Living with liver disease in the era of COVID-19-the impact of the epidemic and the threat to high-risk populations.

The cardinal symptoms of severe acute respiratory syndrome coronavirus 2 infection as the pandemic began in 2020 were cough, fever, and dyspnea, thus characterizing the virus as a predominantly pulmonary disease. While it is apparent that many patients presenting acutely to the hospital with coronavirus disease 2019 (COVID-19) infection have complaints of respiratory symptoms, other vital organs and systems are also being affected. In fact, almost half of COVID-19 hospitalized patients were found to have evidence of some degree of liver injury. Incidence and severity of liver injury in patients with underlying liver disease were even greater. According to the Centers of Disease Control and Prevention, from August 1, 2020 to May 31, 2022 there have been a total of 4745738 COVID-19 hospital admissions. Considering the gravity of the COVID-19 pandemic and the incidence of liver injury in COVID-19 patients, it is imperative that we as clinicians understand the effects of the virus on the liver and conversely, the effect of underlying hepatobiliary conditions on the severity of the viral course itself. In this article, we review the spectrum of novel studies regarding COVID-19 induced liver injury, compiling data on the effects of the virus in various age and high-risk groups, especially those with preexisting liver disease, in order to obtain a comprehensive understanding of this disease process. We also provide an update of the impact of the new Omicron variant and the changing nature of COVID-19 pathogenesis.

Septic Portal Vein Thrombosis, Clinical Presentation, and Management.

Pylephlebitis, otherwise known as septic portal vein thrombosis, is an infective suppurative thrombosis of the portal vein and/or its intra-hepatic branches. It is a diagnosis that is frequently missed but easily treated with antibiotics. Therefore, it should be considered early on in any patient presenting with fever, abdominal pain, leukocytosis, and evidence of portal vein thrombosis on a CT scan. In this case report, we discuss a case of pylephlebitis as well as the etiologies, diagnosis, and treatment of septic portal vein thrombosis.

Elevated Adrenocorticotropic Hormone, Hypercortisolism, and Marked Hypernatremia.

We present a case of refractory hypernatremia in a patient with elevated adrenocorticotropic hormone (ACTH) and hypercortisolism. Cortisol's effect in tissues results in various outcomes, from maintaining blood pressure to increasing serum glucose levels. In addition, cortisol, cortisone, and aldosterone activate mineralocorticoid receptors with the same affinity; therefore, the activation of mineralocorticoid receptors by elevated cortisol levels leads to increased sodium reabsorption, increased potassium secretion, and metabolic alkalosis. Hypernatremia in our patient was initially refractory to fluid replacement but was eventually corrected with intravenous fluid and desmopressin. Overall, we suggest that hypercortisolism should be considered a differential diagnosis in hypernatremia refractory to fluids replacement.

Influenza A virus utilizes noncanonical cap-snatching to diversify its mRNA/ncRNA.

Influenza A virus (IAV) utilizes cap-snatching to obtain host capped small RNAs for priming viral mRNA synthesis, generating capped hybrid mRNAs for translation. Previous studies have been focusing on canonical cap-snatching, which occurs at the very 5' end of viral mRNAs. Here we discovered noncanonical cap-snatching, which generates capped hybrid mRNAs/noncoding RNAs mapped to the region ∼300 nucleotides (nt) upstream of each mRNA 3' end, and to the 5' region, primarily starting at the second nt, of each virion RNAs (vRNA). Like canonical cap-snatching, noncanonical cap-snatching utilizes a base-pairing between the last nt G of host capped RNAs and a nt C of template RNAs to prime RNA synthesis. However, the nt upstream of this template C is usually A/U rather than just U; prime-realignment occurs less frequently. We also demonstrate that IAV can snatch capped IAV RNAs in addition to host RNAs. Noncanonical cap-snatching likely generates novel mRNAs with start AUG encoded in viral or host RNAs. These findings expand our understanding of cap-snatching mechanisms and suggest that IAV may utilize noncanonical cap-snatching to diversify its mRNAs/ncRNAs.

A convenient strategy to clone small RNA and mRNA for high-throughput sequencing.

High-throughput sequencing has become a standard tool for analyzing RNA and DNA. This method usually needs a cDNA/DNA library ligated with specific 5' and 3' linkers. Unlike mRNA, small RNA often contains modifications including 5' cap or triphosphate and 2'-O-methyl, requiring additional processing steps before linker additions during cloning processes; due to low expression levels, it is difficult to clone small RNA with a small amount of total RNA. Here we present a new strategy to clone 5' modified or unmodified small RNA in an all-liquid-based reaction carried out in a single PCR tube with as little as 20 ng total RNA. The 7-h cloning process only needs ∼1 h of labor. Moreover, this method can also clone mRNA, simplifying the need to prepare two cloning systems for small RNA and mRNA; the barcoded PCR primers are also compatible with non-cDNA cloning applications, including the preparation of genomic libraries. Not only is our method more convenient for cloning modified RNA than available methods, but it is also more sensitive, versatile, and cost-effective. Moreover, the all-liquid-based reaction can be performed in an automated manner.