Case Report: Severe Immune-Related Cholestatic Hepatitis and Subsequent Pneumonia After Pembrolizumab Therapy in a Geriatic Patient With Metastic Gastric Cancer

Background: Immune checkpoint inhibitors have provided significant clinical benefits to many patients with advanced cancer; however, severe immune-related adverse events (irAEs) have occurred. Detecting and treating irAEs early could improve patient prognoses. Therefore, clinicians and patients should understand that these irAEs exist, especially those that are rare and serious.Case Presentation: In this report, an 86-year-old male patient, diagnosed with metastatic gastric cancer involving the peritoneum and retroperitoneal lymph nodes was treated with 5-cycle pembrolizumab therapy (100 mg q 2 weeks), achieving a partial response. However, the patient developed Grade 3 cholestatic hepatitis and delayed pneumonia 10 days and 2 months after the final pembrolizumab dose, respectively. After discontinuing the pembrolizumab therapy and excluding obstructive jaundice with imaging studies, the patient received steroid therapy, with a gradual symptom improvement. However, the patient developed delayed pneumonia with type 1 respiratory failure 1-month post-discharge. Several microbiologic tests were negative, and immune-associated pneumonia was suspected, but we could not exclude an opportunistic infection. The patient recovered with steroids and antibiotics and remained in partial remission 5 months after pembrolizumab withdrawal.Conclusions: Cholestatic hepatitis is a rarely reported toxicity of immune checkpoint inhibitors, which should be suspected and addressed once obstructive jaundice is ruled out. In addition, clinicians should be aware that irAEs can occur at any time in patients treated with immune checkpoint inhibitors and that a timely diagnosis should be made.

Aseptic meningitis, hepatitis and cholestasis induced by trimethoprim/sulfamethoxazole: a case report

Background Drug-induced aseptic meningitis is a rare, but challenging diagnosis, most commonly reported with nonsteoroidal anti-inflammatory drugs (NSAIDs) and antibiotics. Trimethoprim/sulfamethoxazole (TMP/SMX) is a sulfonamide that is widely used in clinical practice for the treatment and prophylaxis of various infections. The most common side effects associated with TMP/SMX are generally mild and self-limited, but serious side effects have been reported, including liver injury and aseptic meningitis. Case presentation We report a 2,5 year old Dutch girl with both drug-induced aseptic meningitis and drug-induced liver injury while using TMP/SMX prophylaxis. Ursodeoxycholic acid was started because of cholestatic injury. After cessation of TMP/SMX, full convalescence was reached within weeks. Conclusions This is the first report of a young patient with both aseptic meningitis and drug-induced liver injury caused by TMP/SMX. Drug-induced aseptic meningitis and cholestatic hepatitis constitute a considerable diagnostic challenge to clinicians. In addition to a thorough evaluation for infectious causes, clinicians should be aware of drug-induced aseptic meningitis and cholestatic hepatitis.

Coombs-Negative Haemolytic Anaemia, Direct Hyperbilirubinaemia and Splenomegaly: A Rare Amalgam

Introduction: Epstein-Barr virus (EBV) is notorious for its varied presentation in adults. Reactivation of EBV can occur at any time and is often due to weakened cellular immunity. Case Description: Here we report the case of a young woman with no previous medical history who presented with cholestatic hepatitis, Coombs-negative haemolytic anaemia and splenomegaly. Due to the initial disjointed picture with no other localizing symptoms, she underwent extensive work-up for the same. Discussion: EBV has been associated with many malignancies, autoimmune diseases and chronic fatigue syndrome. EBV causes elevated liver enzymes; however, cholestatic hepatitis is exceedingly rare, with only a few cases reported. Haemolytic anaemia is a common complication of EBV infection and is often Coombs positive. Conclusion: EBV testing should be considered before more invasive and expensive work-up in a patient presenting with multi-systemic abnormalities.

Efficiency of Double Plasma Molecular Absorption System on the Acute Severe Cholestatic Hepatitis

<b><i>Background:</i></b> Cholestasis may lead to hepatic cirrhosis and a longer hospital stay. A part of the patients with cholestasis requires liver transplantation. However, most of the treatment efficiency of cholestatic hepatitis (CH) is not satisfactory. For the patients with severe CH after artificial liver support, there was a lack of systemic evaluation on the treatment efficiency of double plasma molecular absorption system (DPMAS) for acute severe CH. <b><i>Objective:</i></b> We aim to investigate the treatment efficiency of DPMAS on acute severe CH. <b><i>Methods:</i></b> This retrospective study involved 309 cases diagnosed with acute severe CH admitted to the First Affiliated Hospital, Zhejiang University. We compared the prognosis of patients received standard medical therapy (SMT) and SMT + DPMAS. Besides, the effects of DPMAS on total bilirubin (TBIL) and prothrombin time (PT) were investigated. <b><i>Results:</i></b> DPMAS could significantly reduce the requirements for liver transplantation in the CH patients. After DPMAS therapy, significant decline was noticed in the TBIL, direct bilirubin (DBIL), total bile acid, and cholesterol. The baseline ratio of neutrophil showed significant elevation in the patients received 4 or more DPMAS compared with those received less DPMAS. <b><i>Conclusions:</i></b> DPMAS could significantly eliminate the necessity of liver transplantation. The artificial liver support system should be conducted to bring down the bilirubin level and the ratio of cases with severe conditions. In general, DPMAS should be preferred as an artificial liver support therapy for the patients with acute severe CH.