mycophenolic-acid and Hepatitis--Chronic

The objectives of this study were to describe the clinical findings, treatment and outcomes of six dogs with presumed idiopathic chronic hepatitis treated with mycophenolate mofetil (MMF).. Medical records were retrospectively searched to identify dogs in which idiopathic chronic hepatitis was diagnosed on histopathology between January 2010 and June 2022 that were treated with MMF for at least two weeks with >2 follow-up examinations. Data recorded from each dog included signalment, clinical signs, diagnostic test results and treatment.. Six dogs were treated with MMF at a median initial dosage of 9.6 mg/kg PO q 12 h. Reported adverse effects from MMF included decreased appetite, vomiting and diarrhoea. In all six dogs, MMF was used successfully long term for the treatment of idiopathic chronic hepatitis as determined by 46% or greater improvement of alanine aminotransferase (ALT) between 4 and 18 weeks of starting MMF. Three dogs were also temporarily treated for 4-6 months on a tapering dose of prednisone. In two dogs, ALT remained within the reference interval, and in one dog, it was very mildly elevated when on MMF alone. In all six dogs, owners reported that the medication was well tolerated.. To the authors' knowledge, this is the first report describing the use of MMF with and without a tapering dose of prednisone for the treatment of idiopathic chronic hepatitis in six dogs. Based on the outcomes of the dogs in this report, MMF can be effective for the long-term treatment of idiopathic chronic hepatitis as measured by reduction in ALT and improvement of clinical signs.

Topics: Animals; Dog Diseases; Dogs; Drug Therapy, Combination; Hepatitis, Chronic; Immunosuppressive Agents; Mycophenolic Acid; Prednisone; Retrospective Studies

Topics: Aged; Alanine Transaminase; Antiviral Agents; Graft Rejection; Hepatitis E; Hepatitis E virus; Hepatitis, Chronic; Humans; Immunocompromised Host; Immunoglobulin M; Immunosuppressive Agents; Kidney Transplantation; Male; Mycophenolic Acid; Polycystic Kidney Diseases; Polymerase Chain Reaction; Ribavirin; RNA, Viral; Tacrolimus; Viral Load

Topics: Aged; Drug Therapy, Combination; Enzyme Inhibitors; Female; Hepatitis E; Hepatitis E virus; Hepatitis, Chronic; Humans; Immunocompromised Host; Immunologic Factors; Mycophenolic Acid; Rituximab; Sjogren's Syndrome

Many recipients of organ transplants develop chronic hepatitis, due to infection with the hepatitis E virus (HEV). Although chronic HEV infection is generally associated with immunosuppressive therapies, little is known about how different immunosuppressants affect HEV infection.. A subgenomic HEV replication model, in which expression of a luciferase reporter gene is measured, and a full-length infection model were used. We studied the effects of different immunosuppressants, including steroids, calcineurin inhibitors (tacrolimus [FK506] and cyclosporin A), and mycophenolic acid (MPA, an inhibitor of inosine monophosphate dehydrogenase) on HEV replication in human hepatoma cell line Huh7. Expression of cyclophilins A and B (the targets of cyclosporin A) were knocked down using small hairpin RNAs.. Steroids had no significant effect on HEV replication. Cyclosporin A promoted replication of HEV in the subgenomic and infectious models. Knockdown of cyclophilin A and B increased levels of HEV genomic RNA by 4.0- ± 0.6-fold and 7.2- ± 1.9-fold, respectively (n = 6; P < .05). A high dose of FK506 promoted infection of liver cells with HEV. In contrast, MPA inhibited HEV replication. Incubation of cells with guanosine blocked the antiviral activity of MPA, indicating that the antiviral effects of this drug involve nucleotide depletion. The combination of MPA and ribavirin had a greater ability to inhibit HEV replication than MPA or ribavirin alone.. Cyclophilins A and B inhibit replication of HEV; this might explain the ability of cyclosporin A to promote HEV infection. On the other hand, the immunosuppressant MPA inhibits HEV replication. These findings should be considered when physicians select immunosuppressive therapies for recipients of organ transplants who are infected with HEV.

Topics: Antiviral Agents; Calcineurin; Calcineurin Inhibitors; Cell Line, Tumor; Cyclophilin A; Cyclophilins; Cyclosporine; Dose-Response Relationship, Drug; HEK293 Cells; Hepatitis E; Hepatitis E virus; Hepatitis, Chronic; Humans; Immunosuppressive Agents; Mycophenolic Acid; Ribavirin; RNA Interference; RNA, Viral; Time Factors; Transfection; Virus Replication