Semaglutide-Induced Lupus Erythematosus With Multiorgan Involvement.

We report the case of a 76-year-old female who presented with a new onset of petechial rash in her lower extremities after the introduction of a new agent, semaglutide. She started taking this medication three months before her presentation at an initial dosage of 0.5 mg subcutaneously every week. She noticed a 15-pound weight loss and debilitating fatigue within that timeframe. She stopped taking the medication due to nontolerance and GI upset (nausea and vomiting) about a week before her hospitalization. She denied the use of any other agents. Initial lab work revealed elevated transaminases, alkaline phosphatase, total bilirubin, and inflammatory markers. A CT of the abdomen revealed mild cirrhosis and hepatosplenomegaly. Other causes for cirrhosis were effectively ruled out with negative viral hepatitis, ceruloplasmin levels, and the HFE gene. An autoimmune panel was conducted, yielding positive antinuclear antibody (ANA), anti-histone antibodies, elevated double-stranded DNA, as well as low complement levels supporting evidence of drug-induced lupus (DIL). Anti-mitochondrial M2 and anti-smooth antibodies were also detected, indicating a possible overlap syndrome with autoimmune hepatitis. Perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA) and anti-neutrophil cytoplasmic autoantibodies (C-ANCA) were negative and ruled out the possibility of ANCA-associated vasculitis. The patient's condition improved with pulse-dose steroids, leading to an improvement in liver function tests. Consequently, the decision to perform skin and liver biopsies was deferred. She was discharged with a tapering dose of steroids and scheduled for outpatient follow-up to monitor her progress. This case report can offer insights to healthcare providers regarding the potential side effects of GLP-1 RAs in their patient population.

Drug-Induced Autoimmune Hepatitis: An Unusual Adverse Event of Atorvastatin Therapy.

Drug-induced autoimmune hepatitis (AIH) is characterized by acute or chronic hepatic injury coupled with autoantibody development, hypertransaminasemia, and idiopathic AIH features on liver biopsy. Atorvastatin-induced AIH is a rare but well-documented life-threatening adverse event. We report a case of atorvastatin-induced AIH in a 57-year-old female who presented with worsening fatigue, jaundice, and deranged liver function tests. She had been prescribed atorvastatin 20 mg daily three months prior. Her clinical presentation, imaging findings, and serological testing were suggestive of drug-induced AIH. A liver biopsy confirmed a drug-induced autoimmune picture, and she was diagnosed with atorvastatin-induced AIH after ruling out all other possible causes. Her clinical presentation and liver enzymes improved after prolonged treatment with prednisone.

Denosumab-induced autoimmune hepatitis: Case report.

This report described a patient not known to have a hepatic disease, found to have a drug-induced autoimmune hepatitis from denosumab. This is an unreported side effect, and here, we presented the possible predisposing factors and suggested monitoring parameters.

Unusual Presentation and Outcome in Acute Cocaine Intoxication With Multiorgan Failure: A Case Report.

Cocaine overdose remains a significant public health concern worldwide, with potentially life-threatening consequences. The range of presentation can vary from mild autonomic hyperactivity to severe vasoconstriction, causing multiorgan ischemia and even death. In cases of high-dose intoxication, the presentation can be atypical. In this case report, we present a compelling case of a patient who initially presented with cardiac arrest and atypical signs. The patient made a remarkable recovery and returned almost to her baseline. This case provides valuable prognostic insight into the outcomes of severe multiorgan failure resulting from cocaine toxicity.

Role of Extracellular Vesicles in Liver Diseases.

Extracellular vesicles (EVs) are cell-derived membrane structures that are formed by budding from the plasma membrane or originate from the endosomal system. These microparticles (100 nm-100 µm) or nanoparticles (>100 nm) can transport complex cargos to other cells and, thus, provide communication and intercellular regulation. Various cells, such as hepatocytes, liver sinusoidal endothelial cells (LSECs) or hepatic stellate cells (HSCs), secrete and take up EVs in the healthy liver, and the amount, size and content of these vesicles are markedly altered under pathophysiological conditions. A comprehensive knowledge of the modified EV-related processes is very important, as they are of great value as biomarkers or therapeutic targets. In this review, we summarize the latest knowledge on hepatic EVs and the role they play in the homeostatic processes in the healthy liver. In addition, we discuss the characteristic changes of EVs and their potential exacerbating or ameliorating effects in certain liver diseases, such as non-alcoholic fatty liver disease (NAFLD), alcoholic fatty liver disease (AFLD), drug induced liver injury (DILI), autoimmune hepatitis (AIH), hepatocarcinoma (HCC) and viral hepatitis.

Ustekinumab-induced autoimmune hepatitis: a case report.

Ustekinumab is a fully human monoclonal antibody that binds to interleukin (IL)-12/23. Ustekinumab-related liver injury (UST) is rare. There is limited data available on the potential for ustekinumab-liver interaction. We report the case of a patient from our institution followed for colitis ulcerative who developed autoimmune hepatitis (AIH) during treatment with ustekinumab. The diagnosis of autoimmune hepatitis was retained on the simplified criteria for autoimmune hepatitis. Therapeutic management consisted of stopping ustekinumab and starting corticosteroids and immunosuppressants, with regression of cytolysis at 2 months. The purpose of the article is to alert readers and encourage them to report similar cases for better knowledge of the drug.

Selective Androgen Receptor Modulators (SARMs)-Induced Liver Injury: A Case Report and Review of Literature.

Drug-induced liver injury (DILI) is one of the leading causes of death from acute liver failure (ALF) in the United States, accounting for approximately 13% of ALF cases in the United States. Selective androgen receptor modulators (SARMs) were first developed to increase muscle mass while avoiding the side effects of conventional androgenic steroids. Although not Food and Drug Administration (FDA) approved, they are widely available online and are consumed to enhance athletic performance. We report a 22-year-old, previously healthy male, who presented with a two-week history of worsening jaundice, nausea, fatigue, pruritus, dark urine, and light stools. He reported taking the SARM, RAD-140, for 16 weeks. Examination showed scleral icterus. The liver panel showed alkaline phosphatase (ALP) 5.3 µkat/L, alanine transaminase (ALT) 1.66 µkat/L, aspartate transaminase (AST) 1.18 µkat/L, direct bilirubin 294 µmol/L, total bilirubin 427.5 µmol/L, and international normalized ratio (INR) 0.9. Viral hepatitis and autoimmune panel were unremarkable. Alpha-1 antitrypsin and ceruloplasmin levels were within normal limits. Bile sludge was seen on ultrasound. Magnetic resonance cholangiopancreatography (MRCP) abdomen showed segmental narrowing of the intrahepatic ducts. Endoscopic retrograde cholangiopancreatography (ERCP) was unremarkable. Liver biopsy showed mixed portal hepatitis, cholestasis, and biliary reactive changes with ceroid-loaded macrophages; a picture consistent with DILI. The patient was treated supportively and discharged with scheduled hepatology follow-up. At the one-month follow-up, his total bilirubin had fallen from a peak of 530 mol/L to 188 mol/L. The diagnosis of DILI can be made based on the timing of exposure and the exclusion of other etiologies. Liver enzymes normalized three to 12 months after product discontinuation. We hope this report will remind primary care physicians of the potential hepatotoxic side effects of muscle-building compounds and encourage them to report suspected DILI to the FDA using the MedWatch system.

The relationship between relative telomere length and anti-tuberculosis drug-induced hepatitis : A case-control study.

AIM: Anti-tuberculosis drug-induced hepatitis (AT-DIH) is a common and serious adverse drug reaction of tuberculosis treatment. Evidence demonstrated that many factors could affect the occurrence of AT-DIH, such as ageing, smoking, alcohol, oxidative stress, etc., while these factors could also promote telomere shortening. Therefore, relative telomere length (RTL) is indirectly related to the occurrence of AT-DIH. The present study aimed to explore and validate this relationship in Chinese tuberculosis patients. METHODS: A 1:4 matched case-control study was undertaken using 202 AT-DIH cases and 808 controls. Logistic regression models were used to estimate the association between RTL and AT-DIH with odds ratios (ORs) and 95% confidence intervals (CIs). The area under receiver operating characteristic curve (AUC) was calculated to estimate the discriminative performance for distinguishing AT-DIH cases from controls. RESULTS: The average RTL in AT-DIH cases was significantly shorter than that in controls (1.24 vs. 1.46, P=0.002). Patients with longer RTL were at a reduced risk of AT-DIH (OR=0.79, 95% CI: 0.66-0.94, P=0.009), and a dose-response relationship also existed between RTL and lower AT-DIH risk (P for trend=0.012). Under the optimal RTL cut-off value of 1.22, the corresponding AUCs were 0.57 (95% CI: 0.53-0.62, P=0.001) in the univariate model and 0.62 (95% CI: 0.57-0.66, P<0.001) in the multivariate model. CONCLUSION: This study showed that the shorter the RTL, the higher the risk of AT-DIH during an anti-tuberculosis treatment. The short RTL could potentially serve as a risk factor or a predictive test of the hepatotoxic risk associated with anti-tuberculosis treatments.

Unmasking of Metamizole-induced Liver Injury by Simult aneous Development of Characteristic Agranulocytosis.

BACKGROUND: Metamizole is one of the most used analgesic, antipyretic, and spasmolytic agents in many countries worldwide. While metamizole-induced agranulocytosis is an, albeit seldom, well-known adverse event, metamizole-associated drug-induced liver injury has been reported rarely in the literature and hence often remains unconsidered. Here, we present a unique case where metamizole-induced hepatotoxicity got unmasked by the simultaneous development of characteristic agranulocytosis. CASE REPORT: A 22-year-old woman without known conditions presented with a new onset of fever, jaundice, and maculopapular rash and explicitly denied intake of any new substances. Laboratory tests showed liver injury, granulopenia, and positive anti-nuclear and anti-mitochondrial (AMA-M2) antibodies. Liver biopsy revealed a histological pattern characteristic of drug-induced liver injury and bone marrow biopsy, the classical picture of metamizole-induced agranulocytosis. Indeed the in-depth interview of the patient unveiled metamizole consumption over the last two months. Therefore, we could diagnose metamizole-induced hepato- and myelotoxicity. Accordingly, steroid therapy led to normalization of liver parameters and stimulation with granulocyte colony- stimulating factor to leukocyte recovery. CONCLUSION: This case report is intended to increase the awareness of metamizole-associated druginduced liver injury which should always be kept in mind due to its occasionally life-threatening course. Diagnosis can be difficult particularly if anamnesis and written records are without hints for prior metamizole intake.

Hepatic Encephalopathy Caused by Long-Term Amiodarone Use.

This case describes a 72-year-old Japanese woman with hypertrophic cardiomyopathy and non-sustained ventricular tachycardia who had received a total of 215 g of amiodarone over six years and presented with hepatic encephalopathy. The abdominal non-contrast computed tomography showed diffusely increased attenuation of the liver parenchyma. The liver biopsy revealed drug-induced steatohepatitis. No genetic variations in the urea cycle were found. She was ultimately diagnosed with drug-induced steatohepatitis and urea cycle abnormalities caused by long-term amiodarone use. Amiodarone may cause drug-induced steatohepatitis and urea cycle abnormalities, which could induce hyperammonemia. Although case reports of amiodarone-induced hyperammonemia and hepatic encephalopathy have already been reported, we present a typical picture of an amiodarone-induced bright liver, including the mechanism of amiodarone-induced hyperammonemia, to provide an educational learning point for many readers.

Marijuana-Induced Acute Hepatitis: A Case Report.

Marijuana is among the most widely used recreational drugs in the United States. The most common side effects of marijuana include mood changes, impaired memory, impaired body movements, and hallucination. Chronic use of marijuana is associated with transaminitis and hepatomegaly. Reported cases of acute hepatitis secondary to heavy marijuana smoking are very rare.

Treatment response and complications during management of Pott's spine.

The global incidence of TB in 2016 was 10.4 million and India accounts for a quarter of the global burden of TB. It is estimated that there are 2.79 million people with TB in India. About 10% of extra pulmonary TB involves bone and joints. Spinal TB accounts for half the cases of skeletal TB. The incidence of spinal TB is 1-4% of total TB cases, then it is estimated that only in India approximately 60,000 spinal TB cases exist. To report the pattern of recovery and predictors of outcome of Pott's spine. The intervention comprised of four drug antitubercular treatment, rest, immobilization, and ultrasonography or computerized tomography guided aspiration or biopsy as indicated outcome measures were six months Nurick grade, and mRS and complications like drug induced hepatitis (DIH) and paradoxical worsening. Seventy-three patients with Pott's spine, median age 36 (11-73) years, 32 (43.8%) females were included. The neurological signs were present in 44 (64.4%) patients. At six months, median Nurick grade improved from 4 to 2 and;and 70% patients had a good outcome as defined by mRS.The predictors of poor outcome were weight loss, non-ambulatory state on admission and paradoxical worsening. It is concluded that neurological involvement in Pott's spine was present in 64% patients, paradoxical worsening (deterioration in symptoms after one month of ATT) in 11% and DIH in 16%. Weight loss, non-ambulatory state on admission and paradoxical worsening predicted poor outcome.

Antituberculous Drug-Induced Hepatitis in a Patient With Congenital Adrenal Hyperplasia: A Clinical Challenge.

Pulmonary tuberculosis (TB) is highly prevalent in Pakistan, and immunosuppressed individuals (including those on long-term corticosteroid therapy) are at an especially high risk of infection. Owing to the limited number of effective antituberculous drugs, treating resistant cases or patients who develop unfavorable side effects from the first-line agents becomes a daunting task. We discuss a patient with congenital adrenal hyperplasia (CAH) suffering from pulmonary TB who developed drug-induced hepatitis after being started on recommended first-line anti-TB drugs.

Ceftriaxone-induced hepatotoxicity in patients with common medical infections in Qatar: A retrospective study.

INTRODUCTION: Ceftriaxone, a third-generation cephalosporin, is frequently used for the treatment of various bacterial infections as a broad-spectrum antibiotic for many decades. Although ceftriaxone is a well-tolerated drug in most cases, it can lead to serious liver injury, which can be a real challenge to the treating physician. Given the potentially serious adverse effects that can vary from mild biochemical abnormalities to complete liver failure, we intend to assess the spectrum of liver injury based on biochemical criteria for patients treated with ceftriaxone for common bacterial infections in Qatar. OBJECTIVES: This study aimed to explore the incidence of ceftriaxone-induced liver injury at Hazm Mebaireek General Hospital, Qatar, and to evaluate the relationship of the ceftriaxone dose, if any, with liver dysfunction. METHODS: This retrospective study included hospitalized adult patients treated with ceftriaxone at our hospital from January 2019 to December 2019 and analyzed demographic and clinical data obtained from electronic medical records. This study determined the incidence of liver injury (primary outcome) in patients treated with ceftriaxone (2 g/day) for ≥ 2 consecutive days by reviewing liver function test results until the day of discharge and at the first outpatient follow-up. RESULTS: The final data analysis included a total of 634 patients admitted and treated with ceftriaxone from January 2019 to December 2019.In the multivariate analysis with propensity score adjustment, ceftriaxone was independently associated with liver injury, especially when combined with other agents utilizing hepatic metabolism. CONCLUSIONS: Ceftriaxone was associated with a significantly higher incidence of liver injury (19.7%) when used along with other medications that are metabolized in the liver, as found in the present study compared with other similar studies (approximately 2.9%-13.9%). Furthermore, the incidence was too high to be ignored in clinical practice.

Acute Multi-Organ Toxicity During 24-Hour Dosing of Intravenous Amiodarone: A Case Report.

We present a unique case of a 60-year-old male with congestive heart failure who was admitted for a pre-syncopal episode and found to be in atrial fibrillation with rapid ventricular response (RVR). In order to effectively rate control the patient, he was administered an amiodarone bolus and intravenous (IV) infusion over 24 hours, along with a single oral 200 mg dose the following day. The patient subsequently developed acute hepatotoxicity along with features of acute kidney injury (AKI), pulmonary distress, and leukocytosis. After ruling out other etiologies for acute liver, pulmonary, and kidney injury, amiodarone-induced multi-organ toxicity was suspected and amiodarone was discontinued. Within hours of amiodarone discontinuation, the patient's clinical status and organ function improved remarkably. In the setting of a patient being treated with IV amiodarone and presenting with sudden signs of dyspnea, acute elevation of transaminases and AKI within one to two days of initial dosing, acute amiodarone-induced organ toxicity should be considered.

A Plausible Association Between the Use of Elderberry and Autoimmune Hepatitis.

Hepatic injury due to dietary and herbal supplements can often share similar clinical characteristics with autoimmune hepatitis (AIH). Sambucus species, commonly known as elderberry, have been used in traditional medicine for centuries to prevent and treat respiratory problems. Although there are no clear reports on the association of elderberry with AIH or drug-induced hepatitis, there have been concerns about negative health manifestations linked to elderberry and the overproduction of inflammatory cytokines. In this article, we discuss a case of a patient who developed autoimmune hepatitis while on long-term elderberry-containing supplements and a probable association between the two.

Drug Reaction With Eosinophilia and Systemic Symptoms Syndrome in a Patient Taking Lamotrigine: A Case Report Based Literature Review.

A 29-year-old patient presented to the hospital with worsening generalized rash for the last two days from a mental health facility. The patient was commenced on lamotrigine two weeks earlier, and he developed fever and generalized macular rash on his body. His blood tests showed deranged liver function tests (LFTs) and clotting with raised eosinophil count, and he was treated for lamotrigine-induced drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. The patient was commenced on prednisolone 50 mg once daily with a proton pump inhibitor cover, and lamotrigine was suspended on advice from Dermatology. The patient showed improvement after 3-4 days of treatment. His skin biopsy showed prominent suppurative granulomatous folliculitis, mild perivascular chronic inflammation, and red blood cell extravasation, including the rare eosinophil. He was weaned off from prednisolone by 5 mg weekly and had complete resolution of symptoms.

Rare case of norethisterone-induced hepatitis: A case report.

We report a case of probable norethisterone-related liver injury, manifesting as a significant rise in liver transaminases in a 62-year-old woman. Upon discontinuation of norethisterone, liver transaminases decreased to normal level within two weeks. Knowledge of rare adverse effects of drugs such as norethisterone is necessary for rapid identification and management, especially in patients with risk factors such as non-alcoholic liver disease and obesity.

Liver Abnormalities in Systemic Lupus Erythematosus: A Prospective Observational Study.

Objectives In this study, we aimed to examine and analyze liver abnormalities among patients with systemic lupus erythematosus (SLE), including both newly diagnosed patients and those being followed up, as well as the prevalence of lupus hepatitis. Methods This was a prospective observational study. Clinical data, liver function tests (LFTs), and the findings from the ultrasonography of the abdomen among the patients were prospectively recorded and evaluated. Results Overall, 28 of the total 135 (20.7%) patients had liver abnormalities, including biochemical and those detected via ultrasonography. Ten patients had transaminitis, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels >2 times the upper limit of normal (ULN). Nine patients had elevated alkaline phosphatase (ALP) or gamma-glutamyl transferase (GGT) of >2 times ULN. In three patients, transaminitis was due to anti-tubercular therapy (ATT)-induced hepatitis; in seven (5.2%), no specific cause for transaminitis could be identified, and hence they were classified as cases of lupus hepatitis. On comparing clinical features between patients with (n=7) and without lupus hepatitis (n=128), the condition was more prevalent in newly diagnosed SLE patients compared to those who had been on follow-up [six (85.7%) vs. 30 (23.6%), p=0.002]. All seven patients with lupus hepatitis had complete resolution of the transaminitis on follow-ups. However, one patient who had received ATT (isoniazid, rifampicin, ethambutol, and pyrazinamide) died. Ultrasonography showed fatty liver in seven patients and chronic liver disease in one patient. Conclusion In this study, transaminitis due to lupus hepatitis was seen in newly diagnosed lupus patients and was not associated with disease activity. Before diagnosing lupus hepatitis, drug-induced liver disease has to be ruled out, and if persistent LFT abnormalities are present, further workup is suggested to rule out overlap with primary biliary cirrhosis and/or autoimmune hepatitis.

Checkpoint inhibitor induced hepatitis and the relation with liver metastasis and outcome in advanced melanoma patients.

BACKGROUND: Checkpoint inhibitor-induced hepatitis is an immune-related adverse event of programmed cell death protein 1 (PD-1) inhibition, cytotoxic T-lymphocyte associated 4 (CTLA-4) inhibition or the combination of both. Aim of this study was to assess whether checkpoint inhibitor-induced hepatitis is related to liver metastasis and outcome in a real-world nationwide cohort. METHODS: Data from the prospective nationwide Dutch Melanoma Treatment Registry (DMTR) was used to analyze incidence, risk factors of checkpoint inhibitor-induced grade 3-4 hepatitis and outcome. RESULTS: 2561 advanced cutaneous melanoma patients received 3111 treatments with checkpoint inhibitors between May 2012 and January 2019. Severe hepatitis occurred in 30/1620 (1.8%) patients treated with PD-1 inhibitors, in 29/1105 (2.6%) patients treated with ipilimumab and in 80/386 (20.7%) patients treated with combination therapy. Patients with hepatitis had a similar prevalence of liver metastasis compared to patients without hepatitis (32% vs. 27%; p = 0.58 for PD-1 inhibitors; 42% vs. 29%; p = 0.16 for ipilimumab; 38% vs. 43%; p = 0.50 for combination therapy). There was no difference in median progression free and overall survival between patients with and without hepatitis (6.0 months vs. 5.4 months progression-free survival; p = 0.61; 17.0 vs. 16.2 months overall survival; p = 0.44). CONCLUSION: Incidence of hepatitis in a real-world cohort is 1.8% for PD-1 inhibitor, 2.6% for ipilimumab and 20.7% for combination therapy. Checkpoint inhibitor-induced hepatitis had no relation with liver metastasis and had no negative effect on the outcome.