A Case of Primary Biliary Cirrhosis With New Onset Hyperthyroidism and Supratherapeutic INR

Introduction: Hyperthyroidism is known to increase catabolism of vitamin-K-dependent clotting factors (II, VII, IX, X) and increase the response of vitamin K antagonists, usually warfarin. Primary biliary cirrhosis (PBC) has been associated with thyroid dysfunction (TD), especially with autoimmune thyroid disease. In the below case, a patient with known PBC on warfarin is found to have severely elevated INR related to new-onset hyperthyroidism with clinical consequences of hemorrhage including upper GI bleed. Case Description/Methods: A 64-year-old female with PBC and antiphospholipid antibody syndrome on warfarin was admitted for hemorrhagic epiglottitis requiring emergency intubation and supratherapeutic INR. Her PBC was diagnosed as stage II on biopsy 23 years ago and has remained clinically stable on ursodiol therapy. On presentation, the patient was tachycardic, tachypneic, and had O2 saturations <90% on HFNC prior to intubation. Physical exam significant for larger goiter with diffuse upper airway swelling. She was admitted and found to have COVID-19 infection, INR .16.0 and PT>200.0 (limit of lab), WBC of 22.8, and lactate of 2.5. LFTs WNL aside from albumin of 2.0. TSH was <0.0017 (limit of lab) and free T4 of 3.4, free T3 of 5.3. TSH receptor antibody (TRAB) and thyroid stimulating immunoglobulin (TSI) levels were normal. Her last TSH was normal a year ago. CTA chest found a 5.7cm heterogeneous, partially calcified superior mediastinal mass consistent with multinodular thyroid goiter. Patient was initially given prothrombin complex concentrate and vitamin K with correction of INR over the following few days. She was extubated and started on methimazole. During the hospital course, she was found to have coffee ground emesis for which an EGD was done with findings of non-bleeding gastric ulcer (Forrest Class IIc) and LA Grade D esophagitis with adherent clot and bleeding for which hemostatic spray was applied. Patient was discharged a few days later following resumption of warfarin and on pantoprazole and methimazole. Discussion(s): The above case demonstrates a rare case of PBC and new-onset hyperthyroidism due to multinodular thyroid goiter causing significantly elevated INR in the setting of warfarin use with hospital course complicated by GI bleed. PBC is associated with TD - hyperthyroidism, hypothyroidism, and thyroid cancer. Hyperthyroidism is less commonly associated with PBC compared to other TDs but should be considered especially with a finding of elevated INR.

Protective effect of ursodeoxycholic acid on COVID-19 in patients with chronic liver disease.

Objective: Ursodeoxycholic acid (UDCA) may reduce susceptibility to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection by downregulating angiotensin-converting enzyme 2 (ACE2), based on recent experimental investigation. This study aimed to determine the potential protective effect of UDCA against SARS-CoV-2 infection in patients with chronic liver disease. Methods: Patients with chronic liver disease receiving UDCA (taking UDCA ≥1 month) at Beijing Ditan Hospital between January 2022 and December 2022 were consecutively enrolled. These patients were matched in a 1:1 ratio to those with liver disease not receiving UDCA during the same period by using a propensity score matching analysis with nearest neighbor matching algorithm. We conducted a phone survey of coronavirus disease 2019 (COVID-19) infection during the early phase of the pandemic liberation (from 15 December 2022 to 15 January 2023). The risk of COVID-19 was compared in two matched cohorts of 225 UDCA users and 225 non-UDCA users based on patient self-report. Results: In the adjusted analysis, the control group was superior to the UDCA group in COVID-19 vaccination rates and liver function indicators, including γ-glutamyl transpeptidase and alkaline phosphatase (p < 0.05). UDCA was associated with a lower incidence of SARS-CoV-2 infection (UDCA 85.3% vs. control 94.2%, p = 0.002), more mild cases (80.0% vs. 72.0%, p = 0.047), and shorter median time from infection to recovery (5 vs. 7 days, p < 0.001). Logistic regression analysis showed that UDCA was a significant protective factor against COVID-19 infection (OR: 0.32, 95%CI: 0.16-0.64, p = 0.001). Furthermore, diabetes mellitus (OR: 2.48, 95%CI: 1.11-5.54, p = 0.027) and moderate/severe infection (OR: 8.94, 95%CI: 1.07-74.61, p = 0.043) were more likely to prolong the time from infection to recovery. Conclusion: UDCA therapy may be beneficial in reducing COVID-19 infection risk, alleviating symptoms, and shortening the recovery time in patients with chronic liver disease. However, it should be emphasized that the conclusions were based on patient self-report rather than classical COVID-19 detection by experimental investigations. Further large clinical and experimental studies are needed to validate these findings.

L-Ornithine-L-Aspartate and Intermittent Renal Replacement Therapy in Fulminant Hepatitis A: A Case Report

Hepatitis A is a common viral infection worldwide that is transmitted via the fecal-oral route. Since the introduction of an efficient vaccine, the incidence of infection has decreased but the number of cases has risen due to widespread community outbreaks among unimmunized individuals. Classic symptoms include fever, malaise, dark urine, and jaundice, and are more common in older children and adults. People are often most infectious 14 days prior to and 7 days following the onset of jaundice. We will discuss the case of a young male patient, diagnosed with acute hepatitis A, leading to fulminant hepatitis refractory to conventional therapy and the development of subsequent kidney injury. The medical treatment through the course of hospitalization was challenging and included the use of L-ornithine-L-aspartate and prolonged intermittent hemodialysis, leading to a remarkable outcome. Hepatitis A is usually self-limited and vaccine-preventable;supportive care is often sufficient for treatment, and chronic infection or chronic liver disease rarely develops. However, fulminant hepatitis, although rare, can be very challenging to manage as in the case of our patient.Copyright © 2023 The Author(s).

Acute hemolytic reaction in patients with novel coronavirus pneumonia induced by high-dose ribavirin injection: report of 2 cases.

Two female patients (patient 1, 22-year-old;patient 2, 50-year-old) received IV infusion of ribavirin injection (4 g in the first dose and the next day 1.2 g thrice daily), oral 2 lopinavir and ritonavir tablets twice daily, and aerosol inhalation of recombinant human interferon alpha2b for injection for novel coronavirus pneumonia. There was no obvious abnormality in blood routine and liver function before treatment. Laboratory tests showed red blood cell count (RBC) 2.89x1012/L, hemoglobin (Hb) 75 g/L, alanine aminotransferase (ALT) 22.8 U/L, aspartate aminotransferase (AST) 33.9 U/L, total bilirubin (TBil) 71.2 mumol/L, and indirect bilirubin (IBil) 63.5 mumol/L in patient 1 on the 2nd day of treatment, and RBC 3.46x1012/L, Hb 95 g/L, ALT 17.7 U/L, AST 21.3 U/L, TBil 86.1 mumol/L, and IBil 67.1 mumol/L in patient 2 on the 3rd day of treatment. The direct antiglobulin test was positive, indirect antiglobulin test was negative, and antinuclear antibody test was negative in both patients. They were diagnosed as having acute hemolytic anemia. Con-sidering the relationship to ribavirin, ribavirin was given in reduced dose and then finally discontinued in patient 1, and was discontinued directly in patient 2. On the basis of continued use of the other 2 drugs, both of them were treated with ursodeoxycholic acid. The Hb and bilirubin level of the 2 patients gradually returned to normal.Copyright © 2020 by the Chinese Medical Association.

Maternal and Fetal Effects of COVID-19 Virus on a Complicated Triplet Pregnancy: a Case Report

Background: Coronavirus disease 2019 (COVLD-19), the global pandemic that has spread throughout the world, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Given the limited scientific evidence on the manifestations and potential impact of this virus on pregnancy, we decided to report this case. Case presentation: The patient was a 38 year-old Iranian woman with a triplet pregnancy and a history of primary infertility, as well as hypothyroidism and gestational diabetes. She was hospitalized at 29 weeks and 2 days gestational age due to elevated liver enzymes, and finally, based on a probable diagnosis of gestational cholestasis, she was treated with ursodeoxycholic acid. On the first day of hospitalization, sonography was performed, which showed that biophysical scores and amniotic fluid were normal in all three fetuses, with normal Doppler findings in two fetuses and increased umbilical artery resistance (pulsatility index [PI] > 95%) in one fetus. On day 4 of hospitalization, she developed fever, cough and myalgia, and her COVID-19 test was positive. Despite mild maternal symptoms, exacerbated placental insufficiency occurred in two of the fetuses leading to the rapid development of absent umbilical artery end-diastolic flow. Finally, 6 days later, the patient underwent cesarean section due to rapid exacerbation of placental insufficiency and declining biophysical score in two of the fetuses. Nasopharyngeal swab COVID-19 tests were negative for the first and third babies and positive for the second baby. The first and third babies died 3 and 13 days after birth, respectively, due to collapsed white lung and sepsis. The second baby was discharged in good general condition. The mother was discharged 3 days after cesarean section. She had no fever at the time of discharge and was also in good general condition. Conclusion(s): This was a complicated triplet pregnancy, in which, after maternal infection with COVID-19, despite mild maternal symptoms, exacerbated placental insufficiency occurred in two of the fetuses, and the third fetus had a positive COVID-19 test after birth. Therefore, in cases of pregnancy with COVID-19 infection, in addition to managing the mother, it seems that physicians would be wise to also give special attention to the possibility of acute placental insufficiency and subsequent fetal hypoxia, and also the probability of vertical transmission.Copyright © 2022 Goldstein and Associates. All rights reserved.

Development of HPLC-CAD method for simultaneous quantification of nine related substances in ursodeoxycholic acid and identification of two unknown impurities by HPLC-Q-TOF-MS.

Ursodeoxycholic acid has gained increasing attention due to its recent discovery of the preventive effect on SARS-CoV-2 infection. Ursodeoxycholic acid has been included in various pharmacopoeias as an old drug, and the latest European Pharmacopoeia lists nine potential related substances (impurities A∼I). However, existing methods in pharmacopoeias and literature can only quantify up to five of these impurities simultaneously, and the sensitivity is inadequate, as the impurities are isomers or cholic acid analogues lacking chromophores. Herein, a novel gradient RP-HPLC method coupled to charged aerosol detection (CAD) was developed and validated for the simultaneous separation and quantification of the nine impurities in ursodeoxycholic acid. The method proved sensitive and allowed the quantification of the impurities as low as 0.02 %. Relative correction factors of the nine impurities were all within the range of 0.8-1.2 in the gradient mode by optimizing chromatographic conditions and CAD parameters. In addition, this RP-HPLC method is fully compatible with LC-MS due to the volatile additives and high percentage of the organic phase, which can be directly used for the identification of impurities. The newly developed HPLC-CAD method was successfully applied to commercial bulk drug samples, and two unknown impurities were identified by HPLC-Q-TOF-MS. The effect of CAD parameters on the linearity and correction factors was also discussed in this study. Overall, the established HPLC-CAD method can improve the methods in current pharmacopoeias and literature and contributes to understanding the impurity profile for process improvement.

CLINICAL AND LABORATORY CHARACTERISTICS OF PATIENTS WITH LIVER DAMAGE IN THE COVID-19 EARLY REHABILITATION PERIOD

The emergence of COVID-19 has set health professionals tasks related to the rapid diagnosis and provision of medical care to patients. Patients with COVID-19 also have extrapulmonary symptoms;including clinical signs of damage to the gastrointestinal tract (GI tract) and the hepatobiliary system which are diagnosed in 26–53% of patients. Aim. The aim of the study was to evaluate clinical and laboratory indicators of liver damage in patients in the early rehabilitation period of COVID-19. Material and methods. There were 243 patients with COVID-19 aged 18–60 years under observation. The criteria for inclusion in the study were: transferred no earlier than 10 days before inclusion in the study COVID-19;at the time of inclusion in the study PCR-negative COVID-19. The indicators of the general blood test, in the blood serum – C-reactive protein, alanine aminotransferase, aspartate aminotransferase, gamma glutamyl aminotransferase, lactate dehydrogenase, alkaline phosphatase, total and direct bilirubin, albumin. Results and discussion. The assessment of the clinical condition of patients showed that the prevalence of respiratory syndrome was 81,48%, dyspeptic – 67,90%, hemorheological – 54,73%, asthenic – 42,39%, encephalopathy – 36,21%. In the general blood test, the hemoglobin level, the number of erythrocytes and platelets were significantly lower than in the control group (p<0,001, p<0,05 and p<0,001). The activity of blood enzymes in post COVID-19 patients included in the study was significantly increased compared to the control group: alanine aminotransferase exceeded the average values in the control group by almost 10 times, aspartate aminotransferase – almost 3 times, lactate dehydrogenase – 3 times, gamma glutamyl aminotransferase and alkaline phosphatase – almost one and a half times. The level of bilirubin b significantly exceeded the indicator recorded in the control group (p<0,001). The concentration of albumin in the peripheral blood of patients was reduced (p<0,001 the significance of the difference with the control group). Conclusion. In patients with liver damage in post COVID-19 patients the early rehabilitation period, the most frequent clinical syndromes were respiratory (81,48%) and dyspeptic (67,90%). Laboratory changes characteristic of hypochromic anemia, consumption thrombocytopenia, mesenchymal-inflammatory activity, liver functional disorders (the presence of cytolytic cholestatic syndromes and a decrease in protein synthesizing liver function) were also revealed. © 2018 the Author (s). Published by Kurdistan University of Medical Sciences.

CLINICAL AND LABORATORY CHARACTERISTICS OF PATIENTS WITH LIVER DAMAGE IN THE COVID-19 EARLY REHABILITATION PERIOD

The emergence of COVID-19 has set health professionals tasks related to the rapid diagnosis and provision of medical care to patients. Patients with COVID-19 also have extrapulmonary symptoms;including clinical signs of damage to the gastrointestinal tract (GI tract) and the hepatobiliary system which are diagnosed in 26–53% of patients. Aim. The aim of the study was to evaluate clinical and laboratory indicators of liver damage in patients in the early rehabilitation period of COVID-19. Material and methods. There were 243 patients with COVID-19 aged 18–60 years under observation. The criteria for inclusion in the study were: transferred no earlier than 10 days before inclusion in the study COVID-19;at the time of inclusion in the study PCR-negative COVID-19. The indicators of the general blood test, in the blood serum – C-reactive protein, alanine aminotransferase, aspartate aminotransferase, gamma glutamyl aminotransferase, lactate dehydrogenase, alkaline phosphatase, total and direct bilirubin, albumin. Results and discussion. The assessment of the clinical condition of patients showed that the prevalence of respiratory syndrome was 81,48%, dyspeptic – 67,90%, hemorheological – 54,73%, asthenic – 42,39%, encephalopathy – 36,21%. In the general blood test, the hemoglobin level, the number of erythrocytes and platelets were significantly lower than in the control group (p<0,001, p<0,05 and p<0,001). The activity of blood enzymes in post COVID-19 patients included in the study was significantly increased compared to the control group: alanine aminotransferase exceeded the average values in the control group by almost 10 times, aspartate aminotransferase – almost 3 times, lactate dehydrogenase – 3 times, gamma glutamyl aminotransferase and alkaline phosphatase – almost one and a half times. The level of bilirubin b significantly exceeded the indicator recorded in the control group (p<0,001). The concentration of albumin in the peripheral blood of patients was reduced (p<0,001 the significance of the difference with the control group). Conclusion. In patients with liver damage in post COVID-19 patients the early rehabilitation period, the most frequent clinical syndromes were respiratory (81,48%) and dyspeptic (67,90%). Laboratory changes characteristic of hypochromic anemia, consumption thrombocytopenia, mesenchymal-inflammatory activity, liver functional disorders (the presence of cytolytic cholestatic syndromes and a decrease in protein synthesizing liver function) were also revealed. © 2018 the Author (s). Published by Kurdistan University of Medical Sciences.

COVID-19 in Patients with Primary Biliary Cholangitis

The aim of the study. To analyze the course of COVID-19 infection in patients with primary biliary cholangitis (PBC). Materials and methods. In a single-center retrospective study, survey and analysis of medical records of 144 patients with PBC was carried out. Results. All patients (n = 144) received basic therapy with ursodeoxycholic acid (UDCA), 5 of them received fibrates as well. Response to therapy (EASL criteria) was obtained in 30 people. Between March 2020 and March 2021, 50 patients (34.7 %) suffered COVID-19, with mean age of 58.8 ± 10.7 years, 16 of which were diagnosed with liver cirrhosis. Mild COVID-19 was observed in 34 (68 %) people, moderate course - in 14 (28 %), severe - in 2 (4 %), cases of extremely severe course were not recorded. 12 patients were hospitalized, 8 of which received oxygen therapy due to a decrease in SpO2 < 94 %, there was no need for the use of other methods of oxygen therapy in any case. The duration of hospitalization was 11.4 ± 5.7 days. There was a higher initial activity of serum alkaline phosphatase (1.8 ± 1.0 versus 1.7 ± 1.4 times of the upper limit of normal, M ± SD, p = 0.04) in patients with COVID-19 infection and lack of UDCA therapy effectiveness was more prominent (40 % vs. 19.1 % of cases, p = 0.04) compared with patients who did not have COVID-19. There were no significant differences in characteristics of the course of PBC (stage, response to therapy) and age in correlation with severity of the course of COVID-19. Among hospitalized patients and those in need of oxygen support, large proportion were older patients (58.3 % and 62.5 %, respectively) and patients with concomitant diseases (62.5 % and 75 %, respectively). Patients who hadn't previously responded to UDCA therapy were more likely to require oxygen support compared to patients responding to basic therapy (p < 0.01). Conclusion. PBC is not a risk factor for severe COVID-19. A protective effect of UDCA in SARS-CoV-2 infection is possible, which requires further investigation. © 2022 Russian Journal of Gastroenterology, Hepatology, Coloproctology

THE EFFECT OF HEPATOPROTECTORS ON THE STATE OF THE LIVER IN POST COVID-19 PATIENTS

Introduction. In previous studies, it was found that MERS-CoV and SARS-CoV cause damage to parenchymal organs, including liver damage in patients with COVID-19. Virus-induced influence on hepatocytes and cholangiocytes is considered one of the possible factors of liver failure. Direct viral damage to the liver can be detected in the infectious period, inflammatory and toxic damage can develop both in the acute period and in the post-infectious phase against the background of the rehabilitation period. Aim. The aim of the study was to study the effect of various hepatoprotectors on the functional state of the liver in patients in the early rehabilitation period of COVID-19. Material and methods. 243 post COVID-19 patients were under observation, depending on the therapy, the patients were divided into 4 groups: group 0 – group (n=60) – therapy without hepatoprotectors;ursodeoxycholic acid group (n=61) – ursodeoxycholic acid was included in therapy;glycyrrhizic acid and phospholipids group (n=63) – glycyrrhizic acid and phospholipids in the form of Phosphogliv tablets are included in therapy;group ademeteonin (n=59) – ademeteonin is included in therapy. The control examination was carried out a month later. The control group consisted of 20 healthy individuals. To assess the functional state of the liver in the blood of patients, the enzymes alanine aminotransferase, aspartate aminotransferase, gamma-glutamylaminotransferase, lactate dehydrogenase, alkaline phosphatase, total and direct bilirubin, albumin was determined. Conclusion. In patients in the early rehabilitation period of COVID-19, there are increase in the levels of enzymes alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase and bilirubin in the blood, which indicates functional liver disorders. The use of hepatoprotectors makes it possible to increase the positive effect of rehabilitation on the severity of markers of cytolytic and cholestatic syndromes. Ursodeoxycholic acid has the most pronounced effect on normalization of alanine aminotransferase, total and direct bilirubin levels. © 2022, LLC "IMC" Modern Clinical Medicine. All rights reserved.

Post-COVID-19 Cholestasis: A Case Series and Review of Literature.

Background: Coronavirus disease-2019 (COVID-19) cholangiopathy is a recently known entity. There are very few reports of liver transplantation (LT) for COVID-19-induced cholangiopathy. It is well known that vaccines can prevent severe disease and improve outcomes. However, there are no reports on the impact of COVID-19 vaccines on cholestasis. Therefore, we aimed to compare the course and outcome of patients who developed cholestasis following COVID-19 infection among vaccinated and unvaccinated individuals. Methods: Patients diagnosed with post-COVID cholestasis during the pandemic were included in the study after excluding other causes of cholestasis. Results: Eight unvaccinated and seven vaccinated individuals developed cholestasis following COVID-19 infection. Baseline demographics, presentation, severity, and management of COVID-19 were similar in both groups. However, patients in the unvaccinated group had a protracted course. The peak ALP was 312 (239-517) U/L in the vaccinated group and 571.5 (368-1058) U/L in the unvaccinated group (P = 0.02). Similarly, the peak γ-glutamyl transpeptidase values were lower in the vaccinated (325 [237-600] U/L) than in the unvaccinated group (832 [491-1640] U/L; P = 0.004). However, the peak values of total bilirubin, transaminases, and INR were similar in both groups. Five patients developed ascites gradually in the unvaccinated group whereas none in the vaccinated group developed ascites. Plasma exchange was done in five patients, and two were successfully bridged to living donor LT in the unvaccinated group. Only two patients recovered with conservative management in the unvaccinated group, whereas all recovered with conservative management in the vaccinated group. The other four patients in the unvaccinated group were planned for LT. Conclusion: Post-COVID-19 cholestasis is associated with high morbidity and mortality, meriting early identification and appropriate management. Vaccination can modify the course of severe COVID-19 infection and improve outcomes.

Ursodeoxycholic acid ameliorates cell migration retarded by the SARS-CoV-2 spike protein in BEAS-2B human bronchial epithelial cells.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by severe acute -respiratory syndrome coronavirus 2 (SARS- CoV-2) through interaction of the spike protein (SP) with the receptor-binding domain (RBD) and its receptor, angiotensin converting enzyme 2(ACE2). Repair mechanisms induced following virus infection can restore the protective barrier through wound healing. Then, cells from the epithelial basal layer repopulate the damaged area, followed by cell proliferation and differentiation, as well as changes in gene expression. METHODS: Using Beas-2B cells and SP, we investigated whether ursodeoxycholic acid (UDCA) contributes to restoration of the bronchial epithelial layer. ACE2 expression was measured by RT-PCR and Western blotting. SP-ACE2 interaction was analyzed by flow cytometry and visualized through immunostaining. Cell migration was assessed using single cell path tracking and wound healing assay. RESULTS: Upon ACE2 overexpression in HeLa, HEK293T, and Beas-2B cells following the transfection of pCMV-ACE2 plasmid DNA, SP binding on each cell was increased in the ACE2 overexpression group compared to pCMV-transfected control cells. SP treatment delayed the migration of BEAS-2B cells compared to the control. SP also reduced cell migration, even under ACE2 overexpression; SP binding was greater in ACE2-overexpressed cells than control cells. UDCA interfered significantly with the binding of SP to ACE2 under our experimental conditions. UDCA also restored the inhibitory migration of Beas-2B cells induced by SP treatment. CONCLSION: Our data demonstrate that UDCA can contribute to the inhibition of abnormal airway epithelial cell migration. These results suggest that UDCA can enhance the repair mechanism, to prevent damage caused by SP-ACE2 interaction and enhance restoration of the epithelial basal layer.

COVID-19 and the biliary tree: Atypicall manifestations of disease during the pandemic

Case report-IntroductionCOVID-19, the infectious disease caused by the novel coronavirus SARS-CoV-2, and first described in Wuhan, China in December 2019, has affected more than 19 million patients worldwide and resulted in more than 700,000 deaths at the time of writing1. Patients with rheumatic diseases and those receiving immunosuppressive treatment are felt to be at greater risk of complications from this illness, though registry and trial data should help refine our understanding of these risks. We hereby describe a case of COVID-19 complicating an unusual rheumatic illness, resulting in severe multi-system disease and premature death.Case report-Case descriptionA 69 year-old male presented to rheumatology and haematology with symmetrical polyarthritis, thrombocytopenia (18 x 109/L), eosinophilia (25.4 x 109/L), raised C-reactive protein (CRP, 43 mg/L), positive rheumatoid factor (>200), antinuclear antibody (ANA) and anti-Ro. Bone marrow biopsy did not demonstrate evidence of haematological malignancy.Seropositive rheumatoid arthritis and connective tissue disease overlap were diagnosed, and treatment with Prednisolone 60mg daily was initiated. Despite rituximab and intravenous immunoglobulins, thrombocytopenia deteriorated on reducing corticosteroids, however the addition of mycophenolate mofetil (MMF) allowed gradual prednisolone tapering to 3mg daily. Hydroxychloroquine was briefly added but discontinued due to headaches. MMF was discontinued after he developed fungal pneumonia followed by jaundice. Liver biopsy was consistent with drug-induced cholestasis, attributed to co-amoxiclav, and his liver function tests (LFTs) improved on ursodeoxycholic acid. Following a further deterioration in thrombocytopenia, hyperferritinaemia and new onset erythema nodosum, he had a repeat bone marrow examination. This demonstrated large areas of fibrosis and granulomatous inflammation with a dense, pleomorphic T-cell infiltrate, but no haemophagocytosis. Haematologists felt this was reactive and prednisolone dose was increased to 10mg daily.Six months later he developed cholangitis. Magnetic resonance cholangiopancreatography (MRCP) demonstrated a tight 4cm stricture of the distal common bile duct (CBD) within the head of pancreas, which was diffusely swollen without any clear focal mass. Serum amylase was mildly elevated (316 units/L). Concurrent CT thorax, abdomen and pelvis demonstrated bilateral ground-glass changes within the lungs, and a SARS-CoV-2 nasopharyngeal PCR test was positive, though he had no respiratory symptoms or oxygen requirement at that stage.Sadly, four days after the CT scan and before a planned endoscopic retrograde cholangiopancreatography (ERCP) could be performed, he became markedly hypoxic with plain chest X-ray features suggestive of COVID-19 pneumonia. Despite medical management, including doubling of his prednisolone dose, he rapidly deteriorated and died.Case report-DiscussionThis case highlights an unusual presentation of COVID-19 in a patient with a complex background of inflammatory arthritis with immune-mediated thrombocytopenia. At the time of his final illness, these conditions were managed with steroid monotherapy. Based on the COVID-19 risk matrix recommended by the British Society for Rheumatology, he was not identified as a patient requiring shielding.Cholangitis was the major problem precipitating his final admission to hospital, and at the time of admission he had no respiratory symptoms. One week prior to this admission, his father-in-law had died of COVID-19 pneumonia, though they had not been in recent direct contact. Interstitial lung changes were incidentally noted on a CT performed to identify the cause of cholangitis, which prompted the nasopharyngeal PCR that detected SARS-CoV-2. This occurred prior to widespread routine testing of hospital inpatients for SARS-CoV-2 by PCR. Unfortunately he then rapidly developed COVID-19 pneumonia and died before the underlying cause of cholangitis could be definitively identified, though an MRCP demonstrated an obstructed CBD within a diffusely swollen pancreas, where a differential diagnosis of pancreatic malignancy or autoimmune pancreatitis was suggested by the reporting radiologist.There are emerging case reports of COVID-19 resulting in significant pancreatic injuryand a further recent laboratory analysis has suggested that ACE2 receptors, which are utilised by SARS-CoV-2 to gain entry to host cells, are highly expressed on cholangiocytes at a comparable level to type II alveolar cells. Whilst the ultimate cause of cholangitis will remain unknown in this patient, this case highlights the potential for atypical presentations and extra-pulmonary manifestations of COVID-19.Case report-Key learning points COVID-19 is a multi-system illness which can cause significant extra-pulmonary as well as pulmonary pathology, with emerging reports that the biliary tract and pancreas are frequently affected.Evidence to inform accurate prediction of which patients with rheumatic diseases are at highest risk of acquiring severe COVID-19 disease remains insufficient, with current shielding guidelines based on expert consensus.This case highlights the importance of widespread testing for COVID-19 in hospital patients, as not all patients carrying the SARS-CoV-2 virus will demonstrate classical respiratory features of the disease at the point of admission.

Merit of an Ursodeoxycholic Acid Clinical Trial in COVID-19 Patients.

Corona Virus Disease 2019 (COVID-19) has affected over 8 million people worldwide. We underscore the potential benefits of conducting a randomized open-label unblinded clinical trial to evaluate the role of ursodeoxycholic acid (UDCA) in the treatment of COVID-19. Some COVID-19 patients are characterized with cytokine storm syndrome that can cause severe and irreversible damage to organs leading to multi-organ failure and death. Therefore, it is critical to control both programmed cell death (apoptosis) and the hyper-immune inflammatory response in COVID-19 patients to reduce the rising morbidity and mortality. UDCA is an existing drug with proven safety profiles that can reduce inflammation and prevent cell death. National Geographic reported that, "China Promotes Bear Bile as Coronavirus Treatment". Bear bile is rich in UDCA, comprising up to 40-50% of the total bile acid. UDCA is a logical and attainable replacement for bear bile that is available in pill form and merits clinical trial consideration.