Acute Intermittent Porphyria in an Adolescent Patient: Diagnostic and Treatment Challenges.

Acute intermittent porphyria (AIP) is a rare inherited metabolic disorder caused by decreased activity of the enzyme porphobilinogen deaminase in the heme synthesis pathway. This leads to the accumulation of toxic porphyrin precursors, such as porphobilinogen and δ-aminolevulinic acid. Clinical manifestations typically include episodic bouts of severe neurovisceral pain and autonomic dysfunction.

Identifying and Linking Patients At Risk for MASLD with Advanced Fibrosis to Care in Primary Care.

Background And Aims: Severity of fibrosis is the driver of liver-related outcomes in metabolic dysfunction-associated steatotic liver disease (MASLD), and non-invasive testing such as fibrosis-4 (FIB-4) score is utilized for risk stratification. We aimed to determine if primary care patients at risk for MASLD and advanced fibrosis were evaluated with subsequent testing. A secondary aim was to determine if at-risk patients with normal aminotransferases had advanced fibrosis.

When Is Suspected Drug-Induced Liver Injury (DILI) Not DILI? An Analysis of Unlikely Cases From the Drug-Induced Liver Injury Network.

Introduction: Diagnosis of drug-induced liver injury (DILI) is difficult. We reviewed cases in the DILI Network prospective study that were adjudicated to have liver injury due to other causes to discover pearls for improved diagnostic accuracy.

Methods: Cases were adjudicated by expert opinion and scored from 1 (definite DILI) to 5 (unlikely DILI).

Ledipasvir/Sofosbuvir Is Effective as Sole Treatment of Porphyria Cutanea Tarda with Chronic Hepatitis C.

Background And Aims: Chronic hepatitis C [CHC] is a risk factor for porphyria cutanea tarda [PCT]. To assess whether ledipasvir/sofosbuvir is effective for treating both PCT and CHC, we treated patients with CHC + PCT solely with ledipasvir/sofosbuvir and followed them for at least 1 year to assess cure of CHC and remission of PCT.

Methods: Between September 2017 and May 2020, 15 of 23 screened PCT + CHC patients were eligible and enrolled.

Telephone-Only Visits Preserved Hepatocellular Cancer Screening Rates in Patients with Cirrhosis Early in the COVID-19 Pandemic.

Background: The coronavirus 2019 (COVID-19) pandemic required an immediate and large-scale transition to telemedicine. Telemedicine includes phone visits and video visits. Studies suggest that hepatocellular cancer (HCC) screening rates fell at the beginning of the COVID-19 pandemic.

Management of Decompensated Cirrhosis in the Surgical ICU: an American Association for the Surgery of Trauma Critical Care Committee Clinical Consensus Document.

Management of decompensated cirrhosis (DC) can be challenging for the surgical intensivist. Management of DC is often complicated by ascites, coagulopathy, hepatic encephalopathy, gastrointestinal bleeding, hepatorenal syndrome, and difficulty assessing volume status. This Clinical Consensus Document created by the American Association for the Surgery of Trauma Critical Care Committee reviews practical clinical questions about the critical care management of patients with DC to facilitate best practices by the bedside provider.

Depression screening in patients with vascular disease.

Objectives: Major depression is associated with increased morbidity and mortality in vascular surgery patients. The US Preventive Services Task Force and American Heart Association recommend routine depression screening for adults, especially those with cardiovascular disease. Since routine depression screening has not been implemented in most vascular surgery clinics across the nation, we sought to determine the feasibility of depression screening and understand the prevalence and predictors of depression in patients presenting to a single institution's vascular surgery clinic over a 4 month period.

Cu-Induced self-assembly and amyloid formation of a cyclic D,L-α-peptide: structure and function.

In a wide spectrum of neurodegenerative diseases, self-assembly of pathogenic proteins to cytotoxic intermediates is accelerated by the presence of metal ions such as Cu. Only low concentrations of these early transient oligomeric intermediates are present in a mixture of species during fibril formation, and hence information on the extent of structuring of these oligomers is still largely unknown. Here, we investigate dimers as the first intermediates in the Cu-driven aggregation of a cyclic D,L-α-peptide architecture.

Current state of endohepatology: Diagnosis and treatment of portal hypertension and its complications with endoscopic ultrasound.

The diagnosis and management of cirrhosis and portal hypertension (PH) with its complications including variceal hemorrhage, ascites, and hepatic encephalopathy continues to evolve. Although there are established "standards of care" in liver biopsy and measurement of PH, gastric varices remain an area without a universally accepted therapeutic approach. The concept of "Endo Hepatology" has been used to describe of the applications of endoscopic ultrasound (EUS) to these challenges.

Porphyric neuropathy.

Acute hepatic porphyrias are inherited metabolic disorders that may present with polyneuropathy, which if not diagnosed early can lead to quadriparesis, respiratory weakness, and death. Porphyric neuropathy is an acute to subacute motor predominant axonal neuropathy with a predilection for the upper extremities and usually preceded by a predominantly parasympathetic autonomic neuropathy. The rapid progression and associated dysautonomia mimic Guillain-Barré syndrome but are distinguished by the absence of cerebrospinal fluid albuminocytologic dissociation, progression beyond 4 wk, and associated abdominal pain.

Toward a Test Protocol for Surface Decontamination Using a Mobile Whole-room UVGI Device.

Mobile whole-room UVGI devices are used in healthcare settings to control surface-borne pathogens. Unfortunately, no standard method comparing the efficacy of these devices is available. We accessed the effect of shadows on UVC 254 nm inactivation.

Givosiran to treat acute porphyria.

Porphyrias are a family of rare diseases chiefly due to inborn errors of heme biosynthesis. The porphyrias are generally characterized either by the main site of overproduction of heme precursors (hepatic or erythropoietic) or the main clinical manifestations (acute or cutaneous). The regulation of 5- (or δ)-aminolevulinic acid synthase 1 (ALAS1) plays a key role in the pathway of normal hepatic heme synthesis, providing insight into the pathophysiologic mechanisms and potential therapeutic targets for the treatment of the porphyrias.

Pilot study of mitochondrial bioenergetics in subjects with acute porphyrias.

Background And Aims: The acute porphyrias are characterized by defects in heme synthesis, particularly in the liver. In some affected patients, there occurs a critical deficiency in a regulatory heme pool within hepatocytes that leads to up-regulation of 5-aminolevulinic acid [ALA] synthase-1, which is the first and normally rate-controlling enzyme in the pathway. In earlier work, we described defects in mitochondrial functions in cultured skin fibroblasts from patients with acute intermittent porphyria [AIP].

Pathogenesis and clinical features of the acute hepatic porphyrias (AHPs).

The acute hepatic porphyrias include four disorders: acute intermittent porphyria [AIP], hereditary coproporphyria [HCP], variegate porphyria [VP], and the rare porphyria due to severe deficiency of ALA dehydratase [ADP]. In the USA, AIP is the most severe and most often symptomatic. AIP, HCP, and VP are due to autosomal dominant genetic abnormalities, in which missense, nonsense, or other mutations of genes of normal hepatic heme biosynthesis, in concert with other environmental, nutritional, hormonal and genetic factors, may lead to a critical deficiency of heme, the end-product of the pathway, in a small but critical 'regulatory pool' within hepatocytes.