Immune checkpoint inhibitors have been incorporated into the treatment of various malignancies. An increasing body of literature is reporting rare but potentially fatal adverse events associated with these agents. In this case series, the authors report the clinical features and outcomes of seven patients who received immune checkpoint inhibitors for different solid organ malignancies and developed a tetrad of immune-related myocarditis, myositis, myasthenia gravis and transaminitis. Herein the authors review the literature and describe the current diagnostic and management approach for this overlapping syndrome. The authors\' series highlights the importance of a high index of clinical suspicion, prompt comprehensive investigations, early multidisciplinary team involvement and initiation of immunosuppressive therapy when immune-related adverse events are suspected.
Cancer immunotherapy is used in the treatment of different cancer types. Immunotherapy activates the immune system to detect and attack cancer cells, but side effects may arise from the immune system inadvertently attacking normal tissues and organs. The increased use of immunotherapy has led to an increase in the reporting of rare but potentially life-threatening treatment-related side effects. In this case series, the authors report the clinical features and outcomes of seven patients who developed inflammation of the heart, muscles, nerve and muscle junctions and liver following treatment with immunotherapy. The authors review the scientific literature and discuss the current understanding of and management approach to this rare syndrome. The authors\' report highlights the importance of a high degree of clinical suspicion, prompt comprehensive testing to confirm diagnosis, early involvement of experts from different specialties and early initiation of treatment in the management of this unique syndrome.

We observed in the literature that irritable bowel syndrome (IBS) may be linked to irregular parameters of the metabolic system (MS) and liver function. For that reason, we conducted this systematic review to comprehensively analyze the association of transaminitis (elevated alanine transaminase (ALT)) with IBS. This review was designed by following methods described in the Cochrane Handbook for Systematic Reviews of Interventions. Published peer-reviewed journal articles were included. Data were extracted based on study design, age, gender, author, date of publication or availability online, publication type, participants, gender (M/F), and types of IBS. Our electronic multiple databases yielded a total of 519 preliminary studies; we then removed duplicate studies and left with 326 studies. After reviewing the full text of these articles, a total of 83 studies were eliminated and lastly, three studies were selected for this systematic review for quantitative and qualitative analysis. All the enrolled subjects in included studies were diagnosed with IBS by the Rome II and III criteria and among these sub-jects, 50.4% had IBS-D, 13.8% had IBS-C, 30.3% had IBS-M, and 3.5% had IBS-U. The prevalence of elevated ALT with other liver enzymes (γ-GT levels and aspartate aminotransferase (AST)) in patients with irritable bowel syndrome whether their body mass index (BMI) was high or not (16.9% vs. 7.7%; p=0.015) and γ-GT (24.1% vs. 11.5%; p=0.037), Lee et al., 2016. The IBS-D subtype was seen more commonly in patients whose alcohol intake was significantly high however their study data showed no significant change in elevation of ALT. The upper limits normal values for serum liver enzymes were de-fined as 41 international per liter in males and 31 international units per liter in females for ALT. No significant relationships were observed between IBS status and elevated γ-GT (OR, 1.647; 95% CI, 0.784-3.461). The review study proposes a potential relation between elevated ALT levels, MS, and IBS, and this review might be the first review in IBS patients to observe the association of elevated ALT in the IBS population. Although further additional trials with a large sample size will be required to confirm these results. Furthermore, for assessing the efficacy of the manipulation of gut microbiota ran-domized controlled trials in a large population of IBS patients are needed to establish a causal-resultant relationship between IBS, MS, and liver damage.

Giant cell hepatitis (GCH) is a rare diagnosis in adults that is found in 0.25% of liver biopsies. GCH has been associated with multiple causes including drugs (6-mercaptopurine, methotrexate), toxins, viruses and autoimmune. GCH has been described in few patients with chronic lymphocytic leukemia (CLL). Here we describe three patients diagnosed with GCH thought to be related to underlying CLL and its management. All of our patients were treated with a combination of immunosuppression as well as CLL-directed therapy to address CLL and concomitant liver disease. GCH is a rare manifestation of active CLL and should be ruled out with prompt liver biopsy in patients with CLL with persistent transaminitis without another attributable cause. Prompt treatment of GCH with immunosuppression is required to prevent long-term liver toxicity. If transaminitis does not improve with immunosuppression alone, the addition of CLL directed therapy should be considered in patients who carry this diagnosis to prevent long-term liver toxicity.

Liver enzyme levels are commonly obtained in the evaluation of many conditions. Elevated alanine transaminase and aspartate transaminase have traditionally been considered a \"hepatocellular\" pattern concerning for ischemic, viral, or toxic hepatitis. Elevations in these levels pose a diagnostic dilemma in patients without a clinical picture consistent with liver disease. On the other hand, elevated alkaline phosphatase historically represents a \"cholestatic\" pattern concerning for gallbladder and biliary tract disease. Often, patients present with a \"mixed\" picture of elevation in all 3 liver enzymes, further confounding the clinical scenario. We present 4 cases of women with severe upper abdominal pain and markedly elevated transaminases. Three of the patients had accompanying jaundice. A higher rise in enzyme levels was seen in those who had greater bile duct dilation. All patients saw a rapid decrease in transaminases after biliary decompression, along with a fall in alkaline phosphatase and total bilirubin levels. No evidence of liver disease was found, nor were there any signs of hepatocellular disease on imaging. The patients were ultimately found to have choledocholithiasis on endoscopic retrograde cholangiopancreatography with no hepatocellular disease. Furthermore, our cases show that severe abdominal pain in the setting of elevated liver enzymes is likely associated with biliary disease rather than a primary hepatic process. Recognition of this rare pattern of markedly elevated transaminases in isolated biliary disease can aid in avoiding unnecessary evaluation of primary hepatic disease and invasive surgical interventions such as liver biopsy.