key: cord-0741987-3yldceh6
authors: Bartoli, Alessandra; Gitto, Stefano; Sighinolfi, Pamela; Cursaro, Carmela; Andreone, Pietro
title: PRIMARY BILIARY CHOLANGITIS ASSOCIATED WITH SARS-COV2 INFECTION
date: 2021-02-19
journal: J Hepatol
DOI: 10.1016/j.jhep.2021.02.006
sha: 15346f4bc0670c53ae3787e82d1fd161e8dd8a49
doc_id: 741987
cord_uid: 3yldceh6

nan

we would like to present the case of a female patient who developed Primary Biliary Cholangitis (PBC) concomitant with Guillain-Barré Syndrome (GBS) during Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV2) [1] .

A 44 years old obese and hypertensive woman already suffering from Hashimoto's thyroiditis, was admitted to hospital with fever, cough and dyspnoea on March 18, 2020. Chest X-rays showed bilateral interstitial pneumonia and positive SARS-COV2 nasopharyngeal swab. Because of a clinical deterioration, the patient was intubated and treated in the intensive care unit with mechanical ventilation and the following drugs in chronological order: tocilizumab, ceftriaxone, azithromycin, darunavir/cobicistat, anakinra, remdesivir and fluconazole. After two weeks of mechanical ventilation, the patient' conditions began to improve. She was extubated but, because of a respiratory worsening, a non-invasive ventilation was initiated. Then, she presented a rapid deterioration in alert state with coma (Glasgow coma scale 3) with good oxygen saturation and was re-intubated. In the following days the state of consciousness improved with complete recovery but she displayed a proximal hyposthenia at the four limbs without sensitive alterations; osteo-tendons reflexes were absent at the upper limbs, weakly evocable the patellars, present at the heels. The electromyography showed signs of radiculo-neuropathy with prevalent interesting of the proximal section of the four limbs and diffuse signs of active neurogenic sufferance with modest reinnervating activity. An acute motor axonal neuropathy subtype of GBS was diagnosed and the patient was treated with intravenous immunoglobulins with a progressive clinical improvement allowing the transfer to a rehabilitation ward.

During the hospitalization in intensive care, an important rise of the serum gamma-glutamyltransferase (GGT) was observed with initially normal levels of alkaline phosphatase (AP) that progressively increased later ( fig. 1A ). Serum bilirubin was normal or slightly augmented while alanine-amino-transferase (ALT) tended to fluctuate between normal and slightly increased levels Given the AP increase associated with AMA positivity, PBC was suspected however a liver biopsy was performed to exclude a possible concomitant non-alcoholic steato-hepatitis. The histological examination ( Fig. 1B and 1C) showed a preserved architecture and a moderate peri-portal fibrosis. A possible overlap syndrome between PBC and autoimmune hepatitis, advanced during the acute phase, was thereafter excluded following the EASL revised criteria [3] .

Based on these evidences we hypothesize that SARS-COV2 infection could have triggered the expression of PBC and GBS in a genetically predisposed subject already suffering from an autoimmune thyroiditis. This hypothesis is further supported by the fact that SARS-COV2 is an RNA virus capable of inducing a profound activation of the immune system and also by the previous finding that infection by a human RNA beta-retrovirus, related to mouse mammary tumor virus, was suggested as possible trigger factor for PBC development [4] . 

Alessandra Bartoli and Dr. Stefano Gitto shared co-first authorship

Covid-19 -Navigating the Uncharted

Evaluation of a new histologic staging and grading system for primary biliary cirrhosis in comparison with classical systems

European Association for the study of the Liver. EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis

Linking human beta retrovirus infection with primary biliary cirrhosis

We sincerely thank Dr Tatiana Alicandro and Dr Marco Rivi who contributed to the realization of this scientific report.J o u r n a l P r e -p r o o f