mycophenolic-acid and Hepatitis

Immune-mediated hepatitis is recognised as a frequently occurring complication with the use of checkpoint inhibitor immunotherapy drugs. The mainstay of treatment involves the use of immunosuppressive agents, such as corticosteroids. Mycophenolate mofetil is added when steroid resistant. However, there are limited data to guide further management when the hepatitis remains refractory to these therapies. We present two patients who developed severe immunotherapy-induced hepatitis and required prolonged immunosuppressive therapy with three agents in combination before resolution was achieved. We demonstrate that the addition of tacrolimus can be successful when other drugs fail. We also illustrate how a subsequent wean off immunosuppression can be safely performed and highlight the use of concordant antimicrobial prophylaxis to mitigate against opportunistic infections.

Topics: Adrenal Cortex Hormones; Hepatitis; Humans; Immunosuppressive Agents; Immunotherapy; Mycophenolic Acid; Steroids; Tacrolimus

Topics: Hepatitis; Humans; Immunosuppressive Agents; Mycophenolic Acid; Steroids; Treatment Outcome

Topics: Antineoplastic Agents, Immunological; Hepatitis; Humans; Immunologic Factors; Ipilimumab; Male; Melanoma; Middle Aged; Mycophenolic Acid; Neutropenia; Nivolumab

With the recent approval of 5 PD-1/PD-L1 inhibitors for a number of malignancies, PD-1 axis inhibition is drastically changing the treatment landscape of immunotherapy in cancer. As PD-1/PD-L1 are involved in peripheral immune tolerance, inhibition of this immune checkpoint has led to novel immune-related adverse events including colitis, hepatitis, pneumonitis, rash, and endocrinopathies among many others.. In this seminar, we will analyze the incidence of immune-related adverse events for nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab. Then, we will discuss the specific management of the most common immune-mediated adverse events including colitis, hepatitis, pneumonitis, rash, endocrinopathies, nephritis, and neurologic toxicities.. Immune-related adverse events are frequently treated with immunosuppressive medication such as steroids and mycofenolate mofetil.. There are specific immune-related adverse events which are frequently seen by the treating oncologist from checkpoint inhibitors. It is essential to understand the recommended treatment options to minimize toxicity and mortality from this important class of anti-neoplastic therapies.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; B7-H1 Antigen; Colitis; Exanthema; Hepatitis; Humans; Immunosuppressive Agents; Immunotherapy; Mycophenolic Acid; Neoplasms; Nephritis; Neurodegenerative Diseases; Nivolumab; Pneumonia; Programmed Cell Death 1 Receptor

Systemic lupus erythematosus-related hepatitis, known as lupus hepatitis, is a rare manifestation of systemic lupus erythematosus, and is usually subclinical with mild abnormalities of serum liver enzymes. While cases with clinically significant and refractory lupus hepatitis are uncommon, treatment options for lupus hepatitis are to be established. Here, we report the case of a 45-year-old man with progressive lupus hepatitis accompanied by autoimmune haemolytic anaemia. Lupus hepatitis of this patient was refractory to tacrolimus, azathioprine and cyclophosphamide, but was successfully treated by mycophenolate mofetil. Mycophenolate mofetil might be an effective therapeutic option for refractory lupus hepatitis.

Topics: Anemia, Hemolytic, Autoimmune; Biopsy; Diagnosis, Differential; Drug Resistance; Drug Substitution; Hepatitis; Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Liver Function Tests; Lupus Erythematosus, Systemic; Male; Middle Aged; Mycophenolic Acid; Predictive Value of Tests; Remission Induction; Treatment Outcome

We describe a case of a patient from Far North Queensland, Australia, with life-threatening hepatotoxicity caused by ipilimumab induced immune-related adverse events (irAEs). Our patient presented with non-specific symptoms including malaise, lethargy and fevers. Her work up revealed acute hepatitis, which was presumed to be related to ipilimumab treatment for her metastatic melanoma. Causality for ipilimumab was assessed with the CIOMS scale (Council for International Organizations of Medical Sciences) and provided a causality level of 'highly probable' (score +9). She was started on methylprednisolone as per guidelines for ipilimumab induced irAEs. On the second day of treatment her transaminases enzymes unexpectedly rose several hundred times. Investigations for other causes of acute hepatitis including abdominal imaging were negative. She was started up front on equine antithymocyte globulin, mycophenolate moefetil and continued on methylprednisolone. She recovered clinically and biochemically in 2 weeks and continues to remain well.

Topics: Animals; Antibodies, Monoclonal; Antilymphocyte Serum; Australia; Chemical and Drug Induced Liver Injury; Female; Hepatitis; Horses; Humans; Immunosuppressive Agents; Ipilimumab; Melanoma; Methylprednisolone; Middle Aged; Mycophenolic Acid

Recently, we reported that immunoglobulin subtype 4 (IgG4) is involved in autoimmune hepatobiliary diseases, such as autoimmune hepatitis, sclerosing cholangitis, and pancreatitis. However, the association of IgG4 with autoimmune hepatic disease after living donor liver transplantation (LDLT) has not been investigated.. Of the 72 LDLT recipients, four patients (5.6%) were suspected of having autoimmune-related hepatic disease after LDLT. The diagnosis was made based on a histological diagnosis following an examination of a biopsy liver specimen in three cases, while in one case a pemphigoid appeared in the flank with liver fibrosis of unknown cause. Human leukocyte antigen (HLA) mismatches were 3, 2, 2, and 2, respectively. The serum level of IgG4 in the patients was measured, and IgG4 immunohistochemical staining in the liver biopsy specimens was also performed.. In all cases, steroid pulse therapy or recycle treatment and subsequent increased steroid dose as well as additional azathioprine or mycophenolate mofetil were effective. While a few positive-stained cells for IgG4 were observed in the liver of one case, negative staining for IgG4 was observed in the other cases. All serum subclasses of IgG4 were within normal limits.. In our series of LDLT, IgG4-related immune disorder is unlikely to be involved in post-transplant, autoimmune-related liver disease.

Topics: Adult; Autoimmune Diseases; Azathioprine; Drug Therapy, Combination; Female; Hepatitis; Histocompatibility Testing; HLA Antigens; Humans; Immunoglobulin G; Immunosuppressive Agents; Liver; Liver Transplantation; Living Donors; Male; Middle Aged; Mycophenolic Acid; Pulse Therapy, Drug; Steroids; Time Factors; Treatment Outcome

Topics: Alemtuzumab; Anemia, Hemolytic, Autoimmune; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antibodies, Neoplasm; Antineoplastic Agents; Azathioprine; Biopsy; Celiac Disease; Child, Preschool; Coombs Test; Cyclosporine; Diagnosis, Differential; Follow-Up Studies; Glucocorticoids; Hepatitis; Humans; Immunologic Factors; Immunosuppressive Agents; Infant; Liver; Liver Function Tests; Male; Methylprednisolone; Mycophenolic Acid; Prednisone; Rare Diseases; Remission Induction; Rituximab

Topics: Acute Disease; Adult; Anemia, Aplastic; Antibodies, Monoclonal; Antilymphocyte Serum; Basiliximab; Cyclosporine; Drug Therapy, Combination; Hepatitis; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Recombinant Fusion Proteins; Remission Induction; T-Lymphocytes

Topics: Aged; Antilymphocyte Serum; Azathioprine; Cyclosporine; Female; Graft Rejection; Hepatitis; Humans; Immunosuppressive Agents; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Liver Transplantation; Male; Methylprednisolone; Middle Aged; Mycophenolic Acid; Prednisone