Drug-induced acute pancreatitis in a bodybuilder: a case report.

BACKGROUND: Unregulated use of a variety of drugs and supplements by bodybuilders and athletes is common and can lead to severe adverse complications. Only a small proportion of acute pancreatitis cases are drug induced, and case reports are essential for identifying potential drug-related risks for pancreatitis. Here we present the first case report published of acute pancreatitis linked to recreational use of anabolic-androgenic steroids, subcutaneous growth hormone, and clenbuterol in a previously healthy male after excluding all other causes of pancreatitis. CASE PRESENTATION: A 31-year-old Arab male bodybuilder presented with acute abdominal pain associated with nausea and sharp pain radiating to the back. The patient was not using tobacco or alcohol but was using multiple drugs related to bodybuilding, including anabolic-androgenic steroids, subcutaneous growth hormone, clenbuterol, and multiple vitamin supplements. Laboratory studies revealed a normal white blood cell count, elevated C-reactive protein, minimally elevated aspartate aminotransferase and total bilirubin with normal remaining liver tests, and elevated amylase and lipase. The patient had no hypertriglyceridemia or hypercalcemia, and had had no recent infections, abdominal procedures, trauma, or scorpion exposure. Imaging and laboratory investigations were negative for biliary disease and IgG4 disease. Abdominal computed tomography revealed hepatomegaly and diffuse thickening and edema of the body and tail of the pancreas with peripancreatic fat stranding. An abdominal ultrasound showed slight hepatomegaly with no evidence of cholelithiasis. Genetic testing for hereditary pancreatitis-related mutations was negative. A diagnosis of drug-induced acute pancreatitis was made, and he was treated with aggressive intravenous hydration and pain management. The patient has avoided further use of these drugs and supplements and had no further episodes of pancreatitis during 1 year of follow-up. CONCLUSIONS: This case describes a patient with drug-induced acute pancreatitis after the intake of anabolic-androgenic steroids, subcutaneous growth hormone, and clenbuterol, where all other common causes of acute pancreatitis were excluded. Clinicians should be alert to the possibility of drug-induced acute pancreatitis occurring in bodybuilders and athletes using similar drug combinations.

Serum and Fecal Oxylipins in Patients with Alcohol-Related Liver Disease.

BACKGROUND: Alcohol-related liver disease is one of the most prevalent chronic liver diseases worldwide. Mechanisms involved in the pathogenesis of alcohol-related liver disease are not well understood. Oxylipins play a crucial role in numerous biological processes and pathological conditions. Nevertheless, oxylipins are not well studied in alcohol-related liver disease. AIMS: (1) To characterize the patterns of bioactive ω-3 and ω-6 polyunsaturated fatty acid metabolites in alcohol use disorder and alcoholic hepatitis patients and (2) to identify associations of serum oxylipins with clinical parameters in patients with alcohol-related liver disease. METHODS: We performed a comprehensive liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis of serum and fecal oxylipins derived from ω-6 arachidonic acid, ω-3 eicosapentaenoic acid, and docosahexaenoic acid in a patient cohort with alcohol-related liver disease. RESULTS: Our results show profound alterations in the serum oxylipin profile of patients with alcohol use disorder and alcoholic hepatitis compared to nonalcoholic controls. Spearman correlation of the oxylipins with clinical parameters shows a link between different serum oxylipins and intestinal permeability, aspartate aminotransferase, bilirubin, albumin, international normalized ratio, platelet count, steatosis, fibrosis and model for end-stage liver disease score. Especially, higher level of serum 20-HETE was significantly associated with decreased albumin, increased hepatic steatosis, polymorphonuclear infiltration, and 90-day mortality. CONCLUSIONS: Patients with alcohol-related liver disease have different oxylipin profiles. Future studies are required to confirm oxylipins as disease biomarker or to connect oxylipins to disease pathogenesis.

Integrated Care Increases Treatment and Improves Outcomes of Patients With Chronic Hepatitis C Virus Infection and Psychiatric Illness or Substance Abuse.

BACKGROUND & AIMS: Patients with hepatitis C virus (HCV) infection with psychiatric disorders and/or substance abuse face significant barriers to antiviral treatment. New strategies are needed to improve treatment rates and outcomes. We investigated whether an integrated care (IC) protocol, which includes multidisciplinary care coordination and patient case management, could increase the proportion of patients with chronic HCV infection who receive antiviral treatment (a combination of interferon-based and direct-acting antiviral agents) and achieve a sustained virologic response (SVR). METHODS: We performed a prospective randomized trial at 3 medical centers in the United States. Participants (n = 363 patients attending HCV clinics) had been screened and tested positive for depression, post-traumatic stress disorder, and/or substance use; they were assigned randomly to groups that received IC or usual care (controls) from March 2009 through February 2011. A midlevel mental health practitioner was placed at each HCV clinic to provide IC with brief mental health interventions and case management, according to formal protocol. The primary end point was SVR. RESULTS: Of the study participants, 63% were non-white, 51% were homeless in the past 5 years, 64% had psychiatric illness, 65% were substance abusers within 1 year before enrollment, 57% were at risk for post-traumatic stress disorder, 71% had active depression, 80% were infected with HCV genotype 1, and 23% had advanced fibrosis. Over a mean follow-up period of 28 months, a greater proportion of patients in the IC group began receiving antiviral therapy (31.9% vs 18.8% for controls; P = .005) and achieved a SVR (15.9% vs 7.7% of controls; odds ratio, 2.26; 95% confidence interval, 1.15-4.44; P = .018). There were no differences in serious adverse events between groups. CONCLUSIONS: Integrated care increases the proportion of patients with HCV infection and psychiatric illness and/or substance abuse who begin antiviral therapy and achieve SVRs, without serious adverse events. ClinicalTrials.gov # NCT00722423.

Supplementation of saturated long-chain fatty acids maintains intestinal eubiosis and reduces ethanol-induced liver injury in mice.

BACKGROUND & AIMS: Alcoholic liver disease is a leading cause of mortality. Chronic alcohol consumption is accompanied by intestinal dysbiosis, and development of alcoholic liver disease requires gut-derived bacterial products. However, little is known about how alterations to the microbiome contribute to pathogenesis of alcoholic liver disease. METHODS: We used the Tsukamoto-French mouse model, which involves continuous intragastric feeding of isocaloric diet or alcohol for 3 weeks. Bacterial DNA from the cecum was extracted for deep metagenomic sequencing. Targeted metabolomics assessed concentrations of saturated fatty acids in cecal contents. To maintain intestinal metabolic homeostasis, diets of ethanol-fed and control mice were supplemented with saturated long-chain fatty acids (LCFA). Bacterial genes involved in fatty acid biosynthesis, amounts of lactobacilli, and saturated LCFA were measured in fecal samples of nonalcoholic individuals and patients with active alcohol abuse. RESULTS: Analyses of intestinal contents from mice revealed alcohol-associated changes to the intestinal metagenome and metabolome, characterized by reduced synthesis of saturated LCFA. Maintaining intestinal levels of saturated fatty acids in mice resulted in eubiosis, stabilized the intestinal gut barrier, and reduced ethanol-induced liver injury. Saturated LCFA are metabolized by commensal Lactobacillus and promote their growth. Proportions of bacterial genes involved in fatty acid biosynthesis were lower in feces from patients with active alcohol abuse than controls. Total levels of LCFA correlated with those of lactobacilli in fecal samples from patients with active alcohol abuse but not in controls. CONCLUSIONS: In humans and mice, alcohol causes intestinal dysbiosis, reducing the capacity of the microbiome to synthesize saturated LCFA and the proportion of Lactobacillus species. Dietary approaches to restore levels of saturated fatty acids in the intestine might reduce ethanol-induced liver injury in patients with alcoholic liver disease.

Increasing antiviral treatment through integrated hepatitis C care: a randomized multicenter trial.

Most individuals infected with the hepatitis C have not received antiviral treatment, with mental health and substance abuse problems being the primary barrier. Interventions have been developed to address these barriers among HCV patients considered "high-risk" for antiviral treatment. We present the design and methods of a prospective, randomized controlled multisite trial being conducted in the Veterans Affairs Healthcare System. The study employed a parallel design and the three study sites randomized a total of 364 VA patients with HCV to either Integrated Care (IC) or Usual Care (UC). The IC intervention consisted of a mental health provider (MHP) performing a) brief interventions to address risk factors; b) collaborative consultation with the HCV treatment clinicians; and c) case management prior to and during antiviral treatment. Clinical outcomes were abstracted from patient medical records and self-report questionnaires were completed at baseline, 4-months, 16-months, and 22-months after enrollment. The primary outcome of the study was sustained viral response (SVR). Secondary clinical outcomes were HCV treatment initiation and completion rates. Other secondary outcomes included substance use, depression, PTSD symptoms, quality of life, healthcare satisfaction, and healthcare utilization. The Integrated Care intervention has the potential to transform HCV antiviral treatment by increasing the number of HCV-infected individuals that can be successfully treated.

Cysteine-rich domains of muc3 intestinal mucin promote cell migration, inhibit apoptosis, and accelerate wound healing.

BACKGROUND & AIMS: Muc3 intestinal mucin contains an extracellular cysteine-rich domain with 2 epidermal growth factor (EGF)-like motifs. The aim of this study was to determine the functional properties of Muc3 proteins. METHODS: Glutathione S-transferase-fusion proteins containing both Muc3 EGF-like domains (m3EGF1,2) or truncated versions (m3EGF1 and m3EGF2) were purified from Escherichia coli. Mouse colon (young adult mouse colon) and human A431 and LoVo cells were examined for migration and tyrosine phosphorylation in response to recombinant proteins. LoVo cells were transfected with a human MUC3A transmembrane-EGF1,2 construct and a stable clone was isolated (LhM3c14). Endogenous MUC3A in LoVo was inhibited by specific small interfering RNA transfection. Apoptosis was quantitated by nuclear morphology or terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling assay. Colitis was induced in mice by oral 5% dextran sodium sulfate or rectal 5% acetic acid, followed by enema treatments. RESULTS: m3EGF1,2 stimulated cell migration in all cell lines, but did not induce proliferation. Migration was inhibited by a tyrosine phosphorylation inhibitor, genistein, but not by the EGF receptor inhibitor, tyrphostin (AG1478). Inhibition of endogenous MUC3A in LoVo reduced baseline migration. Tyrosine phosphorylation of ErbB receptors was not observed after treatment of cells with m3EGF1,2. LoVo cells pretreated with m3EGF1,2 and transfected LhM3c14 cells showed reduced apoptosis in response to tumor necrosis factor alpha or Fas-receptor stimulation. Administration of m3EGF1,2 per rectum significantly reduced mucosal ulceration and apoptosis in experimental acute colitis. Truncated proteins m3EGF1 and m3EGF2 had no effect. CONCLUSIONS: The Muc3 mucin cysteine-rich domain plays an active role in epithelial restitution, and represents a potential novel therapeutic agent for intestinal wound healing.