Little is known about the incidence of drug-induced liver injury (DILI) in the general population. We investigated the incidence and the quantitative risk of DILI in a population-based cohort.
We performed a prospective study and collected data from 96 individuals diagnosed with DILI in Iceland from 2010 through 2011 (54 women; median age, 55 y). Liver injury was defined based on levels of alanine aminotransferase that were more than 3-fold the upper limit of normal and/or alkaline phosphatase levels more than 2-fold the upper limit of normal. Patients with acetaminophen toxicity were excluded. Drug history and clinical outcome were analyzed. Causality was assessed using the Roussel Uclaf Causality Assessment Method. The patients were registered in prescription databases for outpatients and inpatients.
The crude annual incidence rate of DILI was 19.1 (95% confidence interval [CI], 15.4-23.3) cases per 100,000 inhabitants. DILI was caused by a single prescription medication in 75% of cases, by dietary supplements in 16% of cases, and by multiple agents in 9% of cases. The most commonly implicated drugs were amoxicillin-clavulanate (21 of 96; 22%), diclofenac (6%), azathioprine (4%), infliximab (4%), and nitrofurantoin (4%). The median duration of therapy was 20 days (range, 8-77 days); 26 patients had jaundice (27%) and 22 patients were hospitalized (23%) for a median of 5 days (range, 2-8 days). Overall 35,252 patients received amoxicillin-clavulanate as outpatients, and DILI occurred in 1 of 2350 (43 of 100,000; 95% CI, 24-70). DILI also occurred in 1 of 9480 patients taking diclofenac (11 of 100,000; 95% CI, 4-24), 1 of 133 patients taking azathioprine (752 of 100,000; 95% CI, 205-1914), 1 of 148 patients taking infliximab (675 of 100,000; 95% CI, 184-718), and 1 of 1369 patients taking nitrofurantoin (73 of 100,000; 95% CI, 20-187).
In a population-based study in Iceland, the incidence of DILI was the highest reported to date. Amoxicillin-clavulanate was the most commonly implicated agent. The highest risk of hepatotoxicity was associated with azathioprine and infliximab, but the actual number of cases attributed to these agents was small.
Stearoyl-coenzyme A desaturase-1 (SCD1) is a key enzyme in fatty acid and energy metabolism. Increased hepatic SCD1 activity is associated with obesity and obesity-related diseases. We examined the relations of two plasma SCD activity indices (16:1n-7/16:0, 18:1n-9/18:0) with body composition, and the association of lifestyle and dietary variables with the plasma SCD indices.
This population-based, cross-sectional study of 2021 elderly (71-74 y) men and women from the Hordaland Health Study in Western Norway was conducted using a validated food frequency questionnaire, body composition measurements by dual-energy X-ray absorptiometry and determination of the plasma fatty acid profile.
In multivariate regression analyses, plasma SCD indices were positively associated with BMI and body fat (P
The transition from regular use of cyclosporine to the newer calcineurin-inhibitors, such as tacrolimus, has been suggested as a contributing factor to the "era effect" of worsening outcomes of post-transplant HCV recurrence. This retrospective medical chart review of 458 patients was undertaken to evaluate the role of immunosuppressant choice (cyclosporine vs. tacrolimus) in determining virologic response and clinical outcomes of post-liver transplant HCV infection recurrence. Our results showed that patients undergoing interferon-based treatment taking cyclosporine have significantly better odds (OR: 2.59, P = 0.043) of presenting a sustained viral response (66.7%) compared to tacrolimus (52.8%). This did not result in a significant effect on post-liver transplantation clinical events including HCV-related deaths, graft loss, fibrosing cholestatic hepatitis, hepatocellular carcinoma or graft rejection. Other variables, which showed a significant relationship with the achievement of sustained viral response included donor age (OR 0.96, P = 0.001) and HCV genotype 1 infection (OR 0.05, P
Genome-wide association studies (GWAS) have successfully identified several loci associated with primary biliary cirrhosis (PBC) risk. Pathway analysis complements conventional GWAS analysis. We applied the recently developed linear combination test for pathways to datasets drawn from independent PBC GWAS in Italian and Canadian subjects. Of the Kyoto Encyclopedia of Genes and Genomes and BioCarta pathways tested, 25 pathways in the Italian dataset (449 cases, 940 controls) and 26 pathways in the Canadian dataset (530 cases, 398 controls) were associated with PBC susceptibility (P
Safe and effective retraction of the liver is essential in providing adequate working space and a proper view of the stomach during laparoscopic bariatric surgery. Conventional liver retractors are expensive, require additional ports, resulting in pain and scarring, and cannot be utilized for single-port surgeries. To overcome these limitations we present a novel technique, using an indigenous "T-suspension tape," for liver and gallbladder retraction.
A retrospective analysis of the first 12 bariatric procedures using the "T-suspension tape" for liver retraction is presented here. The tape was created using the Teflon(®) (Dupont, Wilmington, DE) tail of a Jackson-Pratt drain secured to a Prolene™ (Ethicon, Blue Ash, OH) suture on a long straight needle. The liver was retracted by transparenchymal passage of the needle, which was exteriorized and secured to the anterior abdominal wall.
There were 11 female patients and 1 male patient. The mean age was 30 years (range, 20-42 years), and the mean preoperative body mass index was 37.37 kg/m(2) (range, 33.14-48.98 kg/m(2)). There were six laparoscopic sleeve gastrectomies (including one single-incision procedure), two laparoscopic Roux-en-Y gastric bypasses, four laparoscopic adjustable gastric banded plications, and three concomitant cholecystectomies. Mean time for retraction was 4 minutes 33 seconds (range, 38 seconds to 20 minutes 20 seconds). The liver and also the gallbladder could be effectively retracted, providing excellent working space and visualization of the entire stomach. There were no complications or conversions associated with this technique.
The "T-tape suspension" technique is simple, safe, and inexpensive and provides efficient retraction of the liver and gallbladder during bariatric surgery.
There are limited data on length of stay (LOS) following liver transplantation (LT), yet this is an important health services metric that directly correlates with early post-LT health care costs. The primary objective of this study was to examine the relationship between early allograft dysfunction (EAD) and LOS after LT. The secondary objective was to identify additional recipient, donor, and operative factors associated with LOS.
Adult patients undergoing primary LT over a 32-month period were prospectively examined at a single center. Subjects fulfilling standard criteria for EAD were compared with those not meeting the definition. Variables associated with increased LOS on ordinal logistic regression were identified.
Subjects with EAD had longer mean hospital LOS than those without (42.5 ± 38.9 days vs 27.4 ± 31 days; P = .003). Subjects with EAD also had longer mean intensive care LOS (8.61 ± 10.28 days vs 5.45 ± 11.6 days; P = .048). Additional factors significantly associated with LOS included Model for End-Stage Liver Disease (MELD) score, recipient location before LT, and postoperative surgical complications.
EAD is associated with longer hospitalization after LT. MELD score, preoperative recipient location, and postoperative complications were significantly associated with LOS. From a cost-containment perspective, these findings have implications on resource allocation.
Americium-241 (²4¹Am) is the second most significant radiation hazard after ²³?Pu at some of the Mayak Production Association facilities. This study summarizes current data on the accumulation, distribution, and excretion of americium compared with plutonium in different organs from former Mayak PA workers. Americium and plutonium were measured in autopsy and bioassay samples and correlated with the presence or absence of chronic disease and with biological transportability of the aerosols encountered at different workplaces. The relative accumulation of ²4¹Am was found to be increasing in the workers over time. This is likely from ²4¹Pu that increases with time in reprocessed fuel and from the increased concentrations of ²4¹Am and ²4¹Pu in inhaled alpha-active aerosols. While differences were observed in lung retention with exposures to different industrial compounds with different transportabilities (i.e., dioxide and nitrates), there were no significant differences in lung retention between americium and plutonium within each transportability group. In the non-pulmonary organs, the highest ratios of ²4¹Am/²4¹Am + SPu were observed in the skeleton. The relative ratios of americium in the skeleton versus liver were significantly greater than for plutonium. The relative amounts of americium and plutonium found in the skeleton compared with the liver were even greater in workers with documented chronic liver diseases. Excretion rates of ²4¹Am in ‘‘healthy’’ workers were estimated using bioassay and autopsy data. The data suggest that impaired liver function leads to reduced hepatic ²4¹Am retention, leading to increased ²4¹Am excretion.
Previous studies have indicated a high risk of hepatocellular carcinoma in acute hepatic porphyrias. In this retrospective study we present the incidence of primary liver cancer and clinical characteristics in a cohort of 179 acute porphyria patients above the age of 50 years.
Twenty-three cases with primary liver cancer were found either by a surveillance program or due to clinical suspicion. Standardized rate ratio was used to estimate the relative risk of primary liver cancer after indirect standardization. Survival data were calculated using the Kaplan-Meier method.
The mean age at diagnosis was 69 years. Hepatocellular carcinoma was found in 19 patients while four patients had cholangiocarcinoma or a combination of the two. Four patients had underlying cirrhosis. Mean tumour size was 4.3 cm in the surveillance group and 10.3 cm in the non-surveillance group (p = 0.01). The overall relative risk of primary liver cancer was 86 above the age of 50: 150 for women and 37 for men. Mean survival time was 5.7 years.
Acute hepatic porphyria carries a high risk of primary liver cancer above the age of 50 which warrants ultrasound surveillance. Sex distribution and frequency of cirrhosis differs from more common aetiologies of primary liver cancer.
The liver is known to play a central part in carrying out the main phases of intermediate metabolism, in supplying the other organs and tissues with structure and energy substances. The investigations on the liver function of man in the process of organism adaptation to a variety of factors in northern regions are practically non-existent. This article has as its purpose a combined clinical and biochemical investigation of the main functions of the liver in people with various length of stay in extreme northern regions. The analysis of changes in the indices of the basic liver functions in practically healthy people during the process of adaptation to the extreme environmental conditions of the North show, that with a short-term adaptation these shifts were generally of a temporary character, whereas with a long-term adaptation of the newcomers there were relatively permanent changes in a number of indices.
The introduction of cyclosporine A in 1980 greatly improved the survival of children with end-stage liver disease undergoing orthotopic liver transplantation. The average 1-year survival rate following hepatic transplantation increased from 30% in 1963 to 70% in 1980. This report summarizes the initial experience of two pediatric hospitals in Montreal--H?pital Ste-Justine and Montreal Children's Hospital. Since December 1985, 13 orthotopic liver transplantations have been performed in 11 patients: six females and five males. The median age was 18 months (range, 13 months to 17 years) and the median weight was 10 kg (range, 8.5 to 38 kg). The indications for transplantation were biliary atresia (5 patients), tyrosinemia (2 patients), biliary hypoplasia (1 patient), Amerindian cirrhosis (1 patient), Crigler-Najjar syndrome, type I (1 patient), and fulminant non-A, non-B hepatitis with grade IV encephalopathy (1 patient). Immunosuppression was ensured by cyclosporine A, azathioprine, and steroids. The function of 11 grafts was immediate following revascularization of the grafts. One graft had delayed function due to preservation injury, and one had primary nonfunction. Surgical complications included bile peritonitis (1), ruptured aneurysm of an aortic conduit (1), and thrombosis of the hepatic artery necessitating retransplantation (2). Three of our patients died, one from postoperative cerebral edema, one of primary nonfunction of the graft, and one of ruptured aneurysm of an aortic conduit. Our overall survival rate was 72% with a follow-up of 3 to 32 months. Pediatric liver transplantation can now provide successful treatment and cure of liver diseases considered, until recently, dismal and hopeless.