Jared Kaltwasser

Patients with chronic hepatitis C virus (HCV) infection often have poor responses to 

 vaccination even if they have been treated for HCV and achieved sustained viral response (SVR), according to a new study.

The data offer new insights into the limitations of the HBV vaccine, and could help identify which patients are most likely to benefit from vaccination, and which patients might not.

More than 170 million people worldwide have HCV infection, and 400 million people are believed to be infected by HBV. It is not clear how many patients have both, though some studies have suggested that 

in patients who are hepatitis B surface antigen (HBsAg)-positive is as high as 30%.That’s a significant public health problem, because patients with both infections face higher rates of cirrhosis and other liver damage, explained corresponding author Ekram Wassim, MBChB, MPH, PhD, of the High Institute of Public Health at Alexandria University, in Egypt, and colleagues.

Previous reports have suggested that the HBV vaccine is less effective in patients with HCV infection and in patients with isolated HBV core antibodies (HBcAb). The development of direct-acting antivirals (DAAs) has led to an effective cure for HCV, but it is not fully understood how treatment for HCV might affect responsiveness to 

Current guidelines suggest that any patient prescribed DAAs for HCV infection should also be assessed for HBsAg, hepatitis B surface antibody (HBsAb), and HBcAb. HBV vaccination is recommended for any patient deemed susceptible to HBV infection. In Egypt, Wassim and colleagues said, all patients with HCV infection who achieve SVR are given a full series of HBV vaccination, regardless of their vaccination history, HBV immune status, or serological profile.

Given the apparent conflict between widespread use of HBV vaccination in patients with HCV and the questionable efficacy of the vaccine in such patients, Wassim and colleagues decided to take a closer look at vaccine responsiveness among patients treated for HCV.

The investigators recruited 118 patients with chronic HCV who took 12 weeks of DAAs and were evaluated for HBV serological markers. Of those, 98 patients received HBV vaccines.

Among the vaccinated, 57.1% responded to the vaccine, but only 5.1% achieved a seroprotective level of HBsAb titer. Among those with HBcAb, the response rate was just 5.6%, compared to 64.5% in patients without. A multivariate analysis suggested that advanced age, and presence of isolated HBcAb were linked with poor responses. 

Wassim and colleagues noted that the idea that isolated HBcAb limits responsiveness to HBV vaccine is controversial. Their data supports the link, but it does not appear to be the only answer.

“Nevertheless, this cannot account on its own for the high rate of hyporesponsiveness to HBsAg, which rather may be caused by the longstanding HCV infection,” they wrote.

The authors noted that the findings suggest Egypt’s aggressive approach to HBV vaccination might not be cost-effective.

The paper analyzes 3 models of vaccination strategies. The most cost-effective model involved testing all HCV-treated individuals for HBcAb, and not offering HBV vaccines to those patients who are seropositive. Among seronegative patients, a second analysis would be performed to test for HBsAb. Those patients with protective HBsAb levels would also not be offered a vaccine. However, those who were seronegative on the second test would be offered a three-dose HBV vaccine regimen.

 that public health officials in countries with high rates of HCV should take note of the findings. She noted that Egypt has made hepatitis eradication a national health priority.

“Our work should be considered by stakeholders who might change the policy based on the promising findings,” she said. “This will add to the success of the HCV control program launched in 2014.”

Effectiveness of hepatitis B vaccination in chronic HCV patients after successful generic direct acting antiviral therapy: significance of isolated hepatitis B core antibodies

Articles

New data affirms a low rate of hepatitis B vaccination responsiveness among patients with hepatitis B core antibodies.

Study Explores Limits of HBV Vaccination in Patients Treated for HCV

New data show a pediatric formulation of the direct-acting antiviral (DAAs) therapy glecaprevir/pibrentasvir (GLE/PIB) is highly effective and well-tolerated in pediatric patients with 

, since the data suggest that the dramatic results DAAs have brought about in adults can also be realized in children as young as 3.

Corresponding author Maureen M. Jonas, MD, of Boston Children’s Hospital and Harvard Medical School, said she was pleased with the way the drug’s manufacturer, AbbVie, embraced the effort to make the therapy available to children, something that does not happen in every therapeutic area.

“Often, we have to wait many years for things to percolate down to children,” she told 

. “But these companies across the board addressed the issue of pediatric (patients) relatively early in the process.”

The drugs have a good safety profile in adults, and Jonas said there was good reason to believe they would be successful in children, in part because an earlier phase of the study showed success in children ages 12 up to 18. About 13.2 million of the world’s estimated 71 million people with HCV infection are children between the ages of 1 and 15.

The challenge of the present phase, which focused on children between the ages of 3 and 12, was to find the right dose and also to find a formulation that children would take. In this case, the winning formulation turned out to be small film-coated granules of 

The study enrolled 80 patients with chronic HCV infection, genotypes 1-6, with or without compensated cirrhosis. The children were split into three age-based cohorts and given weight-based doses for either 8, 12 or 16 weeks. The primary endpoints were sustained virologic response at 12 weeks (SVR12) and steady-state exposure.

Of the 80 patients in the study, 77 achieved SVR12. One patient on the initial dose ratio had relapsed within 4 weeks of the end of treatment and 2 non-responders discontinued the study.

In the end, the investigators found doses of 250 mg GLE and 100 mg PIB were efficacious for children weighing 30 up to 45 kg. A dose of 200 mg GLE plus 80 mg PIB worked for children from 20 up to 30 kg, and the smallest patients (those 12-20 kg) achieved results at a dose of 150 mg GLE plus 60 mg PIB. No serious drug-related adverse events were reported and pharmacokinetic exposures were comparable to those of adults.

The majority of children become infected with HCV as a result of vertical transmission. While a minority of patients (roughly one-quarter) will see their infection resolve on its own, most patients will develop long-term infections. The ability to successfully treat HCV when the patients are young could prevent potential long-term damage, the investigators wrote. Jonas said the therapy would also open up new possibilities for organ donation, since the organs of patients with HCV infection could be transplanted to patients in need and the recipients could then be treated with DAAs to cure the infection.

Perhaps the bigger question, Jonas said, is not so much whether the therapy will work in children, but rather whether it will be available to children. She noted that DAAs typically have a steep price tag. While patients in wealthier regions, such as the United States and Europe, might be able to easily access the therapies, that access is not guaranteed in many developing countries. She said the highest prevalence of the disease is in less-wealthy regions like Egypt, Asia, southeast Asia, and Africa.

“If we really want to eradicate it and decrease global prevalence we’ve got to get out there and not just the developing world,” she said.

Pharmacokinetics, safety, and efficacy of glecaprevir/pibrentasvir in children with chronic hepatitis C virus: part 2 of the DORA study

Direct-acting antivirals have been a major milestone in the treatment of hepatitis C virus, new data show they also work in nearly all children, without serious adverse events.

DAA Safe, Effective in Children with HCV Infection, Study Finds

People with unstable housing are most likely to not complete treatment for 

, and patients whose primary insurance is Medicaid are less likely to return for sustained virologic response (SVR) testing, according to a new study of more than 300 patients with HCV.

The report highlights the opportunities, but also the limitations, of comprehensive primary care centered on harm-reduction.

Corresponding author Jacob Ziff, a medical school student at the Icahn School of Medicine at Mt. Sinai, and colleagues, sought to better understand how social determinants of health impact the success of treatment for patients with HCV. To find out, they conducted a retrospective cohort analysis of patients who began treatment using direct-acting antivirals (DAAs) at the 

Respectful and Equitable Access to Comprehensive Healthcare (REACH) primary care program at Mt. Sinai

. The clinic is located in East Harlem, New York, an area with a high prevalence of HCV. It aims to provide wide-ranging services to meet the needs of patients who 

, including medical, mental health, social work, and patient navigation services.

The study’s cohort included 329 patients who began therapy with DAAs between December 2014 and March 2018. Those patients were tracked for 2 primary endpoints: HCV treatment completion and return for SVR testing 12 weeks after the completion of testing. Those outcomes were analyzed alongside a range of factors, such as substance use, psychiatric history, housing instability, and treatment regimen, in order to see what correlations might exist.

Overall, 92% of patients completed the treatment. Of those, only one factor emerged as a significant predictor of treatment completion: housing. Those with unstable housing were significantly less likely to complete treatment (odds ratio [OR], 0.3; 95% confidence interval [CI], 0.1-0.9).

Among the 302 patients who completed treatment, three-quarters returned for SVR assessment. Again, just one factor appeared to correlate with a patient’s likelihood of return. In this case, it was having Medicaid as their primary insurances, compared to other insurances (OR, 0.3; 95% CI, 0.1-0.7).

 that, since the REACH model is built on addressing social determinants of health, he was not surprised to find that 

those the clinic was designed and well-positioned to address—were not predictive of outcomes.

“There is a large body of research that demonstrates that patients with active substance use can do equally well on HCV treatment as compared to those without, when provided with adequate support and resources,” he said.

Unfortunately, he added, housing instability and Medicaid status, “are much less readily mutable” than other factors. And insofar as the success of the patients in this study was due to the comprehensive approach of the REACH model, he conceded that not every clinic will be able to provide the same level of support.

Ziff said the study demonstrates how public policy can support and bolster healthcare providers, but can also limit access to care, such as when states place restrictions on Medicaid authorization for HCV treatment. However, he said providers still have room to work around the constraints.

“[I]t is vital that we as healthcare providers not only try to push for policy that improves our community’s health, but that we also seek and utilize practices that allow us to navigate within the existing policy paradigm in order to best serve our patients,” he said.

Such efforts include things like patient navigation, using the Psychosocial Readiness Evaluation and Preparation for Hepatitis C Treatment (PREP-C) tool, and streamlining prior authorization.

“So yes, while unstable housing and Medicaid seem like more upstream, less actionable problems for us as healthcare providers to impact, it is at the very least our responsibility to adjust our care in the attempt to balance the resulting inequities that result from [the upstream problems] in current treatment,” he said.

Predictors of hepatitis C treatment outcomes in a harm reduction-focused primary care program in New York City

More than 90% of patients with hepatitis C who sought care at a comprehensive community health clinic completed treatment, and three-quarters of those returned for sustained virologic response testing.

Housing, Insurance Are Key Factors in Success of HCV Treatment

Direct-acting antivirals (DAA) appear to be associated with the alleviation of symptoms of oral lichen planus (OLP) in patients with 

, but more research is needed to fully understand the links between the infection and the inflammatory condition.

 for patients with HCV. Some of those patients with HCV also have OLP, an inflammatory condition affecting mucous membranes in the mouth, which can lead to burning sensations and pain. 

 of HCV, though the potential causal relationship between HCV and OLP remains a topic of scientific disagreement, and only a small percentage of patients with OLP are believed to be infected by HCV.

Investigator Aldo Marrone, MD, of the University of Campania Luigi Vanvitelli, in Italy, and colleagues, wanted to better understand the issue by finding out whether eradication of HCV might also lead to relief from OLP’s clinical manifestations. Such an outcome has been reported in 

The investigators recruited a total of 18 patients, 13 of whom were female and 5 of whom were male. All of the patients had a histologic diagnosis of OLP and chronic HCV infection. The patients had a median age of 75 years.

All of the patients in the study were given DAA therapy and monitored for liver function and antiviral response. Oral examinations were given at baseline and then again 8 weeks after completing their treatment. The patients were also examined in subsequent follow-up visits, at a median of 92 weeks.

Though the patients had different genotypes, all had cleared HCV RNA with a sustained virologic response at final follow-up, Marrone and colleagues reported. In terms of OLP symptoms, at baseline, 5 patients had reticular and bilateral white lesions, 7 patients had erosive OLP, and 6 had a mixed form.

On average percentages of oral sites involved were 30% at baseline (±13.9). By 8 weeks following treatment, that percentage had dropped to 20.8% (±12.9). At the final follow-up, it was 16.2% (±15.2).

On a patient-by-patient basis, oral lesions improved in 9 patients by 8 weeks following the end of therapy and 10 patients at the final follow-up. Six of those 10 patients saw complete remission. One patient developed oral cancer during treatment and was therefore excluded from the results.

However, despite that evidence of improvement in OLP symptoms, the investigators were unable to identify correlations between symptom abatement and the particular clinical features of a patient’s HCV infection. Marrone and colleagues failed to find statistically significant links between oral improvement and HCV genotype, viral load, liver status, isolated HBcAb positivity, or type of DAA received.

The authors concluded that while there appeared to be an effect on OLP with DAA therapy, the cause remains a mystery.

“DAA treatment leading to HCV eradication can improve OLP symptoms,” Marrone and colleagues wrote. “However, a causative relationship between HCV infection and OLP pathogenesis is difficult to establish.”

Clinical impact of direct-acting antiviral treatment on patients with hepatitis C virus–related oral lichen planus

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology.

Most patients who were treated with direct-acting antivirals for hepatitis C virus infection saw improvement in oral lichen planus symptoms, including 6 of 10 who saw complete remission.