Gastric intestinal metaplasia and gastric cancer prevention: Watchful waiting.

Gastric intestinal metaplasia (GIM), a common histologic finding, is associated with increased risk of gastric cancer, and GIM associated with Helicobacter pylori infection is classified as an environmental metaplastic atrophic gastritis. Patients may be asymptomatic or present with various dyspeptic symptoms. Autoimmune metaplastic atrophic gastritis is a less common but important cause of chronic gastritis. The Correa cascade describes the evolution of precancerous mucosal changes that lead to development of GIM, with differentiation of 2 histologic types of GIM (complete and incomplete) and the consequences of each type. The risk of progression to malignancy is higher with incomplete GIM. It is also higher for those who immigrate from regions with a high incidence of H pylori infection to areas where the incidence is low. Guidelines regarding endoscopic management of GIM vary by geographic region.

Comparison between metabolic-associated fatty liver disease and nonalcoholic fatty liver disease: From nomenclature to clinical outcomes.

As a result of the obesity epidemic, Nonalcoholic fatty liver disease (NAFLD) and its complications have increased among millions of people. Consequently, a group of experts recommended changing the term NAFLD to an inclusive terminology more reflective of the underlying pathogenesis; metabolic-associated fatty liver disease (MAFLD). This new term of MAFLD has its own disease epidemiology and clinical outcomes prompting efforts in studying its differences from NAFLD. This article discusses the rationale behind the nomenclature change, the main differences, and its clinical implications.

Liver transplantation amidst the COVID-19 era: Our center's experience.

Coronavirus disease 2019 significantly impacted the liver transplant process worldwide. Consequently, it brought significant challenges and limitations to transplant policies and organ allocation forcing liver transplant centers to adjust their protocols to ensure maximum benefit and avoid harm to their patients. Our center, like many others, was obliged to adapt to the challenges. This paper provided an overview of the effects of coronavirus disease 2019 on liver transplantations and detailed our center's experience and efforts during this unprecedented pandemic to serve as a guide for future public health crises.

EMR and ESD: Indications, techniques and results.

Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are two well-known endoscopic resection procedures used for advance gastrointestinal lesions. As compared to standard polypectomy techniques, EMR and ESD provide wider and deeper resection margins and allow en bloc removal of lesions for more detailed pathology with curative intent for early neoplastic gastrointestinal lesions. Both procedures have their advantages and disadvantages which will be discussed in detail in this review article. Recently there have been advancements in the techniques of EMR and ESD with addition in new equipment. We will also discuss current guidelines recommending use of EMR and/or ESD in various clinical scenarios.

Selective Deposition of Candle Soot on a Cellulose Membrane for Efficient Solar Evaporation.

Owing to their natural abundance, seawater together with sunlight has a potential to meet the global challenges in terms of water scarcity and energy crisis. Herein, we demonstrate a solar vapor generator composed of an inner flame candle soot (IFCS) deposited on a cellulose filter paper (FP) prepared by a simple two-step process. The resultant IFCS/FP device exhibits a high photothermal conversion ability owing to the broadband solar absorption of the IFCS layer along with the multiple scattering of the incoming sunlight in the porous microstructure of the cellulose FP. Additionally, the low thermal conductivity of the IFCS effectively localizes the photothermally generated heat at the IFCS/FP surface, thereby significantly suppressing the conduction heat losses to the underlying bulk water. Meanwhile, the capillary action of the FP supplies an adequate amount of water to the heated surface for accelerating the evaporation process. Benefitting from the synergistic effect of these characteristics, the IFCS/FP achieves high evaporation rates of ∼1.16 and ∼4.09 kg m-2 h-1 and their corresponding efficiencies of ∼75.1 and 90.9% under one and three sun illumination, respectively. Moreover, the IFCS/FP device presents an excellent longevity owing to the persistent performance over 15 repeated cycles under one and three sun illumination. Hence, the facile fabrication, fine mechanical strength, desalination, and the salt-resistance ability of our IFCS/FP make it a suitable candidate for practical applications.

Selective Growth and Robust Valley Polarization of Bilayer 3R-MoS2.

Noncentrosymmetric transition-metal dichalcogenides, particularly their 3R polymorphs, provide a robust setting for valleytronics. Here, we report on the selective growth of monolayers and bilayers of MoS2, which were acquired from two closely but differently oriented substrates in a chemical vapor deposition reactor. It turns out that as-grown bilayers are predominantly 3R-type, not more common 2H-type, as verified by microscopic and spectroscopic characterization. As expected, the 3R bilayer showed a significantly higher valley polarization compared with the centrosymmetric 2H bilayer, which undergoes efficient interlayer scattering across contrasting valleys because of their vertical alignment of the K and K' points in momentum space. Interestingly, the 3R bilayer showed even higher valley polarization compared with the monolayer counterpart. Moreover, the 3R bilayer reasonably maintained its valley efficiency over a very wide range of excitation power density from ∼0.16 kW/cm2 to ∼0.16 MW/cm2 at both low and room temperatures. These observations are rather surprising because valley dephasing could be more efficient in the bilayer via both interlayer and intralayer scatterings, whereas only intralayer scattering is allowed in the monolayer. The improved valley polarization of the 3R bilayer can be attributed to its indirect-gap nature, where valley-polarized excitons can relax into the valley-insensitive band edge, which otherwise scatter into the contrasting valley to effectively cancel out the initial valley polarization. Our results provide a facile route for the growth of 3R-MoS2 bilayers that could be utilized as a platform for advancing valleytronics.

Highly Efficient Solar Vapor Generation via a Simple Morphological Alteration of TiO2 Films Grown on a Glassy Carbon Foam.

Effectively utilizing eco-friendly solar energy for desalination and wastewater purification has immense potential to overcome the global water crisis. Herein, we demonstrate a highly efficient solar vapor generator (SVG) developed via a simple morphological alteration, from a two-dimensional (2D) TiO2 film (TF) to one-dimensional (1D) TiO2 nanorods (TNRs) grown on a glassy carbon foam (CF). Given that evaporation is primarily a surface physical phenomenon, the 1D morphology of TNRs provides a higher evaporation surface area compared to their 2D counterpart. Additionally, the superhydrophilic nature of TNRs ensures an adequate supply of water to the evaporation surface via effective capillary action. Consequently, the 1D TNRs properly utilize photothermal heat, which results in a significant reduction in the convection heat loss. Owing to the synergistic effect of these characteristics, TNRs/CF acquires a high evaporation rate of ∼2.23 kg m-2 h-1 and an energy utilization efficiency of ∼67.1% under one sun irradiation. Moreover, the excellent stability, desalination, self-cleaning capabilities, and the facile fabrication method make TNRs/CF suitable for cost-effective, large-scale device application.

Monitoring of field-evolved resistance to flonicamid, neonicotinoid, and conventional insecticides in the Oxycarenus hyalinipennis costa.

Oxycarenus hyalinipennis Costa is a polyphagous insect pest and can develop insecticide resistance. The resistance of O. hyalinipennis to neonicotinoids (clothianidin and dinotefuran), flonicamid, and conventional insecticides; carbamates (methomyl and carbosulfon), organophosphates (chlorpyrifos and malathion), and pyrethroids (cypermethrin and zeta-cypermethrin) was evaluated. The O. hyalinipennis populations were sampled from four locations in Pakistan and performed bioassays against the insecticides by leaf dip protocol. The O. hyalinipennis' populations showed low resistance to carbosulfan (resistance ratio (RR) = 2.06-6.34) and methomyl (RR = 2.78-7.27), moderate to high resistance to chlorpyrifos (RR = 30-45), malathion (RR = 20.29-88.19), and flonicamid (RR = 14.24-46.97), in comparison with the susceptible strain. Susceptibility to low resistance against cypermethrin (RR = 1.27-2.82), zeta-cypermethrin (RR = 2.62-3.38), and clothianidin (RR = 1.74-3.40), and low to moderate resistance to dinotefuran (RR = 3.84-13.43) in the field populations, was observed compared to the susceptible strain. A rotational usage of carbamates and pyrethroids with an integrated pest management tool should be considered to deal with O. hyalinipennis' insecticide resistance.

Role of Ferromagnetic Monolayer WSe2 Flakes in the Pt/Y3Fe5O12 Bilayer Structure in the Longitudinal Spin Seebeck Effect.

The spin Seebeck effect (SSE) has attracted renewed interest as a promising phenomenon for energy harvesting systems. A noteworthy effort has been devoted to improving the SSE voltage by inserting ultrathin magnetic layers including Fe70Cu30 interlayers in Pt/Y3Fe5O12 (Pt/YIG) systems with increased spin-mixing conductance at the interfaces. Nevertheless, the responsible underlying physics associated with the role of the interlayer in Pt/YIG systems in the SSE is still unknown. In this paper, we demonstrate that with a monolayer tungsten diselenide (ML WSe2) interlayer in the Pt/YIG bilayer system, the longitudinal SSE (LSSE) voltage is significantly increased by the increased spin accumulation in the Pt layer; the spin fluctuation in ML WSe2 amplifies the spin current transmission because the in-plane-aligned WSe2 spins are coupled to thermally pumped spins under nonequilibrium magnetization conditions in the LSSE configuration at room temperature. The thermopower (VLSSE/ΔT) improves by 323% with respect to the value of the reference Pt/YIG bilayer sample in the LSSE at room temperature. In addition, the induced ferromagnetic properties of the ML WSe2 flakes on YIG increase the LSSE voltage (VLSSE) of the sample; the ferromagnetic properties are a result of the improved magnetic moment density in the ML WSe2 flakes and their two-dimensional (2D) ML nature in the LSSE under nonequilibrium magnetization conditions. The results can extend the application range of the materials in energy harvesting and provide important information on the physics of the LSSE with a transition metal dichalcogenide intermediate layer in spin transport.

Spectral, Anti-Inflammatory, Anti-Pyretic, Leishmanicidal, and Molecular Docking Studies, Against Selected Protein Targets, of a New Bisbenzylisoquinoline Alkaloid.

A new bisbenzylisoquinoline named as chondrofolinol (1) and four reported compounds (2-5) were isolated and characterized from the roots of Berberis glaucocarpa Stapf. Anti-inflammatory, anti-pyretic, and leishmanicidal studies were performed against carrageenan-induced paw edema, yeast-induced pyrexia, and the promastigotes of Leishmania tropica, respectively. The new compound significantly reduced the paw volume in carrageenan-induced paw edema and rectal temperature in yeast-induced pyrexia at 10 and 20 mg/ kg of body weight. Chondrofolinol caused almost 100% inhibition of the promastigotes of Leishmania tropica. All the compounds displayed minimal cytotoxicity against THP-1 monocytic cells. In order to ascertain the potential macromolecular targets of chondrofolinol responsible for the observed anti-inflammatory and anti-leishmanial activities, a molecular docking study was carried out on relevant protein targets of inflammation and Leishmania. Protein targets of human endoplasmic reticulum aminopeptidase 2 (ERAP2) and human matrix metalloproteinase-1 (MMP-1) for inflammation and protein targets of N-myristoyltransferase (NMT), tyrosyl-tRNA synthetase (TyrRS), and uridine diphosphate-glucose pyrophosphorylase (UGPase) for Leishmania major were selected after thorough literature search about protein targets responsible for inflammation and Leishmania major. Chondrofolinol showed excellent docking to ERAP2 and to MMP-1. The Leishmania major protein targets with the most favorable docking scores to chondrofolinol were NMT, TyrRS, and UGPase. The study indicated that bisbenzylisoquinoline and isoquinoline alkaloids possess anti-pyretic, anti-inflammatory, and anti-leishmanial properties with minimal cytotoxicity and therefore, need to be further explored for their therapeutic potential.

Risk Factors Associated With Postendoscopic Mucosal Resection Bleeding in Patients With Cirrhosis: A Retrospective Multicenter Cohort Study.

BACKGROUND AND AIM: There is limited data regarding the safety of endoscopic mucosal resection (EMR) in the cirrhotic population. Our study aimed to evaluate the safety of colonoscopic EMR in cirrhosis. MATERIALS AND METHODS: This was a retrospective review of cirrhotics who underwent colonic EMR at 8 Cleveland Clinic Centers between January 1, 2006, and December 31, 2018. Patient data including polyp details and complications occurring within 30 days of the procedure were noted. Univariable and multivariable logistic regression analyses were conducted to find risk factors for post-EMR bleeding. RESULTS: A total of 238 patients who underwent EMR were included. There were 145 males (60.9%) and the mean age was 61.9±8.6 years. Immediate and delayed bleeding, and postpolypectomy syndrome rates were 9.2%, 5.8%, and 1.3%, respectively. Significant risk factors for postpolypectomy bleeding were: increased age (P=0.001), procedure duration >37 minutes (P=0.001), antiplatelet use within 5 days (P=0.023), and lesion diameter >15 mm (P=0.004). Multivariable analysis revealed independent predictors of procedure-related bleeding: age above 65 years [odds ratio (OR) 2.14, P=0.044], antiplatelet use within 5 days (OR 2.42, P=0.047), right colon polyp (OR 3.51, P=0.001), and lesion diameter >15 mm (OR 3.22, P=0.003). CONCLUSIONS: EMR in cirrhotics has an acceptable bleeding risk. Age above 65 years, right colon polyp, polyp size >15 mm, and use of antiplatelets within 5 days are independent risk factors for bleeding.

Multiloculated Liver Abscess Caused by Fusobacterium: Role of Karius Testing in Diagnosis.

Pyogenic liver abscess can be a major diagnostic and therapeutic challenge despite advances in cutting edge technologies. A patient presented with fever, right upper quadrant pain and diarrhea. CT revealed multiple hypodensities in both lobes of liver. The largest lesion was in the left lobe of liver and was multiloculated with thick septations. The causative organism was identified to be Fusobacterium nucleatum by Karius testing. The patient was discharged on six weeks of ertapenem therapy, which resulted in complete resolution. This is the first case of liver abscess where Karius testing was used to identify microorganism. It also highlights that multiloculated and difficult to drain liver abscesses caused by highly sensitive organisms can potentially be treated by intravenous antibiotics alone in immunocompetent patients.

Colon mucosal neoplasia referred for endoscopic mucosal resection: Recurrence of adenomas and prediction of submucosal invasion.

BACKGROUND: Endoscopic mucosal resection (EMR) is an effective and minimally invasive alternative to surgery for large polyps and laterally spreading lesions. Gross morphology and surface characteristics may help predict submucosal invasion of the lesion (SMIL) during endoscopic evaluation. This is one of the largest single-center studies reporting endoscopic mucosal resection for larger (≥ 20 mm) colorectal lesions in the United States. AIM: To determine the recurrence rate of adenomas and endoscopic features that may predict submucosal invasion of colonic mucosal neoplasia. METHODS: This is a retrospective cohort study of all the patients referred for endoscopic mucosal resection for lesions ≥ 20 mm, spanning a period from January 2013 to February 2017. The main outcome measure was identifying features that may predict submucosal invasion of mucosal lesions and predict recurrence of adenomas on follow-up surveillance colonoscopy performed at 4-6 mo. RESULTS: A total of 480 patients with 500 lesions were included in the study. The median age was 68 (Inter quantile range: 14) with 52% males. The most common lesion location was ascending colon (161; 32%). Paris classification 0-IIa (Flat elevation of mucosa - 316; 63.2%); Kudo Pit Pattern IIIs (192; 38%) and Granular surface morphology (260; 52%) were most prevalent. Submucosal invasion was present in 23 (4.6%) out of 500 lesions. The independent risk factors for SMIL were Kudo Pit Pattern IIIL + IV and V (Odds ratio: 4.5; P value < 0.004) and Paris classification 0-IIc (Odds ratio: 18.2; P value < 0.01). Out of 500, 354 post-endoscopic mucosal resection scars were examined at surveillance colonoscopy. Recurrence was noted in 21.8% (77 cases). CONCLUSION: There was overall low prevalence of SMIL in our study. Kudo pit pattern (IIIL + IV and V) and Paris classification 0-IIc were the only factors identified as an independent risk factor for submucosal invasion. The independent risk factor for recurrence was adenoma size (> 40 mm). Almost all recurrences (98.8%) were treated endoscopically.

Hyperplastic Gastric Polyp Causing Upper Gastrointestinal Hemorrhage and Acute Blood Loss Anemia.

Hyperplastic polyps are the second most common type of gastric polyp in the United States with equal incidence in both genders, usually found incidentally during endoscopic examinations. It is a well-known fact that they are associated with iron-deficiency anemia due to chronic blood loss. We present a case of a 69-year-old man with a relatively small hyperplastic gastric polyp with acute upper gastrointestinal bleeding, presenting with melena and acute blood loss anemia requiring admission to intensive care unit and urgent endoscopic intervention with hot snare removal of the polyp and cautery of surrounding area with excellent hemostasis. The pathology revealed focal intestinal metaplasia and low-grade dysplasia with no evidence of malignancy. He was subsequently discharged with outpatient follow-up with gastroenterology.

Focal Active Colitis Presented With Chronic Diarrhea.

There are various etiologies of colonic injury and inflammation. The most commonly described colitides in clinical practice are associated with infection, inflammatory bowel disease, ischemia, radiation and medications. The colonic wall has a limited set of responses to different types of injury; therefore, there is overlap between many of these disorders. Focal active colitis is characterized by isolated neutrophilic cryptitis with the background mucosa displaying normal crypt architecture. This inflammatory pattern can be easily unnoticed by pathologists because on low-power examination the mucosa may have almost normal appearance. General practitioners also may not be familiar with this term, underlying etiologies, associated risk factors, course, available therapies and follow up.  We present a case of an 82-year-old female with chronic diarrhea and weight loss. She had a negative infectious workup and normal radiology series. She subsequently underwent endoscopic evaluation in lieu of persistent and debilitating symptoms which revealed nonspecific macroscopic findings with pathology noting focal active colitis. She was empirically treated with a 14-day course of Xifaxan and responded well to management with almost complete resolution of her symptoms and no recurrence on six-month follow-up.

Comparing Transcatheter Aortic Valve Replacement (AVR) With Surgical AVR in Lower Risk Patients: A Comprehensive Meta-Analysis and Systematic Review.

BACKGROUND: Transcutaneous aortic valve replacement (TAVR) is a novel percutaneous procedure for severe aortic stenosis and has been recently approved by Food and Drug Administration in lower risk patients. We performed the first ever meta-analysis and literature review of clinical trials comparing both 30-day and 1-year outcomes in lower risk patients undergoing TAVR vs. surgical aortic valve replacement (SAVR, having Society of Thoracic Surgeons score < 4% or equivalent). METHODS: Using predefined selection criteria as above, 68 articles were identified. Seven eligible articles were selected after extensive review. Primary effect outcomes were 30-day and 1-year all-cause mortality using risk ratio (RR) with significant P value of < 0.05. RESULTS: A total of 4,859 subjects were included. Risk of 30-day all-cause mortality was 40.1% less in TAVR group, RR 0.59 (95% confidence interval (CI): 0.38 - 0.92, P = 0.02) with no significant heterogeneity. Six studies except Schymik et al also reported 1-year risk. This was, however, not statistically significant with a 21% decrease in the TAVR group, RR 0.79 (95% CI: 0.57 - 1.09, P = 0.15). Six studies reported 30-day risk of secondary outcomes. The risk of 30-day stroke was 36% less in TAVR group, although this was not statistically significant, RR 0.64 (95% CI: 0.38 - 1.9, P = 0.10). The risk of acute kidney injury (AKI) stage 2 and above was 56% less in post-TAVR patients, RR 0.43 (95% CI: 0.35 - 0.54, P < 0.001) with no heterogeneity. For vascular complications, RR was high in TAVR group 4.62 (95% CI: 1.42-15.18, P = 0.01). Significant heterogeneity was demonstrated though (I2 = 81). The risks for permanent pacemaker (PPM) were also higher in the TAVR group, RR 3.30 (95% CI: 2.04 - 5.33, P < 0.001) and significant heterogeneity was observed. After removing Thyregod et al and Partner 3 trial from the analysis, heterogeneity was removed, but the RR was still high 3.21 (95% CI: 2.54 - 4.068, P < 0.001). Post-operative incidence of endocarditis among TAVR patients was low but not statistically significant. The 30-day risk for infective endocarditis was RR 0.67 (95% CI: 0.13 - 3.48, P = 0.63). The 1-year risk was similarly low but not significant, RR 0.73 (95% CI: 0.28 - 1.92, P = 0.53). CONCLUSIONS: Among low risk patients, TAVR was found to be superior in short-term all-cause mortality and 1-year stroke, a result that was statistically significant for TAVR and close to significance for stroke. TAVR patients were also less likely to have post-operative bleeding and AKI stage 2 and beyond. Post-operative incidence of endocarditis among TAVR patients was low but not statistically significant. However, the rates of PPM and vascular complications are higher in TAVR patients. The results of TAVR in low risk population are thus extremely encouraging. However, the issue of long-term valve durability in this group needs further studies. Also, caution needs to be exercised while extending the indications to extremely young patients due to lack of enough studies.

Effect of Temperature on 1H NMR Spectra, Antitrypanosomal Activity, Conformational Analysis, and Molecular Docking of Curine Derivatives from Berberis brevissima.

The ethanolic root extract of Berberis brevissima afforded a new bisbenzylisoquinoline alkaloid, 13-nitrochondrofoline (2), and two known bisbenzylisoquinoline alkaloids, chondrofoline (1) and curine (4). The acetylation of chondrofoline (1) gave O-acetylchondrofoline (3). The dimeric structures of 1 and 2 were studied through variable-temperature 1H NMR spectroscopy at 25, 40, 60, and 80 °C and conformational analysis, using density functional theory employing the M06-2X functional and the 6-31G* basis set. The in vitro antitrypanosomal activity of compounds 1, 2, 3, and 4 against Trypanosoma brucei showed significant potential with MIC values of 2.6, 2.2, 2.3, and 3.8 µM, respectively. Molecular docking evaluation of alkaloids 1, 2, 3, and 4 against known T. brucei protein targets revealed T. brucei phosphodiesterase B1 to be the preferred target. The docking energies of the alkaloids with Tb6PGL (PDB 3EB9) ranged from -88.8 to -106.0 kJ/mol and was comparable to the cocrystallized ligand, citrate (Edock = -78.3 kJ/mol). It seems reasonable that the curine alkaloids may compete with the natural substrates for these protein targets and serve as leads in designing and developing more potent and selective drugs against T. brucei.

A Rare Complication of Cardiac Ablation: Atrial-esophageal Fistula Presenting as Odynophagia.

Radiofrequency catheter ablation has been commonly used for the treatment of drug-refractory atrial fibrillation. The esophageal injury along with the development of atrial-esophageal fistula (AE fistula) is fairly rare but is a devastating complication of catheter ablation. Described in 2004 for the first time, it is the most lethal of all the complications of catheter ablation with a high mortality rate. The clinical presentation of an AE fistula is variable, however, early diagnosis and treatment can prevent a fatality. We have reported a case of an AE fistula post catheter ablation for drug-resistant atrial fibrillation, along with its treatment, diagnosis, and possible preventive measures.

Splenic injuries secondary to colonoscopy: Rare but serious complication.

BACKGROUND: Colonoscopy is a safe and routine diagnostic and therapeutic procedure for evaluation of large bowel diseases. Most common procedure related complications include bleeding and perforation but rarely a splenic Injury. AIM: To investigate the reason for colonoscopy, presentation of patient with spleen injury, types of injury, diagnosis, management and outcomes of patients. METHODS: A structured search on four databases was done and 45 articles with 68 patients were selected. The reason for colonoscopy, presentation of patient with spleen injury, types of injury, diagnosis, management and outcomes of patients were identified and analyzed using SPSS. RESULTS: The mean age of the patients was 62.7 years with 64% females. Twenty two percent had a complete splenic rupture with colonoscopy while 63% had subcapsular hematoma, spleen laceration and spleen avulsion. The most common reason for colonoscopy was screening (46%) followed by diagnostic colonoscopy (28%). Eighty seven percent of patients presented with abdominal pain. Patients with spleen rupture mostly required splenectomy (47%), while minor spleen hematomas and lacerations were managed conservatively (38%). Six percent of the patients were managed with proximal splenic artery splenic embolization and 4% were managed with laparoscopic repair. The overall mortality was 10% while 77% had complete recovery. The reason of colonoscopy against presentation specifically, abdominal pain showed no statistical significance P = 0.69. The indication of colonoscopy had no significant impact on incidence of splenic injury (P = 0.89). Majority of the patients (47%) were managed with splenectomy while the rest were managed conservatively (P = 0.04). This association was moderately strong at a cramer's V test (0.34). The Fisher exact test showed a higher mortality with spleen rupture (P = 0.028). CONCLUSION: Spleen rupture due to colonoscopy is a significant concern and is associated with high mortality. The management of the patients can be individualized based on clinical presentation.

Proprotein convertase subtilisin/Kexin type-9 (PCSK-9) inhibitors induced liver injury - a retrospective analysis.

Background: Proprotein convertase subtilisin/Kexin type 9 (PCSK-9) inhibitors induced liver dysfunction in patients with or without previous liver injury, and this is not well discussed in the previous literature. Methods: A total sample of 202 patients were retrospectively reviewed at the University of Missouri, Kansas City, from the year 2015 to 2018 based on predefined selection criteria. Inclusion criteria involved patients with dyslipidemia, with or without PCSK-9 inhibitors, liver function tests and lipid profile at baseline and at a mean of 6-month follow-up. The variables, including age, gender, and confounding factors like other medications (statin, oral antidiabetic, and antihypertensive) induced, or chronic secondary liver diseases causing liver injury were taken into consideration. Exclusion criteria included patients without dyslipidemia. Results: The mean age of the study population was 64 ± 11 years (63% males and 37% females). The lipid profile including triglyceride and cholesterol levels during 6-month follow-up visit showed a mean of 184 ± 260 and 163 ± 50 mg/dL as compared to that at baseline of 227 ± 603 and 181 ± 70 mg/dL, respectively. In terms of clinical efficacy, a 6-month follows-up showed a drop in triglyceride and cholesterol levels by 38 and 15 mg/dL, respectively. A liver function test at 6 months in patients taking PCSK-9 inhibitors showed an increase in alanine transaminase (ALT) and aspartate transaminase (AST) by 5.8 mg/dL (p = 0.037) and 6.2 mg/dL (p = 0.008), respectively, from baseline values. Conclusion: PCSK-9 inhibitors should be used cautiously with a follow-up liver function test.