Persistent severe hypomagnesemia caused by proton pump inhibitor resolved after laparoscopic fundoplication.

Magnesium deficiency can cause a variety of symptoms, including potentially life-threatening complications such as seizures, cardiac arrhythmias and secondary electrolyte disturbances. Hypomagnesemia can be a serious adverse effect to proton pump inhibitor (PPI) therapy, which is worrying due to the widespread use of PPIs. Current evidence suggest that the mechanism of PPI induced hypomagnesemia is impaired intestinal magnesium absorption. In this report, we present the case of a long-term PPI user with persistent hypomagnesemia with severe symptoms at presentation. He was unable to stop PPI treatment because of severe reflux symptoms, and was dependent on weekly intravenous magnesium infusions, until his magnesium levels finally normalized without the need for supplementation after a successful laparoscopic fundoplication.

Presence of alcoholic steatohepatitis, but no selective histological feature, indicates an increased risk of cirrhosis and premature death.

OBJECTIVE: The prognostic impact of early stages of histologically confirmed alcoholic liver disease is uncertain. Our aim was to determine the risk of cirrhosis and premature death, and identify prognostic markers, in patients with biopsy-proven alcoholic steatohepatitis - and to compare prognosis in patients with alcoholic pure fatty liver and the general population. MATERIAL AND METHODS: Patients with biopsy-proven alcoholic fatty liver disease diagnosed during 1976-1987 were identified. Data were collected from medical records, the Danish National Patient Registry and the Registry of Causes of Death. All biopsies were re-examined and morphological findings assessed. A reference cohort matched for age and gender was created. Cox proportional hazard models adjusted for age and gender were used to analyse differences in mortality and cirrhosis development, as well as the prognostic impact of histological and biochemical parameters. RESULTS: Two hundred and twenty-five patients with fatty liver and 111 with steatohepatitis were followed for median 13 and 9.7 years, respectively. There was a significantly higher risk of developing cirrhosis amongst patients with steatohepatitis compared to both patients with fatty liver (p < 0.001) and the reference cohort (p < 0.001). Mortality was significantly higher in patients with steatohepatitis compared to patients with fatty liver (p = 0.046) and the general population (p < 0.001). No histological or biochemical parameters with prognostic significance for mortality were identified. CONCLUSION: Presence of steatohepatitis indicates an increased risk of cirrhosis and premature death. However, none of the histological parameters defining steatohepatitis can independently identify patients at risk for premature death.

Low incidence of non-alcoholic steatohepatitis in a Danish liver unit.

INTRODUCTION: Non-alcoholic fatty liver disease encompasses a spectrum of histological lesions ranging from steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. Simple steatosis is generally benign, while NASH can progress to severe liver disease. The aim of the present study was to quantify the number of patients with NASH and assess the prognosis associated with the condition in a large Danish referral centre for liver disease. MATERIAL AND METHODS: Through the pathology archives at Hvidovre Hospital, 348 patients with steatohepatitis diagnosed during the 1976-1987-period were identified. Data were systematically collected by review of available medical records. These data were supplemented by data from the Danish National Hospital Registry and the Registry of Causes of Death. RESULTS: A total of 100 patients referred from other hospitals were excluded as their records were missing and 236 patients were excluded, mainly due to a history of alcohol abuse; this left 14 patients to constitute the study population. At the end of the follow-up period which had a median duration of 16.7 years, ten of the patients had died: four of cardiovascular disease, four of extra-hepatic neoplasm and two of unknown causes. There were no liver-related deaths and only one patient developed cirrhosis. CONCLUSION: In a specialised referral centre, only few patients were diagnosed with NASH 25-30 years ago and those who were identified had a low risk of progression to cirrhosis and premature death. FUNDING: The local research council and the foundation for the study of liver diseases at Hvidovre Hospital provided funding for this study. TRIAL REGISTRATION: not relevant.

First-line treatment with cephalosporins in spontaneous bacterial peritonitis provides poor antibiotic coverage.

OBJECTIVE: Spontaneous bacterial peritonitis is a common infection in cirrhosis, associated with a high mortality. Third-generation cephalosporins are recommended as first-line treatment. The aim was to evaluate the epidemiology of microbiological ascitic fluid findings and antimicrobial resistance in Denmark. MATERIAL AND METHODS: All patients with cirrhosis and a positive ascitic fluid culture, at three university hospitals in the Copenhagen area during a 7-year period, were retrospectively evaluated. Patients with apparent secondary peritonitis were excluded from the study. RESULTS: One hundred and forty cases with 187 microbiological isolates were identified. The findings were: Gram-positive cocci, n = 86 (45.9%); Enterobacteriaceae, n = 59 (31.7%), with Escherichia coli identified in 31 cases; anaerobes, n = 14 (7.5%); yeast, n = 12 (6.4%); and cutaneous flora, n = 15 (8.0%). One case of Listeria monocytogenes was identified (0.5%). Overall antibiotic coverage was 57% for cephalosporins, 73% for piperacillin-tazobactam, and 72% for meropenem. Mortality rates in patients with isolates susceptible or resistant to the initial antibiotic treatment at 30 days follow-up were 35% and 55%, respectively (p = 0.017, Log-rank test). CONCLUSION: Almost half of the isolates were Gram-positive cocci, and as the overall antibiotic coverage with a cephalosporin was only 57%, and survival significantly dependent on whether the microbial etiology was susceptible to initial antibiotic treatment or not, a change of standard empiric antibiotic regime should be considered. Piperacillin-tazobactam could be a favorable choice.

The role of the glutathione S-transferase genes GSTT1, GSTM1, and GSTP1 in acetaminophen-poisoned patients.

The aim of this study was to assess if genetic variants in the glutathione-S-transferase genes GST-T1, M1, and P1 reflect risk factors in acetaminophen (APAP)-poisoned patients assessed by investigation of the relation to prothrombin time (PT), which is a sensitive marker of survival in these patients. A total of 104 APAP-poisoned patients were genotyped for deletion polymorphisms in the GSTT1 and GSTM1 genes and for the GSTP1 Ile105Val polymorphism. We found a borderline association (p = 0.05) between the GSTT1 homozygous deletion genotype and high trough PT (a marker of prognosis in APAP poisoning) compared to carrying two functioning copies of the gene. No significant association was found between any of the GSTM1 and GSTP1 genotypes and PT. The frequency of GSTP1 Val/Val genotypes was significantly lower in the patients than in the background population (p = 0.047). The results suggest that the GSTT1 homozygous deletion genotype may be associated with a better prognosis after APAP poisoning and that carriers of the GSTP1 homozygous variant genotype may have a decreased risk of being APAP poisoned.

[Hepatotoxicity of dietary supplements and herbals is mostly unknown]. / [Omfanget af naturprodukters hepatotoksisitet er i vidtgaende grad unkendt]

The use of herbals and dietary supplements is considerable and increasing. Several cases of serious hepatotoxic side effects and a wide range of clinical manifestations have been described. As toxic hepatitis often arises in an unpredictable and dose-independent manner, diagnosis may be difficult. Increased public awareness of the potential risks of herbals and dietary supplements is desirable in order to ensure that suspected adverse effects and interactions are formally reported.

Prednisolone treatment affects the performance of the QuantiFERON gold in-tube test and the tuberculin skin test in patients with autoimmune disorders screened for latent tuberculosis infection.

BACKGROUND: During screening for latent tuberculosis infection (LTBI), before anti-tumor-necrosis-factor-α treatment, most patients are already receiving immunosuppressive therapy. The objective was to evaluate the performance of the QuantiFERON Gold In-Tube (QFT-IT) and the Tuberculin Skin Test (TST). METHODS: A prospective multicenter study included 248 patients with ulcerative colitis (39), Crohn's disease (54), rheumatoid arthritis (111), and spondylo-arthropathy (44). RESULTS: QFT-IT was positive in 7/248 (3%), negative in 229 (92%), and indeterminate in 12 (5%). TST was positive in 54/238 (23%) patients. Chest x-ray was suspect for tuberculosis in 5/236 (2%), and 35/167 (21%) had ≥1 risk-factors for infection with Mycobacterium tuberculosis. The main finding was a pronounced negative effect on QFT-IT and TST performance associated with prednisolone treatment. During prednisolone treatment interferon gamma (IFN-γ) response to mitogen stimulation was impaired (median IFN-γ response 4.9 IU/mL; interquartile range [IQR] 0.8 to ≥10.0) compared to patients 1) not receiving corticosteroids (median ≥10.0; IQR 5.0 to ≥10.0; P = 0.0015) or 2) receiving long-acting corticosteroids (median >10.0; IQR 9.7 to >10.0; P = 0.0058). Prednisolone treatment was strongly associated with negative TST, adjusted odds ratio (AOR) 0.22 (0.1-0.8; P = 0.018), and with an increased risk of indeterminate QFT-IT results AOR 16.1 (4.1-63.2; P < 0.001), whereas no negative effect was found for long-acting corticosteroids. Doses of ≥10 mg prednisolone were associated with a 27% risk of indeterminate results. Single use of azathioprine, methotrexate, or 5-aminosalicylate (5-ASA) did not affect the test results. CONCLUSIONS: Oral prednisolone severely suppressed QFT-IT and TST performance, whereas the long-acting corticosteroids methotrexate, azathioprine, and 5-ASA did not have a similar detrimental effect. Patients should be screened for LTBI with QFT-IT or TST prior to initiation of prednisolone therapy and negative QFT-IT or TST results interpreted with caution in patients treated with any corticosteroid until further data are available.

[Toxic hepatitis following consumption of the herbal medicinal product Cascara Sagrada]. / Toksisk hepatitis efter indtagelse af kosttilskuddet purshianabark.

Herbal medicinal products can cause toxic hepatitis. This case report presents a patient who developed severe toxic hepatitis with beginning liver failure following four weeks of consumption of the herbal medicinal product Cascara Sagrada. A similar case was reported from the United States. Cascara Sagrada is found in 30-40 herbal medicinal products in Denmark. We recommend that herbal medicinal products containing Cascara Sagrada be withdrawn from the market.

A descriptive cross-sectional study of the prevalence of 25-hydroxyvitamin D deficiency and association with bone markers in a hospitalized population.

Patients with gastrointestinal disease may be in particular risk of hypovitaminosis D because of reduced intestinal uptake or metabolism in the liver. The aim of the present study was to evaluate the prevalence of vitamin D deficiency in several groups of patients with various gastroenterologic diseases compared with patients without any chronic disease. We tested the hypothesis that persons with a gastrointestinal disease are at higher risk of hypovitaminosis D than persons with no chronic disease and whether this group needs special attention regarding their nutrition. We included patients admitted to our department of gastroenterology. The concentration of 25-hydroxyvitamin D (25(OH)D2+D3) was defined as insufficient when less than 50 nmol/L, deficient when less than 25 nmol/L, and severely deficient when less than 12.5 nmol/L. We included 146 patients with a mean age of 55 years (range, 16-93 years). 25(OH)D was sufficient in 47%, insufficient in 29%, deficient in 12%, and severely deficient in 11% of the population. Participants without chronic disease had a significantly higher mean level of 25(OH)D (57 nmol/L) compared to participants with cirrhosis (15 nmol/L, P = .002) and alcoholism (31 nmol/L, P = .003). A linear relationship between 25(OH)D and alkaline phosphatase could be demonstrated (Spearman rho, -0.299; P < .001). Participants with severe 25(OH)D deficiency had higher levels of total alkaline phosphatase (149.5 vs 76 U/L, P = .001) and parathyroid hormone (5.1 vs 2.8 pmol/L; P = .001). We recommend measuring the level of 25(OH)D and parathyroid hormone in patients with chronic diseases, especially alcoholism and cirrhosis.

[Treatment of fistulating pouchitis with tumour necrosis factor-alpha-inhibitor (infliximab)]. / Behandling af fistulerende pouchitis med tumornekrosefaktor-alpha-hsemmer (infliximab).

The surgical first choice treatment for patients with ulcerative colitis (UC) involves total proctocolectomy with ileal pouch-anal anastomosis (IPAA). Postoperative development of pouch-related fistula is a rare complication, but it is associated with significant morbidity, a high recurrence rate and is a major cause of pouch failure. We report the use of infliximab, a monoclonal antibody to tumour necrosis factor-alpha, in three patients who developed pouch-related fistula after undergoing IPAA surgery for UC.

Pharmacological approach to acute pancreatitis.

The aim of the present review is to summarize the current knowledge regarding pharmacological prevention and treatment of acute pancreatitis (AP) based on experimental animal models and clinical trials. Somatostatin (SS) and octreotide inhibit the exocrine production of pancreatic enzymes and may be useful as prophylaxis against post endoscopic retrograde cholangiopancreatography pancreatitis (PEP). The protease inhibitor gabexate mesilate (GM) is used routinely as treatment to AP in some countries, but randomized clinical trials and a meta-analysis do not support this practice. Nitroglycerin (NGL) is a nitrogen oxide (NO) donor, which relaxes the sphincter of Oddi. Studies show conflicting results when applied prior to ERCP and a large multicenter randomized study is warranted. Steroids administered as prophylaxis against PEP has been validated without effect in several randomized trials. The non-steroidal anti-inflammatory drugs (NSAID) indomethacin and diclofenac have in randomized studies showed potential as prophylaxis against PEP. Interleukin 10 (IL-10) is a cytokine with anti-inflammatory properties but two trials testing IL-10 as prophylaxis to PEP have returned conflicting results. Antibodies against tumor necrosis factor-alpha (TNF-alpha) have a potential as rescue therapy but no clinical trials are currently being conducted. The antibiotics beta-lactams and quinolones reduce mortality when necrosis is present in pancreas and may also reduce incidence of infected necrosis. Evidence based pharmacological treatment of AP is limited and studies on the effect of potent anti-inflammatory drugs are warranted.