Liver injury from herbals and dietary supplements in the U.S. Drug-Induced Liver Injury Network.

UNLABELLED: The Drug-Induced Liver Injury Network (DILIN) studies hepatotoxicity caused by conventional medications as well as herbals and dietary supplements (HDS). To characterize hepatotoxicity and its outcomes from HDS versus medications, patients with hepatotoxicity attributed to medications or HDS were enrolled prospectively between 2004 and 2013. The study took place among eight U.S. referral centers that are part of the DILIN. Consecutive patients with liver injury referred to a DILIN center were eligible. The final sample comprised 130 (15.5%) of all subjects enrolled (839) who were judged to have experienced liver injury caused by HDS. Hepatotoxicity caused by HDS was evaluated by expert opinion. Demographic and clinical characteristics and outcome assessments, including death and liver transplantation (LT), were ascertained. Cases were stratified and compared according to the type of agent implicated in liver injury; 45 had injury caused by bodybuilding HDS, 85 by nonbodybuilding HDS, and 709 by medications. Liver injury caused by HDS increased from 7% to 20% (P < 0.001) during the study period. Bodybuilding HDS caused prolonged jaundice (median, 91 days) in young men, but did not result in any fatalities or LT. The remaining HDS cases presented as hepatocellular injury, predominantly in middle-aged women, and, more frequently, led to death or transplantation, compared to injury from medications (13% vs. 3%; P < 0.05). CONCLUSIONS: The proportion of liver injury cases attributed to HDS in DILIN has increased significantly. Liver injury from nonbodybuilding HDS is more severe than from bodybuilding HDS or medications, as evidenced by differences in unfavorable outcomes (death and transplantation). (Hepatology 2014;60:1399-1408).

Catechins in dietary supplements and hepatotoxicity.

BACKGROUND: Many herbal dietary supplements (HDS) contain green tea extract (GTE) and its component catechins, although their presence may not always be indicated on the product label. PURPOSE: Because GTE and catechins have been implicated in human hepatotoxicity in several case reports, our objective was to determine whether catechins were present in HDS that were implicated in hepatotoxicity, even if not identified among the labeled ingredients, and whether these compounds could be associated with liver injury. METHODS: We assayed 97 HDS implicated in human hepatotoxicity for catechins. RESULTS: We found that 29 of 73 HDS (39.7%) that did not identify GTE or any of its component catechins on their label contained catechins. Among patients with confirmed hepatotoxicity, there was no statistically significant association between the presence of catechin or the dose consumed and liver injury causality score, severity, or pattern of liver injury. Catechin levels tended to be highest in products used for weight loss, although catechin concentrations were low in most products. CONCLUSIONS: Many HDS commonly contain catechins that are implicated in hepatotoxicity, although their presence may not be indicated on the product label. Although our results did not establish an association between GTE or catechins with hepatotoxicity, they highlight some of the many complexities and uncertainties that surround the attribution of drug-induced liver injury (DILI) to HDS.

Over-the-counter analgesics in cirrhotic patients: a case-control study examining the risk of hospitalization for liver-associated events.

OBJECTIVE: To assess the association between over-the-counter analgesic (OTCA) use and hospitalization for liver-associated events in cirrhotic patients. MATERIAL AND METHODS: Ninety adult cirrhotics admitted with liver-associated events and 126 non-hospitalized cirrhotic controls were enrolled prospectively into a case-control study. Standardized questionnaires were used to obtain predictor variables, including detailed 30-day OTCA use. Data were analyzed via logistic regression. RESULTS: Hepatitis C (43%), alcohol (34%), and cryptogenic (13%) were the most common etiologies of cirrhosis. OTCA use was similar between cases and controls in the 30 days prior to enrollment (34% vs. 44%; odds ratio, OR = 0.66, 95% confidence interval, CI = 0.37-1.16, p = 0.148). Adjusted analyses also found no significant association between OTCA use and hospitalization for liver-associated events (OR = 0.73, 95% CI = 0.38-1.38, p = 0.330). Furosemide (p = 0.001), lactulose (p = 0.026), and number of prior liver-associated events (p = 0.002) were positively associated with hospitalization, while propranolol showed an inverse association (p = 0.008). CONCLUSION: Our data suggest that non-excessive OTCA use is not significantly associated with hospitalization for liver-associated events.

Severe and protracted cholestasis in 44 young men taking bodybuilding supplements: assessment of genetic, clinical and chemical risk factors.

BACKGROUND: Bodybuilding supplements can cause a profound cholestatic syndrome. AIM: To describe the drug-Induced liver injury network's experience with liver injury due to bodybuilding supplements. METHODS: Liver injury pattern, severity and outcomes, potential genetic associations, and exposure to anabolic steroids by product analysis were analysed in prospectively enrolled subjects with bodybuilding supplement-induced liver injury with causality scores of probable or higher. RESULTS: Forty-four males (mean age 33 years) developed liver injury with a median latency of 73 days. Forty-one per cent presented with hepatocellular pattern of liver injury as defined by the R > 5 ([Fold elevation of ALT] ÷ [Fold elevation of Alk Phos] (mean, range = 6.4, 0.5-31.4, n = 42) despite all presenting with clinical features of cholestatic liver injury (100% with jaundice and 84% with pruritus). Liver biopsy (59% of subjects) demonstrated a mild hepatitis and profound cholestasis in most without bile duct injury, loss or fibrosis. Seventy-one per cent were hospitalised, and none died or required liver transplantation. In some, chemical analysis revealed anabolic steroid controlled substances not listed on the label. No enrichment of genetic variants associated with cholestatic syndromes was found, although mutations in ABCB11 (present in up to 20%) were significantly different than in ethnically matched controls. CONCLUSIONS: Patients with bodybuilding supplements liver injury uniformly presented with cholestatic injury, which slowly resolved. The ingested products often contained anabolic steroids not identified on the label, and no enrichment in genetic variants was found, indicating a need for additional studies.

The Incidence of Drug- and Herbal and Dietary Supplement-Induced Liver Injury: Preliminary Findings from Gastroenterologist-Based Surveillance in the Population of the State of Delaware.

BACKGROUND AND AIM: The population-based incidence rate of drug-induced liver injury (DILI) in the USA is not known. The Drug-Induced Liver Injury Network (DILIN) accrues cases of hepatotoxicity due to medications and herbal and dietary supplements (HDS) from limited geographical areas. The current analysis was an ancillary study of DILIN aimed at determining the annual incidence of DILI in the USA on a population basis, through surveillance in the state of Delaware. METHODS: At the outset of the study, there were 41 gastroenterologists in the state of Delaware and all agreed to participate in surveillance for DILI, which comprised active reporting of suspected cases to the DILIN. The gastroenterologists underwent training in the diagnosis of DILI and were provided with DILIN inclusion criteria. Only cases that met the DILIN laboratory inclusion criteria in 2014 were included in the incidence calculation, and these patients were invited to participate in the DILIN Prospective Study. The number of suspected cases that met inclusion criteria served as the numerator and the 2014 Delaware adult population as the denominator. RESULTS: During 2014, 23 patients were identified by the surveillance network, 20 of whom met DILIN laboratory inclusion criteria, leading to an incidence of 2.7 cases of DILI per 100,000 adult residents [95% confidence interval (CI) 1.5-3.9 per 100,000]. Fourteen subjects agreed to participate in the DILIN; six declined. Among enrolled cases, the mean age was 51 years, 57% were women, and 71% were white. Eight cases were attributed to antibiotics (36%) and other drugs (21%) and six to HDS (43%). The pattern of injury was hepatocellular in all HDS cases, but only 50% of conventional drug cases (p = 0.05), which more commonly presented with eosinophilia (p = 0.47) and higher alkaline phosphatase levels (p = 0.05). Half of patients were jaundiced, none developed liver failure, and all recovered without the need for transplantation. CONCLUSION: Prospective, gastroenterologist-based surveillance for suspected DILI in Delaware yielded an incidence of 2.7 cases per 100,000 adults in 2014; this is the first prospective estimate of DILI for the USA. Because surveillance was limited to subspecialists, the actual incidence of DILI is likely to be higher. These findings provide a benchmark statistic for the epidemiology of DILI in the United States, to be refined with expansion of the surveillance period.

Prevalence of HCV risk factors in Hispanic-American sub populations.

To assess the prevalence of HCV risk factors among Hispanic-American subpopulations in Philadelphia. Patients from four primary care practices in Philadelphia were enrolled. Demographics and HCV risk factors were ascertained using a self-administered questionnaire. Five hundred and three patients who identified themselves as Hispanic or Latino were included in the study. Approximately half were born in Puerto Rico or mainland US and the remaining participants were born in 19 other countries. One quarter or less of individuals born in these countries reported having a HCV risk factor. In comparison, 45% of individuals born in Puerto Rico and mainland US reported having a HCV risk factor. With each year individuals born outside the US live in the US, odds of having a risk factor increased by approximately 7% (P = 0.014). US born Hispanics are more likely to have a HCV risk factor than Hispanics born outside the US. Furthermore, the prevalence of risk factors increase among Hispanic immigrants after living in the US. These findings have a direct public health impact by providing rationale to focus HCV prevention efforts on recent immigrants.