COVID19-FOIE National Observatory

1. Background and objectives:

Coronavirus infection 2019 (COVID-19), linked to the SARS-Cov-2 virus, is rapidly
spreading worldwide. After the city of Wuhan and the province of Hubei, European
healthcare systems are facing an outbreak of seriously ill patients, but few are fully
equipped to manage this health crisis.

On the occasion of this pandemic, the hepatologist associations of United States ,
Europe and France as well as the French Federation of Digestive Cancer have proposed
modalities for the management of patients with chronic liver disease likely to guarantee
them maximum safety. The level of scientific evidence for these proposals is very low,
given the small amount of objective clinical data available to date on the relationship
between COVID-19 and liver.

Some preliminary Chinese data indicates that:

- 2-11% of patients treated for COVID19 had underlying chronic liver disease

- an increase in transaminases is observed in 25-35% of patients, generally moderate
(median 23-39 IU/L), with a higher rate in symptomatic and/or severe forms and/or
requiring hospitalization in intensive care unit as well as in patients who later
die . The mechanism involved is uncertain to date. Indeed, the data suggesting the
possibility of localization of the virus in the liver are too preliminary, and it
is reasonable to incriminate the elements of inflammatory reaction syndrome. Liver
damage can be explained during these infections by hepatic hypoxia, related to a
frequent viral myocarditis in this situation. Finally, other more classic causes
may also be associated, including drug (paracetamol, antibiotics), or an
exacerbation of an underlying chronic liver disease, known or unknown. Control of
viral serologies B and C is therefore recommended in this situation.

- elderly patients, patients with cirrhosis, patients with immune hepatitis under
immunosuppressive drugs and patients before and after transplantation under
immunosuppressive therapy would be the subjects most at risk of severe COVID19

- very strict preventive measures have proven their effectiveness in terms of
mortality in 111 patients with decompensated cirrhosis, including 2/3 hospitalized
and 1/3 ambulatory.

In this totally new and unexpected context, the board meeting of the AFEF proposes the
national observatory COVID19-FOIE, intended to collect data of patients with liver
disease (all stages combined) or liver transplants that developed COVID19 confirmed by
PCR on nasopharyngeal sampling and/or thoracic CT.

2. Population:

All patients with acute or chronic liver disease treated by a member of the AFEF with an
established diagnosis of COVID 19 confirmed by PCR on nasopharyngeal and/or thoracic CT.

3. Methodology:

This is an epidemiological, observational, prospective, descriptive, prognostic and
evaluative observational cohort study. This study does not change the patient's
management; it consists of analyzing clinical-biological data collected as part of the
patient's usual follow-up.

4. Objectives:

Primary Objective:

Evaluate the mortality related to Covid-19 in patients with a chronic liver disease

Secondary objectives:

- Evaluate the mortality (liver-related and no liver-related) due to the Covid-19
according to the cirrhotic status, an history of hepatocellular carcinoma, an
immunosuppressive treatment and this type, the etiology-ies of liver disease at the
infection (viral hepatitis -B and/or C-, related to alcohol consumption, metabolic
syndrome, hemochromatosis, immune liver disease, other or unknown), and
comorbidities

- Evaluate the liver morbidity related to Covid-19, including :

- incidence of liver biochemical abnormalities in patients with normal liver enzymes
values or of a 2-fold increase of usual values for AST, ALT, GGT, alcalines
phosphatasis

- incidence of liver complications (acute hepatitis, liver insufficiency,
decompensation of cirrhosis, encephalopathy, renal insufficiency)

5. Criteria:

Primary criteria: mortality rate related to Covid-19 in patients with a chronic liver
disease

Secondary criteria:

- mortality rate according the stage of fibrosis and the cirrhotic status defined
with liver biopsy or non invasive tests of fibrosis or according the opinion of
clinician

- mortality related to Covid-19 according an history of hepatocellular carcinoma, an
immunosuppressive treatment and this type (treatment related to a liver
transplantation or to an auto-immune liver disease or to other indication), the
etiology-ies of liver disease at the infection (viral hepatitis -B and/or C-,
related to alcohol consumption, metabolic syndrome, hemochromatosis, immune liver
disease, other or unknown), and comorbidities, particularly diabetes, hypertension,
overweight -BMI from 26 to 30- or obesity-BMI > 30)

- Incidence of liver complications (acute hepatitis, liver insufficiency,
decompensation of cirrhosis, encephalopathy, renal insufficiency)

6. Effective and duration of the study:

All consecutive patients included in the observatory with registered data in the eCRF
until 31/12/20.

7. Population of the study:

- Inclusion criteria:

- all patients with acute or chronic liver disease managed by a member of AFEF with
positive diagnosis of COVID-19 by PCR and/or specific abnormalities at the thoracic
TDM

- patients with history of liver transplantation

- patients affiliated with social security

- Non inclusion criteria: age equal or higher 18 years

8. Conduct of the research:

After informing patients and making available a non opposition form, the main demographic and
clinical data related to a chronic liver disease, in one hand and, on the other hand, the
COVID19, already collected in the patient's medical record will be collected in a dedicated
eCRF. All contributors will be associated with the publications resulting from this
observatory and the COVID-Foie working group.