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Background and Aims: The prevalence of nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) is increasing at an alarming rate. The role of bile acids in the development and progression of NAFLD to NASH and cirrhosis is poorly understood. This study aimed to quantify the bile acid metabolome in healthy subjects and patients with non-cirrhotic NASH under fasting conditions and after a standardized meal.Methods: Liquid chromatography tandem mass spectroscopy was used to quantify 30 serum and 16 urinary bile acids from 15 healthy volunteers and 7 patients with biopsy-confirmed NASH. Bile acid concentrations were measured at two fasting and four post-prandial time points following a high-fat meal to induce gallbladder contraction and bile acid reabsorption from the intestine.Results: Patients with NASH had significantly higher total serum bile acid concentrations than healthy subjects under fasting conditions (2.2- to 2.4-fold increase in NASH; NASH 2595-3549 µM and healthy 1171-1458 µM) and at all post-prandial time points (1.7- to 2.2-fold increase in NASH; NASH 4444-5898 µM and healthy 2634-2829 µM). These changes were driven by increased taurine- and glycine-conjugated primary and secondary bile acids. Patients with NASH exhibited greater variability in their fasting and post-prandial bile acid profile.Conclusions: Results indicate that patients with NASH have higher fasting and post-prandial exposure to bile acids, including the more hydrophobic and cytotoxic secondary species. Increased bile acid exposure may be involved in liver injury and the pathogenesis of NAFLD and NASH. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article presents two case studies related to liver transplantation. A 45- year-old woman who had an orthotopic liver transplant was discharged in 13 days from the hospital after a simple operation. She had problems with hepatic encephalopathy, ascites and peripheral edema before the transplantation. A 55-year-old male was transplanted for cryptogenic cirrhosis. The article discusses about liver transplantation and post-transplant portal hypertension.

LINKED CONTENT: This article is linked to Kim et al papers. To view these articles, visit https://doi.org/10.1111/apt.16674 and https://doi.org/10.1111/apt.16705 [ABSTRACT FROM AUTHOR]

Antibody to hepatitis C as measured by the ELISA method is common in alcoholics. The presence of antibody to C 100-3 has been associated with more advanced disease. However, few studies have investigated the clinical significance of hepatitis C infection an defined by the presence of circulating viral RNA in alcoholics. We have prospectively examined 48 consecutive alcoholic patients for the presence of antibody to hepatitis C by an ELISA for antibody to the C100-3 antigen and by the reverse transcriptase polymerase chain reaction (PCR) using nested primers for the 5′ nontranslated region of the viral RNA. Patients with liver disease were scored for disease severity by the combined clinical and laboratory index (CCLI). Overall, 12 of 48 patients (25%) were ELISA positive and eight of 48 (16%) were PCR positive. Among the 34 patients with liver disease, 10 (29%) were ELISA positive and six (18%) were PCR positive. All PCR-positive patients were also ELISA positive. There was no significant difference in the disease severity score (CCLI) or the duration of clinical disease in PCR-positive versus PCR-negative patients with liver disease. However, PCR-positive patients were significantly younger (43 ± 6 vs. 55 ± 10 yr, p = 0.001), indicating an earlier onset of severe disease in PCR-positive patients. there were no false-negative ELISA tests in either those with or those without liver disease. Among the 34 patients with liver disease, four of 10 patients with positive antibody were negative by PCR. Neither individual immunoglobulin levels (lgG, lgM, IgA) nor total globulins w ere significantly different between the ELISA-positive/PCR-negative patients and ELISA-positive/PCR-positive patients. When the entire group of 34 patients with liver disease was considered, we could not detect a significant correlation between ELISA absorbance and total globulins, and only a weak correlation between absorbance and immunoglobulin G (p = 0.49). These data ... [ABSTRACT FROM AUTHOR]

Comments on several articles about disorders and complications in human beings. Usefulness of cardiopulmonary resuscitation; Overview of the reforms needed in medical practice and education; Reactions to palmar-plantar erythrodysesthesia associated with fluorouracil.

Presents letters to the editor on various issues related to the practice of medicine in the U.S. Study of involuntary weight loss; Tax deduction for nurses; Pregnancy and Hodgkin's disease; Details on ovarian cancer.

The article discusses a study that examined the possible impact of a mix of physician specialties on outcomes in patients dually diagnosed with compensated cirrhosis and diabetes. Hospitalizations and decompensation events were analyzed. Results showed that patients with complex chronic conditions may benefit from care by both generalist and specialist physicians.

Objective: To describe hepatotoxicity due to amiodarone and dronedarone from the DILIN and the US FDA's surveillance database. Methods: Hepatotoxicity due to amiodarone and dronedarone enrolled in the U.S. Drug Induced Liver Injury Network (DILIN) from 2004 to 2020 are described. Dronedarone hepatotoxicity cases associated with liver biopsy results were obtained from the FDA Adverse Event Reporting System (FAERS) from 2009 to 2020. Results: Among DILIN's 10 amiodarone and 3 dronedarone DILIN cases, the latency for amiodarone was longer than with dronedarone (388 vs 119 days, p = 0.50) and the median ALT at DILI onset was significantly lower with amiodarone (118 vs 1191 U/L, p = 0.05). Liver biopsies in five amiodarone cases showed fibrosis, steatosis, and numerous Mallory-Denk bodies. Five patients died although only one from liver failure. One patient with dronedarone induced liver injury died of a non-liver related cause. Nine additional cases of DILI due to dronedarone requiring hospitalization were identified in the FAERS database. Three patients developed liver injury within a month of starting the medication. Two developed acute liver failure and underwent urgent liver transplant, one was evaluated for liver transplant but then recovered spontaneously, while one patient with cirrhosis died of liver related causes. Conclusion: Amiodarone hepatotoxicity resembles that seen in alcohol related liver injury, with fatty infiltration and inflammation. Dronedarone is less predictable, typically without fat and with a shorter latency of use before presentation. These differences may be explained, in part, by the differing pharmacokinetics of the two drugs leading to different mechanisms of hepatotoxicity. [ABSTRACT FROM AUTHOR]

Background & Aims It is not clear whether evidence-based recommendations for inpatient care of patients with cirrhosis are implemented widely or are effective in the community. We investigated changes in inpatient outcomes and associated features over time. Methods By using the Healthcare Cost and Utilization Project, National Inpatient Sample, we analyzed 781,515 hospitalizations of patients with cirrhosis from 2002 through 2010. We compared data with those from equal numbers of hospitalizations of patients without cirrhosis and patients with congestive heart failure (CHF), matched for age, sex, and year of discharge. The primary outcome was a change in discharge status over time. Factors associated with outcomes were analyzed by Poisson modeling. Results The mortality of patients with and without cirrhosis, and patients with CHF, decreased over time. The absolute decrease was significantly greater for patients with cirrhosis (from 9.1% to 5.4%) than for patients without cirrhosis (from 2.6% to 2.1%) or patients with CHF (from 2.5% to 1.4%) ( P < .01). However, relative decreases were similar for patients with cirrhosis (41%) and patients with CHF (44%). For patients with cirrhosis, the independent mortality risk ratio decreased steadily to 0.50 by 2010 (95% confidence interval, 0.48–0.52), despite patients’ increasing age and comorbidities. Hepatorenal syndrome, hepatocellular carcinoma, variceal bleeding, and spontaneous bacterial peritonitis were associated with a higher mortality rate, but the independent mortality risks for each decreased steadily. Sepsis was associated strongly with increased mortality, and the risk increased over time. Conclusions Among patients with cirrhosis in the United States, inpatient mortality decreased steadily from 2002 through 2010, despite increases in patient age and medical complexity. Improvements in cirrhosis care may have contributed to increases in patient survival beyond those attributable to general improvements in inpatient care. Further improvements might require an increased use of proven therapies and the development of new treatments—particularly for sepsis. [ABSTRACT FROM AUTHOR]

Background & Aims: There is no histologic classification system to determine prognoses of patients with alcoholic hepatitis (AH). We identified histologic features associated with disease severity and created a histologic scoring system to predict short-term (90-day) mortality. Methods: We analyzed data from 121 patients admitted to the Liver Unit (Hospital Clinic, Barcelona, Spain) from January 2000 to January 2008 with features of AH and developed a histologic scoring system to determine the risk of death using logistic regression. The system was tested and updated in a test set of 96 patients from 5 academic centers in the United States and Europe, and a semiquantitative scoring system called the Alcoholic Hepatitis Histologic Score (AHHS) was developed. The system was validated in an independent set of 109 patients. Interobserver agreement was evaluated by weighted κ statistical analysis. Results: The degree of fibrosis, degree of neutrophil infiltration, type of bilirubinostasis, and presence of megamitochondria were independently associated with 90-day mortality. We used these 4 parameters to develop the AHHS to identify patients with a low (0–3 points), moderate (4–5 points), or high (6–9 points) risk of death within 90 days (3%, 19%, and 51%, respectively; P < .0001). The AHHS estimated 90-day mortality in the training and test sets with an area under the receiver operating characteristic value of 0.77 (95% confidence interval, 0.71–0.83). Interrater agreement values were 0.65 for fibrosis, 0.86 for bilirubinostasis, 0.60 for neutrophil infiltration, and 0.46 for megamitochondria. Interestingly, the type of bilirubinostasis predicted the development of bacterial infections. Conclusions: We identified histologic features associated with the severity of AH and developed a patient classification system that might be used in clinical decision making. [Copyright &y& Elsevier]

Background & Aims: Diagnostic paracentesis is recommended for patients with cirrhosis who are admitted to the hospital for ascites or encephalopathy. However, it is not known whether clinicians in the United States adhere to this recommendation; a relationship between paracentesis and clinical outcome has not been reported. We analyzed a U.S. 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 who were 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, 0.55; 95% confidence interval, 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 (odds ratio, 1.26; 95% confidence interval, 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 who 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. [Copyright &y& Elsevier]

Background Non-alcoholic fatty liver disease ( NAFLD) affects 20%-30% of adults with risk factors like obesity and insulin resistance putatively acting through chronic low-grade inflammation. Because periodontitis elicits low-grade inflammation, we hypothesized that it could contribute to NAFLD occurrence. Objective To investigate epidemiologic associations between periodontitis and the incidence of NAFLD among 2,623 participants of the Study of Health in Pomerania. Methods Periodontitis at baseline was defined as the percentage of sites (0%, <30%, ≥30%) with (i) clinical attachment level ( CAL) ≥3 mm; (ii) probing pocket depth ( PD) ≥4 mm. Incident NAFLD was defined as a significant increase in liver echogenicity on ultrasound relative to the kidneys, with the diaphragm indistinct or the echogenic walls of the portal veins invisible. Results After a median 7.7 years of follow-up, 605 incident NAFLD cases occurred at a rate of 32.5 cases per 1,000 person-years. Relative to participants without CAL ≥3 mm, NAFLD incidence was elevated slightly in participants with <30% of sites affected and moderately in participants with ≥30% of sites affected (multivariable-adjusted incidence rate ratio = 1.28, 95% CI, 0.84, 1.95 and 1.60, 95% CI, 1.05-2.43), respectively. A similar dose-response relationship was not observed for PD. Conclusion History of periodontitis may be a risk factor for NAFLD. [ABSTRACT FROM AUTHOR]

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. [Copyright &y& Elsevier]

INTRODUCTION: Patients with hepatic encephalopathy (HE) suffer from significant symptoms and impaired quality of life. Improved understanding on the potential benefits of first-line HE therapies may aid patientprovider discussions regarding expected benefits of HE treatments. We aimed to perform a systematic review to assess the effects of lactulose and rifaximin on patient-reported outcomes (PROs). METHODS: We searched MEDLINE, EMBASE, and Cochrane Library databases for randomized trials or prospective cohort studies using lactulose and/or rifaximin for the management of HE and assessing changes inPRO using PRO instruments. Physician reviewers independently reviewed titles, abstracts, and full texts and extracted data independently. We performed random-effects meta-analyses to examine the effects of lactulose and rifaximin on PROs. RESULTS: We identified 16 studies representing 1,376 patients that met inclusion criteria. Most studies assessed treatment of covert HE. In patients with covert HE, lactulose significantly improved overall patientreported health-related quality of lifemeasured by the Sickness Impact Profile with an estimated pooled mean difference of 6.92 (95% confidence interval: 6.66-7.18) and showed improvements in several subscales. Conversely, rifaximin demonstrated a nonstatistically significant mean difference in the total Sickness Impact Profile of 4.76 (95% confidence interval: 24.23 to 13.76), with strong evidence of heterogeneity between these studies. Studies examining otherPROinstruments showed improvements in overall health-related quality of life, social functioning, and sleep from both lactulose and rifaximin. DISCUSSION: Patients with HE treated with lactulose or rifaximin reported improvements in important PROs. These results may inform provider-patient communication and help manage patient expectations regarding the potential benefits of HE therapies. [ABSTRACT FROM AUTHOR]

Background: Turmeric is a commonly used herbal product that has been implicated in causing liver injury. The aim of this case series is to describe the clinical, histologic, and human leukocyte antigen (HLA) associations of turmeric-associated liver injury cases enrolled the in US Drug-Induced Liver Injury Network (DILIN).Methods: All adjudicated cases enrolled in DILIN between 2004 and 2022 in which turmeric was an implicated product were reviewed. Causality was assessed using a 5-point expert opinion score. Available products were analyzed for the presence of turmeric using ultra-high-performance liquid chromatography. Genetic analyses included HLA sequencing.Results: Ten cases of turmeric-associated liver injury were found, all enrolled since 2011, and 6 since 2017. Of the 10 cases, 8 were women, 9 were White, and median age was 56 years (range 35-71). Liver injury was hepatocellular in 9 patients and mixed in 1. Liver biopsies in 4 patients showed acute hepatitis or mixed cholestatic-hepatic injury with eosinophils. Five patients were hospitalized, and 1 patient died of acute liver failure. Chemical analysis confirmed the presence of turmeric in all 7 products tested; 3 also contained piperine (black pepper). HLA typing demonstrated that 7 patients carried HLA-B*35:01, 2 of whom were homozygous, yielding an allele frequency of 0.450 compared with population controls of 0.056-0.069.Conclusion: Liver injury due to turmeric appears to be increasing in the United States, perhaps reflecting usage patterns or increased combination with black pepper. Turmeric causes potentially severe liver injury that is typically hepatocellular, with a latency of 1 to 4 months and strong linkage to HLA-B*35:01. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to a study related to the treatment of acute biliary pancreatitis by Sheung-Tat Fan and colleagues in the January 28, 2007 issue.

Introduction: Aim was to study the early impact of acuity circle‐based allocation implementation system on liver transplantation for hepatocellular carcinoma (HCC) patients. Methods: We assessed characteristics of HCC and non‐HCC deceased donor orthotopic liver transplants (OLT) in the year before (2/2019–2/2020) and after (3/2020–2/2021) introduction of the acuity circle policy using the Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) database. Results: Total OLTs reduced from 6699 in the preacuity circle era to 6660 in the postacuity circle era (−.6%); this decrease is mostly driven by a decrease in HCC transplants (1529 to 1351; −11.6%). Six out of 11 regions had a reduction in the absolute number and percentage of HCC transplants with significant reductions in regions 2 (−37.8%, p <.001) and 4 (−28.3%, p =.001). Discussion: The introduction of median model for end‐stage liver disease (MELD) at transplant minus 3 (MMaT‐3) exception points, has created differential opportunities for HCC patients, in low‐MELD as opposed to high‐MELD areas, despite having the same disease. This effect has become more prominent following the implementation of acuity circle‐based allocation system. Ongoing investigation of these trends is needed to ensure that HCC patients are not disparately disadvantaged due to their location. [ABSTRACT FROM AUTHOR]

Background & Aims Pretransplant renal failure is commonly reported to be a poor prognostic indicator affecting survival after liver transplantation ( LT). However, whether the impact of renal failure on patient outcome varies according to the aetiology of the underlying liver disease is largely unknown. Methods We investigated the association between renal failure at the time of LT and patient outcome in patients with alcoholic liver disease ( ALD) ( n = 6920), non-alcoholic steatohepatitis ( NASH) ( n = 2956) and hepatitis C ( HCV) ( n = 14 922) using the United Network for Organ Sharing ( UNOS) database between February 2002 and December 2013. A total of 24 798 transplant recipients were included. Results The presence of renal failure was more frequently seen in patients with ALD (23.95%) and NASH (23.27%) compared to patients with HCV (19.38%) ( P < 0.001). In multivariate analysis, renal failure was an independent predictor of poor survival. Renal failure showed detrimental effect on patient survival in the overall series ( HR = 1.466, P < 0.0001). Importantly, the impact of renal failure was less marked in patients with ALD ( HR = 1.31, P < 0.0001) than in patients with NASH ( HR = 1.73, P < 0.0001) or HCV ( HR = 1.52, P < 0.0001). Despite a higher model for end-stage liver disease ( MELD) score at the time of LT, ALD patients with renal failure had better long-term prognosis than non- ALD patients. Conclusions Renal failure at the time of LT conferred a lower patient and graft survival post- LT. However, renal failure has less impact on the outcome of patients with ALD than that of patients with non-alcoholic liver disease after LT. [ABSTRACT FROM AUTHOR]

Aims: Type 2 diabetes (T2D) accelerates progression of chronic liver disease to cirrhosis, yet the effects of most glucose-lowering drugs (GLDs) on cirrhosis risk in T2D are unknown. To address this gap, we compared cirrhosis risk following initiation of newer second-line GLDs vs. thiazolidinediones (TZDs), which improve histology in non-alcoholic fatty liver disease.Materials and Methods: Using the US Medicare Fee-for-Service database (2007-2015) and an active comparator, new-user design, we estimated crude incidence rates (IRs) and propensity-score adjusted hazard ratios (aHR) for incident cirrhosis, comparing newer GLDs (dipeptidyl peptidase-4 inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists (GLP1RA), and sodium-glucose co-transporter 2 inhibitors (SGLT2i)) vs. TZDs.Results: Among 239,549 total initiators, we observed 318, 151, and < 30 cirrhosis events when comparing DPP4i vs. TZD, GLP1RA vs. TZD, and SGLT2i vs. TZD, respectively. IRs ranged from 1.7 [95% CI, 0.8-3.6] to 3.6 [2.5-5.2] events per 1000 person-years. Point aHR estimates for cirrhosis were elevated among newer GLD initiators vs. TZD (DPP4i: 1.15 [0.89-1.50]; GLP1RA: 1.34 [0.82-2.20]; SGLT2i: 1.16, [0.44-3.08]), although estimates were imprecise due to short durations of drug exposure.Conclusions: We observed mildly elevated cirrhosis risk with newer GLDs vs. TZD; however, uncertainty remains due to imprecise and statistically non-significant effect estimates. [ABSTRACT FROM AUTHOR]

Background: Patients with decompensated cirrhosis have a higher risk of hospitalization, ICU admission, and death from COVID-19. The impact of demographics on these outcomes remains uncertain., Methods: The SECURE-Liver and COVID-Hep databases were utilized to evaluate disparities in COVID-19 outcomes. Patients were stratified by North American and European cohorts. Bivariate and multivariable logistic regression was performed., Results: A total of 718 cirrhosis patients with COVID-19 were evaluated. In the North American cohort, Black patients had more comorbidities (CI: 1.86 vs. 1.83, p  < 0.01), higher rates of hospitalization (77% vs. 85%, p < 0.01), ICU admission (27% vs. 40%, p  = 0.05), and death (18% vs. 28%, p  = 0.07). Hispanic patients had the lowest adverse outcome rates. In the European cohort, White patients had more comorbidities (CI; 1.63 vs. 1.31, p  = 0.02), but non-White patients had higher hospitalization rates (82% vs. 67%, p  = 0.01), ICU admissions (15% vs. 18%, p  = 0.04), and lower mortality rates (28% vs. 34%, p = 0.01)., Conclusion: Black patients in North America had higher hospitalization, ICU admission, and death rates. In the European subgroup, White patients had higher death rates than non-White patients. These disparities became statistically insignificant after adjusting for confounders, suggesting that non-liver-related comorbidities might increase the risk of adverse outcomes., Competing Interests: A. Sidney Barritt IV and Andrew Moon are consultants for TARGET RWE., (© 2024 The Author(s). JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Introduction: Hyman Zimmerman observed that hepatocellular (HC) drug-induced liver injury (DILI) with jaundice had a mortality rate of ≥ 10% (Hy Law). Hy Law does not specify the timing of liver tests nor the definition of HC DILI versus cholestatic or mixed (C/M) DILI. We aimed to assess the validity of Hy Law in the prospective DILI Network (DILIN) cohort., Methods: Drugs with ≥10 confirmed DILI cases with jaundice were analyzed. Four permutations of Hy Law were applied: R ≥ 5 using initial (1) or peak (2) alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase levels, and the Food and Drug Administration associated criteria of alanine aminotransferase or aspartate aminotransferase ≥ 3x upper limit of normal with alkaline phosphatase ≤ 2x upper limit of normal using initial (3) or peak values (4). Mortality was death or liver transplant adjudicated to be due to DILI., Results: Using initial R values, mortality was 11.1% for HC vs 2.0% for C/M ( P < 0.001); using peak R values, mortality was 10.3% vs 1.6% ( P < 0.001). Using Food and Drug Administration-associated definition, mortality was 7.9% vs 3.9% ( P = 0.04) using initial values and 7.9% vs 3.0% ( P = 0.01) using peak values. Using initial R values, drugs that frequently caused HC injury generally had mortality rates ≥ 10%, while drugs that typically caused C/M injury all had rates < 10%. Occasional agents that caused HC injury with jaundice were associated with low mortality., Discussion: Initial R values were the most reliable means of identifying Hy Law cases. There were some drugs that caused HC injury with jaundice but with mortality rates < 10%. Refinement of Hy Law is warranted., (Copyright © 2024 by The American College of Gastroenterology.)

Background:  The attribution of drug-induced liver injury (DILI) to specific herbal and dietary supplements (HDS) is confounded by inaccurate labels and undisclosed ingredients. The US Drug-Induced Liver Injury Network (DILIN) determines the attribution of injury to an agent through its structured expert opinion causality assessment process, but without the use of chemical analysis data of HDS. We aimed to determine the impact of chemical analysis of HDS products on prior causality assessment scores., Methods: Obtained samples of HDS consumed by DILIN-enrolled patients were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS). Chemical analysis data were compared to label accuracy and detect whether the product contained botanical and non-botanical compounds. A comparison of the causality scores reassessed with chemical analysis was compared with the original scores., Results: A total of 54 previously adjudicated cases with chemical analysis available were reassessed for causality with chemical analysis data; reviewers were blinded to original causality scores. Using the chemical analysis data, 37% (n = 20) of the 54 cases were scored with a higher likelihood of DILI compared with the original causality scores; 14 of the 20 (70%) moved from probable to highly likely; 52% had no change in causality score; and 11% of cases were scored as a lower likelihood of DILI., Conclusions:  Our study demonstrates that there is value in using HDS chemical analysis data in the causality assessment process for DILI. In more than a third of cases, chemical analysis of products led to an increased confidence in DILI attribution to HDS. These findings suggest that chemical analysis is an important tool in causality assessment for HDS agents, specifically in challenging situations, and further studies are needed to confirm its applicability in clinical practice., (© 2024. The Author(s).)