Anti-SARS-CoV-2 antibodies important in diagnostics of acute hepatitis in children

The most common causes of acute hepatitis in children are hepatitis A and autoimmune hepatitis. Hepatitis in the course of Wilson's disease is sporadically registered in adolescents. An increase of activity of aminotransferases both in the course of multisystem inflammatory syndrome in children (MIS-C) and in the course of COVID-19 has been observed. Hepatitis is common in children with MIS-C and is associated with a more severe presentation and persistent elevation of liver function tests. To date, no cases of acute hepatitis in children due to COVID-19 have been reported. We present 2 cases of acute hepatitis in children where the only cause seems to be a previous asymptomatic SARS-CoV-2 infection.Copyright © 2023 Termedia Publishing House Ltd.. All rights reserved.

Rare Case of Immune-Mediated Necrotizing Myopathy With Isolated Dysphagia as Presenting Symptom

Introduction: Immune mediated necrotizing myopathy (IMNM) is a rare, but progressive disease that accounts for about 19% of all inflammatory myopathies. Dysphagia occurs in 20-30% of IMNM patients. It often follows proximal muscle weakness and ensues in the later stages of the disease. We report a rare case of IMNM, presenting with dysphagia as the initial symptom, followed by proximal muscle weakness. Case Description/Methods: A 74-year-old male with a past medical history of coronary artery disease, hypertension, and hyperlipidemia presented to the ED with 2-3 weeks of intractable nausea, vomiting, and dysphagia for solids and liquids. Vital signs were stable, and initial labs displayed an AST of 188 U/L and ALT of 64 U/L with a normal bilirubin. Computed tomogram of the chest, abdomen, and pelvis were negative. An esophagram showed moderate to severe tertiary contraction, no mass or stricture, and a 13 mm barium tablet passed without difficulty. Esophagogastroduodenoscopy exhibited a spastic lower esophageal sphincter. Botox injections provided no significant relief. He then developed symmetrical proximal motor weakness and repeat labs demonstrated an elevated creatine kinase (CK) level of 6,357 U/L and aldolase of 43.4 U/L. Serology revealed positive PL-7 autoxantibodies, but negative JO-1, PL-12, KU, MI-2, EJ, SRP, anti-smooth muscle, and anti-mitochondrial antibodies. Muscle biopsy did not unveil endomysial inflammation or MHC-1 sarcolemmal upregulation. The diagnosis of IMNM was suspected. A percutaneous endoscopic gastrostomy feeding tube was placed as a mean of an alternative route of nutrition. He was started on steroids and recommended to follow up with outpatient rheumatology. He expired a month later after complications from an unrelated COVID-19 infection. Discussion(s): The typical presentation of IMNM includes painful proximal muscle weakness, elevated CK, presence of myositis-associated autoantibodies, and necrotic muscle fibers without mononuclear cell infiltrates on histology. Dysphagia occurs due to immune-mediated inflammation occurring in the skeletal muscle of the esophagus, resulting in incoordination of swallowing. Immunotherapy and intravenous immunoglobulin are often the mainstay of treatment. Our patient was unique in presentation with dysphagia as an initial presenting symptom of IMNM, as well as elevated enzymes from muscle breakdown. It is critical as clinicians to have a high degree of suspicion for IMNM due to the aggressive nature of the disease and refractoriness to treatment.

Syphilis: "The Great Imitator" Presenting as Acute Hepatitis

Introduction: Syphilis is a multi-systemic disease caused by spirochete Treponema pallidum. Very rarely, it can affect the liver and cause hepatitis. Since most cases of hepatitis are caused by viral illnesses, syphilitic hepatitis can be missed. Here, we present a case of syphilitic hepatitis in a 35-year-old male. Case Description/Methods: Patient was a 35-year-old male who presented to the hospital for jaundice and mild intermittent right upper quadrant abdominal pain. His medical history was only significant for alcohol abuse. His last drink was 4 weeks ago. He was sexually active with men. On exam, hepatomegaly, mild tenderness in the right upper quadrant, jaundice, and fine macular rash on both hands and feet were noted. Lab tests revealed an ALT of 965 U/L, AST of 404 U/L, ALP of 1056 U/L, total bilirubin of 9.5 mg/dL, direct bilirubin of 6.5 mg/dL, INR of 0.96, and albumin of 2.0 g/dL. Right upper quadrant ultrasound showed an enlarged liver but was negative for gallstones and hepatic vein thrombosis. MRI of the abdomen showed periportal edema consistent with hepatitis without any gallstones, masses, or common bile duct dilation. HIV viral load and Hepatitis C viral RNA were undetectable. Hepatitis A & B serologies were indicative of prior immunization. Hepatitis E serology and SARS-CoV-2 PCR were negative. Ferritin level was 177 ng/mL. Alpha-1-antitrypsin levels and ceruloplasmin levels were normal. Anti-Smooth muscle antibody titers were slightly elevated at 1:80 (Normal < 1:20). Anti-Mitochondrial antibody levels were also slightly elevated at 47.9 units (Normal < 25 units). RPR titer was 1:32 and fluorescent treponemal antibody test was reactive which confirmed the diagnosis of syphilis. Liver biopsy was then performed which showed presence of mixed inflammatory cells without any granulomas which is consistent with other cases of syphilitic hepatitis. Immunohistochemical stain was negative for treponemes. Patient was treated with penicillin and did have Jarisch-Herxheimer reaction. ALT, AST, ALP, and total bilirubin down trended after treatment. Repeat tests drawn exactly 1 month post treatment showed normal levels of ALT, AST, ALP, and total bilirubin (Figure). Discussion(s): Liver damage can occur in syphilis and can easily be missed because of the non-specific nature of presenting symptoms. In our patient, the fine macular rash on both hands and feet along with history of sexual activity with men prompted us to test for syphilis which ultimately led to diagnosis and treatment in a timely manner. (Figure Presented).

Clinical, Histological and Serological Features of Autoimmune-Like Acute Liver Injury after Sars-Cov-2 Vaccination

Introduction and Objectives: Acute autoimmune-like liver injury has been increasingly reported after vaccination against SARS-CoV-2. Pathogenesis, steroid requirement and long-term prognosis are unknown. This study aimed to evaluate clinical, serological and histological features, response to treatment and prognosis in patients with post-vaccination acute hepatitis. Material(s) and Method(s): We included patients without known pre-existing liver diseases with transaminase levels >= 2.5 upper limits of normal within 90 days after the SARS-CoV-2 vaccine with an available liver biopsy. Clinical data and outcomes after a six months follow-up were collected. Result(s): 17 patients were included,12 females, median age 60 (51,5/66) exposed to vectorial (Sputnik V n=7, AstraZeneca n=6), inactivated (Sinopharm n=3) or ARNm Vaccines (Moderna=1). In 8 patients, liver injury developed after the first dose and in 7 after the second dose and in 2 after the third dose. The median time to the development of injury was 33(23,50/53,50) days. Eight patients had a history of extrahepatic autoimmune disease and five patients had metabolic syndrome and used statins. Immune serology showed anti-antinuclear antibody in 10 (58,8%), anti-smooth muscle antibody in 5(29,4%). 14/17 patients presented with elevated IgG levels. Liver histology showed lobular hepatitis in 13/17, portal hepatitis in 17/17 with plasmocytic lymphocytic infiltrate and 4/17 had eosinophils, 6/17 with severe interface hepatitis, and one patient had fibrosis Ishak stage >=3. 12/17 (70,5%) were treated with steroids. Transaminases improved in 17 cases and normalized in 6/12 by month 6. Only 1/17 developed liver function deterioration, yet no patient required liver transplantation. Most patients tolerated the tapering of steroids and in 6 azathioprine was started before month 3. Conclusion(s): Long-term follow-up might help to differentiate between induced classical autoimmune hepatitis, autoinflammatory self-limited events, or drug-induced liver injury in these patients.Copyright © 2023

Histological and serological features of acute liver injury after SARS-CoV-2 vaccination

Background & Aims: Liver injury with autoimmune features after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is increasingly reported. We investigated a large international cohort of individuals with acute hepatitis arising after SARS-CoV-2 vaccination, focusing on histological and serological features. Methods: Individuals without known pre-existing liver diseases and transaminase levels ≥5x the upper limit of normal within 3 months after any anti-SARS-CoV-2 vaccine, and available liver biopsy were included. Fifty-nine patients were recruited;35 females;median age 54 years. They were exposed to various combinations of mRNA, vectorial, inactivated and protein-based vaccines. Results: Liver histology showed predominantly lobular hepatitis in 45 (76%), predominantly portal hepatitis in 10 (17%), and other patterns in four (7%) cases;seven had fibrosis Ishak stage ≥3, associated with more severe interface hepatitis. Autoimmune serology, centrally tested in 31 cases, showed anti-antinuclear antibody in 23 (74%), anti-smooth muscle antibody in 19 (61%), anti-gastric parietal cells in eight (26%), anti-liver kidney microsomal antibody in four (13%), and anti-mitochondrial antibody in four (13%) cases. Ninety-one percent were treated with steroids ± azathioprine. Serum transaminase levels improved in all cases and were normal in 24/58 (41%) after 3 months, and in 30/46 (65%) after 6 months. One patient required liver transplantation. Of 15 patients re-exposed to SARS-CoV-2 vaccines, three relapsed. Conclusion: Acute liver injury arising after SARS-CoV-2 vaccination is frequently associated with lobular hepatitis and positive autoantibodies. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. A close follow-up is warranted to assess the long-term outcomes of this condition. Impact and implications: Cases of liver injury after vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) have been published. We investigated a large international cohort of individuals with acute hepatitis after SARS-CoV-2 vaccination, focusing on liver biopsy findings and autoantibodies: liver biopsy frequently shows inflammation of the lobule, which is typical of recent injury, and autoantibodies are frequently positive. Whether there is a causal relationship between liver damage and SARS-CoV-2 vaccines remains to be established. Close follow-up is warranted to assess the long-term outcome of this condition. © 2022 The Author(s)

Severe progression of autoimmune hepatitis in a young COVID-19 adult patient: A case report

Rationale: The impact of COVID-19 in patients with autoimmune liver disease treated with immunosuppressive therapy has not been described so far. This case report describes the clinical course of a patient with autoimmune hepatitis (AIH) who developed COVID-19 and the features of cytokine syndrome leading to its deterioration in our intensive care unit. Patient's Concern: A 28-year-old male presented with generalized anasarca for two weeks and chronic liver disease for 8 months. Diagnosis: AIH and Covid-19 with features of cytokine storm syndrome. Interventions: Intravenous furosemide, mannitol, syrup lactulose, steroids (prednisolone 40 mg), azathioprine 1 mg/kg body weight, rifaximin, vitamin K, and blood products. Outcomes: The patient had hepatic encephalopathy and AIH and died on the 10th day after admission despite ventilatory support, sustained low-efficiency hemodialysis, and resuscition. Lessons: The dramatic release of cytokines and the inflammatory-immune responses not only alter the pathophysiology but also affects the onset and severity of disease progression in patients with AIH.

LIVER INJURY ASSOCIATED WITH TURMERIC&≤x2013;A GROWING PROBLEM: NINE CASES FROM THE DRUG-INDUCED LIVER INJURY NETWORK [DILIN]

BACKGROUND: Turmeric (curcumin) is a commonly used over-the-counter herbal product whose uses include diarrhea, arthritis, cancer and even COVID-19. Recently turmeric has been implicated in cases of clinically apparent liver injury with jaundice. The aim of this case series is to describe the clinical, histologic and human leukocyte antigen (HLA) associations of turmeric-associated hepatotoxicity as seen in the U.S. Drug Induced Liver Injury Network (DILIN) Prospective Study. METHODS: All adjudicated cases enrolled in DILIN between 2003-2020 with turmeric as an implicated product were reviewed. Causality was assessed using a 5-point expert opinion score. Available products were collected and analyzed for the presence of turmeric using ultra-high-performance liquid chromatography. Genetic analyses included HLA sequencing. RESULTS: Of 1697 cases of drug-induced liver injury judged to be definite, highly likely or probable (high confidence), nine (0.5%) were attributed to turmeric, all of which were enrolled since 2012, and 6 since 2017 (Figure). The 9 cases included 7 women, 8 whites, with a mean age of 51 years (range, 35-62 years) and BMI 25 kg/m2 (range, 15-40). Seven patients used alcohol, but none to excess, and none had underlying liver disease. Turmeric was used for an average of 102 days before onset of injury (range, 30-425 days). Initial mean ALT was 1179 U/L (range, 328-2245), ALP 211 U/L (41-441), total bilirubin 5.9 mg/dL (1.2-10.8), and INR 1.0 (0.9-1.2). Six patients developed jaundice, and serum bilirubin peaked at 9.6 mg/dL (0.8-26), and INR 2.3 (1.0- 9.7). Liver injury was hepatocellular in 8 patients (mean R = 22). Five patients had elevated antinuclear antibody (ANA) titer and two anti-smooth muscle (ASM) antibody, but none were treated with corticosteroids. Liver biopsy in 5 patients showed portal and lobular mixed inflammatory infiltrates with lymphocytes and eosinophils typical of drug-induced liver injury. Five patients were hospitalized, and one patient died of acute liver failure. Chemical analysis confirmed the presence of turmeric in all 7 products analyzed;3 also contained piperine (black pepper), and none contained green tea. Of 7 patients with HLA typing available, 4 carried HLA-B*35:01, a class I HLA allele previously implicated in both green tea and Polygonum multiflorum hepatotoxicity. CONCLUSION: Liver injury due to turmeric appears to be increasing, perhaps, reflecting usage patterns or increased combination with black pepper, which increases its absorption. Turmeric liver injury, similar to that caused by other polyphenolic herbal products, is typically hepatocellular, with a latency of 1 to 6 months, and is linked to HLA-B*35:01. While most cases are self-limited, the injury can be severe and result in death or liver transplantation.

AUTOIMMUNE HEPATITIS FOLLOWING COVID-19 VACCINATION: A SYSTEMATIC REVIEW OF THE LITERATURE

Introduction COVID-19 vaccines have been shown to be effective in preventing hospitalization due to COVID-19 infection. However, safety remains a concern. Some studies have linked the vaccine to the development of autoimmune diseases such as myocarditis and immune thrombocytopenic purpura. During the summer of 2021, an increasing number of case reports began to emerge documenting a small number of individuals who developed autoimmune hepatitis (AIH) following COVID-19 vaccination. These cases are rare, novel, and very little is known. In our systematic review, we analyzed every published case of AIH and reviewed their characteristic findings, treatment, and outcomes. Methods We searched PubMed, Embase, and Web of Science from 1 December 2019 to 1 November 2021. Keywords included but were not limited to “COVID-19,” “vaccine,” and “autoimmune hepatitis.” Two researchers independently extracted information from the articles about vaccine type, patient history, characteristics, laboratory values, histology results, treatment regimens, and disease course. Results Thirty-two patients developed AIH after receiving a COVID-19 vaccine (16 Pfizer-BioNTech, 13 Moderna, 3 Oxford-AstraZeneca), of whom 17 were from the United States, 11 were from Europe, 3 were from Asia, and 1 was from Australia. Sixty-nine percent of patients were women and 58% had no history of liver or autoimmune disease. Jaundice was the most common symptom (81%). Nineteen percent of patients were initially asymptomatic and presented with abnormal liver enzymes found during routine bloodwork. (Table 1) Mean ALT, AST, and bilirubin were 1231 U/L, 921 U/L, and 14 mg/dL. Anti-nuclear antibody and anti-smooth muscle antibody were positive in 56% and 28% of patients. Liver biopsy was performed in 81% of patients with findings strongly suggestive of AIH. Corticosteroids were used in 74% of patients with a mean time to disease resolution of 28 days. Improvement or complete resolution was seen in 97% of patients. (Table 2) One patient died despite aggressive steroid treatment. Discussion COVID- 19 vaccine-induced AIH is extremely rare with just 32 documented cases in the literature. Although causality cannot be proved, this phenomenon should not be treated as coincidence. Clinicians should be aware of this rare but real complication and suspect vaccine-induced AIH in patients who present with jaundice and abnormal liver enzymes following COVID- 19 vaccination. Treatment with corticosteroids appears to be highly effective, with improvement or resolution in 97% of patients. Our findings highlight the rarity of COVID-19 vaccine-induced AIH and should under no circumstances deter individuals from getting vaccinated as the benefits of vaccination far outweigh the risks. (Table Presented)

ACUTE HEPATITIS AND RASH LINKED THROUGH EPSTEIN-BARR VIRUS

Epstein-Barr virus (EBV) hepatitis is well established, and most cases involves asymptomatic liver enzyme abnormalities. Albeit rare, viruses such as EBV have been reported to induce generalized pustular psoriasis (GPP);and exanthems such as GPP have been associated with acute hepatitis. This case describes a unique case of cholestatic hepatitis due to EBV, followed by a diffuse pustular rash suggestive of GPP. After complete resolution of the cholestatic hepatitis, the patient returned over a year later with concurrent hepatitis and diffuse pustular rash. Case: An obese 26 year-old African-American female presented to the hospital on three separate occasions over a 15 month span with slightly varying symptoms. At the index hospitalization she presented with fatigue and jaundice. Liver chemistries revlead a mixed pattern liver injury, see Table 1. Extensive serological evaluation was unremarkable, though antinuclear antibody and anti-smooth muscle antibody were mildly and non-specifically elevated, but IgG was normal. A liver biopsy was performed revealing portal and lobular inflammation with predominantly lymphocytic moderate micro-vesicular steatosis (Figure 1). EBV PCR returned positive at 20,737 IU/mL yielding a diagnoses of EBV-induced hepatitis. She returned to the hospital one week later due to a diffuse pruritic and painful rash. She had scleral icterus and diffuse erythematous plaques with tiny pustules dispersed over the body sparing the palms, soles, and mucosal surfaces. Laboratory values were overall improved as noted in Table 1. Punch biopsy of the right arm was suggestive of EBV induced GPP. She rapidly stabilized and was discharged the following day with triamcinolone 0.1% ointment. The patient had an uneventful convalescence and liver chemistries returned to normal. Approximately 15 months after her initial hospitalization, she presented with both recurrent hepatitis and a pustular, pruritic, erythematous rash with perioral and periorbital swelling. She denied taking any new medications or supplements. Labs revealed recurrent, though now primarily cholestatic liver injury, see Table 1. Results of a repeat thorough serological evaluation were negative, including for EBV-PCR and COVID-19. Abdominal ultrasound revealed a 16 cm hepatic length. Pustules, spongiosis, and edema were found on repeat skin biopsy, suggestive of GPP. She recovered quickly with systemic steroids. Awareness of GPP induced hepatitis can guide a judicious assessment of abnormal liver chemistries. Furthermore, unnecessary healthcare utilization can be avoided by providing appropriate and timely pharmacotherapy (i.e., corticosteroid taper) for on demand flares. (Figure Presented) (Table Presented) (Figure Presented)

ATYPICAL HAEMOLYTIC UREMIC SYNDROME ASSOCIATED WITH COVID-19: CASE REPORT

BACKGROUND AND AIMS: Renal manifestations are common in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report here the case of a patient with confirmed SARS-CoV-2 infection with the clinical picture of atypical haemolytic uremic syndrome (aHUS). METHOD: Case report RESULTS: Our case is a 31-year-old man with a nasopharyngeal swab with real-time reverse-transcriptase polymerase chain reaction (RT-PCR) for SARS-CoV-2 positive, who was hospitalized in the Clinic of Infectious Diseases. His medical history had a respiratory illness of 7-day evolution characterized by cough, fever, dyspnoea, muscle pain, nausea, vomiting and non-bloody diarrhoea, and decreased urine output with dark colour urine. The chest computed tomography (CT) scan showed few rounded ground-glass opacities. Laboratory tests at admission revealed the following: (i) acute kidney injury stage 3 with a serum creatinine of 3.85 mg/dL (basal value 0.9 mg/dL);serum urea 221 mg/dL. His urinary volume in the first 24 h of hospitalization was 800 mL. (ii) Severe haemolytic anaemia with haemoglobin (Hgb) level of 3.7 g/dL, and peripheral smear showing large number of schistocytes, haptoglobin <10 mg/dL and indirect bilirubin 9.7 mg/dL, direct coombs testing was negative;reticulocyte count 8.9%. (iii) Severe thrombocytopaenia with platelet count of 25 000/μL, prothrombin time 45%, international normalized ratio 1.7, D-dimer 1082 ng/dL and fibrinogen 880 mg/dL. Increased blood levels of enzymes and inflammatory markers were present: lactate dehydrogenase 1867 U/L and protein C reactive 9.1 mg/dL. Electrolyte disturbances characterized by hyperkalaemia, hyperphosphatemia, hypocalcaemia and severe metabolic acidosis. Dynamic changes of laboratory data are presented in Table 1. The usual liver panel tests, alkaline phosphatase, γ -glutamyl transferase and albuminemia were normal. Toxic hepatitis was excluded. Hepatobiliary and spleen imaging (ultrasonography) was normal. ELISA serologic tests for HIV, hepatitis B, hepatitis C virus and cytomegalovirus were negative. Serological and virological tests for hepatitis A, B, C, HIV and CMV were negative. Stool was negative for Shiga toxin-producing Escherichia coli (STEC). The results of antinuclear antibodies and anti-smooth-muscle antibodies were negative, C3 serum level was mildly depressed (82 mg/dL;normal range 88- 201 mg/dL) and C4 serum level was normal (20 mg/dL;normal range 10-44 mg/dL). ADAMTS13 activity was 90% on day 10. He was treated with broad spectrum antibiotics, intravenous dexamethasone and supportive therapy. One week from admission, renal function recovered, and 1 week after intravascular haemolysis and thrombocytopaenia recovered. The patient was hospitalized for 21 days. CONCLUSION: Close monitoring and early intervention can help for a better outcome of SARS-CoV-2 patients complicated with aHUS.

The correlation of anti-heart antibodies levels with clinical manifestations and outcomes in patients with COVID-19

Purpose: To evaluate the blood level of anti-heart antibodies (AHA) and its correlation with clinical outcomes in patients with severe and moderate COVID-19. Methods: The study included 34 patients (11 females and 23 males, mean age 58.3±17.6 years, from 20 to 87 years) who underwent treatment for moderate and severe COVID-19 at the Sechenov University hospital in April-June 2020. The diagnosis was confirmed by 50% using nasopharyngeal smears. In other cases, the diagnosis of COVID-19 was based on the following criteria: contact with a serologically confirmed COVID-19 patient, persistent fever of at least 38 degrees Celsius, typical CT findings of viral pneumonia, typical changes in blood tests in the absence of evidence for other diseases. Besides standard medical examination the AHA blood levels by immunoassay were observed, including antinuclear antibodies (ANA), antiendothelial cell antibodies (AECA), anti-cardiomyocyte antibodies (AbC), anti-smooth muscle antibodies (ASMA) and cardiac conducting tissue antibodies (CCTA). Median hospital length of stay was 14 [13;18] days. Results: AHA levels were increased in 25 (73.5%) patients. The patients were divided into the five groups: 1.Patients with previous chronic myocarditis who had already been receiving immunosuppressive therapy at the admission (n=4). Moderate titer increase was noted only in one patient. 2.Patients with severe COVID-19 and high inflammatory activity, in whom the degree of AHA increase matched the general disease activity. 3. Patients with severe COVID-19 and high inflammatory activity without AHA increase. 4. Patients with moderate COVID-19, in whom high AHA titers may reflect chronic latent myocarditis not associated with SARS-Cov2. 5. Patients with moderate COVID-19 and nearly normal / normal AHA titers. Significant correlation (p<0.05) of AHA levels with cardiovascular manifestations (r=0.459) was found. AbC levels correlated significantly with pneumonia severity (r=0.472), respiratory failure (r=0.387), need for invasive ventilation (r=0.469), chest pain (r=0.374), low QRS voltage (r=0.415) and high levels of CRP (r=0.360) and LDH (r=0.360). ASMA levels were found to correlate significantly with atrial fibrillation (r=0.414, p<0.05). ANA and AbC levels correlated significantly with pericardial effusion (r=0.721 and r=0.745 respectively, p<0.05). The lethality rate was 8.8%. AbC and ASMA levels correlated significantly with lethality (r=0.363, and r=0.426 respectively, p<0.05) and were prognostically important. Conclusion: Elevated titres of AHA were found in 73.5% of patients. AHA correlated with lethality, in most cases reflecting the overall activity and severity of the disease and may be considered within the systemic immune and inflammatory response in COVID-19. At the same time, the correlation with signs of myocardial injury and pericardial effusion, confirms the direct role of AHA in the inflammatory heart disease (myopericarditis).

Herbal Immune Booster-Induced Liver Injury in the COVID-19 Pandemic - A Case Series.

The COVID-19 pandemic has resulted in widespread use of complementary and alternative medicines. Tinospora cordifolia is a widely grown shrub which has been commonly used in India's traditional system of Ayurveda for its immune booster properties and has been extensively used as prophylaxis against COVID-19. Six patients (4 women, 2 men) with a median (IQR) age of 55 years (45-56) and with an history of Tinospora cordifolia consumption presented with symptoms of acute hepatitis during the study period of 4 months in the COVID-19 pandemic. The median (IQR) duration of Tinospora cordifolia consumption was 90 days (21-210). The median (IQR) peak bilirubin and AST were 17.5 mg/dl (12.2-24.9) and 1350 IU/ml (1099-1773), respectively. The patients had either a definite (n = 4) or probable (n = 2) revised autoimmune hepatitis score with an autoimmune pattern of drug-induced liver injury on biopsy. Four of these patients (all women) had underlying silent chronic liver disease of possible autoimmune etiology associated with other autoimmune diseases - hypothyroidism and type 2 diabetes mellitus. One of the three patients treated with steroids decompensated on steroid tapering. The other five patients had resolution of symptoms, liver profile, and autoimmune serological markers on drug withdrawal/continuing steroid treatment. The median (IQR) time to resolution from discontinuing the herb was 86.5 days (53-111). Tinospora cordifolia consumption seems to induce an autoimmune-like hepatitis or unmask an underlying autoimmune chronic liver disease, which may support its immune stimulant mechanism. However, the same mechanism can cause significant liver toxicity, and we recommend that caution be exercised in the use of this herb, especially in those predisposed to autoimmune disorders. Besides, in patients presenting with acute hepatitis, even in the presence of autoimmune markers, a detailed complementary and alternative medicine history needs to be elicited.