) in the pegylated-IFN plus ribavirin (PEG-IFN/RBV, 2008–2011), pegylated-IFN plus ribavirin and telaprevir (PEG-IFN/RBV/PI, 2011–2013), and IFN-free DAA therapy eras (2014). Results are displayed using forest plots.

Results. The proportion of patients who achieved HCV SVR in the PEG-IFN/RBV, PEG-IFN/RBV/PI, and IFN-free DAA therapy eras increased from 38.4% (95% confidence interval [CI], 23.2–53.7) and 48% (95% CI, 28.4–67.6) to 83.3% (95% CI, 70.0–96.7), respectively. Similar proportions of patients with ongoing barriers to care were treated during the PEG-IFN/RBV (25 of 39 [64%]), PEG-IFN/RBV/PI (14 of 25 [56%]), and IFN-free DAA (16 of 30 [53%]) eras. Hepatitis C virus SVR among patients with ongoing barriers to care improved from 40% (95% CI, 21–59) to 76.5% (95% CI, 56–97) in the PEG-IFN/RBV and IFN-free DAA eras, respectively. After stratification for factors associated with HCV SVR such as HCV genotype and cirrhosis, HCV SVR were similar in patients regardless of the presence of ongoing barriers to care.

Conclusions. Using IFN-free DAA and an inclusive HCV treatment protocol, 76.5% of HIV/HCV-treated patients with ongoing barriers to care achieved HCV SVR.

Below:  Error bars plot depicting proportion of hepatitis C virus sustained viral response (SVR) achieved during each treatment era in an unadjusted model (left panel) and adjusted multiple logistic regression model of treatment period controlling for barriers to care (drug/alcohol abuse, psychiatric disease, unstable housing), genotype 1, cirrhosis, and presence of severe concurrent medical comorbidities (right panel). Abbreviations: C.I., confidence interval; DAA, direct-acting antivirals; pIF/RBV/PI, pegylated-interferon, ribavirin and HCV protease inhibitor (telaprevir) era.

Full article at:   http://goo.gl/JspckK

By:   Edward R. Cachay,1,2 David Wyles,1,2 Lucas Hill,3 Craig Ballard,1,3 Francesca Torriani,1,2 Bradford Colwell,1,3Alexander Kuo,4 Robert Schooley,2 and Christopher W. Mathews1

¹Department of Medicine, Owen Clinic

²Department of Medicine, Division of Infectious Diseases

³Skaggs School of Pharmacy and Pharmaceutical Sciences

⁴Department of Medicine, Division of Gastroenterology and Hepatology, University of California San Diego

Correspondence: Edward R. Cachay, MD, MAS, University of California at San Diego, 200 W. Arbor Drive, San Diego, CA 92103-8681 (Email:ude.dscu@yahcace).

  

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The Cascade of Care for an Australian Community-Based Hepatitis C Treatment Service

Hepatitis C treatment uptake in Australia is low. To increase access to hepatitis C virus treatment for people who inject drugs, we developed a community-based, nurse-led service that linked a viral hepatitis service in a tertiary hospital to primary care clinics, and resulted in hepatitis C treatment provision in the community.

A retrospective cohort study of patients referred to the community hepatitis service was undertaken to determine the cascade of care. Logistic regression analyses were used to identify predictors of hepatitis C treatment uptake.

Four hundred and sixty-two patients were referred to the community hepatitis service; 344 attended. Among the 279 attendees with confirmed chronic hepatitis C, 257 (99%) reported ever injecting drugs, and 124 (48%) injected in the last month. Of 201 (72%) patients who had their fibrosis staged, 63 (31%) had F3-F4 fibrosis. Fifty-five patients commenced hepatitis C treatment; 26 (47%) were current injectors and 25 (45%) had F3-F4 fibrosis. Nineteen of the 27 (70%) genotype 1 patients and 14 of the 26 (54%) genotype 3 patients eligible for assessment achieved a sustained virologic response. Advanced fibrosis was a significant predictor of treatment uptake in adjusted analysis (AOR 2.56, CI 1.30–5.00, p = 0.006).

Our community hepatitis service produced relatively high rates of fibrosis assessment, hepatitis C treatment uptake and cure, among people who inject drugs. These findings highlight the potential benefits of providing community-based hepatitis C care to people who inject drugs in Australia–benefits that should be realised as direct-acting antiviral agents become available.

Below:  HCV Cascade of care in Australia

Full article at:  http://goo.gl/FW9kYs

By: 

Amanda J. Wade, Joseph S. Doyle, Margaret E. Hellard

Centre for Population Health, Burnet Institute, Melbourne, Victoria, Australia

Amanda J. Wade, Margaret E. Hellard

School of Public Health and Preventive Medicine, Monash University, Alfred Hospital, Melbourne, Victoria, Australia

Diana M. Macdonald, Joseph S. Doyle, Margaret E. Hellard

Department of Infectious Diseases, The Alfred, Melbourne, Victoria, Australia

Alexander J. Thompson

Department of Gastroenterology, St Vincent’s Hospital, Melbourne, Victoria, Australia

Adam Gordon, Stuart K. Roberts

Department of Gastroenterology, The Alfred, Melbourne, Victoria, Australia

Stuart K. Roberts, Alexander J. Thompson

Department of Medicine, Monash University, Melbourne, Victoria, Australia

Joseph S. Doyle

Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia

 

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Effect of Abacavir on Sustained Virologic Response to HCV Treatment in HIV/HCV Co-Infected Patients, Cohere in Eurocoord

Contradicting results on the effect of abacavir (ABC) on hepatitis C virus (HCV) treatment responses in HIV/HCV co-infected patients have been reported. We evaluated the influence of ABC on the response to pegylated interferon (pegIFN) and ribavirin (RBV)-containing HCV treatment in HIV/HCV co-infected patients in a large European cohort collaboration, including data from different European countries.

HIV/HCV co-infected patients were included if they were aged ≥16 years, received pegIFN alfa-2a or 2b and RBV combination treatment and were enrolled in the COHERE cohort collaboration. Logistic regression was used to evaluate the impact of abacavir on achieving a sustained virologic response (SVR) to HCV treatment.

In total 1309 HIV/HCV co-infected patients who had received HCV therapy were included, of whom 490 (37 %) had achieved an SVR. No statistically significant difference was seen for patients using ABC-containing regimens compared to patients using an emtricitabine + tenofovir (FTC + TDF)-containing backbone, which was the most frequently used backbone. In the multivariate analyses, patients using a protease inhibitor (PI)-boosted regimen were less likely to achieve an SVR compared to patients using a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen (OR: 0.61, 95 % CI: 0.41–0.91). The backbone combinations zidovudine&lamivudine (AZT + 3TC) and stavudine&lamivudine (d4t + 3TC) were associated with lower SRV rates (0.45 (0.24–0.82) and 0.46 (0.22–0.96), respectively).

The results of this large European cohort study validate that SVR rates are generally not affected by ABC. Use of d4T or AZT as part of the HIV treatment regimen was associated with a lower likelihood of achieving an SVR.

Full article at: http://goo.gl/99tVkR

By: Colette Smit^*, Joop Arends, Lars Peters, Antonella d’Arminio Montforte, Francois Dabis,Robert Zangerle, George Daikos, Christina Mussini, Josep Mallolas, Stephane de Wit,Annelies Zinkernagel, Jaime Cosin, Genevieve Chene, Dorthe Raben, Jürgen Rockstroh andFor the Hepatitis C- working group for COHERE in Eurocoord

Stichting HIV Monitoring, Meibergdreef 9, Amsterdam, 1105AZ, The Netherlands

  

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