A 21-year old woman was admitted to hospital with a two-week history of painless jaundice, fatigue and anorexia having previously been fit and well. One month prior to presentation, the patient had ...taken a five-day course of amoxicillin-clavulanic acid for an infected skin cyst. Otherwise, she was only on the oral contraceptive pill and reported minimal alcohol intake. On examination, she was deeply jaundiced, but alert and oriented with no asterixis. She had no stigmata of chronic liver disease, but hepatomegaly extending 3 cm from below the right subcostal margin was evident. Investigations showed: white cell count 13.4 × 109/L (normal 3.6–9.3), haemoglobin 11.8 g/dl (normal 11–15), platelet count 356 × 109/L (normal 170–420), sodium 138 mmol/L (normal 134–144), potassium 3.5 mmol/L (normal 3.5–5.0), creatinine 32 µmol/L (normal 40–75), albumin 30 g/L (normal 35–48), alanine aminotransferase 707 IU/L (normal 15–54), alkaline phosphatase 151 IU/L (normal 30–130), bilirubin 384 µmol/L (normal 7–31) and prothrombin time 27.2 s (normal 11.7–14). Screening for hepatitis A, B, C, E, Epstein-Barr virus, cytomegalovirus and autoimmune hepatitis was negative. Tests for anti-smooth muscle, antinuclear, and anti-liver-kidney microsomal-1 antibodies were negative; immunoglobulin levels and ceruloplasmin levels were normal. Liver ultrasonography demonstrated a liver of normal contour with no biliary dilatation, a normal spleen size and patent vessels. Liver biopsy revealed severe portal interface hepatitis with lobular inflammation and scant plasma cells.
Her clinical condition deteriorated in the following days with prothrombin time and bilirubin rising to 56.6 s and 470 µmol/L, respectively. At follow-up after 11 days, her alanine aminotransferase level was 1,931 IU/L. She developed grade 2 hepatic encephalopathy 14 days after presentation, and was listed for a super-urgent liver transplant. Human leucocyte antigen (HLA) typing was performed as a part of preparatory investigations and showed the patient carried the HLA haplotype HLA-DRB1∗15:02-DQB1∗06:01. Following orthotopic transplantation of a deceased donor graft her explant histology revealed severe ongoing hepatitis with multi-acinar necrosis (Fig. 1A and B).
This case raised a number of important questions about the diagnosis of drug-induced liver injury and tools available for clinicians to make the best decisions for patient care:I.How is the diagnosis of drug-induced liver injury made?II.What are the risk factors, including genetic risk factors?III.What are the mechanisms of liver injury?IV.What prognostic factors can be considered?V.What are the potential therapeutic options? In this Grand Rounds article, we will explore these questions, describing the pathophysiology, diagnostic and prognostic biomarkers, and clinical management of drug-induced liver injury. We will also discuss ongoing areas of uncertainty.
Whilst vaccination for the SARS-CoV-2 virus has been successful in reducing the severity and burden of the COVID-19 pandemic, there have been recent reports of mRNA vaccines triggering autoimmune ...hepatitis in the native liver. There have been no descriptions thus far of recurrent ‘autoimmune hepatitis’ after liver transplantation in the context of SARS-CoV-2 vaccination. We describe a patient transplanted for autoimmune hepatitis who was stable for many years until they had immune-mediated flares coinciding with Pfizer-BioNTech mRNA vaccination. Intravenous steroid treatment was required to suppress histologically evident interface hepatitis. We firmly believe that mRNA vaccination was responsible for this ‘recurrence’ and that clinicians should be vigilant for this reaction in patients transplanted for autoimmune hepatitis.
IntroductionHepatotoxicity from T-cell checkpoint blockade is an increasingly common immune-related adverse event, but remains poorly characterised and can be challenging to manage. Such toxicity is ...generally considered to resemble autoimmune hepatitis, although this assumption is extrapolated from limited clinicopathological reports of anti-cytotoxic T-lymphocyte-associated protein 4-induced hepatotoxicity.MethodsHere we report, with full clinicopathological correlation, three cases of T-cell checkpoint inhibitor-induced hepatotoxicity associated with anti-programmed cell death protein 1 agents.ResultsWe find that a major feature of these cases is biliary injury, including a unique case of vanishing bile duct syndrome, and that such toxicity was poorly responsive to long-term immunosuppression (corticosteroids and mycophenolate mofetil). Any potential benefits of long-term immunosuppression in these cases were outweighed by therapy-related complications.DiscussionWe discuss potential aetiologies and risk factors for immune-mediated biliary toxicity in the context of the limited literature in this field, and provide guidance for the investigation and supportive management of affected patients.
Combined hepatocellular-cholangiocarcinoma (cHCC-ICC) is an uncommon and aggressive form of primary liver cancer. Currently, there are no international guidelines for optimal management. For ...localized tumors, radical resection represents the preferred treatment option, whereas for advanced tumors, systemic therapies recommended for intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are often selected. Emerging information from comparative cohort studies, genomic and transcriptomic data sets are starting to build a case for rationalized approaches to systemic treatment in the advanced setting specific to cHCC-ICC.
Acute liver failure as the initial presentation of Wilson’s disease is usually associated with onset in childhood, adolescence or early adulthood. Outcomes after transplantation for late-onset ...presentations, at or after 40 years, are seldom reported in the literature.
We report a case, review the literature and provide unpublished data from the UK Transplant Registry on late-onset acute liver failure in Wilson's disease.
We describe the case of a 62-year-old man presenting with acute liver failure who was successfully treated with urgent liver transplantation. We identified 7 cases presenting at age 40 years or over in the literature, for which individual outcomes were reported; 3 were treated with transplantation and 2 survived. We identified a further 8 cases listed for transplantation in the UK between 1995 and 2014; 7 were treated with transplantation and 6 survived. One patient was de-listed for unknown reasons.
Wilson's disease should be considered in older adults presenting with acute liver failure. We suggest that urgent liver transplantation has good outcomes for late-onset presentations and recommend that urgent transplantation should always be considered in Wilson's disease presenting as acute liver failure.
Wilson's disease is a rare inherited disease that causes copper accumulation in the liver and brain and usually manifests during childhood, adolescence or early adulthood. We report the case of a 62-year-old who developed acute liver failure and was successfully treated with urgent liver transplantation. We discuss the outcomes of other late-onset cases of acute liver failure due to Wilson's disease in the literature and provide additional data from the UK Transplant Registry.
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•We describe the case of a 62-year-old transplanted for acute liver failure in Wilson's disease.•Outcomes after transplantation were previously reported in 3 late-onset cases.•We describe a further 7 late-onset cases from the UK Transplant Registry.•Wilson's disease should be considered in acute liver failure presenting at any age.•Transplantation should always be considered in acute liver failure presentations.
Malignant pleural effusion is common in mesothelioma. We report a case of viscous recurrent malignant mesothelioma pleural effusion. The viscosity was due to the presence of hyaluronic acid and ...resulted in prolonged drainage time. The use of intrapleural hyaluronidase significantly reduced fluid viscosity and drainage duration. No adverse reactions were noted. This novel case highlights the feasibility and safety of the use of intrapleural hyaluronidase in the management of hyaluronic acid-rich viscous malignant pleural effusion.
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