Hepatotoxicity of Antibiotics and Antifungals and Their Safe Use in Hepatic Impairment.

Idiosyncratic drug-induced liver injury (DILI) is a rare and unpredictable form of hepatotoxicity. While its clinical course is usually benign, cases leading to liver transplantation or death can occur. Based on modern prospective registries, antimicrobials including antibiotics and antifungals are frequently implicated as common causes. Amoxicillin-clavulanate ranks as the most common cause for DILI in the Western World. Although the absolute risk of hepatotoxicity of these agents is low, as their usage is quite high, it is not uncommon for practitioners to encounter liver injury following the initiation of antibiotic or antifungal therapy. In this review article, mechanisms of hepatoxicity are presented. The adverse hepatic effects of well-established antibiotic and antifungal agents are described, including their frequency, severity, and pattern of injury and their HLA risks. We also review the drug labeling and prescription guidance from regulatory bodies, with a focus on individuals with hepatic impairment.

Roadmap to DILI research in Europe. A proposal from COST action ProEuroDILINet.

In the current article the aims for a constructive way forward in Drug-Induced Liver Injury (DILI) are to highlight the most important priorities in research and clinical science, therefore supporting a more informed, focused, and better funded future for European DILI research. This Roadmap aims to identify key challenges, define a shared vision across all stakeholders for the opportunities to overcome these challenges and propose a high-quality research program to achieve progress on the prediction, prevention, diagnosis and management of this condition and impact on healthcare practice in the field of DILI. This will involve 1. Creation of a database encompassing optimised case report form for prospectively identified DILI cases with well-characterised controls with competing diagnoses, biological samples, and imaging data; 2. Establishing of preclinical models to improve the assessment and prediction of hepatotoxicity in humans to guide future drug safety testing; 3. Emphasis on implementation science and 4. Enhanced collaboration between drug-developers, clinicians and regulatory scientists. This proposed operational framework will advance DILI research and may bring together basic, applied, translational and clinical research in DILI.

Development of severe alcohol related liver disease over four decades in Iceland: impact of increased access and use of alcohol.

OBJECTIVE: Limited data exist on the association between per capita alcohol consumption and incidence of alcohol related liver disease (ARLD). The aims were to analyse this relationship and assess prevalence of ARLD in Iceland and among patients treated for alcohol use disorder (AUD) and its impact on outcomes. METHODS: A retrospective study on all patients diagnosed with severe ARLD: alcohol related cirrhosis (ARC) and alcohol related hepatitis (ARH) in Iceland 1984-2020. Medical records were scrutinized for clinical features, severity of ARLD, proportion undergoing treatment for AUD, data on abstinence and long-term outcomes. RESULTS: A total of 314 patients, males 76%, median age 56 years, fulfilled the predetermined criteria for ARLD. Median MELD was 17, 73% with Child-Pugh B/C and 70/314 (22%) who had ARH. Incidence of ARLD increased from 0.77 cases per 100 000 inhabitants annually 1984-2000 to 6.1 per 100 000 in 2016-2020. Per capita alcohol consumption increased from 4.3 Liters to 7.5 L in in the same time periods. Overall 220/314 (70%) with ARLD had undergone treatment for AUD. Of all individuals who had AUD treatment during the study period (n = 21.845), 1% were diagnosed with ARLD. Patients who underwent treatment for AUD after the ARLD diagnosis had better prognosis than those who had treatment prior to ARLD diagnosis (hazard ratio 2.5 [95% CI 1.3-5.0]). CONCLUSIONS: The incidence of ARLD increased 8-fold during the study period coinciding with 74% increase in per capita alcohol consumption. Patients with prior diagnosis of AUD had worse prognosis that needs special attention.

Incidence and outcomes in patients with acute cholangitis: a population-based study.

OBJECTIVE: The importance of early ERCP (endoscopic retrograde cholangiopancreatography) in patients with acute cholangitis (AC) is controversial. The aims were to compare outcomes in those who had early ERCP within 24 h from diagnosis and those who had ERCP undertaken later and examine the general prognosis of AC patients. METHODS: A prospective endoscopic database was used to identify all patients who underwent ERCP 2010-2021 at Landspitali University Hospital, diagnosed with cholangitis (k83.0) or calculus of bile duct with cholangitis (k80.3) according to ICD-10 diagnostic codes. Tokyo guidelines were used to verify the diagnosis and severity. Sepsis was analyzed by the Sepsis-3 criteria. RESULTS: A total of 240 patients met the inclusion criteria, 107 women (45%), median age 74 years, mostly due to gallstones (75%) and malignancy (19%), 61 (25%) underwent ERCP early. Overall 30-day mortality was 3.3% and was not significantly different between the early and late ERCP groups (4.9% vs 2.5% respectively). Patients who underwent early ERCP were more likely to have severe cholangitis according to the Tokyo guidelines criteria than those who underwent ERCP later (31% vs 18%, p = 0.047) but had a shorter median hospital stay (4 vs. 6 days, p = 0.006). Sepsis was more common among those who had ERCP early than those who had late ERCP (33% vs 19%, p = 0.033). CONCLUSIONS: The results indicate that for patients with AC the timing of ERCP is an important factor influencing the hospital stay, with shorter hospital stay for patients receiveing ERCP within 24 h, despite more severe cholangitis at diagnosis.

Incidence and prognosis of patients with small intestinal neuroendocrine tumors in a population based nationwide study.

BACKGROUND & AIMS: Small intestinal neuroendocrine tumours (SI-NETs) are the most frequent malignant tumours of the small intestine. Population based studies on SI-NETs are scarce. We aimed to examine the incidence, presentation of disease and prognosis of SI-NET and to determine patient prognosis in those undergoing emergency or elective surgery. METHODS: This was a retrospective population-based study. Information on all patients diagnosed with neuroendocrine tumours of the small intestine (excluding duodenum) from the beginning of the Icelandic Cancer Registry and the pathology departments in the country (1966-2017). Detailed phenotypic information was obtained from medical records on symptoms at diagnosis, treatment, recurrence and survival. RESULTS: A total of 113 patients with SI-NETs were identified, 3 patients were excluded due to lack of data and/or diagnostic error, leaving 110 patients for final analysis. The incidence of SI-NET was 0.78/100,000 and did not increase during the study period. A total of 42 % (n = 46) of patients were diagnosed incidentally. Long-term prognosis, after a landmark of 12 months, was better in patients who were diagnosed incidentally (HR 0.52; p = 0.03). Overall 89 % (n = 98) of cases underwent surgical resection of the primary tumor, 31 % (n = 30) patients acute or semi-acute surgery and 69 % (n = 68) elective surgery. Emergency surgery was associated with a 6-fold risk of death in the first 12 months after surgery (HR: 5.99; p = 0.01) and associated with more severe surgical complications. However, there was no difference in the long-term risk of death after the first 12 months (HR: 1.39; p = 0.27). CONCLUSIONS: The incidence of SI-NETs has not changed significantly in the last decades. Incidentally diagnosed SI-NET was associated with a favorable long-term prognosis. Emergency surgery in patients with SI-NET was associated with a significantly worse short-term risk of mortality compared to those who underwent elective surgery.

Dili is rare amongst patients without liver metastases receiving cancer treatment in Iceland: a population-based cohort study.

BACKGROUND: There is limited information on the frequency of idiosyncratic drug-liver injury (DILI) among cancer patients. The aim of the study was to evaluate the frequency of DILI due to cancer treatment in a population-based setting. MATERIAL AND METHODS: All patients diagnosed with genitourinary cancer, breast cancer or metastatic malignant melanoma in 2007-2018 were matched with a database containing laboratory results for all major hospitals in Iceland. Medical chart review was performed for cases with ALT/AST ≥5× upper limit of normal (ULN), ALP ≥2× ULN or bilirubin ≥2× ULN. Patients with liver-, and/or bone metastases and isolated elevations of ALP and patients with other etiologies of liver enzyme elevations were excluded. Cases with a RUCAM score of probable or highly probable were included. RESULTS: Among 4956 patients, 840 patients had liver enzyme elevations. Overall, nine (0.2%) cases of DILI were identified, seven women (78%), median age 59 years (IQR 52-66). Four patients had kidney cancer, four breast cancer and one metastatic prostate cancer. In eight cases, a single agent was implicated: Pazopanib (n = 3), axitinib, docetaxel, gemcitabine, letrozole and paclitaxel. In all cases, the treatment was interrupted or discontinued due to the liver injury. No patient developed jaundice or liver failure and no death was linked to DILI. Time to normalization of liver enzymes was 17 days (IQR 25-120). CONCLUSION: DILI was found to be rare and no cases of severe liver injury occurred. However, approximately 90% of patients switched to another treatment which might have affected prognosis.

Drug-induced liver injury: Pathogenesis, epidemiology, clinical features, and practical management.

Drug-induced liver injury (DILI) is an important but rare adverse event which can range from mild liver enzyme elevations to liver failure, transplantation or death. A large proportion of commonly used medications, in addition to herbal and dietary supplements, can cause liver injury. DILI has been categorized as direct or idiosyncratic but indirect liver injury has emerged as a third type of drug-induced liver injury. These types of liver injury may warrant different clinical approach and treatment. Associations of HLA genotypes and risk of DILI have highlighted the importance of the immune system in the pathogenesis of DILI. Furthermore, novel agents affecting the immune response can lead to liver injury, often associated with autoimmune features in serologic tests and liver biopsies. Overall, the diagnosis of DILI remains a challenge as it is requires detailed case evaluation in addition to reviewing the hepatotoxic potentials and clinical signatures of the implicated agents. Biochemical profiles vary between agents and although individual drugs tend to portray a consistent clinicopathologic signature, many drugs have multiple signatures. Thanks to multicenter prospective studies on DILI and websites in the public domain such as LiverTox, physicians are provided with tools to investigate suspected DILI cases to increase the likelihood of establishing adiagnosis. The pathogenesis of DILI, epidemiology and current challenges in the diagnosis and management of the disease are reviewed in the paper.

Incidence of diverticular bleeding: a population-based study.

OBJECTIVE: To determine the incidence of diverticular bleeding (DB) and examine the time trend of the incidence. Furthermore to study prognosis with regard to therapy and rebleeding. METHODS: A retrospective, population-based study of patients with DB in a National University Hospital from 2006 to 2016. Patients were identified in an electronically stored colonoscopy database. Definite diverticular bleeding was defined as active bleeding, a nonbleeding visible vessel or adherent clot. Presumptive diverticular bleeding was defined as acute painless rectal bleeding leading to hospitalization with visible diverticula but no evidence of bleeding and no other colonic lesions or bleeding sites identified on endoscopy. A 30-day re-bleeding was determined after discharge. RESULTS: A total of 3683 colonoscopy reports were reviewed, including 345 patients (males 51%) with presumptive 95% (n = 327) or definitive 5% (n = 18) diverticular bleeding. Overall 96% were treated conservatively, 3% endoscopically and 0.3% surgically. Only 5.8% of patients had a 30-day rebleed. After exclusion, 315 patients were included in the incidence calculations. The mean cumulative incidence of diverticular bleeding was 14/100,000 inhabitants per year. A time trend analysis of the incidence of DB revealed no significant change in incidence during the study period. CONCLUSIONS: The mean incidence of colonic diverticular bleeding was found to be approximately 14 cases per 100,000 inhabitants and year. The incidence does not seem to have changed in the past decade. The vast majority of patients with diverticular bleeding did not require endoscopic therapy and could be managed with conservative treatment.

Treatment as Prevention for Hepatitis C (TraP Hep C) - a nationwide elimination programme in Iceland using direct-acting antiviral agents.

A nationwide programme for the treatment of all patients infected with hepatitis C virus (HCV) was launched in Iceland in January 2016. By providing universal access to direct-acting antiviral agents to the entire patient population, the two key aims of the project were to (i) offer a cure to patients and thus reduce the long-term sequelae of chronic hepatitis C, and (ii) to reduce domestic incidence of HCV in the population by 80% prior to the WHO goal of HCV elimination by the year 2030. An important part of the programme is that vast majority of cases will be treated within 36 months from the launch of the project, during 2016-2018. Emphasis is placed on early case finding and treatment of patients at high risk for transmitting HCV, that is people who inject drugs (PWID), as well as patients with advanced liver disease. In addition to treatment scale-up, the project also entails intensification of harm reduction efforts, improved access to diagnostic tests, as well as educational campaigns to curtail spread, facilitate early detection and improve linkage to care. With these efforts, Iceland is anticipated to achieve the WHO hepatitis C elimination goals well before 2030. This article describes the background and organization of this project. Clinical trial number: NCT02647879.

The incidence and outcome of ischemic colitis in a population-based setting.

OBJECTIVE: Population-based studies on patients with ischemic colitis (IC) are limited. We aimed to determine the incidence, risk factors and outcome of patients with IC. METHODS: A retrospective nationwide study was conducted on adult patients with histologically confirmed IC in 2009-2013 in Iceland. IC patients were matched for age and gender with patients hospitalized with lower gastrointestinal bleeding. Data were collected on clinical presentation, comorbidities, smoking habits, management and outcome. RESULTS: Eighty-nine patients, 61 (69%) females and mean age of 65 years (±17), fulfilled the predetermined criteria. Females were older than males, 68 years (±14) vs. 59 years (±20) (p = .0170). The mean cumulative incidence was 7.3 cases per 100,000 inhabitants. A total of 57 (64%) patients presented with abdominal pain, hematochezia and diarrhea. IC was localized in the left colon in 78 (88%) patients. Overall, 62 (70%) patients had cardiovascular disease vs. 53 (60%) of control group (NS) and 55 (62%) had a history of smoking vs. 53 (60%) in control group (NS). Ten (11%) patients required surgery and/or died within 30-days from hospital admission. At the end of follow-up, 7 (9%) patients had experienced recurrence of IC with an estimated 3-year recurrence rate of 15%. CONCLUSIONS: IC is a common clinical phenomenon that affects a wide range of age groups, but is most prominent among elderly women. It typically presents with a clinical triad of abdominal pain, hematochezia and diarrhea. Most cases are mild and self-limiting with a good prognosis.

Helicobacter pylori infection in Icelandic children.

OBJECTIVE: The prevalence of Helicobacter pylori (HP) infection is decreasing in the western world. The seroprevalence among 25-50-year-old Icelandic adults was recently shown to be 30-40%. Information on the seroprevalence in Nordic children is limited. We aimed at ascertaining the infection prevalence among healthy Icelandic children. METHODS: The infection status in stored frozen blood samples from two cross-sectional studies on the health of 7-9-year-old children (n = 125) and 16-18-year-old adolescents (n = 80) was determined by enzyme-linked immunosorbent assay (ELISA). Information on family demographics and GI symptoms was obtained by standardized questionnaires. RESULTS: Overall, 3.4% (7/205) of the children were infected with H. pylori. The prevalence was 2.6% (5/190), missing data n = 3, among children with both parents born in a low prevalence country compared to 17% (2/12) among those with at least one parent born in a high prevalence area (p = .026). When at least one parent was born in a high prevalence country, the odds ratio for being H. pylori seropositive was 2.2 (95% CI, 1.02-54.67), when adjusted for the educational status of the mother. There was no significant association between H. pylori infection and gastrointestinal symptoms. CONCLUSION: Prevalence of H. pylori infection in Iceland has become very low, suggesting a great reduction in transmission from older generations. There was an association between H. pylori infection and origin from high prevalence areas but not with gastrointestinal symptoms. The results mirror recent studies of children of Scandinavian ancestry.

Use of statins in patients with liver disease.

Statins are generally well tolerated and shown to have a good safety profile. In clinical trials a similar proportion of patients randomized to statins and placebo treated developed abnormal liver tests. However, idiosyncratic drug-induced liver injury (DILI) is a rare adverse reaction and clinical trials are underpowered to detect uncommon side effects. Although probably very rare, idiosyncratic DILI due to statins has been reported among other drugs in all major prospective and retrospective series on DILI. A summary of 40 cases of statin hepatoxicity has been published and, a series of 76 cases suspected statin induced liver injury has recently been published. In the last mentioned series, three patients died and/or underwent liver transplantation and three cases had a rechallenge with the same statin which produced a similar pattern of liver injury. Statin therapy appears to be safe in the treatment of non-alcoholic fatty liver disease, in compensated patients with chronic hepatitis B or C. Statins have also been shown to have an inhibitory effect on hepatitis C virus replication in vitro. Retrospective data as well as data from a recent randomized controlled trial suggest that statin therapy might be a useful adjunct to standard combination antiviral therapy in patients with chronic hepatitis C. Statin therapy seems to be related to a reduced risk for hepatocellular carcinoma in patients with chronic liver disease, but randomized data are lacking.

Health-related quality of life improves during one year of medical and surgical treatment in a European population-based inception cohort of patients with inflammatory bowel disease--an ECCO-EpiCom study.

BACKGROUND & AIMS: Health-related quality of life (HRQoL) is impaired in patients with Inflammatory Bowel Disease (IBD). The aim was prospectively to assess and validate the pattern of HRQoL in an unselected, population-based inception cohort of IBD patients from Eastern and Western Europe. METHODS: The EpiCom inception cohort consists of 1560 IBD patients from 31 European centres covering a background population of approximately 10.1 million. Patients answered the disease specific Short Inflammatory Bowel Disease Questionnaire (SIBDQ) and generic Short Form 12 (SF-12) questionnaire at diagnosis and after one year of follow-up. RESULTS: In total, 1079 patients were included in this study. Crohn's disease (CD) patients mean SIBDQ scores improved from 45.3 to 55.3 in Eastern Europe and from 44.9 to 53.6 in Western Europe. SIBDQ scores for ulcerative colitis (UC) patients improved from 44.9 to 57.4 and from 48.8 to 55.7, respectively. UC patients needing surgery or biologicals had lower SIBDQ scores before and after compared to the rest, while biological therapy improved SIBDQ scores in CD. CD and UC patients in both regions improved all SF-12 scores. Only Eastern European UC patients achieved SF-12 summary scores equal to or above the normal population. CONCLUSION: Medical and surgical treatment improved HRQoL during the first year of disease. The majority of IBD patients in both Eastern and Western Europe reported a positive perception of disease-specific but not generic HRQoL. Biological therapy improved HRQoL in CD patients, while UC patients in need of surgery or biological therapy experienced lower perceptions of HRQoL than the rest.

Health care and patients' education in a European inflammatory bowel disease inception cohort: an ECCO-EpiCom study.

BACKGROUND AND AIMS: The EpiCom study and inception cohort was initiated in 2010 in 31 centers from 14 Western and 8 Eastern European countries, covering a 10.1million person background population. Our aim was to investigate whether there is a difference between Eastern and Western Europe in health care and education of patients with inflammatory bowel disease (IBD). METHODS: A quality of care (QoC) questionnaire was developed in the EpiCom group consisting of 16 questions covering 5 items: time interval between the onset of symptoms and diagnosis, information, education, empathy and access to health care providers. RESULTS: Of 1,515 patients, 947 (217 east/730 west) answered the QoC questionnaire. Only 23% of all patients had knowledge about IBD before diagnosis. In Eastern Europe, significantly more patients searched out information about IBD themselves (77% vs. 68%, p<0.05), the main source was the Internet (92% vs. 88% p=0.23). In Western Europe, significantly more patients were educated by nurses (19% vs. 1%, p<0.05), while in Eastern Europe, gastroenterologists were easier to contact (80% vs. 68%, p<0.05). CONCLUSION: Health care differed significantly between Eastern and Western Europe in all items, but satisfaction rates were high in both geographic regions. Because of the low awareness and the rising incidence of IBD, general information should be the focus of patient organizations and medical societies. In Western Europe IBD nurses play a very important role in reducing the burden of patient management.

East-West gradient in the incidence of inflammatory bowel disease in Europe: the ECCO-EpiCom inception cohort.

OBJECTIVE: The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe. The reasons for these changes remain unknown. The aim of this study was to investigate whether an East-West gradient in the incidence of IBD in Europe exists. DESIGN: A prospective, uniformly diagnosed, population based inception cohort of IBD patients in 31 centres from 14 Western and eight Eastern European countries covering a total background population of approximately 10.1 million people was created. One-third of the centres had previous experience with inception cohorts. Patients were entered into a low cost, web based epidemiological database, making participation possible regardless of socioeconomic status and prior experience. RESULTS: 1515 patients aged 15 years or older were included, of whom 535 (35%) were diagnosed with Crohn's disease (CD), 813 (54%) with ulcerative colitis (UC) and 167 (11%) with IBD unclassified (IBDU). The overall incidence rate ratios in all Western European centres were 1.9 (95% CI 1.5 to 2.4) for CD and 2.1 (95% CI 1.8 to 2.6) for UC compared with Eastern European centres. The median crude annual incidence rates per 100,000 in 2010 for CD were 6.5 (range 0-10.7) in Western European centres and 3.1 (range 0.4-11.5) in Eastern European centres, for UC 10.8 (range 2.9-31.5) and 4.1 (range 2.4-10.3), respectively, and for IBDU 1.9 (range 0-39.4) and 0 (range 0-1.2), respectively. In Western Europe, 92% of CD, 78% of UC and 74% of IBDU patients had a colonoscopy performed as the diagnostic procedure compared with 90%, 100% and 96%, respectively, in Eastern Europe. 8% of CD and 1% of UC patients in both regions underwent surgery within the first 3 months of the onset of disease. 7% of CD patients and 3% of UC patients from Western Europe received biological treatment as rescue therapy. Of all European CD patients, 20% received only 5-aminosalicylates as induction therapy. CONCLUSIONS: An East-West gradient in IBD incidence exists in Europe. Among this inception cohort--including indolent and aggressive cases--international guidelines for diagnosis and initial treatment are not being followed uniformly by physicians.

Bleeding-related symptoms in colorectal cancer: a 4-year nationwide population-based study.

BACKGROUND: Little is known about the major presenting features of patients with colorectal cancer (CRC) in a population-based setting, especially regarding bleeding-related symptoms. AIM: To determine the proportion of CRC patients presenting with bleeding-related symptoms, to compare bleeders and nonbleeders and to explore the role of anticoagulants in bleeders. METHODS: This was a nationwide, population-based, retrospective study, investigating all patients diagnosed with CRC in Iceland from 2008 to 2011. Bleeding-related symptoms were defined as overt bleeding, iron deficiency anaemia or a positive faecal occult blood test. Obstructive symptoms were defined as a confirmed diagnosis of ileus or dilated intestines on imaging. RESULTS: Data were available for 472/496 (95%) patients, males 51%, mean age 69 (±13) years. In all, 348 (74%) patients had bleeding-related symptoms; of these 348 patients, 61% had overt bleeding. Bleeders were less likely than nonbleeders to have metastases at diagnosis, 19% vs. 34% (P < 0.001). Overt bleeders were less likely than nonbleeders to have obstructive symptoms, 2% vs. 16% respectively (P < 0.0001). Occult bleeders were more likely to have proximal cancer (69%) than both overt (17%) and nonbleeders (44%) (P < 0.0001); however, they were less likely than nonbleeders to have metastases (22% vs. 35%, P < 0.05). Bleeders were more likely to use warfarin than nonbleeders (9% vs. 3%, P < 0.05); the use of low-dose aspirin was the same (24%). CONCLUSIONS: The majority of patients with CRC present with bleeding-related symptoms. Bleeders with CRC present earlier than nonbleeders. Warfarin use may induce bleeding in some patients, resulting in an earlier diagnosis.

Environmental factors in a population-based inception cohort of inflammatory bowel disease patients in Europe--an ECCO-EpiCom study.

BACKGROUND AND AIMS: The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe possibly due to changes in environmental factors towards a more "westernised" standard of living. The aim of this study was to investigate differences in exposure to environmental factors prior to diagnosis in Eastern and Western European IBD patients. METHODS: The EpiCom cohort is a population-based, prospective inception cohort of 1560 unselected IBD patients from 31 European countries covering a background population of 10.1 million. At the time of diagnosis patients were asked to complete an 87-item questionnaire concerning environmental factors. RESULTS: A total of 1182 patients (76%) answered the questionnaire, 444 (38%) had Crohn's disease (CD), 627 (53%) ulcerative colitis (UC), and 111 (9%) IBD unclassified. No geographic differences regarding smoking status, caffeine intake, use of oral contraceptives, or number of first-degree relatives with IBD were found. Sugar intake was higher in CD and UC patients from Eastern Europe than in Western Europe while fibre intake was lower (p<0.01). Daily consumption of fast food as well as appendectomy before the age of 20 was more frequent in Eastern European than in Western European UC patients (p<0.01). Eastern European CD and UC patients had received more vaccinations and experienced fewer childhood infections than Western European patients (p<0.01). CONCLUSIONS: In this European population-based inception cohort of unselected IBD patients, Eastern and Western European patients differed in environmental factors prior to diagnosis. Eastern European patients exhibited higher occurrences of suspected risk factors for IBD included in the Western lifestyle.

Patient satisfaction after gut-directed hypnotherapy in irritable bowel syndrome.

BACKGROUND: Gut-directed hypnotherapy is an effective treatment option for irritable bowel syndrome (IBS). However, clinical observations suggest that patient satisfaction with hypnotherapy is not always associated with improvement in IBS symptoms. METHODS: We evaluated 83 patients with IBS treated with gut-directed hypnotherapy (1 h week(-1), 12 weeks). After the treatment period, patients reported their satisfaction with the treatment (ranging from 1 = not at all satisfied, to 5 = very satisfied) and completed questionnaires to assess IBS symptom severity, quality of life, cognitive function, sense of coherence, depression, and anxiety before and after treatment. KEY RESULTS: After hypnotherapy improved IBS symptom severity, quality of life, cognitive function, and anxiety were seen. Thirty patients (36%) were very satisfied with the treatment and 57 (69%) patients scored 4 or 5 on the patient satisfaction scale. Patient satisfaction was associated with less severe IBS symptoms and better quality of life after the treatment. In a multiple linear regression analysis, only the quality of life domain sexual relations was independently associated with patient satisfaction after hypnotherapy, explaining 22% of the variance. Using 25% reduction of IBS symptom severity to define an IBS symptom responder, 52% of the responders were very satisfied with hypnotherapy, but this was also true for 31% in the non-responder group. CONCLUSIONS & INFERENCES: Patient satisfaction with gut-directed hypnotherapy in IBS is associated with improvement of quality of life and gastrointestinal (GI) symptoms. However, other factors unrelated to GI symptoms also seems to be of importance for patient satisfaction, as a substantial proportion of patients without GI symptom improvement were also very satisfied with this treatment option.

Risk factors for Clostridium difficile toxin-positive diarrhea: a population-based prospective case-control study.

Increased incidence and severity of Clostridium difficile infections (CDIs) is of major concern. However, by minimizing known risk factors, the incidence can be decreased. The aim of this investigation was to calculate the incidence and assess risk factors for CDI in our population. A 1-year prospective population-based nationwide study in Iceland of CDIs was carried out. For risk factor evaluation, each case was matched with two age- and sex-matched controls that tested negative for C. difficile toxin. A total of 128 CDIs were identified. The crude incidence was 54 cases annually per 100,000 population >18 years of age. Incidence increased exponentially with older age (319 per 100,000 population >86 years of age). Community-acquired origin was 27 %. Independent risk factors included: dicloxacillin (odds ratio [OR]: 7.55, 95 % confidence interval [CI]: 1.89-30.1), clindamycin (OR: 6.09, 95 % CI: 2.23-16.61), ceftriaxone (OR: 4.28, 95 % CI: 1.59-11.49), living in a retirement home (OR: 3.9, 95 % CI: 1.69-9.16), recent hospital stay (OR: 2.3, 95 % CI: 1.37-3.87). Proton pump inhibitors (PPIs) were used by 60/111 (54 %) versus 91/222 (41 %) (p = 0.026) and ciprofloxacin 19/111 (17 %) versus 19/222 (9 %) (p = 0.027) for cases and controls, respectively. In all, 75 % of primary CDIs treated with metronidazole recovered from one course of treatment. CDI was mostly found among elderly patients. The most commonly identified risk factors were broad-spectrum antibiotics and recent contact with health care institutions. PPI use was significantly more prevalent among CDI patients.

Case definition and phenotype standardization in drug-induced liver injury.

Drug-induced liver injury (DILI) is the most frequent reason cited for the withdrawal of approved drugs from the market and accounts for up to 15% of the cases of acute liver failure. Investigators around the globe have begun to identify and study patients with DILI; several large registries and tissue banks are being established. In order to gain the maximum scientific benefit from these efforts, the definitions and terminology related to the clinical phenotypes of DILI must be harmonized. For this purpose, an international DILI Expert Working Group of clinicians and scientists reviewed current DILI terminology and diagnostic criteria so as to develop more uniform criteria that would define and characterize the spectrum of clinical syndromes that constitute DILI. Consensus was established with respect to the threshold criteria for definition of a case as being DILI, the pattern of liver injury, causality assessment, severity, and chronicity. Consensus was also reached on approaches to characterizing DILI in the setting of chronic liver diseases, including autoimmune hepatitis (AIH).