Elevated Liver Enzymes in Patients with COVID-19: Look, but Not Too Hard

Coronavirus Disease 2019 (COVID-19), due to infection with the virus termed SARS-CoV-2, has complicated the evaluation of elevated liver enzymes. Elevated liver enzymes occur in a median of 15% [1] and up to 58% [2] of patients with COVID-19. Though the most common patterns of liver enzyme abnormalities in patients with SARS-CoV-2 include elevated aminotransferases, with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) typically 1–2 times the upper limit of normal [2], the prognostic significance of abnormal liver biochemistries remains uncertain. There are many potential contributing etiologies to elevated liver enzymes in patients with SARS-CoV-2 including direct liver injury, associated inflammatory responses, congestive hepatopathy, hepatic ischemia, drug-induced liver injury (DILI), and muscle breakdown [3, 4]. In one meta-analysis, an estimated 3% of patients had recognized chronic liver disease at the time of COVID-19 infection [5]. As a result, consultations for abnormal liver biochemistries in patients with COVID-19 are likely common and difficult to resolve. Clarifying a diagnosis is further complicated by the desire to limit exposure of staff assisting with or performing diagnostic testing (e.g., abdominal ultrasound or liver biopsy). In this context, there is need for more information on how best to evaluate these patients

Paracentesis is Associated with Reduced Mortality in Patients Hospitalized with Cirrhosis and Ascites

Diagnostic paracentesis is recommended for patients with cirrhosis admitted to the hospital for ascites or encephalopathy. However, it is not known if clinicians in the United States adhere to this recommendation; a relationship between paracentesis and clinical outcome has not been reported. We analyzed a US database to determine the frequency of paracentesis and its association with mortality. Methods The 2009 Nationwide Inpatient Sample (which contains data from approximately 8 million hospital discharges each year) was used to identify patients with cirrhosis and ascites admitted with a primary diagnosis of ascites or encephalopathy. In-hospital mortality, length of stay, and hospital charges were compared for those who did and did not undergo paracentesis. Outcomes were compared for those who received an early paracentesis (within 1 day of admission) and those who received one later. Results Of 17,711 eligible admissions, only 61% underwent paracentesis. In-hospital mortality was reduced by 24% among patients who underwent paracentesis (6.5% vs 8.5%, adjusted odds ratio [OR], 0.55; 95% confidence interval [CI], 0.41–0.74). Most paracenteses (66%) occurred ≤1 day after admission. In-hospital mortality was lower among patients who received early paracentesis than those who received it later (5.7% vs 8.1%; P=.049), although this difference was not significant after adjustment for confounders (OR, 1.26; 95% CI, 0.78–2.02). Among patients who underwent paracentesis, the mean hospital stay was 14% longer, and hospital charges were 29% greater than for patients that did not receive the procedure. Conclusions Paracentesis is underused for patients admitted to the hospital with ascites; the procedure is associated with increased short-term survival. These data support practice guidelines derived from expert opinion. Studies are needed to identify barriers to guideline adherence

Maximizing Opportunities and Avoiding Mistakes in Triple Therapy for Hepatitis C Virus

Recently developed drugs and innovative strategies for the treatment of chronic infection with genotype 1 hepatitis C virus (HCV) have become the standard of care. The protease inhibitors telaprevir (Incivek) and boceprevir (Victrelis) are the first direct-acting antiviral (DAA) agents approved, and many more are being developed. These drugs substantially increased rates of sustained virologic response in treatment-naïve and -experienced patients, in conjunction with peginterferon and ribavirin (triple therapy), in phase 3 trials. The efficacy of triple therapy depends on appropriate selection of patients, although the population of patients that receive triple therapy could be expanded as the risk/benefit ratio improves. Attention to details that reflect the standard of care, such as appropriate dosing, anticipation of adverse effects, and strict adherence to stopping rules, will insure the success of these drugs and lead the way for new combination therapies

Persistent Portosystemic Shunts After Liver Transplantation Causing Episodic Hepatic Encephalopathy

We describe two cases of post liver transplant encephalopathy caused by persistent portosystemic shunts despite good graft function. Such recurrence of encephalopathy due to persistent shunting has not been reported in the deceased donor liver transplant literature. Our patients had episodic hepatic encephalopathy concordant with elevated serum ammonia levels due to well documented persistent portosystemic shunts. In one of our cases, the shunt was obliterated via coil embolization. This patient's encephalopathy resolved completely and has not recurred over seven months of follow up. The second patient has declined an intervention, but has remained symptom free on maintenance lactulose and rifaximin

Detective Work in Drug-Induced Liver Injury: Sometimes It Is All About Interviewing the Right Witness

Diagnosing drug-induced liver injury (DILI) relies on history as there are no definitive diagnostic tests. We report four cases where DILI was missed or the drug misidentified when physicians relied solely on patient history

Predicting Liver Transplant Capacity Using Discrete Event Simulation

The number of liver transplants (LTs) performed in the US increased until 2006 but has since declined despite an ongoing increase in demand. This decline may be due in part to decreased donor liver quality and increasing discard of poor-quality livers. We constructed a discrete event simulation (DES) model informed by current donor characteristics to predict future LT trends through the year 2030. The data source for our model is the United Network for Organ Sharing database, which contains patient-level information on all organ transplants performed in the US. Previous analysis showed that liver discard is increasing and that discarded organs are more often from donors who are older, are obese, have diabetes, and donated after cardiac death. Given that the prevalence of these factors is increasing, the DES model quantifies the reduction in the number of LTs performed through 2030. In addition, the model estimatesthe total number of future donors needed to maintain the current volume of LTs and the effect of a hypothetical scenario of improved reperfusion technology.We also forecast the number of patients on the waiting list and compare this with the estimated number of LTs to illustrate the impact that decreased LTs will have on patients needing transplants. By altering assumptions about the future donor pool, this model can be used to develop policy interventions to prevent a further decline in this lifesaving therapy. To our knowledge, there are no similar predictive models of future LT use based on epidemiological trends

Disparities between research attention and burden in liver diseases: implications on uneven advances in pharmacological therapies in Europe and the USA

Effective oral therapies for hepatitis B and C have recently been developed, while there are no approved pharmacological therapies for alcoholic and non-alcoholic fatty liver diseases (ALD and NAFLD). We hypothesise that fewer advances in fatty liver diseases could be related to disparities in research attention

Letter: are opioid prescriptions associated with hepatic encephalopathy in patients with compensated cirrhosis? Authors’ reply

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154393/1/apt15669.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154393/2/apt15669_am.pd

Opioid prescriptions are associated with hepatic encephalopathy in a national cohort of patients with compensated cirrhosis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154367/1/apt15639_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154367/2/apt15639.pd

Trends in Characteristics of Patients Listed for Liver Transplantation Will Lead to Higher Rates of Waitlist Removal Due to Clinical Deterioration

BACKGROUND: Changes in the epidemiology of end-stage liver disease may lead to increased risk of dropout from the liver transplant waitlist. Anticipating the future of liver transplant waitlist characteristics is vital when considering organ allocation policy. METHODS: We performed a discrete event simulation to forecast patient characteristics and rate of waitlist dropout. Estimates were simulated from 2015 to 2025. The model was informed by data from the Organ Procurement and Transplant Network, 2003 to 2014. National data are estimated along with forecasts for 2 regions. RESULTS: Nonalcoholic steatohepatitis will increase from 18% of waitlist additions to 22% by 2025. Hepatitis C will fall from 30% to 21%. Listings over age 60 years will increase from 36% to 48%. The hazard of dropout will increase from 41% to 46% nationally. Wait times for transplant for patients listed with a Model for End-Stage Liver Disease (MELD) between 22 and 27 will double. Region 5, which transplants at relatively higher MELD scores, will experience an increase from 53% to 64% waitlist dropout. Region 11, which transplants at lower MELD scores, will have an increase in waitlist dropout from 30% to 44%. CONCLUSIONS: The liver transplant waitlist size will remain static over the next decade due to patient dropout. Liver transplant candidates will be older, more likely to have nonalcoholic steatohepatitis and will wait for transplantation longer even when listed at a competitive MELD score. There will continue to be significant heterogeneity among transplant regions where some patients will be more likely to drop out of the waitlist than receive a transplant