An older adult patient was admitted with epigastric pain and vomiting and found to have an abdominal mass, increased cholestatic liver enzymes and markedly elevated serum lactate dehydrogenase (LDH). Imaging revealed extensive liver metastases of unknown primary but also an unusual splenic metastasis diagnosed by liver biopsy as malignant melanoma. The patient became lethargic and developed mental status changes associated with asterixis, abnormal EEG, and increased serum ammonia levels. All reversed with high-dose lactulose and had no alternative explanation other than an unusual hepatic encephalopathy secondary to portosystemic shunts bypassing the extensively metastatic liver.
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http://dx.doi.org/10.1093/qjmed/hcae176 | DOI Listing |
Nat Med
January 2025
Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Up to 50-70% of patients with liver cirrhosis develop hepatic encephalopathy (HE), which is closely related to gut microbiota dysbiosis, with an unclear mechanism. Here, by constructing gut-brain modules to assess bacterial neurotoxins from metagenomic datasets, we found that phenylalanine decarboxylase (PDC) genes, mainly from Ruminococcus gnavus, increased approximately tenfold in patients with cirrhosis and higher in patients with HE. Cirrhotic, not healthy, mice colonized with R.
View Article and Find Full Text PDFACS Chem Biol
January 2025
Harvard University, Department of Chemistry and Chemical Biology, Cambridge, Massachusetts 02138, United States.
Hyperammonemia is characterized by the accumulation of ammonia within the bloodstream upon liver injury. Left untreated, hyperammonemia contributes to conditions such as hepatic encephalopathy that have high rates of patient morbidity and mortality. Previous studies have identified gut bacterial urease, an enzyme that converts urea into ammonia, as a major contributor to systemic ammonia levels.
View Article and Find Full Text PDFHepatol Commun
December 2024
Macquarie Medicine School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, Australia.
Background: HE is a neuropsychiatric complication of liver disease characterized by systemic elevation in ammonia and proinflammatory cytokines. These neurotoxins cross the blood-brain barrier and cause neuroinflammation, which can activate the kynurenine pathway (KP). This results in dysregulated production of neuroactive KP metabolites, such as quinolinic acid, which is known to cause astrocyte and neuronal death.
View Article and Find Full Text PDFHepatology
January 2025
Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
Background Aims: In clinical practice, the reduction of porto-caval pressure gradient (PCPG) following trans-jugular intra-hepatic porto-systemic shunt (TIPS) does not always meet the recommendation of current guidance. We evaluated the impact of different degrees of PCPG reduction, measured at the end of an elective TIPS, on ascites control, recurrence of portal hypertension-related bleeding (PHRB) and survival.
Approach And Results: Cirrhotic patients receiving TIPS for refractory ascites (RA) or for the secondary prophylaxis of PHRB were consecutively enrolled.
Hepatology
January 2025
Department for Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.
Background Aims: Clinically-significant portal hypertension (CSPH) in liver cirrhosis patients can lead to refractory ascites. A transjugular-intrahepatic-portosystemic shunt (TIPS) treats CSPH but may cause overt hepatic encephalopathy (oHE). Our aim was to determine the optimal reduction of the portal pressure gradient (PPG) via TIPS to control ascites without raising oHE risk.
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