Most Individuals With Advanced Cirrhosis Have Sleep Disturbances, Which Are Associated With Poor Quality of Life.

BACKGROUND & AIMS: Sleep disturbances are common in patients with cirrhosis, but their determinants and effects on health-related quality of life are not well-understood. We investigated the prevalence of disturbed sleep in these patients, factors associated with sleep disruption, and effects on quality of life. METHODS: We performed a prospective, cross-sectional study of 193 stable ambulatory patients with cirrhosis (154 with decompensated cirrhosis). Participants completed the Pittsburgh Sleep Quality Index (to assess sleep quality), the Chronic Liver Disease Questionnaire (CLDQ), and muscle cramp questionnaires and underwent neurocognitive testing. Actigraphy was performed in a subset of patients with normal and disturbed sleep. We collected serum samples from subjects with normal and disturbed sleep and performed non-targeted metabolomic analyses. RESULTS: Of the study subjects, 157 (81%) had disturbed sleep, with Pittsburgh Sleep Quality Index scores >5. Disturbed sleep was associated with muscle cramps, daytime somnolence, and decreased quality of life on the basis of CLDQ scores. Factors independently associated with disturbed sleep in logistic regression analysis included hypoalbuminemia, opiate therapy, and muscle cramps. Disturbed sleep was independently associated with CLDQ score (correlation parameter, -36.6; 95% confidence interval, -24 to -49; P < .001) on linear regression. Disturbed sleep was associated with neurocognitive impairment and with significantly delayed bedtime and decreased total sleep time, measured by actigraphy. Disturbed sleep was associated with metabolome signatures of alterations to the intestinal microbiome and lipid, arginine, and urea cycle metabolism. CONCLUSIONS: Most patients with advanced cirrhosis (81%) have disturbed sleep. This has negative effects on quality of life and is associated with disruptions of several metabolic pathways, including metabolism by the intestinal microbiota.

Relationship between characteristics of medications and drug-induced liver disease phenotype and outcome.

BACKGROUND & AIMS: It is not known whether specific characteristics of medication are associated with type of drug-induced liver injury (DILI) or outcome. We examined the relationships among select characteristics of medications and DILI phenotype and outcome. METHODS: We analyzed 383 cases of DILI caused by a single orally administered prescription agent from the DILI Network Prospective Study with causalities of definite, highly likely, or probable. Relationship of daily dosage (≥50 mg vs ≤49 mg), preponderance of hepatic metabolism (≥50% vs <50%), or Biopharmaceutics Drug Disposition Classification System (BDDCS) class (1-4, based on solubility and metabolism of the drug) were compared with clinical characteristics and outcomes. RESULTS: Compared with cases of DILI in the ≤49 mg/day group, those associated with daily dosages ≥50 mg had shorter latency (median, 38 days vs 56 days; P = .03) and a different biochemical pattern of liver injury (P = .04); no differences in recovery, severity, or outcome were observed. Patients with DILI caused by medications with or without preponderant hepatic metabolism did not differ in clinical characteristics or outcomes. Compared with other classes of BDDCS, DILI caused by BDDCS class 1 medications had significantly longer latency (P < .001) and greater proportion of hepatocellular injury (P = .001). However, peak liver biochemical values and patients' time to recovery, disease severity, and outcomes did not differ among the 4 BDDCS classes. CONCLUSIONS: Characteristics of medications (dosage, hepatic metabolism, and solubility) are associated with features of DILI such as latency and pattern of liver injury, but not with recovery, severity, or outcome.

EVALI - E-Cigarette or Vaping Product Use-Associated Lung Injury: A Case Report.

The use of electronic cigarettes among the young adult and adolescent population has increased over the past decade. Vaping is the process of inhaling an aerosol that is produced by heating a liquid or wax containing substances, such as nicotine, cannabinoids (e.g., tetrahydrocannabinol (THC), cannabidiol), flavoring, and additives (e.g., glycerol, propylene glycol) using an e-cigarette. A multistate epidemic associated with vaping prompted the Centers for Disease Control and Prevention (CDC) to issue an official health advisory on e-cigarette or vaping product use-associated lung injury (EVALI). EVALI is a diagnosis of exclusion with no specific diagnostic test. We present a case of EVALI before the COVID-19 pandemic time in a 23-year-old immunocompetent male student with an eight-year history of vaping. He presented to the emergency department with fever, shortness of breath, tachypnea, nausea, and diarrhea. The patient had no past medical history. The patient denied illicit drug abuse or known drug allergies. The patient was admitted with a diagnosis of sepsis and pneumonia. The patient's urine drug screen was positive for cannabinoids with a history of vaping. Community-acquired pneumonia due to Legionella, Pneumococcal, Mycoplasma bacteria was ruled out. Influenza A/B, Parainfluenza, Rhino, and Adenoviruses were negative. A computed tomographyscan of the chest showed bilateral infiltrates. He was treated with high dose steroids, empiric antibiotics, high flow oxygen and managed in ICU for seven days. The patient was discharged on tapering doses of steroid and counseled to quit vaping. EVALI outbreak is strongly linked to vitamin E acetate in vaping products. EVALI is a diagnosis of exclusion with a history of vaping and responds well to steroids.

Incidence, risk factors and outcomes of de novo malignancies post liver transplantation.

Liver transplantation (LT) is associated with a 2 to 7 fold higher, age and gender adjusted, risk of de novo malignancy. The overall incidence of de novo malignancy post LT ranges from 2.2% to 26%, and 5 and 10 years incidence rates are estimated at 10% to 14.6% and 20% to 32%, respectively. The main risk factors for de novo malignancy include immunosuppression with impaired immunosurveillance, and a number of patient factors which include; age, latent oncogenic viral infections, tobacco and alcohol use history, and underlying liver disease. The most common cancers after LT are non-melanoma skin cancers, accounting for approximately 37% of de novo malignancies, with a noted increase in the ratio of squamous to basal cell cancers. While these types of skin cancer do not impact patient survival, post-transplant lymphoproliferative disorders and solid organ cancer, accounting for 25% and 48% of malignancies, are associated with increased mortality. Patients developing these types of cancer are diagnosed at more advanced stages, and their cancers behave more aggressively compared with the general population. Patients undergoing LT for primary sclerosing cholangitis (particularly with inflammatory bowel disease) and alcoholic liver disease have high rates of malignancies compared with patients undergoing LT for other indications. These populations are at particular risk for gastrointestinal and aerodigestive cancers respectively. Counseling smoking cessation, skin protection from sun exposure and routine clinical follow-up are the current approach in practice. There are no standardized surveillance protocol, but available data suggests that regimented surveillance strategies are needed and capable of yielding cancer diagnosis at earlier stages with better resulting survival. Evidence-based strategies are needed to guide optimal surveillance and safe minimization of immunosuppression.