In the example of a rat model with chronic hepatoencephalopathy (HE), changes in the organ morphology of rats affect the balance of metabolites of the tricarboxylic acid (TCA) cycle and metabolites of the glutamine-glutamate (Gln-Glu) cycle, namely α-ketoglutarate (αKG) and α-ketoglutaramate (αKGM), as well as the enzymes associated with them, ω-amidase (ωA) and glutamine transaminase (GTK). This model of rats was obtained as a result of 2-22 weeks of consumption by animals of hepatotoxin thioacetamide (TAA) added to drinking water at a concentration of 0.4 g/L. The control (n = 26) and TAA-induced (n = 55) groups of rats consisted of 11 cohorts each. The control cohorts consisted of 2-4 rats, and the TAA-induced cohorts consisted of 4-7 individuals. Every two weeks, samples of blood plasma, liver, kidney, and brain tissues were taken from the next cohort of rats (a total of 320 samples). By the end of the experiment, irreversible morphological changes were observed in the organs of rats: the weight of the animals was reduced up to ~45%, the weight of the kidneys up to 5%, the brain up to ~20%, and the weight of the liver increased up to ~20%. The analysis revealed: (i) a decrease in the activity of ωA and GTK in the tissues of the brain, kidneys, and liver of rats with chronic HE (by ~3, 40, and 65% and ~10, 60, and 70%, respectively); and (ii) the appearance of a significant imbalance in the content of metabolites of the Gln-Glu cycle, αKG, and αKGM. It is indicative that a ~1.5-12-fold increase in the level of αKG in the blood plasma and tissues of the organs of rats with chronic HE was accompanied by a synchronous, ~1.2-2.5-fold decrease in the level of αKGM. The data obtained indicate an essential involvement of the Gln-Glu cycle in the regulation of energy metabolism in rats under conditions of chronic HE. Attention is focused on the significance of the αKG/αKGM ratio, which can act as a potential marker for diagnosing the degree of HE development.

Combined oxidative phosphorylation deficiency-1 (COXPD1) resulting from a mutation in the G elongation factor mitochondrial 1 (GFM1) gene is an autosomal recessive multisystem disorder arising from a defect in the mitochondrial oxidative phosphorylation system. Death usually appears in the first weeks or years of lifespan.
We report a male patient with ventriculomegaly diagnosed in the 8th month of pregnancy. The delivery was done by caesarean section and respiratory failure occurred immediately after birth. Hypoglycemia, lactic acidosis, elevated gamma-glutamyl transferase and hepatomegaly were confirmed. The brain MRI detected hypoplasia of the cerebellar hemispheres, dilated lateral ventricles, and markedly immature brain parenchyma. Epilepsy had been present since the third month. At 5 months of age, neurological follow-up showed his head circumference to be 37 cm, with plagiocephaly, a low hairline, a short neck, axial hypotonia and he did not adopt any developmental milestones. A genetic mutation, a missense variant in the GFM1 gene, was confirmed: c.748C > T (p.Arg250Trp) was homozygous in the GFM1 gene.
To the best of our knowledge, 28 cases of COXPD1 disease caused by mutations in the GFM1 gene have been described in the literature. COXPD1 should be considered due to symptoms and signs which begin during intrauterine life or at birth. Signs of impaired energy metabolism should indicate that the disease is in the group of metabolic encephalopathies.

Hepatic encephalopathy (HE), a neuropsychiatric disorder developing in patients with severe hepatic dysfunction, has been known for more than a century. However, pathogenetic mechanisms of cerebral dysfunction associated with liver disease are still poorly understood. There is a consensus that the primary cause of HE is accumulation of ammonia in the brain as a result of impaired liver detoxification capacity or the portosystemic shunt. Current evidence suggests that ammonia toxicity is mediated by hyperactivation of glutamate receptors, mainly N-methyl-D-aspartate receptors (NMDARs), and affects brain aerobic metabolism, which provides energy for multiple specific functions and neuronal viability. Recent reports on the presence of functional NMDARs in erythrocytes and the data on the deviations of blood parameters from their normal ranges indicate impaired hemodynamics and reduced oxygen-carrying capacity of erythrocytes in most patients with HE, thus suggesting a relationship between erythrocyte damage and cerebral dysfunction. In order to understand how hyperammonemia (HA)-induced disturbances in the energy metabolism in the brain (which needs a constant supply of large amounts of oxygen in the blood) lead to encephalopathy, it is necessary to reveal ammonia-induced impairments in the energy metabolism and antioxidant defense system of erythrocytes and to explore a potential role of ammonia in reduced brain oxygenation. To identify the said missing link, the activities of antioxidant enzymes and concentrations of reduced glutathione (GSH), oxidized glutathione (GSSG), and H2O2 were measured in the erythrocytes of rats with HA that were injected with the noncompetitive NMDAR antagonist MK-801. We found that in rats with HA, ammonia was accumulated in erythrocytes (cells lacking ammonia removal enzymes), which made them more susceptible to the prooxidant environment created during oxidative stress. This effect was completely or partially inhibited by MK-801. The data obtained might help to identify the risk factors in cognitive disorders and facilitate prediction of unfavorable outcomes of hypoperfusion in patients with a blood elevated ammonia concentration.

While coronavirus disease 2019 (COVID-19) is well known to cause significant lower respiratory symptoms, recent literature has documented numerous cases of multi-systemic involvement that can present with atypical symptoms. We report a case of an 83-year-old man, recovering from abdominal aortic aneurysm repair complicated by colonic injury requiring colostomy rendering him dependent on gastrostomy tube feedings for 3 years, who was transferred from a nursing care facility to the emergency department with altered mental status, fever and jaundice. Abdominal imaging and biopsy studies eventually identified duodenitis and ampullitis complicated by a suspected Klatskin tumor leading to biliary obstruction, sepsis and hepatoencephalopathy. Polymerase chain reaction (PCR) for COVID-19 was positive. Despite the severity of the initial presentation, the patient had no respiratory symptoms or abnormal chest X-ray findings on admission and developed hypoxia late into the disease course. Thus, this case is a report of an abnormal initial COVID-19 presentation with gastrointestinal and hepatobiliary involvement leading to hepatoencephalopathy but no lung findings, highlighting the importance of investigating extrapulmonary processes in COVID-19-positive patients regardless of pulmonary symptoms.

OBJECTIVE: The purpose of this study is to investigate the long-term safety and efficacy of a small-diameter expandable transjugular intrahepatic portosystemic shunt (TIPS) in the management of portal hypertension.
METHODS: This single-center retrospective study included 28 patients (12 women and 16 men; mean age, 56.9 years) who underwent small-diameter expandable TIPS creation between 2008 and 2010 for refractory ascites (n = 15; mean [± SD] model for end-stage liver disease [MELD] score, 15.5 ± 5.3) or gastrointestinal variceal bleeding (n = 13; mean MELD score, 15.2 ± 8.4). An expandable TIPS was created by deploying a covered stent inside a balloon expandable stent. For patients with recurrent symptoms, TIPS adjustment was made by balloon expandable stent balloon dilation. The TIPS diameter was defined as the diameter of the final angioplasty balloon. TIPS patency and efficacy and the rate of post-TIPS hepatic encephalopathy were evaluated.
RESULTS: The median diameter of the initial TIPS was 8 mm in the group with variceal bleeding compared with 6 mm in the group with ascites (p = 0.003). The primary patency rate at 1 and 5 years was 90.8% and 73.3%, respectively. Eighty percent of patients with ascites required no or less-frequent large-volume paracentesis. The clinical success rate for patients with acute variceal bleeding was 92.3%. Six patients with ascites (initial TIPS diameter, 6 mm) and two patients with variceal bleeding (initial diameter, 6 mm and 8 mm) required subsequent TIPS adjustment. Of the 22 patients with no prior history of enecphalophy, seven patients (31.8%) experienced new hepatic encephalopathy within 90 days.
CONCLUSIONS: A small-diameter expandable TIPS is technically feasible and safe, with efficacy falling within the range of that of conventional TIPS. This technique offers the possibility of individualizing the degree of portal decompression.