COVID-19 leads to challenges ‘at every single step’ of HCV care cascade

The COVID-19 pandemic has had “a tremendously negative impact” on efforts to eliminate hepatitis C, according to Ricardo Franco, MD.

“Curative HCV treatment is the last step in the HCV care cascade that starts with robust screening and linkage to care — and that doesn’t change, regardless of the status of the pandemic,” Franco, an associate professor of medicine (infectious diseases) at the University of Alabama at Birmingham and an associate scientist at the UAB Center for AIDS Research, told Healio.

Ricardo Franco

Franco outlined earlier steps in the HCV care cascade, including a physical evaluation and “a lot of attention” to competing priorities that may affect patients, such as other medical conditions that may not be well controlled, psychological barriers, limited transportation, unstable housing and food insecurity. These factors do not change because of the pandemic; in fact, they may become more significant, according to Franco.

Implementation approaches enable providers to shorten the care cascade in HCV, he continued. One step in this process is the ability to test patients for HCV, treat them and cure the disease, but those strategies “can only flourish in ideal situations that the pandemic does not allow.”

The pandemic “creates an extra layer of challenges at every single step of the HCV care cascade because it shifts public health priorities away from HCV work,” Franco said. These challenges include financial hardship, job insecurity, interruptions to family and social interactions, uncertainty and anxiety, all of which have “a tremendously negative impact” on patients, clinicians, health care systems and public health experts working to coordinate a concerted response to HCV, with the ultimate goal of eliminating the disease.

According to Franco, modeling studies from the United Kingdom and Italy that examined the impact of postponing HCV treatment because of the pandemic demonstrated a negative effect on disease elimination goals.

“Some of these models propose coordinated prioritization of patients with advanced fibrosis and cirrhosis to continue moving the care cascade,” he said. “Otherwise, we could even see an increase in HCV-related mortality as a delayed consequence of the problems we’re having now. The more you look at it, the more concerning it becomes.”

Further, patients with HCV are vulnerable, according to Franco; they may be hard to reach and experiencing stigma. COVID-19 only increases these challenges.

However, these challenges may present a unique opportunity for providers, Franco continued.

“I feel like my role in the clinic is more important than ever, because you have opportunities to try to remain engaged with patients, even the ones who cannot make clinic visits. You can stay engaged with them through telemedicine or simple phone calls,” he said. “The basic needs of patients with HCV urgently require attention. They may not have access to their primary care physician. They may have questions about COVID-19. As a gatekeeper to the UAB health care system, I can refer patients if they have other issues that would benefit from a visit with a colleague at UAB.”

Questions remain about COVID-19’s effect on liver, use of HCV drugs

While the impact of COVID-19 on the care cascade is clear, the question of whether HCV makes COVID-19 more severe has not been fully elucidated, according to Franco.

“More structured research is needed to truly determine if HCV by itself — and other chronic liver diseases — independently correlates with a greater risk for severe COVID-19 compared with patients without chronic liver disease,” he said. “We don’t have high-quality research yet on this, but we have observed many patients with COVID-19 to see how the liver behaves.”

Patients with COVID-19 can experience increased liver enzyme levels, indicating that — at least temporarily — the liver may be damaged, according to Franco. One study of 148 patients from a Chinese cohort demonstrated that length of stay increased among hospitalized patients with abnormal liver function, regardless of the medications given. Additionally, it appears that liver damage occurs more often among patients with severe COVID-19, Franco continued. However, he noted that the exact cause of the liver dysfunction is “hard to tease out.”

“Is the increase in liver enzymes directly related to the virus causing liver damage? Or is the liver damage the result of other factors?” Franco said. “Especially among patients who require ICU care, liver damage can come from septic shock, from multiorgan dysfunction, from drug-related toxicity, even from the generalized inflammatory response that these patients have in the ICU, the so-called cytokine storm.”

According to Franco, there have been several reports of vascular thrombosis causing ischemic liver injury. The question, he continued, then becomes: Is vascular thrombosis also causing emboli to the liver and inducing liver failure that way?

“Clinicians are always attentive to the positive pressures in mechanical ventilation. Those can cause liver congestion and liver damage; septic shock, especially, causes hypotension and poor liver perfusion,” he said. “In a critically ill patient, teasing out the role of each of these factors in liver damage can be difficult. Also, doing studies of this nature is challenging because there are so many factors in the same ICU patient. It’s hard to tease out if HCV alone would be a predisposing factor for severe disease, but I’ll say — and most clinicians would agree — that, if a patient with severe COVID-19 has pre-existing liver disease, and perhaps a limited liver reserve, they are certainly at greater risk for death or a longer ICU stay because of that and because, often times, patients clinical liver disease — HCV or other types — also have a depressed immune system.”

The laboratory studies that examined the use of the HCV drugs sofosbuvir and daclatasvir represent another element of the questions surrounding the connections between HCV and COVID-19. Research presented at AIDS 2020 demonstrated that using these two direct-acting antivirals, in combination with standard care, resulted in better 14-day recovery rates and a shorter hospital stay. The researchers emphasized the need for larger studies to confirm the results before the treatment was widely adopted.

The premise of repurposing drugs for COVID-19 “is extremely important,” according to Franco, “We’re in desperate need of treatment options.”

The results with sofosbuvir and daclatasvir were interesting, Franco noted, but he does not believe there will be “a race to access DAAs” for COVID-19 to the point that there would be a shortage of these medications for HCV.

“If this observational data had been released in March, I would be very concerned. There were these large epicenters in China, and then Italy, and eventually New York, and clinicians did not know what to do,” Franco said. “They were willing to accept the risks of unproven treatments not yet tested in clinical trials because they felt the situation justified it. It was an extreme situation.”

COVID-19 is behaving differently now, according to Franco. The burden that the health care system is experiencing “is still extremely concerning,” but researchers understand a great deal more about the disease, and a standard of care treatment has been developed: remdesivir for hospitalized patients with mild to moderate disease and remdesivir plus dexamethasone for hospitalized patients with moderate to severe disease.

Further, physicians have learned — perhaps “the hard way,” according to Franco — the implications of committing to fast-track an unproven treatment. The most significant example of this is hydroxychloroquine.

“Researchers have to pause and really think about how promising the data are before spending resources on a trial where you might not get the return on the effort you’re expending,” he said. “Also, regulatory agencies would be more resistant to the idea of fast-tracking DAAs after what occurred with hydroxychloroquine. I also don’t see clinicians pressing to create that quick of a demand.”

Pandemic provides opportunities, challenges

The COVID-19 pandemic has, out of necessity, increased the use of telemedicine across medical specialties. In gastroenterology, the American College of Gastroenterology published guidelines to enable rapid introduction of this approach into practice. The use of telemedicine, and attempts to decrease in-person visits in all aspects of health care, have resulted in opportunities as well as challenges.

Franco believes this widespread use of telemedicine will likely “shape clinical practice down the line, even after the pandemic is over.” He has found it “very productive” to speak with patients before a visit and assess their comfort level with a clinic visit.

“All of the sudden, I find myself walking a patient through the process of being evaluated for HCV, of securing treatment and providing prior authorization,” Franco said. “Some patients do not even know they have HCV. They had been diagnosed, but somehow communication fell apart and suddenly they are right in front of me. I’ve started asking the patient ‘What brings you here today?’ because, otherwise, I could find myself breaking the news about HCV to someone who has been referred to the specialist but still does not know he is HCV-infected.”

The outcomes of this, however, have been largely positive, according to Franco. He believes such experiences enable patients to make better decisions about their health care and make them more invested in their own care.

“I suspect, in the near future, once circulation of people becomes easier, the rate of people who show up for clinic might increase, because they’ll understand the reason why the appointment was made,” he said.

One of the major negative effects of the pandemic, however, is the delaying or halting of public health efforts. In HCV care, efforts to loosen Medicaid restrictions on DAAs, as well as treatment services for people who use drugs, “have been on hold” because of COVID-19, according to Franco.

“Of course, public health efforts have been hit really hard financially, just like everything else,” Franco said. “There’s a perceived inability to make room for additional costs related to expanding DAA access at this time.”

The impact on services for people who use drugs is more uncertain, Franco noted. First, the negative effects of COVID-19 on health services. The scope of that problem — access to care for people who use drugs — is not yet fully understood, but “is very likely to have a very high impact,” Franco said.

“Treatment services for people who use drugs is chronically underfunded in the United States and, before the pandemic, was already in great need of expansion,” he said. “If we do not make treatments available, and if we assume that drug circulation will continue despite the pandemic, the injection drug use problem very likely will become worse. If that becomes worse, I would be very concerned that could result in an increasing incidence of new HCV infections.”

References:

• Blach S, et al. J Hepatol. 2020;doi: 10.1016/j.jhep.2020.07.042.
• Karimi-Sari H, et al. Liver Int. 2020;doi: 10.1111/liv.14486.
• Kondili LA, et al. Dig Liver Dis. 2020;doi: 10.1016/j.dld.2020.05.040 [Epub ahead of print]
• Lau G, Coalition for Global Hepatitis Elimination. Synthesis of Liver Associations Recommendations for Hepatology and Liver Transplant Care During the COVID-19 Pandemic. 2020; https://www.globalhep.org/evidence-base/covid-19/clinical-liver-disease-covid-issue/synthesis-liver-associations. Accessed August 14, 2020.
• Ward JW, Coalition for Global Hepatitis Elimination. COVID-19 and Liver Disease: Synthesis of Current Literature. 2020; https://www.globalhep.org/evidence-base/covid-19/covid-19-and-liver-disease-synthesis-current-literature-updated-4172020. Accessed August 14, 2020.