COVID-19 and Managing Liver Disease: Experts Respond at Penn Medicine

COVID-19, Cirrhosis, and Hepatic Injury

The question for liver disease specialists in the era of COVID-19 is not whether the liver is affected by the coronavirus, but why.

The manifestations of liver injury have appeared in as many as half of persons infected with SARS-CoV-2. But the cause of these events is unknown — and for good reason.

The list of potential contributors to hepatic injury in patients exposed to COVID-19 includes not only the virus, but systemic illness and the ischemic, immune-mediated and drug- and alcohol-induced iterations of liver injury, as well as the various treatments for these conditions.

In addition, the public health safeguards imposed by COVID-19 have brought liver donation and transplant surgeries to a near halt nationwide. This facet alone may have long-lasting effects on patients, who can now add a backlog of routine procedures and clinic visits to the personal burden of liver disease.

The response to this crisis from hepatologists and surgeons has been varied.

While a recently published expert opinion proposed a near-apocalyptic vision for the post-COVID future of liver disease management, for example, a team of specialists from Penn GI Hepatology and the Penn Transplant Institute, responding in the same journal, and from their own experience, offered a measured, constructive and affirmative counter-perspective.

Composed by Marina Serper, MD; Abraham Shaked, MD, PhD; Kim M. Olthoff, MD; Maarouf Hoteit, MD; Brenda Appolo, PA-C; and K. Rajender Reddy, MD, the response appears as a Letter to the Editor in the May issue of the Journal of Hepatology: A local response to COVID-19 for advanced liver disease: Current model of care, challenges and opportunities.

Is Management for Liver Disease Possible in the COVID Era?

Viewing the pandemic as "an unprecedented natural experiment," the authors report on early, coordinated efforts at Penn Medicine to prioritize lifesaving therapies, defer elective procedures, maintain routine care for advanced liver disease, and embrace remote technologies.

Between March and April, 69 percent of liver disease visits shifted to telemedicine, and through a program initiated by the Penn Medicine Center for Health Care Innovation, in-home, cellphone-based monitoring of symptoms in decompensated cirrhosis.

Some procedures were postponed (elective variceal surveillance, for example), while events of a more recent provenance, including new onset of variceal bleeds, jaundice and hepatic decompensation, were maintained. Among other uninterrupted services were those for hepatocellular carcinoma case assessment and therapy and non-elective liver transplantation for patients with high model for end-stage liver disease scores.

To control exposures in the community, outpatient laboratory visits were limited for patients with cirrhosis, and after liver transplant. Recently transplanted patients were provided home nurse or mobile laboratory blood drawing to follow essential care parameters.

Recognizing that difficulties and uncertainty lay ahead, the authors concluded that invaluable lessons had been learned during the pandemic about leveraging technology and the importance of proactive measures in reaching out to patients with liver disease, their caregivers, and referring providers. They noted, too, lessons learned about the rapid refinement of processes to handle ongoing challenges — and the newly acquired knowledge of their own adaptability in the face of adversity.

Best Practice Guidelines for Hepatology and Liver Transplantation in the era of COVID

A contributor to the previous report, Dr. Rajinder K. Reddy was among the experts called upon by the American Association for the Study of Liver Disease (AASLD) in May to provide a best practice advisory for hepatologists and liver transplant providers in the era of COVID-19. One of the world's leading specialists on liver disease and its treatment, Dr. Reddy is a Professor of Medicine at the Perelman School of Medicine at the University of Pennsylvania. He also serves as Co-Director of the Penn Center for Viral Hepatitis.

In a subsequent article, Dr. Reddy summarized the American Association for the Study of Liver Diseases (AASLD) advisory for the treatment of patients with hepatitis C (HCV) and hepatitis B (HBV) during the pandemic.

For patients with recently diagnosed HCV, Dr. Reddy wrote:

• It would seem reasonable to initiate HCV therapy in those not infected with SARS-CoV-2 if adequate resources are available and have not been deployed for COVID-19 activities:
• In individuals with COVID-19 in the background of a recently diagnosed HCV infection, it seems reasonable to defer HCV therapy until a time when COVID-19 has cleared; already initiated therapy can be continued while monitoring for drug-drug interactions.

In patients with HBV:

• It is important to be aware of the risk for HBV reactivation related to medications, such as tocilizumab and corticosteroids, used in the context of COVID-19. Reactivation of HBV following the use of tocilizumab and prednisone has been described, and thus prophylaxis against HBV reactivation should be a consideration.
• Chronic HBV therapy (where indicated as per guidelines) can be initiated in persons with newly diagnosed HBV, and continued if receiving therapy, regardless of COVID-19.

For all patients with advanced liver disease, Dr. Reddy concludes, caution must be exercised in initiating COVID-19-related therapy; thus, "established guidelines on such use need to be followed to minimize the risk for hepatic decompensation, although the risk/benefit of an intervention is likely to weigh in heavily in dealing with the highly lethal condition of COVID-19.

At the Nexus of Telehepatology and COVID-19

In Telemedicine and Telehepatology During the COVID‐19 Pandemic, recently published in Clinical Liver Disease, Marina Serper, MD, and co-author Oren Fix, MD, explore the concept of telehepatology for the routine medical care of patients with advanced liver disease. Dr. Serper is an Assistant Professor of Medicine at Penn GI and Hepatology.

Telehepatology is not new to Penn Medicine. Introduced in 2017, the program had the goal of addressing the national dearth of liver disease specialists amid growing evidence that access to hepatology care led to improved clinical outcomes for patients with advanced liver disease. The creation of the service at this time turned out be a prescient and invaluable addition to the armamentarium at Penn GI and Hepatology — but its success was by no means assured.

Prior to the COVID-19 pandemic, Dr. Serper writes, telehealth was encumbered by myriad regulatory and compensatory obstacles. The Centers for Medicare and Medicaid Services (CMS), for example, restricted telehealth to rural areas and remote locations. The requirement for HIPAA-compliant audiovisual equipment imposed barriers on the ready uptake of telehealth at many hospital and clinics.

This all changed, ironically, with the advent of COVID-19. These barriers to telemedicine were suddenly removed during the pandemic, at which point, according to Drs. Serper and Fix, "providers, hospitals, and health systems rapidly embraced telemedicine or scaled up existing programs to meet the sudden demand for remote, synchronous patient care."

As previously noted, almost 70 percent of in-house visits to Penn GI and Hepatology were shifted to telemedicine in the six weeks following the arrival of COVID-19 in Philadelphia.

Although the success of this transition is not without caveats and challenges, Drs. Serper and Fix write, "While the world is ravaged by COVID-19, perhaps one desirable lasting effect may be the fulfillment of the promise of telemedicine."