Showing posts with label HBV/HCV dual infection. Show all posts
Showing posts with label HBV/HCV dual infection. Show all posts

Friday, February 2, 2018

Hep B reactivation common during direct-acting antiviral therapy for hep C

Reuters Health

Last Updated: 2018-02-02
By Will Boggs MD
NEW YORK (Reuters Health) - Hepatitis B virus (HBV) reactivation is common in patients with chronic HBV and hepatitis C virus (HCV) coinfection receiving direct-acting antiviral (DAA) therapy, according to a systematic review and meta-analysis.
"It is important to identify patients at risk of HBV reactivation," said Dr. Johannes Vermehren from University Hospital Frankfurt, in Frankfurt am Main, Germany.
"HBsAg-positive patients who also have detectable HBV DNA should be closely monitored when treated for hepatitis C with direct antivirals. Alternatively, (nucleoside/nucleotide) prophylaxis may be justified in these patients," he told Reuters Health by email.

Wednesday, January 24, 2018

Hepatitis B Virus Infection and Hepatitis C Virus Treatment in a Large Cohort of Hepatitis C–Infected Patients in the United States

Article in Press
Hepatitis B Virus Infection and Hepatitis C Virus Treatment in a Large Cohort of Hepatitis C–Infected Patients in the United States
Anne C. Moorman, Jian Xing ia Loralee B. Rupp, Stuart C. Gordon Philip R. Spradling Joseph A. Boscarino Mark A. Schmidt Yihe G. Daida Kaiser Eyasu H. Teshale, Scott D. Holmberg

The rare emergence of hepatitis B virus (HBV) reactivation among hepatitis C virus (HCV)-infected patients receiving direct-acting antiviral (DAA) therapy raises questions about how many HCV-infected patients have active, past, or latent/occult HBV co-infection, and their DAA treatment experience1–3 We sought to characterize these factors, including possible post-DAA reactivation, among HCV patients in the Chronic Hepatitis Cohort Study (CHeCS), a “dynamic” observational study conducted at 4 large integrated U.S.

Full Text Online: http://www.gastrojournal.org/article/S0016-5085(17)36689-1/fulltext
Download PDF 

Tuesday, January 23, 2018

Risks for Hepatitis B Reactivation with Newer Hep C Treatments Detailed

Medical News |
PHYSICIAN'S FIRST WATCH

January 22, 2018
Risks for Hepatitis B Reactivation with Newer Hep C Treatments Detailed
By Amy Orciari Herman

Edited by Susan Sadoughi, MD, and André Sofair, MD, MPH

About a quarter of patients with chronic hepatitis B infection experience reactivation of the virus when they receive direct-acting antivirals (DAAs) for hepatitis C infection, according to a meta-analysis in the Lancet Gastroenterology and Hepatology.

The analysis included 17 observational studies among over 1600 patients with chronic or resolved HBV infection who were treated with interferon-free DAA regimens (e.g., ledipasvir plus sofosbuvir) for chronic HCV. Some 24% of those with chronic HBV infection — versus 1.4% of those with resolved infection — had HBV reactivation during treatment. Additionally, 9% of those with chronic HBV experienced hepatitis related to HBV reactivation, versus none of those with resolved HBV.

The authors say their findings "support the use of antiviral prophylaxis in patients with chronic HBV and HCV coinfection" being treated with DAAs. They add, "By contrast, patients with resolved HBV infection might only require close [alanine aminotransferase] or HBV DNA monitoring, or both."

LINK(S): Lancet Gastroenterology and Hepatology article (Free abstract)

Background: Recent NEJM Journal Watch Infectious Diseases coverage of HBV reactivation during HCV treatment (Free)

Tuesday, November 14, 2017

The negative impact of HBV/HCV coinfection on cirrhosis and its consequences

Alimentary Pharmacology & Therapeutics
The negative impact of HBV/HCV coinfection on cirrhosis and its consequences


Full Text Article 
Alimentary Pharmacology & Therapeutics

Hepatitis B virus (HBV)/hepatitis C virus (HCV) confection has been rarely studied in nonasian series.

Dr Pol and colleagues from France compared the characteristics of HBV/HCV coinfected patients to those of HBV- or HCV-monoinfected patients in the ANRS CO22 HEPATHER cohort study.

Of the 20,936 included patients, 95 had HBV/HCV coinfection, and were matched with 375 HBV- and 380 HCV-monoinfected patients on age, gender and time since HBV or HCV diagnosis.

F3-F4 fibrosis was more frequent in coinfected patients than in HBV-, but similar in HCV-monoinfected patients. Decompensated cirrhosis was more frequent in coinfected patients than in HBV- or HCV- monoinfected patients.

Past excessive alcohol use was more frequent in coinfected patients than in HBV, but similar in HCV monoinfected patients.

The researchers found that coinfected patients had a higher proportion with arterial hypertension than HBV- or HCV-monoinfected patients.

The research team confirmed the association between F3-F4 fibrosis and HCV infection in HBV-infected patients, and the association between decompensated cirrhosis and coinfection in HBV infected or HCV infected patients.

Dr Pol's team concludes, "HCV coinfection harmfully affects liver fibrosis in HBV patients, while decompensated cirrhosis is increased in coinfected patients compared with HBV- or HCV-monoinfected patients."

"HCV treatment is as safe and effective in coinfected as monoinfected patients and should be considered following the same rules as HCV monoinfected patients."

Continue to full text - http://onlinelibrary.wiley.com/doi/10.1111/apt.14352/full
  • First published:
  • DOI: 10.1111/apt.14352

  • Monday, June 19, 2017

    Letter: the influence of direct acting agents for hepatitis C, on hepatitis B reactivation

    Volume 46, Issue 2
    July 2017  Page 208

    LETTERS TO THE EDITORS
    Download PDF

    Letter: the influence of direct acting agents for hepatitis C, on hepatitis B reactivation
    C.-C. Wang, J.-H. Kao
    First published: 15 June 2017
    Full publication history DOI: 10.1111/apt.14116  

    SIRS,
    We read with great interest the article by Londono et al.[1] In this study, baseline HBsAg positivity or isolated anti-HBc positivity were 2.8% and 18% in 352 chronic hepatitis C (CHC) patients receiving direct-acting antivirals (DAAs), respectively. They found that 50% of HBsAg-positive and 1.6% of anti-HBc-positive patients had hepatitis B virus (HBV) viral reactivation (> 1 log increase in HBV-DNA level). In addition, the increase in HBV-DNA was modest and early during the course of DAAs treatment. There were no serious clinical events in such patients. They thus suggested that HBV viral reactivation is frequent and early during DAAs treatment; however, the reactivation is modest and without clinical impact. Although these data provide more evidence about the risk of HBV reactivation during DAAs for CHC, several issues are worthy of discussion and further investigations.

    First, this study found HBV reactivation is frequent in HBsAg-positive patients receiving DAAs against HCV. However, only 10 HBV/HCV co-infected patients were included, and they had a higher risk of HBV viral reactivation than those positive for anti-HBc antibody. Among these HBsAg-positive patients, six were inactive carriers and four received anti-HBV agents. Therefore, the frequency and severity of HBV viral reactivation may be underestimated as is observed in clinical practice. It is recommended that HBV status, either chronic active infection, inactive carrier or resolved infection, must be confirmed before starting DAAs, especially in HBV endemic area by measuring serum HBsAg, HBV-DNA, anti-HBc, and anti-HBs antibody. On-treatment HBV-DNA monitoring at Week 4 of DAAs treatment is required for early detection of HBV viral reactivation to prompt anti-HBV treatment and prevent the occurrence of hepatitis flare as well as subsequent fulminant hepatic failure.[2, 3] Second, 24.8% of HBV/HCV co-infected patients had HBeAg-negative chronic hepatitis in our previous study.[4] Our data showed that combination of pegylated interferon plus ribavirin is equally effective for patients with HCV mono-infection and those with dual HBV/HCV infection. In addition, post-treatment HBsAg seroclearance was observed in 11.2% of 161 HBV/HCV co-infected patients. Interferon-based regimen is known active against both HBV and HCV; however, DAAs are only effective for HCV. Whether combination of DAAs and anti-HBV agents is cost-effective for HBV/HCV co-infected patients with high HBV-DNA levels (> 2000 IU/mL) deserves additional studies. Third, a recent study showed a high rate of hepatocellular carcinoma (HCC) recurrence in HCV-related HCC patients receiving DAAs after curative treatment.[5] The possible explanation is the disruption of host immune surveillance after HCV clearance. Since host immune responses play an important role in the interaction between HBV and HCV in HBV/HCV co-infected patients, the dynamic change in immune markers during DAAs therapy for CHC deserves further investigations.

    REFERENCES
    Londono MC, Lens S, Marino Z, et al. Hepatitis B reactivation in patients with chronic hepatitis C undergoing anti-viral therapy with interferon-free regimens. Aliment Pharmacol Ther. 2017;45:1156-1161.
  • 2De Monte A, Courjon J, Anty R, et al. Direct-acting antiviral treatment in adults infected with hepatitis C virus: reactivation of hepatitisB virus coinfection as a further challenge. J Clin Virol. 2016;78:27-30.
  • 3Ende AR, Kim NH, Yeh MM, et al. Fulminant hepatitis B reactivation leading to liver transplantation in a patient with chronic hepatitis C treated with simeprevir and sofosbuvir: a case report. J Med Case Rep. 2015;9:164.
  • 4Liu CJ, Chen PJ, Chen DS, Tseng TC, Kao JH. Perspectives on dual hepatitis B and C infection in Taiwan. J Formos Med Assoc. 2016;115:298-305.
  • 5Reig M, Marino Z, Perello C, et al. Unexpected early tumor recurrence in patients with hepatitis C virus –related hepatocellular carcinoma undergoing interferon-free therapy: a note of caution. J Hepatol. 2016;65:719-726.
  • Tuesday, April 25, 2017

    Hepatitis B Virus Reactivation Associated With Direct-Acting Antiviral Therapy for Chronic Hepatitis C Virus

    No Consistent Pattern of HBV Reactivation With Direct-acting Antivirals for HCV
    NEW YORK (Reuters Health) - The largest case review to date of hepatitis B virus (HBV) reactivation associated with direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection found no consistent pattern in terms of which patients are likely to develop this adverse event.

    There was also no consistency with regard to the DAA regimen most likely to lead to HBV reactivation, suggesting a potential class-effect with DAA agents, researchers from the U.S. Food and Drug Administration (FDA) report in a paper online today in Annals of Internal Medicine.

    HBV reactivation associated with DAA therapy is a “newly identified safety concern in patients previously infected with HBV. Patients with a history of HBV infection require clinical monitoring while receiving DAA therapy,” write Dr. Susan Bersoff-Matcha and colleagues.

    They reviewed 29 cases of HBV reactivation in patients receiving DAAs reported to the FDAs adverse event reporting system between 2013 and 2016.
    Continue reading.....

    Full Text Article
    Annals of Internal Medicine

    Hepatitis B Virus Reactivation Associated With Direct-Acting Antiviral Therapy for Chronic Hepatitis C Virus
    Susan J. Bersoff-Matcha, MD; Kelly Cao, PharmD; Mihaela Jason, PharmD; Adebola Ajao, PhD; S. Christopher Jones, PharmD, MS, MPH; Tamra Meyer, PhD, MPH; and Allen Brinker, MD, MS

    Download Full Text
    PDF

    Abstract
    Background:
    Direct-acting antiviral agents (DAAs) are used increasingly to treat hepatitis C virus (HCV) infection. Reports were published recently on hepatitis B virus (HBV) reactivation (HBV-R) in patients with HBV–HCV co-infection. Hepatitis B virus reactivation, defined as an abrupt increase in HBV replication in patients with inactive or resolved HBV infection, may result in clinically significant hepatitis.

    Objective: To assess whether HBV-R is a safety concern in patients receiving HCV DAAs.

    Design: Descriptive case series.

    Setting: U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).

    Patients: 29 patients with HBV-R receiving HCV DAAs.

    Results:
    The FDA identified 29 unique reports of HBV-R in patients receiving DAAs from 22 November 2013 to 15 October 2016. Two cases resulted in death and 1 case in liver transplantation. Patients in whom HBV-R developed were heterogeneous regarding HCV genotype, DAAs received, and baseline HBV chacteristics. At baseline, 9 patients had a detectable HBV viral load, 7 had positive results on hepatitis B surface antigen (HBsAg) testing and had an undetectable HBV viral load, and 3 had negative results on HBsAg testing and had an undetectable HBV viral load. For the remaining 10 patients, data points were not reported or the data were uninterpretable. Despite provider knowledge of baseline HBV, HBV-R diagnosis and treatment were delayed in 7 cases and possibly 7 others.

    Limitations:
    The quality of information varied among reports. Because reporting is voluntary, HBV-R associated with DAAs likely is underreported.

    Conclusion:
    Hepatitis B virus reactivation is a newly identified safety concern in patients with HBV–HCV co-infection treated with DAAs. Patients with a history of HBV require clinical monitoring while receiving DAA therapy. Studies would help determine the risk factors for HBV-R, define monitoring frequency, and identify patients who may benefit from HBV prophylaxis and treatment. DAAs remain a safe and highly effective treatment for the management of HCV infection.
    Continue to full text article.....

    In The Media
    Direct-acting antiviral therapy for hepatitis C virus associated with hepatitis B virus reactivation in co-infected patients
    April 25, 2017 | Deepti Shroff and Evelyn Nguyen
    HBV-R is a manageable adverse event, and DAAs continue to be a safe and very effective treatment for infection with HCV.

    Full Text Articles
    I highly suggest you follow Henry E. Chang on Twitter if you are interested in reading full text articles about the treatment and management of hepatitis C.

    Friday, April 21, 2017

    Gilead Announces Scientific Presentations Demonstrating Efficacy of Harvoni® in Special Patient Populations With HCV Infection

    Gilead Announces Scientific Presentations Demonstrating Efficacy of Harvoni® (Ledipasvir/Sofosbuvir) in Special Patient Populations With HCV Infection

    Date(s): 21-Apr-2017
    -- Results Presented at The International Liver CongressTM 2017 Highlight Progress for the Treatment of Pediatric HCV and Adult HCV/HBV Co-Infected Patient Populations --

    FOSTER CITY, Calif.--(BUSINESS WIRE)--Apr. 21, 2017-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced results from two Phase 2 studies evaluating Harvoni® (ledipasvir 90 mg/sofosbuvir 400 mg, LDV/SOF) tablets in chronic hepatitis C virus (HCV)-infected patient populations not previously studied in dedicated clinical trials with direct-acting antiviral therapies. The studies demonstrated HCV cure rates of 99 percent in children aged 6 to 11 years (#PS-101), and 100 percent in adult patients co-infected with HCV and hepatitis B virus (HBV) (#PS-098). Detailed results from these studies were presented this week at The International Liver CongressTM 2017 in Amsterdam.

    Harvoni is approved in the United States for the treatment of genotype 1, 4, 5, or 6 chronic HCV infection in adults and pediatric patients 12 years of age or older or weighing at least 35 kilograms. Harvoni is indicated with ribavirin (RBV) for the treatment of chronic HCV genotype 1 or 4 HCV infection in liver transplant recipients without cirrhosis or with compensated cirrhosis and for genotype 1 HCV-infected patients with decompensated cirrhosis.

    Harvoni has a boxed warning in its product label regarding the risk of hepatitis B virus reactivation in HCV/HBV co-infected patients. See below for important safety information.

    "Gilead continues to study the safety and efficacy of our medicines in HCV-infected patients with unmet medical need, to help realize the potential for cure," said Norbert Bischofberger, PhD, Executive Vice President of Research and Development and Chief Scientific Officer, Gilead Sciences. "In these studies of younger children with hepatitis C and HCV/HBV co-infected patients, Harvoni achieved high cure rates and demonstrated safety consistent with the known profile of the drug."

    Children Aged 6 to 11 Years with Chronic HCV
    The estimated prevalence of HCV infection in children is up to 0.4 percent in Europe and the United States and up to 6 percent in resource-limited countries. For children 6-11 years of age weighing less than 35 kilograms, interferon plus RBV for up to 48 weeks remains the standard of care.
    Results from an open-label Phase 2 study, led by Karen F. Murray, MD, Professor of Pediatrics at Seattle Children's Hospital in Seattle, Washington, evaluating an investigational dosage strength of a once-daily single tablet of Harvoni (ledipasvir 45 mg/sofosbuvir 200 mg) in HCV-infected children aged 6 to 11 years, demonstrated cure rates of 99 percent (n=89/90). Genotype 1 patients received 12 weeks of treatment (n=85); one genotype 1 patient who had cirrhosis and prior treatment failure with pegylated interferon plus RBV received 24 weeks of treatment; genotype 3 patients (n=2) received Harvoni plus RBV for 24 weeks; genotype 4 patients (n=2) received Harvoni for 12 weeks. One treatment-naïve genotype 1 patient relapsed; all other patients achieved SVR12, the primary efficacy endpoint. The most common adverse events (>10 percent) all of which were mild to moderate in severity, were abdominal pain, headache, diarrhea, vomiting, nausea, fatigue, pyrexia, cough and oropharyngeal pain. No patients discontinued therapy.

    HCV/HBV Co-infected Patients
    The global prevalence of HCV/HBV co-infection is estimated to be 1.7-3.9 million. Reactivation of HBV infection during treatment of HCV infection with direct-acting antiviral agents has been reported in the postmarketing setting. However, clinical trials to more systematically assess the safety and efficacy of direct-acting antiviral therapy in HCV/HBV co-infected patients with active HBV infection have not been conducted.
    This Phase 2, open-label study led by Chun-Jen Liu, Professor of Medicine at National Taiwan University in Taipei, Taiwan, evaluated 12 weeks of Harvoni in 111 genotype 1 or 2 HCV-infected patients in Taiwan with active HBV co-infection (hepatitis B surface antigen positive), who were not receiving HBV treatment. All patients achieved SVR12 (100 percent, 111/111) including 68 genotype 1 HCV-infected patients, 43 genotype 2 HCV-infected patients, 17 patients with compensated cirrhosis and 37 with prior HCV treatment failure.
    Three patients had serious adverse events that were not considered to be drug-related, including optic neuritis, post-procedural bleeding and duodenal ulcer bleeding. The most common adverse events reported (=5 percent of patients) were headache, upper respiratory infection and fatigue.
    Of the 111 patients enrolled, 23 (21 percent) experienced an increase in HBV DNA of at least 2 log10 IU/mL during or following Harvoni treatment. However, no patient experienced a grade 3 or 4 ALT increase or any clinical manifestations suggestive of HBV reactivation. There were two patients that started HBV treatment based on increases in HBV DNA and mild elevations in ALT without symptoms.

    Further information about the clinical studies described above can be found at www.clinicaltrials.gov.
    Certain uses for Harvoni highlighted above are investigational and have not been determined to be safe or efficacious.

    U.S. Important Safety Information for Harvoni
    BOXED WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN HBV/HCV COINFECTED PATIENTS
    Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with Harvoni.
    HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents.
    Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated.
    Contraindications
    • If Harvoni is used in combination with ribavirin (RBV), all contraindications, warnings and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information.
    Warnings and Precautions
    • Risk of Serious Symptomatic Bradycardia When Coadministered with Amiodarone: Amiodarone is not recommended for use with Harvoni due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.
    • Risk of Reduced Therapeutic Effect of Harvoni Due to P-gp Inducers: Rifampin and St. John's wort are not recommended for use with Harvoni as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations.
    • Related Products Not Recommended: Harvoni is not recommended for use with other products containing sofosbuvir.
    Adverse Reactions
    Most common (=10%, all grades) adverse reactions were fatigue, headache and asthenia.
    Drug Interactions
    • In addition to rifampin and St. John's wort, coadministration of Harvoni is also not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of ledipasvir and sofosbuvir, reducing the therapeutic effect of Harvoni.
    • Coadministration of Harvoni is not recommended with simeprevir due to increased concentrations of ledipasvir and simeprevir. Coadministration is also not recommended with rosuvastatin or co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate due to increased concentrations of rosuvastatin and tenofovir, respectively.
    Consult the full Prescribing Information for Harvoni for more information on potentially significant drug interactions, including clinical comments.

    Wednesday, February 1, 2017

    How Dual Hepatitis B, C Infection Differs from Single Infection

    How Dual Hepatitis B, C Infection Differs from Single Infection
    Feb 01, 2017 | Dava Stewart
    The bodies of patients infected with both hepatitis B virus (HBV) and hepatitis C virus (HCV) respond to the diseases differently than those infected with only one of the two. A recent study conducted by Fei Chen, PhD, of the University of South China, and colleagues compared the virological and immunological features of patients with dual and single infections and found significant differences.

    In some areas, among particularly high-risk populations, HBV/HCV dual infection is relatively common. The researchers noted that there is increasing evidence that such dual infections are more difficult to treat, and that there is a higher likelihood of disease advancement—from chronic hepatitis to cirrhosis and hepatocellular carcinoma. Previous studies seemed to indicate that dual infection has different virologic and immunologic profiles than single infections, but those studies have yielded inconsistent results.

    Continue reading....