"My feelings and my thoughts are my lived experience, not the numbers they show me on a piece of paper": Indigenous experiences of liver transplantation in British Columbia, Canada.

Indigenous Peoples in Canada face healthcare inequities impacting access to solid organ transplantation. The experiences of Indigenous patients during the liver transplant process, and how transplant professionals perceive challenges faced by Indigenous Peoples, has not been studied. Thirteen semi-structured qualitative interviews were conducted via telehealth with Indigenous liver transplant patients (n = 7) and transplant care providers (n = 6) across British Columbia, Canada between April 2021-May 2022. Themes were identified to inform clinical approaches and transplant care planning and validated by Indigenous health experts. Among patient participants: transplants occurred between 1992-2020; all were women; and the mean age at the time of interview was 60 years. Among transplant care provider participants: roles included nursing, social work, and surgery; 83% were women; and the median number of years in transplant care was ten. Three broad themes were identified: Indigenous strengths and resources, systemic and structural barriers, and inconsistent care and cultural safety across health professions impact Indigenous patient care during liver transplantation. This study contributes insights into systemic barriers and Indigenous resilience in the liver transplant journey. Dismantling structural barriers to early linkage to care is needed, and training for transplant clinicians on Indigenous histories, cultural protocols, and cultural safety is strongly recommended.

Efficacy and safety of semaglutide in non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease. The prevalence and disease burden of NAFLD are projected to exponentially increase resulting in significant healthcare expenditures and lower health-related quality of life. To date, there are no approved pharmacotherapies for NAFLD or non-alcoholic steatohepatitis (NASH). Semaglutide has glycemic and weight loss benefits that may be advantageous for patients with NAFLD. AIM: To investigate the efficacy and safety of semaglutide in patients with NAFLD. METHODS: MEDLINE, CENTRAL, and EMBASE were searched from inception to May 1, 2023, to identify eligible randomized controlled trials (RCTs). Meta-analysis was performed using random effects model expressing continuous outcomes as mean differences (MD) or standardized MDs (SMD), and dichotomous outcomes as odds ratios (OR) with 95% confidence intervals (CI). Statistical heterogeneity was assessed using the Cochran's Q test and I2 statistic. RESULTS: Three RCTs involving 458 patients were included. Semaglutide increased the likelihood of NASH resolution (OR: 3.18, 95%CI: 1.70, 5.95; P < 0.001), improvement in steatosis (OR: 2.83, 95%CI: 1.19, 6.71; P = 0.03), lobular inflammation (OR: 1.81, 95%CI: 1.11, 2.96; P = 0.02), and hepatocellular ballooning (OR: 2.92, 95%CI: 1.83, 4.65; P < 0.001), but not fibrosis stage (OR: 0.71, 95%CI: 0.15, 3.41; P = 0.67). Radiologically, semaglutide reduced liver stiffness (SMD: -0.48, 95%CI: -0.86, -0.11; P = 0.01) and steatosis (MD: -4.96%, 95%CI: -9.92, 0.01; P = 0.05). It also reduced alanine aminotransferase (MD: -14.06 U/L, 95%CI: -22.06, -6.07; P < 0.001) and aspartate aminotransferase (MD: -11.44 U/L, 95%CI: -17.23, -5.65; P < 0.001). Semaglutide led to improved cardiometabolic outcomes, including decreased HgA1c (MD: -0.77%, 95%CI: -1.18, -0.37; P < 0.001) and weight loss (MD: -6.53 kg, 95%CI: -11.21, -1.85; P = 0.006), but increased the occurrence of GI-related side effects (OR: 3.72, 95%CI: 1.68, 8.23; P = 0.001). Overall risk of serious adverse events was similar compared to placebo (OR: 1.40, 95%CI: 0.75, 2.62; P < 0.29). CONCLUSION: Semaglutide is effective in the treatment of NAFLD while maintaining a well-tolerated safety profile. Future studies are required to evaluate its effects on fibrosis regression and different phases of NAFLD.

COVID-19 and Liver Disease: An Evolving Landscape.

The COVID-19 pandemic has resulted in significant worldwide morbidity and mortality. In this review, we examine the intricate relationships between COVID-19 and liver diseases. While respiratory manifestations of COVID-19 are well known, its impact and consequences in patients with liver diseases remain an area of ongoing investigation. COVID-19 can induce liver injury through various mechanisms and is associated with higher mortality in individuals with preexisting chronic liver disease. Mortality increases with the severity of chronic liver disease and the level of care required. The outcomes in patients with autoimmune hepatitis remain unclear, whereas liver transplant recipients are more likely to experience symptomatic COVID-19 but have comparable outcomes to the general population. Despite suboptimal immunological response, COVID-19 vaccinations are safe and effective in liver disease, although cases of autoimmune hepatitis-like syndrome have been reported. In conclusion, COVID-19 has significant implications in liver diseases; early recognition and treatments are important for improving patient outcomes.

Review of liver transplantation candidacy and outcomes among patients who use cannabis: Is it time for a change in policy?

Background: Recreational cannabis was legalized in Canada in 2018. A controversial contraindication for liver transplantation is cannabis. There is currently no consensus regarding cannabis use in liver transplant candidates. We aim to investigate liver transplantation candidacy and outcomes among cannabis users. Methods: English peer-reviewed studies on PubMed and Google Scholar were searched on September 9, 2022, using keywords including "cannabis," "liver transplantation," and their synonyms. Titles and abstracts were screened, followed by full texts. Reference lists were reviewed. Studies that investigated liver transplantation candidacy and outcomes among cannabis users were included. Results: The proportion of patients listed for liver transplantation was significantly less among cannabis users than among non-users. Time to listing was longer for cannabis users than non-users. The incidence of delisting was similar. There is an inconsistency between transplant centres regarding transplantation candidacy for cannabis users. While only 14% of Canadian centres had a policy in place and preferred candidates to abstain or decrease cannabis use before transplantation, a third of Canadian centres rejected cannabis users. Observational studies failed to demonstrate significant differences in patient survival between pre-transplantation cannabis users and non-users. However, self-reported mental health ratings were worse in post-transplantation cannabis users than in non-users and former users. Conclusions: Current observational data do not support a link between cannabis use and poor patient survival post-transplantation. However, high-quality prospective studies are needed to better elucidate the impact of cannabis use on liver transplantation outcomes. Liver transplant candidacy should be evaluated through a multidisciplinary and comprehensive approach considering all relevant psychosocial factors.

Liver Transplant Recipients Speak Out on Public Awareness and Education Surrounding Alcohol-Related Health Effects: A Survey Study.

BACKGROUND: Compared to other recreational substances in Canada, alcohol consumption incurs the highest healthcare costs. Liver transplant recipients are unique stakeholders as members of the general public with lived experiences of liver disease. We sought to explore their perspectives on the current state of public education on alcohol-related health effects. METHODS: The most recent 400 liver transplant recipients at Vancouver General Hospital, Canada, were invited to participate in an anonymous online survey on alcohol-related health effects by mail, email, and phone. RESULTS: Of 372 contacted patients, 212 (57%) completed the survey. Most patients were between 60-79 years, 63% were male, and 69% were Caucasian. The most common liver conditions leading to transplant were viral hepatitis (33%), alcohol-related liver disease (16%), autoimmune liver disease (14%), and non-alcoholic fatty liver disease (15%). Most patients knew that alcohol leads to liver failure (85%), but fewer knew about alcohol leading to cancer (54%), heart disease (50%), and damage to other organs (58%). Most common sources of information included public media (61%), family and friends (52%), and physicians (49%), with narrative comments about learning of alcohol-related health effects after liver diagnosis. Most patients believed that public health education at a middle/high school level would have long-term efficacy (72%) compared to health warning labels (33%) and safety messaging in commercials (39%). Current public education was felt to be adequate by only 20% of patients and 73% of patients supported health warning labels. CONCLUSIONS: Liver transplant patients reported a high, but not universal, awareness of alcohol-related health effects. A majority thought that current public health efforts were inadequate; it is critical to implement public health interventions to ensure consumers are able to make an informed decision on alcohol consumption.

Isolated Hepatic Chronic Ductopenic Rejection Requiring Liver Retransplant in the Absence of Kidney Graft Rejection After Combined Liver-Kidney Transplant: A Case Report.

The liver is considered the most immunotolerant organ among all solid-organ transplants. Liver transplant recipients have a lower incidence of rejection and better outcomes after episodes of rejection, with spontaneous operational tolerance developing in up to 20%. In multiorgan transplants, a protective effect of the liver allograft on simultaneously transplanted organs from the same donor has been demonstrated. We describe an unusual case of isolated liver allograft rejection in a patient with polycystic liver and kidney disease who received a combined liver-kidney transplant from the same donor. After initial discharge from the hospital, our patient had 2 episodes of biopsy-proven late acute cellular rejections, despite higher levels of immunosuppression required for her kidney allograft, which were addressed with pulsed steroid therapy. She had no evidence of ischemic cholangiopathy on imaging. Later, a subsequent liver biopsy demonstrated features consistent with chronic ductopenic rejection. She was eventually listed for liver retransplant and has recently received a second liver transplant while continuing to have no concerns with her kidney allograft function. Examination of the explanted liver confirmed graft loss from chronic ductopenic rejection. The exact reasons why our patient developed acute graft rejection progressing to chronic end-stage rejection of the liver allograft despite not developing graft rejection in the kidney allograft from the same donor remains elusive. Our experience demonstrates that graft tolerance in multiorgan transplant recipients can be organ specific and despite the belief of "immunologic privilege," isolated liver allograft rejection can occur in multiorgan transplant, resulting in graft loss.

Outcomes of liver transplant recipients with high MELD scores: an experience from a Canadian centre.

BACKGROUND: The frequency with which patients with high Model for End-Stage Liver Disease (MELD) scores undergo liver transplantation has been increasing. Canadian literature regarding the outcomes of liver transplantation in recipients with high MELD scores is limited. The primary objective of this study was to assess patient and graft survival among recipients with high (> 35) and low (≤ 35) MELD scores. Secondary objectives were to potentially identify independent predictors of graft failure and patient mortality. METHODS: We conducted a retrospective chart review of patients undergoing liver transplantation at a single Canadian centre from 2012 to 2017. RESULTS: A total of 332 patients were included in the study: 280 patients had a MELD score of 35 or lower, and 52 had a MELD score above 35. Patients with high MELD scores had higher rates of pretransplant acute kidney injury and dialysis (p < 0.001), admission to the intensive care unit (ICU) or intubation (p < 0.001), intraoperative blood product transfusions (p < 0.001) and post-transplantation acute kidney injury and dialysis (p < 0.001), as well as longer ICU (p < 0.001) and hospital stays (p = 0.002). One- and 3-year patient survival in recipients with MELD scores of 35 or lower was 93.1% and 84.9% versus 85.0% and 80.0% in recipients with MELD scores above 35 (p = 0.37). One- and 3-year graft survival in recipients with MELD scores of 35 or lower was 91.7% and 90.9% versus 77.2% and 72.8% in recipients with MELD scores above 35 (p < 0.001). Prior liver transplant was an independent predictor of patient mortality, and no independent predictors of graft failure were identified. When MELD was replaced with D-MELD (donor age × recipient MELD), it predicted graft failure but not patient survival. CONCLUSION: No difference in patient mortality was found between MELD groups. Graft survival was significantly lower in recipients with MELD scores above 35. D-MELD may potentially be used as an adjunct in determining risk of graft failure in recipients with high MELD scores.

A Narrative Review of the Efficacy and Design of Safety Labels on Tobacco Products to Promote the Use of Safety Labels on Alcohol Products in Canada.

Alcohol is consumed by approximately three-quarters of Canadians. Alcohol causes acquired liver disease, increases the risk of cancer, has detrimental effects on mental health, and leads to adverse pregnancy outcomes. Alcohol-related morbidity and mortality are high, and urgent public health measures are warranted to prevent and control these. Tobacco safety labels have been shown in numerous studies to reduce tobacco consumption. Much can be learned from the design of tobacco safety labels in creating promising alcohol safety labels that can possibly help reduce alcohol consumption. The aim of this paper is to review the efficacy of tobacco safety labels in reducing tobacco consumption and the design of tobacco safety labels and to propose a promising design for alcohol safety labels based on our findings. English peer-reviewed papers published in western countries since 2000 were searched on PubMed and Google Scholar. Keywords and synonyms were used to search pertinent papers, which were subsequently screened by title and abstract and fully reviewed if relevant. Findings from studies comparing designs of safety labels on alcohol and tobacco products are similar. Graphics, higher emotion content, and greater size are associated with greater attention, awareness, negative emotions, intention to quit, and reduction in consumption. Mixed results are found for testimonials containing safety labels on tobacco products. It is unclear whether testimonials on alcohol safety labels reduce alcohol consumption or not. Safety labels with specific information, such as tobacco-related costs and alcohol-related cancer risks, are more effective in reducing tobacco consumption. In conclusion, preliminary alcohol safety labels show promise. Large safety labels with graphics and high emotional content appear to be most effective and may reduce alcohol consumption.

N-acetylcysteine for non-acetaminophen induced acute liver failure: A review.

The use of N-acetylcysteine (NAC) for non-acetaminophen-induced acute liver failure (NAI-ALF) has been increasing despite controversy in its efficacy. National guidelines are in disagreement for NAC use as standard of care; however, many healthcare centers continue to adopt the use of NAC outside of acetaminophen poisoning. While NAC may have multiple mechanisms of action in treatment of ALF, this has not translated to clinical benefit. Murine models have reported antioxidant and anti-inflammatory properties, as well as improvement in liver-specific microcirculation. Multiple case studies and series have reported positive outcomes of NAC treatment for ALF of various etiologies. While prospective studies suggested the benefit of NAC treatment, these studies have methodological and statistical shortcomings that affect the validity of the results. In this review, we aimed to summarize the existing literature on the efficacy of NAC for NAI-ALF including mechanism of action, case studies and series demonstrating outcomes, and prospective studies that have led to its current widespread use, along with the reported rate of adverse events.

End stage liver disease etiology & transplantation referral outcomes of major ethnic groups in British Columbia, Canada: A cohort study.

ABSTRACT: Liver disease etiology and transplantation outcomes may vary by ethnicity. We aimed to determine if disparities exist in our province.We reviewed the provincial database for liver transplant referrals. We stratified cohorts by ethnicity and analyzed disease etiology and outcomes.Four thousand nine hundred sixteen referrals included 220 South Asians, 413 Asians, 235 First Nations (Indigenous), and 2725 Caucasians. Predominant etiologies by ethnicity included alcohol (27.4%) and primary sclerosing cholangitis (PSC) (8.8%) in South Asians, hepatitis B (45.5%) and malignancy (13.9%) in Asians, primary biliary cholangitis (PBC) (33.2%) and autoimmune hepatitis (AIH) (10.8%) in First Nations, and hepatitis C (35.9%) in Caucasians. First Nations had lowest rate of transplantation (30.6%, P = .01) and highest rate of waitlist death (10.6%, P = .03). Median time from referral to transplantation (268 days) did not differ between ethnicities (P = .47). Likelihood of transplantation increased with lower body mass index (BMI) (hazard ratio [HR] 0.99, P = .03), higher model for end stage liver disease (MELD) (HR 1.02, P < .01), or fulminant liver failure (HR 9.47, P < .01). Median time from referral to ineligibility status was 170 days, and shorter time was associated with increased MELD (HR 1.01, P < .01), increased age (HR 1.01, P < .01), fulminant liver failure (HR 2.56, P < .01) or South Asian ethnicity (HR 2.54, P < .01). Competing risks analysis revealed no differences in time to transplant (P = .66) or time to ineligibility (P = .91) but confirmed increased waitlist death for First Nations (P = .04).We have noted emerging trends such as alcohol related liver disease and PSC in South Asians. First Nations have increased autoimmune liver disease, lower transplantation rates and higher waitlist deaths. These data have significance for designing ethnicity specific interventions.

Successful Liver Transplantation in a Patient With Acute COVID-19 Infection and Acute Liver Failure: A Case Report.

Current liver transplantation societies recommend recipients with active coronavirus disease 2019 (COVID-19) be deferred from transplantation for at least 2 wks, have symptom resolution and at least 1 negative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test.1 This approach does not address patients who require urgent transplantation and will otherwise die from liver failure. We report a successful orthotopic liver transplant (OLT) in a patient with active COVID-19 infection. This is only the second to be reported worldwide and the first in Canada.

Isolated Liver Rejection After Lung and Combined Kidney-Liver Transplantation: A Case Report.

Liver allografts are unique in solid organ transplantation as they are less susceptible to both acute and chronic rejection. Operational tolerance, defined as prolonged graft survival in the absence of immunosuppression, is also achieved more frequently with liver allografts. It is unknown if the presence of multiple allografts in the same individual, levels of immunosuppression, or the presence of cystic fibrosis (CF) impacts the livers ability to ward off rejection or achieve operational tolerance. We describe an unsensitized, ABO-compatible patient with CF who underwent double lung transplantation and several years later a combined liver-kidney transplant. He developed isolated late acute T-cell mediated rejection of his liver allograft despite a high level of immunosuppression (IS) required for his lung and kidney allografts. To our knowledge, this is the first case of isolated liver rejection in a patient with 3 separate organ allografts, or in a patient with CF, to be reported in the literature. This isolated liver rejection is out of keeping with typically accepted ideas about orthotopic liver tolerance.

Occult Hepatitis B Reactivation after Liver Transplant: The Role of a Novel Mutation in the Surface Antigen.

Occult hepatitis B infection is characterized by loss of hepatitis B surface antigen (HBsAg) and persistence of low levels of hepatitis B virus (HBV) replication that may or may not be detectable in plasma/serum. We present a case of HBV reactivation in a male patient who underwent orthotopic liver transplant for hepatocellular carcinoma secondary to active hepatitis C (HCV) infection. Pre-transplant, he was HBsAg-negative and hepatitis B core antibody-positive, with an undetectable HBV viral load that was incidentally found to be positive at a very low HBV viral load on the day of transplant. Post-transplant, his HBsAg remained undetectable, with an undetectable HBV viral load, until eradication of his HCV infection with direct acting antiviral agents. After eradication of HCV, there was reactivation of HBV, with a high viral load and emergence of serum HBsAg. A deep sequencing genetic analysis of his HBV both pre- and post-transplant revealed the presence of a mutation in the "a" determinant of the HBV surface antigen. The role of HBV genotype 'a' determinant mutation in HBV reactivation post-transplant is unknown and needs further examination. Our experience suggests a possible role for antiviral prophylaxis in these patients or monitoring of HBV viral loads post-transplant.

De novo hepatitis B surface antigen (HBsAg)-positive, core antibody (anti-HBc)-negative, hepatitis B virus infection post-liver transplant from an anti-HBc, HBsAg-negative donor.

Liver transplant donors and recipients are routinely screened for hepatitis B virus (HBV) infection by measuring the levels of hepatitis B surface antigen (HBsAg) and hepatitis B core (anti-HBc) antibodies. Organs are accepted from donors who are HB-negative, and increased monitoring is required for organs from donors considered at increased risk. Transplant recipients are vaccinated if there is no sign of previous infection or immunity and monitored for reactivation in case of previous HBV infection. In cases where both the donor and the recipient are HBV-negative, no antiviral prophylaxis is used post transplant. This report describes a case of an HBV-immunized, anti-HBc-negative patient who underwent an orthotopic liver transplant from an anti-HBc-negative donor. The patient did not receive post-transplant antiviral prophylaxis due to mutual anti-HBc-seronegative status. However, the recipient developed HBV infection with isolated HBsAg and persistently negative anti-HBc. Mutations in the core/pre-core regions of the HBV gene were not implicated for unique serology in this case. Immunosuppression post liver transplant is the likely etiology for isolated HBsAg seroconversion despite significantly elevated HBV DNA. Our experience suggests that HBV DNA screening of liver transplant donors and recipients, in addition to HBV DNA monitoring of recipients, may reduce the risk of transplant-associated HBV.

Medical adherence and liver transplantation: a brief review.

Liver transplantation remains the only feasible long-term treatment option for patients with end-stage liver disease. Despite significant medical and surgical advances over the decades, liver transplantation remains a complex undertaking with the need for indefinite immunosuppression and avoidance of patient behaviours that may jeopardize the allograft. Adherence (formerly called "compliance") to medical recommendations in terms of anti-rejection medications and-in the case of alcoholic liver disease, abstinence-is considered a key cornerstone to long-term allograft and patient survival. Not surprisingly, a history of habitual non-adherence is considered a contraindication to liver transplantation, especially re-transplantation. It is often assumed that non-adherence policies are "self-evidential" based on "common sense" and "expert opinion." In fact, non-adherence and its negative effects have been well studied in medicine, including in solid organ transplantation. In this review, we present the evidence that non-adherence to medical advice is clearly associated with worse medical outcomes, supporting the concept that efforts to support patient adherence post-transplant need to be optimized at all times.

Granulocyte colony stimulating factor: A potential therapeutic rescue in severe alcoholic hepatitis and decompensated cirrhosis.

Liver cirrhosis accounts for over 2 million deaths annually worldwide. A subset of these patients - those with alcoholic hepatitis and decompensated cirrhosis, have abysmal short-term survival. Liver transplant is the only intervention of proven survival benefit; however organ availability is a major limitation. It is thus imperative to assess potential benefit of experimental therapies as a bridge to transplant. Stem cell therapies have shown some promise in patients with end-stage liver disease. Of these, bone-marrow derived hematopoietic stem cells have generated the most interest. Animal as well as human data suggest biological plausibility of stem cell translocation from bone marrow to liver, giving credence to cytokine therapies based on bone marrow stimulation. Granulocyte colony stimulating factor has been the most frequently used cytokine for this purpose. This intervention has shown encouraging results in terms of safety as well as survival benefits in small clinical trials. The evidence, however, is sparse and heterogeneous. In this review we describe the biological plausibility, mechanisms of action, and clinical evidence of the use of cytokine based stem cell therapy in patients with end-stage liver disease.

Review of Clinically Relevant Drug Interactions with Next Generation Hepatitis C Direct-acting Antiviral Agents.

In this review, we examine the pharmacokinetics and clinically relevant drug interactions of the newer generation direct-acting antivirals (DAAs) for the treatment of chronic hepatitis C, specifically sofosbuvir/velpatasvir (Epclusa®), sofosbuvir/velpatasvir/voxilaprevir (Vosevi®), glecaprevir/pibrentasvir (Maviret®), and elbasvir/grazoprevir (Zepatier®). We searched MEDLINE (1948-January 2020), Embase (1964-January 2020), Google, and GoogleScholar using the terms pharmacokinetics, drug interaction, drug metabolism, sofosbuvir, velpatasvir, Epclusa, voxilaprevir, Vosevi, glecaprevir, pibrentasvir, Maviret, elbasvir, grazoprevir, and Zepatier, from inception to January 13, 2020. The search was limited to randomized controlled trials, in vitro studies, prospective and retrospective human studies, drug monographs, abstracts, and conference proceedings. All relevant published literature on pharmacokinetic and pharmacodynamic interactions involving DAAs were reviewed and the data extracted. Numerous clinically relevant drug-drug interactions (DDIs) were identified with the newer generation DAAs and commonly prescribed drugs. NS3/4A protease inhibitors are more likely to be involved in DDIs, followed by NS5A inhibitors and NS5B polymerase inhibitor. The majority of clinically relevant DDIs are predictable, according to known pharmacokinetic, pharmacodynamics, and physicochemical properties of DAAs; however, in select cases, unpredictable DDIs do occur. As expected, many drug interactions exist between newer generation DAAs and commonly prescribed medications. While the majority of clinically relevant interactions are predictable, many require therapeutic dose adjustment or careful selection of non-interacting drugs. In select cases, severe and unpredictable drug interactions can occur. Clinicians should consult hepatitis C virus pharmacotherapy experts and tertiary drug interaction resources when initiating DAA therapy in patients taking other medications.

Public awareness of acetaminophen and risks of drug induced liver injury: Results of a large outpatient clinic survey.

Acetaminophen is one of the most commonly consumed analgesics world wide. Generally perceived as a safe medication, it is the most common cause of acute liver failure in the United States with inadvertent hepatotoxicity in half of all cases. We therefore conducted a survey on the public perceptions of acetaminophen in patients attending the outpatient clinic in Vancouver, Canada. Among 928 patients who were asked, 765 completed the survey questionnaire. The majority of respondents were female (59%), Caucasian (61%), and educated beyond the secondary school level (81%). 23% reported using acetaminophen at least once a week. A significant minority were unaware of the potential liver toxicity of acetaminophen (24%), and knowledge of hepatotoxicity did not vary with education status. In terms of the medicinal composition of acetaminophen products, over half of the respondents (58%) did not know that extra strength preparations of acetaminophen contained the same drug but in a different dose. This knowledge was more prevalent among those with higher level of education (49% in graduate school educated respondents), but was still low overall. The knowledge that alcohol use with acetaminophen was more harmful was low (43%), but improved with level of education (P for trend 0.03). Among respondents who consumed alcohol regularly, 21% were consuming over 1.5 grams of acetaminophen at a time. These patients had similar harm perception to liver as patients who consumed lower doses of acetaminophen. Overall, in a large, well-educated cohort of patients, knowledge about the adverse effects of acetaminophen, the additional risks with alcohol and composition of various retailed products was suboptimal. We speculate that consumer ignorance is a significant reason why acetaminophen is a leading cause of acute liver failure.