Introduction:
Treatment is generally not available for drug-induced liver injury (DILI) patients except in some specific circumstances. The management of DILI is based on the withdrawal of the ...responsible drug and monitoring the patients and only a few patients need to be referred to a transplant center. Some studies on the role of ursodeoxycholic acid (UDCA) in DILI have been published. The aim of this study was to perform a systematic review of the role of UDCA in the treatment and prevention of DILI.
Methods:
A search was undertaken in PubMed, with the key words ursodeoxycholic acid, drug-induced liver injury and hepatotoxicity following the PRISMA guidelines.
Results:
A total of 33 publications were identified: 25 case reports and 8 case series. In 18 of the 25 cases reports (22 patients), authors reported improvement of liver injury associated with UDCA therapy whereas 7 case reports did not show clinical or biochemical improvement after UDCA treatment. There were 4 studies evaluating the role of UDCA in the treatment of DILI, three prospective (one being a clinical trial) and one retrospective studies. Three studies observed liver profile improvements associated with UDCA. In addition, four studies evaluated UDCA in the prevention of DILI: one pilot study, two randomized clinical trials (RCT) and one retrospective study. Three of these studies observed a lower percentage of patients with an increase in transaminases in the groups that used UDCA for DILI prevention.
Conclusion:
According to available data UDCA seems to have some benefits in the treatment and prevention of DILI. However, the design of the published studies does not allow a firm conclusion to be drawn on the efficacy of UDCA in DILI. A well designed RCT to evaluate the role of UDCA in DILI is needed.
Gastrointestinal bleeding (GIB) rates for direct oral anticoagulants (DOACs) and warfarin have been extensively compared. However, population-based studies comparing GIB rates among different DOACs ...are limited.
To compare rates of GIB among apixaban, dabigatran, and rivaroxaban.
Nationwide population-based cohort study.
Landspítali-The National University Hospital of Iceland and the 4 regional hospitals in Iceland.
New users of apixaban, dabigatran, and rivaroxaban from 2014 to 2019.
Rates of GIB were compared using inverse probability weighting, Kaplan-Meier survival estimates, and Cox regression.
In total, 2157 patients receiving apixaban, 494 patients receiving dabigatran, and 3217 patients receiving rivaroxaban were compared. For all patients, rivaroxaban had higher overall rates of GIB (3.2 vs. 2.5 events per 100 person-years; hazard ratio HR, 1.42 95% CI, 1.04 to 1.93) and major GIB (1.9 vs. 1.4 events per 100 person-years; HR, 1.50 CI, 1.00 to 2.24) compared with apixaban. Rivaroxaban also had higher GIB rates than dabigatran, with similar point estimates, although the CIs were wider and included the possibility of a null effect. When only patients with atrial fibrillation were included, rivaroxaban was associated with higher rates of overall GIB than apixaban (HR, 1.40 CI, 1.01 to 1.94) or dabigatran (HR, 2.04 CI, 1.17 to 3.55). Dabigatran was associated with lower rates of upper GIB than rivaroxaban in both analyses.
Unmeasured confounding and small subgroup analyses.
Rivaroxaban was associated with higher GIB rates than apixaban and dabigatran regardless of treatment indication.
Icelandic Centre for Research and Landspítali-The National University Hospital of Iceland.
Gastrointestinal bleeding (GIB) is the most common type of bleeding occurring in patients on oral anticoagulation. A meta-analysis of the landmark randomized controlled trials (RCTs) for patients ...with atrial fibrillation demonstrated that direct oral anticoagulants (DOACs) were associated with higher GIB rates compared to warfarin. However, significant heterogeneity existed between studies. While rivaroxaban, high-dose dabigatran, and high-dose edoxaban were associated with higher GIB rates than warfarin, GIB rates were similar between warfarin users and both apixaban and low-dose dabigatran users. Additionally, previous observational studies have yielded conflicting reports on whether GIB rates differ between warfarin and DOACs. Meta-analyses of observational studies demonstrated that warfarin is associated with lower rates of GIB compared to rivaroxaban, similar or lower rates compared to dabigatran, and higher rates compared to apixaban. Importantly, no RCT has compared individual DOACs directly and due to the different selection criteria of the initial RCTs, indirect comparisons between DOACs using these studies are unreliable. The best available information of comparisons between individual DOACs is therefore limited to observational studies. There is mounting evidence that suggests that rivaroxaban is associated with a higher risk of GIB compared to other DOACs. Finally, GIB induced by oral anticoagulation may have some positive aspects. Interestingly, there are studies that indicate oral anticoagulation facilitates colorectal cancer detection. Furthermore, results from RCTs and observational studies suggest that warfarin may even decrease the incidence of cancer.
The combination of high aminotransferases (hepatocellular injury) and jaundice has been reported to lead to a mortality rate of 10% to 50% for different drugs, a phenomenon known as "Hy's rule." ...However, Hy's rule has never been validated, and limited data exist on predictors for outcome in hepatocellular and other forms of drug-induced liver disease. All reports of suspected hepatic adverse drug reactions received by the Swedish Adverse Drug Reactions Advisory Committee (1970-2004) were reviewed. Cases with bilirubin levels 2 or more times the upper limit of normal (ULN) were analyzed. A total of 784 cases were retrieved-409 with hepatocellular injury, 206 with cholestatic injury, and 169 with mixed liver injury. The mortality/transplantation rate was 9.2%, and bilirubin (median 18.7 x ULN IQR 12.6-25; range 4.5-42) was higher (P < .0001) in the deceased/transplant recipients compared with the surviving patients (median 5.5 x ULN IQR 3.3-9.5; range 2.0-38). A total of 7.8% with cholestatic and 2.4% with a mixed pattern died. The mortality rate in hepatocellular injury for different drugs varied from 40% (6 of 15) for halothane to 0% (0 of 32) for erythromycin, in total 12.7%. Using logistic regression analysis, age, aspartate aminotransferase (AST) and bilirubin were found to independently predict death or liver transplantation in the hepatocellular group, whereas among patients with cholestatic/mixed liver injury, bilirubin was the only independent predictor. In conclusion, hepatocellular jaundice has a high but variable mortality rate, depending on the drug involved. The AST and bilirubin levels are the most important predictors of death or liver transplantation.
Objective: To study the outcome of acute pancreatitis and risk factors for recurrent and chronic pancreatitis in a population based cohort of patients with first-time acute pancreatitis.
Methods: All ...patients with first-time acute pancreatitis from 2006-2015 in Iceland were retrospectively evaluated. Medical records were scrutinized and relevant data extracted.
Results: 1102 cases of first-time acute pancreatitis were identified: mean age 56yr, 46% female, 41% biliary, 21% alcohol, 26% idiopathic, 13% other causes, mean follow-up 4yr. 21% had ≥1 recurrent acute pancreatitis which was independently related to alcoholic (vs. biliary hazard ratio (HR) 2.29, 95% confidence interval (CI) 1.51-3.46), male gender (HR 1.48, 95%CI 1.08-2.04), and smoking (HR 1.62, 95%CI 1.15-2.28). 3.7% developed chronic pancreatitis. Independent predictors were recurrent acute pancreatitis (HR 8.79, 95%CI 3.94-19.62), alcoholic (vs. biliary HR 9.16, 95%CI 2.71-30.9), local complications (HR 4.77, 95%CI 1.93-11.79), and organ-failure (HR 2.86, 95%CI 1.10-7.42).
Conclusions: Recurrent acute pancreatitis occurred in one-fifth of patients. Development of chronic pancreatitis was infrequent. Both recurrent acute pancreatitis and chronic pancreatitis were related to alcoholic acute pancreatitis, while recurrent acute pancreatitis was associated with smoking and male gender, and chronic pancreatitis to recurrent acute pancreatitis, organ-failure, and local complications.
Objective: To determine the frequency and nature of liver enzyme elevations among patients presenting with choledocholithiasis (CDL).
Methods: A prospective study identified all patients with serum ...level of alanine aminotransferase (ALT) ≥500 U/L (normal levels: <70 U/L in men, <45 U/L in women) over 1 year. Additionally, other patients with CDL were identified during the same period retrospectively by diagnostic codes and ERCP procedures, providing data on all CDL patients. Symptoms, liver tests, history of cholecystectomy, and radiological imaging were analyzed. Patients with radiologically confirmed CDL or a clinical diagnosis of CDL were included.
Results: During the study period, 110 patients had CDL, 60% women, mean age 65 years. Overall 86/110 (78%) had confirmed CDL on imaging and 24/110 (22%) clinically diagnosed. Overall 26% had undergone cholecystectomy, median bile duct diameter 10.0 mm, median maximal liver tests: ALT 436, ALP 226, bilirubin 60 μmol/L (<25). Overall 9/110 (8%) had ALT ≥1000, 43/110 (39%) ALT levels between 500 and 1000 IU/L and 58/110 (53%) had ALT <500 IU/L. Patients with ALT ≥1000 had smaller bile duct diameter of 7 versus 10 mm (p < .001) but similar proportions of cholecystectomies. In the multivariate analysis age, maximal AST and maximal bilirubin were independent predictors of ALT >500. Maximal AST and bile duct diameter were independent predictors of ALT >1000.
Conclusions: Approximately 8% of patients with CDL had markedly elevated ALT. These patients had smaller bile duct diameter. Pronounced ALT elevation is a part of the clinical spectrum of CDL.
Background & aims
Population‐based studies on the epidemiology of autoimmune hepatitis (AIH) are scarce. Drug‐induced AIH (DIAIH) is increasingly recognized in association with immunomodulatory ...therapy. We aimed to determine the incidence, prevalence and natural history of AIH in a population‐based setting.
Methods
We collected data of new diagnosis of AIH in Iceland from 2006 to 2015. Cases were identified through search of diagnostic codes and text search for AIH within electronical medical records of all hospitals in Iceland and through records of smooth muscle antibodies (SMA) test results by the only laboratory in the country analyzing SMA. Patients were included in the final analysis if they received the clinical diagnosis of AIH or were started on immunosuppressive therapy.
Results
The mean annual incidence of AIH in Iceland was 2.2 cases per 100 000 inhabitants. Point prevalence on 31 December 2015 was 27/100 000. The median age at diagnosis was 56 years and 86% of patients were of female gender. DIAIH was suspected in 13 of 71 patients (18%) of which eight cases were related to infliximab. Immunosuppressive treatment was started in all but two patients. At the end of follow‐up (median 4.8 years) 66 of 71 (93%) patients were alive.
Conclusion
The incidence and prevalence rates of AIH in Iceland are the highest reported so far in a population‐based setting. Higher incidence can partly be explained by the increasing use of biological drugs. Immunosuppressive therapy was very effective in achieving remission and prognosis was favorable.
Background:
The use of proton-pump inhibitors (PPIs) has grown worldwide, and there are concerns about increased unsubstantiated long-term use. The aim of the study was to describe the real-world use ...of PPIs over the past decade in an entire national population.
Methods:
This was a nationwide population-based drug-utilization study. Patterns of outpatient PPI use among adults in Iceland between 2003 and 2015 were investigated, including annual incidence and prevalence, duration of use, and dose of tablet used (lower versus higher), as well as the proportion of PPI use attributable to gastroprotection.
Results:
We observed 1,372,790 prescription fills over the entire study period, of which 95% were for higher-dose PPIs. Annual incidence remained stable across time (3.3–4.1 per 100 persons per year), while the annual prevalence increased from 8.5 per 100 persons to 15.5 per 100 persons. Prevalence increased with patient age and was higher among women than men. Duration of treatment increased with patients’ age (36% of users over 80 years remained on treatment after 1 year compared with 13% of users aged 19–39 years), and was longer among those initiating on a higher dose compared with a lower dose. The proportion of PPI users concurrently using nonsteroidal anti-inflammatory drugs decreased over the study period, while the proportion concurrently using acetylsalicylic acid, oral anticoagulants, or platelet inhibitors increased.
Conclusions:
In this nationwide study, a considerable increase in overall outpatient use of PPIs over a 13-year period was observed, particularly among older adults. Patients were increasingly treated for longer durations than recommended by clinical guidelines and mainly with higher doses.
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