Immune checkpoint inhibitor-related liver toxicity.

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Step by Step: Managing the Complications of Cirrhosis.

According to the Centers for Disease Control and Prevention, chronic liver disease and cirrhosis is the 11th leading cause of death in the United States. Common causes of chronic liver disease include alcohol, viral hepatitis, and non-alcoholic steatohepatitis (NASH). Inflammation is a critical driver in the progression of liver disease to liver fibrosis and ultimately cirrhosis. While the severity of chronic liver disease extends over a continuum, the management is more easily differentiated between compensated and decompensated cirrhosis. In this review, we discuss pathophysiology, clinical features and management of common complications of liver cirrhosis based on literature review and the current clinical practice guidelines of the American Association for the Study of Liver Diseases (AASLD).

Impact of 360° vs 2D Videos on Engagement in Anatomy Education.

Medical education is constantly evolving, especially as students were forced to study from home during the coronavirus disease 2019 (COVID-19) pandemic, and new technologies have driven the rapid development of supplemental online educational resources. In this study, we examine if 360° videos can promote increased engagement over standard two-dimensional (2D) videos among medical students learning anatomy. We enrolled 39 fourth-year medical students to watch two four-minute videos of anatomy lab exercises in a 360° three-dimensional format using an immersive headset or in a 2D format on a laptop computer. Every two minutes, students were asked to rate their engagement from 0-100. Following the videos, they reported their degree of agreement with 14 statements related to engagement, practicality, and interest in the technology. While watching the videos, the average engagement reported by the 360° video group was higher at each time point than the engagement reported by the two-dimensional group. Further, the engagement remained high in the 360° group through the six- and eight-minute timepoints. In the post-video survey, the 360° group reported a statistically significantly higher average engagement in seven of eight measures on the assessment. A 360° video was rated as more practical and interesting than a two-dimensional video. No significant difference existed in the perceived ease of learning. Overall, the use of 360° video may improve engagement for short videos used in medical education. However, developing a better understanding of its impact on learning outcomes will be critical for determining the overall value and effectiveness of this tool.

Smartphone Apps in Graduate Medical Education Virtual Recruitment During the COVID-19 Pandemic.

The COVID-19 pandemic required a shift of graduate medical education recruitment to a virtual format. In order to share information and insight into the culture of our program with applicants, we created a smartphone app for those that were invited for an interview. By collecting the analytics of the app, we were able to follow trends in the timing of applicants downloading the app, their viewing histories, and when information was accessed. The app was mostly downloaded at the time of the interview invite or 48 h prior to the interview day. Around the interview day, applicants tended to access trainee profiles, faculty profiles, and videos about the program and community. Closer to the rank list due date, training information, the graduate medical education (GME) documents, and the diversity and wellness initiatives seemed to have more activity. This analysis from the use of a smartphone app in virtual recruitment gives insight into the use of a smartphone app by applicants, and the information that they find useful during the process.

Coronary Computed Tomography Angiography Demonstrates a High Burden of Coronary Artery Disease Despite Low-Risk Nuclear Studies in Pre-Liver Transplant Evaluation.

We investigated the presence and severity of coronary artery disease (CAD) in orthotopic liver transplantation (OLT) candidates using coronary artery calcium score (CACS) and coronary computed tomography angiography (CCTA) as compared with the prevalence of normal and abnormal single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). A total of 140 prospective OLT candidates without known CAD underwent coronary artery calcium (CAC) scans with (n = 77) or without CCTA and coronary computed tomography angiography-derived fractional flow reserve (FFRCT ; n = 57) using a dual-source computed tomography (CT) and were followed for 2.6 ± 1.4 years. Coronary plaque was quantified using the segment-involvement score (SIS) and segment stenosis score (SSS). The mean age was 59 ± 6 years, and 65.0% of patients were male. Mean Agatston CACS was 367 ± 653, and 15.0% of patients had CACSs of 0; 83.6% received a SPECT MPI, of which 95.7% were interpreted as normal/probably normal. By CCTA, 9.1% had obstructive CAD (≥70% stenosis), 67.5% had nonobstructive CAD, and 23.4% had no CAD. Nonobstructive CAD was diffuse with mean SIS 3.0 ± 2.9 and SSS 4.5 ± 5.4. Only 14 patients had high risk-findings (severe 3v CAD, n = 4, CACS >1000 n = 10) that prompted X-ray angiography in 3 patients who had undergone CCTA, resulting in revascularization of a high-risk obstruction in 1 patient who had a normal SPECT study. Patients with end-stage liver disease have a high prevalence of nonobstructive CAD by CCTA, which is undiagnosed by SPECT MPI, potentially underestimating cardiovascular risk. Deferring X-ray angiography unless high-risk CCTA findings are present is a potential strategy for avoiding unnecessary X-ray angiography.

Coagulation testing and management in liver disease patients.

PURPOSE OF REVIEW: The present article aims to provide clinicians with an overview of coagulation testing in individuals with liver disease, to discuss available procoagulants and the rationale for their use, and to provide management strategies in a variety of common clinical scenarios. RECENT FINDINGS: Clinicians and researchers are gaining an increased understanding of the shortfalls of assessing bleeding risk using traditional tests of coagulation. The use of global tests of clot formation, including viscoelastic testing and thrombin generation analysis, continues to evolve and guide the management of these patients. SUMMARY: Abnormal coagulation testing in individuals with cirrhosis leads to a variety of difficult clinical scenarios that can be challenging for practitioners. With advanced liver disease, changes in the traditional tests of hemostasis such as the international normalized ratio reflect decreased synthesis of procoagulant factors but do not capture concomitant decreases in anticoagulant factors. In this setting, transfusion thresholds targeting platelet and fibrinogen goals may provide an effective strategy to optimize clot formation. Global tests of clot formation provide practical information to clinicians and can help guide decision making, although optimal target levels have not been validated.

Success of Direct-Acting, Antiviral-Based Therapy for Chronic Hepatitis C Is Not Affected by Type 2 Diabetes.

Chronic hepatitis C virus (HCV) is a risk factor for type 2 diabetes. In the era of interferon-based HCV therapy, type 2 diabetes was associated with decreased likelihood of sustained virologic response (SVR). Preliminary studies suggest that type 2 diabetes may not reduce the efficacy of regimens involving direct-acting antiviral (DAA) medications. We aimed to determine whether preexisting type 2 diabetes is associated with a reduced rate of SVR achieved 12 weeks after treatment of HCV with DAA-based regimens.

Clinical Cirrhosis Dilemmas: Survey of Practice from the 7th International Coagulation in Liver Disease Conference.

INTRODUCTION AND AIM: Hemostatic disorders in chronic liver disease and cirrhosis show continued expansion of research efforts. However, clinical decision making is often practiced on an individual patient level as consensus guidelines are lacking. We aimed to better assess individual day-to-day clinical practice through gauging clinicians' responses to common clinical scenarios. MATERIALS AND METHODS: A series of ten clinical scenarios (seven procedural coagulation and three thrombosis management) were posed to conference attendees utilizing real-time polling software (Poll Everywhere). Responses were binomial and were submitted as "Agree" or "Disagree." Results were displayed real time following a standardized response period and an open-forum discussion ensued between conference faculty and attendees following response submission. RESULTS: Twenty conference attendees participated in the clinical scenario plenary session. In general, agreement rates were high. All but one of the ten clinical scenarios had ≥ 70% agreement. Agreement was based both on procedural risk, with greatest agreement seen for low-risk procedures (80-93%), and on peri-procedural coagulation parameters of platelet count and fibrinogen level where > 50,000µ/L and 120 mg/dL were the most agreed upon thresholds, respectively. 75-95% agreement was reached when surveying the need for anticoagulation for mesenteric vein thrombosis in liver transplant candidates; slightly less (71%) agreement was found when deciding to proceed with anticoagulation in non-liver transplant candidates with mesenteric vein thrombosis. CONCLUSIONS: While large-scale, methodologically rigorous randomized controlled trials are lacking to guide clinical decision making in patients with coagulation disorders and chronic liver disease, consensus expert opinion regarding mitigating peri-procedural bleeding risk and treatment of thrombosis appears consistent and strong.

Thrombocytopenia in Chronic Liver Disease and the Role of Thrombopoietin Agonists.

Thrombocytopenia is a common complication of chronic liver disease and creates clinical challenges for patients who need invasive procedures. Options available to increase platelet counts were previously limited to risk-laden therapies such as platelet transfusions, splenic artery embolization, and transjugular intrahepatic portosystemic shunts. Thrombopoietin (TPO) agonists can augment platelet production through TPO receptor agonism. Three oral TPO agents are currently available to increase platelet counts, and in 2018, 2 of these agents (avatrombopag and lusutrombopag) were approved by the US Food and Drug Administration for the purpose of increasing platelet counts in patients with chronic liver disease prior to an invasive procedure. This article summarizes the pathophysiology of thrombocytopenia in chronic liver disease, the clinical challenge that thrombocytopenia poses, and the trials that led to the approval of the TPO agonists. Also discussed are the clinical studies that have been the basis for expert opinions and target platelet levels for cirrhotic patients undergoing procedures. A specific platelet count has not demonstrated a decreased bleeding rate in the periprocedural period in randomized, controlled trials, and using TPO agonists is not devoid of risk. However, the newly approved agents have shown no increase in the rate of portal vein thrombosis in this population and have shown promising results for increasing platelet counts.

The Clinical Anatomy and Imaging Laboratory: Vertical Integration in the Preclerkship Curriculum.

Introduction: As medical schools implement integrated curricula, anatomy education especially has experienced increased pressure to make foundational content clinically relevant. We designed a novel type of integrative anatomy laboratory experience where students could use foundational anatomy concepts in concert with modern imaging/diagnostic techniques to enhance important clinical concepts. Methods: We selected a process called Lesson Study to develop the multidisciplinary Clinical Anatomy and Imaging Laboratory (CAIL) in the cardiovascular and gastrointestinal systems. We utilized soft-embalmed cadavers extensively for their highly realistic tissue appearance and texture, which allowed instructors and students to perform a wide array of procedures in case-based scenarios similar to practicing clinicians. We conducted field observations of participating students, focus-group discussions, and knowledge-based exams to examine efficacy of the CAIL. Results: Approximately 150 first- and second-year students participated in each of the CAIL activities on an annual basis. Most focus-group participants felt the CAIL was a great learning experience. They commented on how the lab provided relevance to anatomy knowledge and helped integrate prior classroom learning more deeply. Instructors noted that students asked more advanced, clinically relevant questions than in a typical anatomy lab. Knowledge improved significantly after the CAIL, although it is unclear if this translates to summative exams. Discussion: The CAIL creates a unique learning experience where students use prior foundational anatomy knowledge in conjunction with modern imaging and diagnostic techniques to reinforce important clinical concepts. We have continued to integrate CAIL experiences into more clinical systems in our medical school curriculum.

Ectopic varices: a potential cause of gastrointestinal bleeding in patients with portal hypertension.

A newly diagnosed 53-year-old woman with cirrhosis has repeated gastrointestinal bleeding with resulting symptomatic anaemia. She underwent routine diagnostic endoscopic evaluation without localisation of the aetiology of her bleed. Ultimately, she was found to have ectopic varices in the small bowel as a result of underlying high portal pressures. She underwent transjugular intrahepatic portosystemic shunt for portal system decompression with resolution in her bleeding.

Treatment of Type-1 Hepatorenal Syndrome with Pentoxifylline: A Randomized Placebo Controlled Clinical Trial.

INTRODUCTION: Type-1 hepatorenal syndrome (HRS-1) portends a poor prognosis in patients with cirrhosis. Currently available medical therapies are largely ineffective, save for liver transplantation. We aimed to determine if pentoxifylline (PTX) therapy in addition to the standard of care of volume expansion with albumin and vasoconstriction with midodrine and octreotide (AMO) is safe and efficacious compared to AMO in HRS-1 treatment. MATERIAL AND METHODS: Hospitalized subjects with decompensated cirrhosis and HRS-1 were enrolled. PTX or placebo was administered with AMO therapy for up to 14 days. The primary endpoint was HRS-1 resolution (serum creatinine ≤ 1.5 g/dL for > 24 h). Secondary endpoints were change in creatinine and MELD score, partial treatment response, 30-and 180-day overall and transplant free survival. RESULTS: Twelve subjects with mean age 58.9 ± 6.2 years were enrolled and randomized. Mean MELD score was 26.5 ± 7.4 and 58.3% were male. Overall cohort 30- and 180-day survival was 58.3% and 33.3% respectively. Two subjects underwent liver transplantation. HRS-1 resolution (16.7% vs. 16.7%, p = 1.000), partial treatment response (33.3% vs. 16.7%, p = 0.505), change in creatinine (+0.48 g/dL, 95% CI -0.49-1.46 vs. +0.03 g/dL, 95% CI -0.64- 0.70, p = 0.427), 30-day survival (66.6% vs. 50.0%, p = 0.558) and 180-day survival (50.0% vs. 16.7%, p = 0.221) were similar between the two groups. Serious adverse events necessitating treatment discontinuation were rare (n = 1, PTX). DISCUSSION: The addition of PTX to AMO in the treatment of HRS-1 is safe when compared to the current standard of care. Future large-scale prospective study to validate the efficacy of this treatment seems warranted.

Therapeutic options for bleeding oesophageal varices: cyanoacrylate and balloon-occluded retrograde obliteration (BRTO).

A 56-year-old male with cirrhosis presented with acute bleeding from cardiofundal gastroesophageal varices (GOV) and was treated with endoscopic cyanoacrylate glue. Glue therapy achieved stabilisation of the patient in the emergent setting. Three months later, the patient suffered rebleeding. At that time, he underwent retreatment with balloon-occluded retrograde obliteration (BRTO), with no recurrence at a follow-up of 14 months.Available treatments for bleeding GOV include methods to (a) directly obstruct the varices (endoscopic variceal ligation , sclerotherapy and cyanoacrylate glue, BRTO) or to (b) decrease portal pressure (surgical portacaval shunts; transportal intrahepatic portosystemic shunt). No precise guidelines are available regarding when to use which modality, and few centres have experience with all of them. This case report illustrates a setting in which both options of cyanoacrylate glue therapy and BRTO were used for acute gastric variceal bleeding.