Autoimmune hepatitis type 2 associated with an unexpected and transient presence of primary biliary cirrhosis-specific antimitochondrial antibodies: a case study and review of the literature.

BACKGROUND: Unlike other autoimmune liver diseases, primary biliary cirrhosis (PBC) has never been reported in early childhood, while type 2 autoimmune hepatitis (AIH) is eminently a paediatric disease. CASE PRESENTATION: We describe a case of type 2 AIH with serological positivity for PBC-specific anti-mitochondrial antibodies (AMA) in a 3-year old girl. We found this observation intriguing as AMA and indeed an overlap with PBC are virtually absent in Type 2 AIH, a pediatric form of AIH which is distinct precisely because it is characterized by pathognomonic anti-liver kidney microsomal type 1 (LKM-1) showing a remarkable antigen-specificity directed against cytochrome P4502D6. We also review the literature in relation to AMA positivity in paediatric age and adolescence. In our case, the presence of AIH-2-specific anti-LKM-1 and PBC-specific AMA was confirmed by indirect immunofluorescence (IIF), and immunoblotting and ELISA based on recombinant mitochondrial antigens. The clinical, laboratory and histological features of the child are given in detail. Interestingly the mother was AMA positive without other features of PBC. The child was successfully treated with immunosuppression and five years after the original diagnosis is on a low dose of prednisolone and azathioprine, with no signs of relapse. Anti-LKM-1 antibodies are still present in low titres. AMA were detectable for the first 4 years after the diagnosis and disappeared later. CONCLUSION: This is the first case report in the literature of AIH type 2 with an unexpected PBC-specific AMA positivity in a young child. Response to immunosuppressive treatment was satisfactory and similar to that described in AIH. A review of published reports on AMA positivity in paediatric age shows that the antibody may arise in the context of immunodeficiency and is variably associated with liver damage.

What gastroenterologists should know about SARS-CoV 2 vaccine: World Endoscopy Organization perspective.

BACKGROUND: The novel Coronavirus (SARS-CoV-2) has caused almost 2 million deaths worldwide. Both Food and Drug Administration and European Medicines Agency have recently approved the first COVID-19 vaccines, and a few more are going to be approved soon. METHODS: Several different approaches have been used to stimulate the immune system in mounting a humoral response. As more traditional approaches are under investigation (inactivated virus vaccines, protein subunit vaccines, recombinant virus vaccines), more recent and innovative strategies have been tried (non-replicating viral vector vaccines, RNA based vaccines, DNA based vaccines). RESULTS: Since vaccinations campaigns started in December 2020 in both the US and Europe, gastroenterologists will be one of the main sources of information regarding SARS-CoV 2 vaccination for patients in their practice, including vulnerable patients such as those with Inflammatory Bowel Disease (IBD), patients with chronic liver disease, and GI cancer patients. CONCLUSIONS: Thus, we must ourselves be well educated and updated in order to provide unambiguous counseling to these categories of vulnerable patients. In this commentary, we aim to provide a comprehensive review of both approved COVID-19 vaccines and the ones still under development, and explore potential risks, benefits and prioritization of vaccination.

Safety of vedolizumab in liver transplant recipients: A systematic review.

Background: The management of inflammatory bowel disease in patients who have previously undergone liver transplantation can be a clinical challenge. There are serious concerns among physicians regarding the use of biologics for treating such immuno-compromised patients. Objective: We performed a systematic review on vedolizumab therapy in transplant recipients to assess its safety. Methods: PubMed/Embase/Scopus were searched up to November 2018 to identify papers regarding liver transplant recipients and therapy with vedolizumab. Primary outcomes were adverse events. Secondary outcomes were liver transplant and inflammatory bowel disease outcomes. Results: Eight studies (31 patients) were included. Nine out of 31 patients experienced an infection within a mean follow-up time ranging from 5-20 months. No malignancies were reported. Inflammatory bowel disease clinical response was experienced by 20/26 patients. Abnormalities in liver tests were recorded in 2/22 patients. Conclusion: Vedolizumab may be considered safe for treating inflammatory bowel disease in liver transplant recipients. Caution is recommended for patients with an unstable liver graft function.

Mediterranean Diet and NAFLD: What We Know and Questions That Still Need to Be Answered.

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and is expected to become the leading cause of end-stage liver disease worldwide over the next few decades. In fact, NAFLD encompasses different clinical scenarios, from the simple accumulation of fat (steatosis) to steatohepatitis (NASH), NASH-cirrhosis, and cirrhosis complications. In this context, it is fundamental to pursue strategies aimed at both preventing the disease and reducing the progression of liver fibrosis once liver damage is already initiated. As of today, no pharmacological treatment has been approved for NAFLD/NASH, and the only recommended treatment of proven efficacy are life-style modifications, including diet and physical exercise pointing at weight loss of 5%-7%. Different dietetic approaches have been proposed in this setting, and in this review, we will discuss the evidence regarding the efficacy of the Mediterranean Diet as a treatment for NAFLD. In particular, we will report the effects on liver-related outcomes.

Advances in pharmacotherapy for primary biliary cirrhosis.

INTRODUCTION: Primary biliary cirrhosis (PBC) is a chronic autoimmune liver disease mostly seen in middle-aged women characterized by progressive nonsuppurative destruction of small bile ducts resulting in intrahepatic cholestasis, parenchymal injury and ultimately end-stage liver disease. Despite major breakthroughs in our understanding of PBC, there remains only one FDA-approved agent for treatment: ursodeoxycholic acid (UDCA) to which one-third of patients are unresponsive. AREAS COVERED: Biochemical response to treatment with UDCA is associated with excellent survival rates in PBC patients. However, there is a need for alternative treatments for nonresponders. Results from human epidemiological and genetic studies as well as preclinical studies in PBC animal models have provided a strong impetus for the development of new therapeutic agents. In this review, we discuss the recent advances in translational research in PBC focusing on promising therapeutic approaches, namely immune-based targeted therapies and agents targeting the synthesis and circulation of bile acids. EXPERT OPINION: We are in a new era for the development of novel therapies for PBC. Data on fibrates, budesonide and obeticholic acid offer encouragement for nonresponders to UDCA.