Case report: progressive familial intrahepatic cholestasis type 3 with compound heterozygous ABCB4 variants diagnosed 15 years after liver transplantation.

BACKGROUND: Progressive familial intrahepatic cholestasis (PFIC) type 3 is an autosomal recessive disorder arising from mutations in the ATP-binding cassette subfamily B member 4 (ABCB4) gene. This gene encodes multidrug resistance protein-3 (MDR3) that acts as a hepatocanalicular floppase that transports phosphatidylcholine from the inner to the outer canalicular membrane. In the absence of phosphatidylcholine, the detergent activity of bile salts is amplified and this leads to cholangiopathy, bile duct loss and biliary cirrhosis. Patients usually present in infancy or childhood and often progress to end-stage liver disease before adulthood. CASE PRESENTATION: We report a 32-year-old female who required cadaveric liver transplantation at the age of 17 for cryptogenic cirrhosis. When the patient developed chronic ductopenia in the allograft 15 years later, we hypothesized that the patient's original disease was due to a deficiency of a biliary transport protein and the ductopenia could be explained by an autoimmune response to neoantigen that was not previously encountered by the immune system. We therefore performed genetic analyses and immunohistochemistry of the native liver, which led to a diagnosis of PFIC3. However, there was no evidence of humoral immune response to the MDR3 and therefore, we assumed that the ductopenia observed in the allograft was likely due to chronic rejection rather than autoimmune disease in the allograft. CONCLUSIONS: Teenage patients referred for liver transplantation with cryptogenic liver disease should undergo work up for PFIC3. An accurate diagnosis of PFIC 3 is key for optimal management, therapeutic intervention, and avoidance of complications before the onset of end-stage liver disease.

Patterns of fish and whale consumption in relation to methylmercury in hair among residents of Western Canadian Arctic communities.

BACKGROUND: Methylmercury contamination of the environment represents a substantial environmental health concern. Human exposure to methylmercury occurs primarily through consumption of fish and marine mammals. Heavily exposed subgroups include sport or subsistence fishers residing in Arctic communities. We aimed to estimate the association of fish/whale consumption patterns of Canadian Arctic subsistence fishers with the internal dose of methylmercury as measured in hair. METHODS: This research was conducted within ongoing community projects led by the CANHelp Working Group in Aklavik and Fort McPherson, Northwest Territories and Old Crow, Yukon. We interviewed each participant using a fish-focused food-frequency questionnaire during September-November 2016 and collected hair samples concurrently. Methylmercury was measured in the full-length of each hair sample using gas chromatography inductively-coupled plasma-mass spectrometry. Multivariable linear regression estimated beta-coefficients and 95% confidence intervals (CIs) for the effect of fish/whale consumption on hair-methylmercury concentrations. RESULTS: Among 101 participants who provided hair samples and diet data, the mean number of fish/whale species eaten was 3.5 (SD:1.9). The mean hair-methylmercury concentration was 0.60 µg/g (SD:0.47). Fish/whale consumption was positively associated with hair-methylmercury concentration, after adjusting for sex, hair length and use of permanent hair treatments. Hair-methylmercury concentrations among participants who consumed the most fish/whale in each season ranged from 0.30-0.50 µg/g higher than those who consumed < 1 meal/week. CONCLUSIONS: In this population of Canadian Arctic subsistence fishers, hair-methylmercury concentration increased with fish/whale consumption, but the maximum concentrations were below Health Canada's 6.0 µg/g threshold for safe exposure.

Burden of disease from Helicobacter pylori infection in western Canadian Arctic communities.

BACKGROUND: Indigenous communities across the circumpolar north have elevated H. pylori (Hp) prevalence and stomach cancer incidence. We aimed to describe the Hp-associated disease burden among western Canadian Arctic participants in community-driven projects that address concerns about health risks from Hp infection. METHODS: During 2008-2013, participants underwent Hp screening by urea breath test and gastroscopy with gastric biopsies. We estimated Hp prevalence and prevalence by Hp status of endoscopic and histopathologic diagnoses. RESULTS: Among 878 participants with Hp status data, Hp prevalence was: 62% overall; 66% in 740 Indigenous participants; 22% in 77 non-Indigenous participants (61 participants did not disclose ethnicity); 45% at 0-14 years old, 69% at 15-34 years old, and 61% at 35-96 years old. Among 309 participants examined endoscopically, visible mucosal lesions were more frequent in the stomach than the duodenum: the gastric to duodenal ratio was 2 for inflammation, 8 for erosions, and 3 for ulcers. Pathological examination in 308 participants with gastric biopsies revealed normal gastric mucosa in 1 of 224 Hp-positive participants and 77% (65/84) of Hp-negative participants with sharp contrasts in the prevalence of abnormalities between Hp-positive and Hp-negative participants, respectively: moderate-severe active gastritis in 50 and 0%; moderate-severe chronic gastritis in 91 and 1%; atrophic gastritis in 43 and 0%; intestinal metaplasia in 17 and 5%. CONCLUSIONS: The observed pattern of disease is consistent with increased risk of stomach cancer and reflects substantial inequity in the Hp-associated disease burden in western Arctic Canadian hamlets relative to most North American settings. This research adds to evidence that demonstrates the need for interventions aimed at reducing health risks from Hp infection in Indigenous Arctic communities.

Acute Liver Failure from Tumor Necrosis Factor-α Antagonists: Report of Four Cases and Literature Review.

BACKGROUND: Tumor necrosis factor-α antagonists (anti-TNF-α) have been associated with drug-induced liver injury. However, cases of anti-TNF-α-associated acute liver failure have only been rarely reported. AIMS: To identify cases of anti-TNF-α-associated acute liver failure and evaluate patterns of liver injury and common characteristics to the cases. METHODS: The United States Acute Liver Failure Study Group database was searched from 1998 to 2014. Four subjects were identified. A PubMed search for articles that reported anti-TNF-α-associated acute liver failure identified five additional cases. RESULTS: The majority of individuals affected were female (eight of nine cases). Age of individual ranged from 20 to 53 years. The most common anti-TNF-α agent associated with acute liver failure was infliximab (n = 8). The latency between initial drug exposure and acute liver failure ranged from 3 days to over a year. Of the nine cases, six required emergency LT. Liver biopsy was obtained in seven cases with a preponderance toward cholestatic-hepatitic features; none showed clear autoimmune features. CONCLUSIONS: Anti-TNF-α-associated acute liver failure displays somewhat different characteristics compared with anti-TNF-α-induced drug-induced liver injury. Infliximab was implicated in the majority of cases. Cholestatic-hepatitic features were frequently found on pre-transplant and explant histology.

Case 235: Hepatic Adenomatosis Due to Inflammatory Adenomas.

History An asymptomatic 33-year-old woman was referred to the Hepatology Department in 2013 for work-up of indeterminate multifocal liver masses. These lesions were discovered incidentally at multiphase contrast material-enhanced multidetector computed tomography (CT) performed in 2004 to investigate right lower quadrant pain. Imaging surveillance at sporadic intervals revealed slow progressive growth of the lesions over time; however, the number of lesions remained constant. There was no history of cancer, nor were there predisposing factors for chronic liver disease or cirrhosis. The patient had a history of menorrhagia, which was managed with oral contraceptive use for 20 years; this was stopped in 2013 after hysterectomy. The patient's γ-glutamyl transferase (77 U/L [1.28 µkat/L]; normal level, <55 U/L [<0.92 µkat/L]) and C-reactive protein (97.1 mg/L [924.8 nmol/L]; normal level, <8 mg/L [<76.2 nmol/L]]) levels were chronically elevated at serum testing. In 2013, 9 years after the initial CT examination, magnetic resonance (MR) imaging with gadoxetic acid (Primovist; Bayer Healthcare, Whippany, NJ) was performed. Finally, ultrasonography (US)-guided biopsy of one of the lesions (in segment 5/6) was performed a year after MR imaging.

Percutaneous transhepatic cholangioscopy for indeterminate biliary strictures using the SpyGlass system: a case series.

Peroral cholangioscopy is useful in differentiating benign from malignant biliary strictures. However, when conventional biliary access via endoscopic retrograde cholangiopancreatography (ERCP) fails, percutaneous transhepatic cholangioscopy (PTCS) via the SpyGlass cholangioscopy system can be used to achieve a diagnosis. Four patients with biliary strictures in whom conventional ERCP was not possible and percutaneous brushings were either nondiagnostic or unsatisfactory were investigated with PTCS. The technique of PTCS involves insertion of the SpyGlass cholangioscope through a percutaneous transhepatic sheath, placed just prior to the procedure, to visualize the stricture and obtain biopsies with the SpyBite forceps. On the basis of our early observations, we conclude that PTCS using the SpyGlass cholangioscopy system for the assessment of biliary strictures is feasible, safe, and provides high diagnostic accuracy.

Impact of combination antiretroviral therapy in the NOD.c3c4 mouse model of autoimmune biliary disease.

BACKGROUND & AIMS: The NOD.c3c4 mouse model develops autoimmune biliary disease characterized by spontaneous granulomatous cholangitis, antimitochondrial antibodies and liver failure. This model for primary biliary cirrhosis (PBC) has evidence of biliary infection with mouse mammary tumour virus (MMTV), suggesting that the virus may have a role in cholangitis development and progression of liver disease in this mouse model. We tested the hypothesis that MMTV infection is associated with cholangitis in the NOD.c3c4 mouse model by investigating whether antiretroviral therapy impacts on viral levels and liver disease. METHODS: NOD.c3c4 mice were treated with combination antiretroviral therapy. Response to treatment was studied by measuring MMTV RNA in the liver, liver enzyme levels in serum and liver histology using a modified Ishak score. RESULTS: Combination therapy with the reverse transcriptase inhibitors, tenofovir and emtricitabine, resulted in a significant reduction in serum liver enzyme levels, attenuation of cholangitis and decreased MMTV levels in the livers of NOD.c3c4 mice. Furthermore, treatment with the retroviral protease inhibitors, lopinavir and ritonavir, in addition to the reverse transcriptase inhibitors, resulted in further decrease in MMTV levels and attenuation of liver disease in this model. CONCLUSIONS: The attenuation of cholangitis with regimens containing the reverse transcriptase inhibitors, tenofovir and emtricitabine, and the protease inhibitors, lopinavir and ritonavir, suggests that retroviral infection may play a role in the development of cholangitis in this model.

Success of Helicobacter pylori Guideline-based Treatment of Newly Diagnosed and Previously Treated Patients During 2007-2021 in Edmonton, Alberta.

Background: Updated 2016 Helicobacter pylori consensus guidelines recommend treatment for 14 days with concomitant therapy (proton-pump inhibitor (PPI)-amoxicillin-metronidazole-clarithromycin (PAMC) or bismuth-based quadruple therapy (PPI-bismuth-metronidazole-tetracycline, PBMT)) as first line, PBMT or PPI-amoxicillin-levofloxacin (PAL) as second or third line, and PPI-amoxicillin-rifabutin (PAR) as fourth line for 10 days. Objectives: This was a retrospective cohort study to describe and compare the efficacy of anti-Helicobacter treatment regimens over the periods 2007-2015 and 2016-2021 as well as antibiotic resistance. Methods: A modified intention-to-treat (mITT) analysis was used to analyze the success rate of therapies. mITT includes all patients who were prescribed H. pylori treatment and had at least one follow-up test-of-cure. This included patients who could not complete treatment or were non-adherent with treatment. Risk factors for treatment failures were analyzed by univariate and multivariate logistic regression. Resistance testing was done in a small subset of patients. Results: H. pylori-positive patients who received treatment in Edmonton, Alberta were included in a mITT analysis: 334/387(86%) from 2007 to 2015 and 193/199 (97%) from 2016 to 2021. During 2016-2021, 78% (150/193) of patients underwent cumulative guideline-based treatment with a successful cure in 80% (120/150) of patients. In those who were newly diagnosed, the cure rate was 88% (52/59) versus those with previous treatment failure 75% (68/91) (P < 0.05, risk difference [RD] 14%, 95% confidence interval [CI] 1.7-26.3%). The most effective first-line regimens were PAMC for 14 days (87% [45/52]) in 2016-2021 and sequential therapy in 2007-2015 (83% [66/80]) (P = 0.535, RD 4%, 95% CI -8.5-16.5%). When other treatments failed, success with PAR was 50% (2/4) from 2007 to 2015 and 57% (21/37) from 2016 to 2021. Recent (2016-2021) resistance rates to clarithromycin and metronidazole are high at 78% (50/64) and 56% (29/52), respectively. From 2007 to 2015, clarithromycin and metronidazole resistance rates were 80% (36/45) and 83% (38/46), respectively. Levofloxacin resistance increased significantly from 2007-2015 to 2016-2021 (28% [13/46] to 61% [35/57], P < 0.05, RD 33%, 95% CI 11.6-54.4%). Conclusions: Algorithmic treatment with PAMC first line followed by PBMT, PAL, and PAR cures H. pylori in 88% of newly diagnosed patients. PAR therapy shows suboptimal cure rates (50-57% success) but can be considered as third instead of fourth line given increasing levofloxacin resistance rates. Antibiotic resistance in H. pylori is common to clarithromycin, metronidazole, and levofloxacin and frequently accounts for treatment failures.

Liver transplantation for overlap syndromes of autoimmune liver diseases.

BACKGROUND/AIMS: The term overlap syndrome describes variant forms of autoimmune hepatitis (AIH) that present in combination with either characteristics of primary biliary cirrhosis (PBC), or primary sclerosing cholangitis (PSC). This study analysed the outcomes and evidence of recurrent liver disease after liver transplantation in patients with overlap syndromes compared with patients transplanted for single autoimmune liver disease. METHODS: We evaluated 231 adult patients who received a liver transplant as a result of autoimmune liver diseases; including 103 with PBC, 84 with PSC, 32 with AIH and 12 with overlap syndrome (7 AIH-PBC and 5 AIH-PSC). RESULTS: Patients with overlap syndromes had a higher probability of recurrence than patients with a single autoimmune liver disease (5 years: 53% vs. 17%; 10 years 69% vs. 29%, P = 0.001). Furthermore, median time for recurrence in overlap syndrome was shorter when compared with patients with single autoimmune liver disease (67 ± 20 vs. 172 ± 9 months, P = 0.001). The diagnosis of overlap syndrome was independently associated with a higher risk to develop recurrent disease than patients transplanted with a single disease (HR 3.39, P = 0.007). Median graft survival for overlap syndrome was 123 ± 16 months and 180 ± 8 months in patients with single autoimmune liver diseases (P = 0.9), and median patient survival for overlap syndrome was 135 ± 13 months and 193 ± 8 months in patients with single autoimmune liver disease (P = 0.6). CONCLUSIONS: Patients that received an allograft for end-stage liver disease secondary to overlap syndrome had a higher rate of disease recurrence when compared with transplant recipients with single autoimmune liver disorders, but the overall survival was comparable.

Multimodality imaging findings of pheochromocytoma with associated clinical and biochemical features in 53 patients with histologically confirmed tumors.

OBJECTIVE: The purpose of this study was to determine the spectrum of imaging appearances of pheochromocytoma and the associated clinical and biochemical features. MATERIALS AND METHODS: In this retrospective study, a citywide pathology database (2000-2011) was searched to identify the records of patients with pheochromocytoma. The search yielded the cases of 53 patients (28 men, 25 women; mean age, 50 years). The institutional PACS and radiology information system records, hospital charts, and the provincial electronic health records of these patients were reviewed. Imaging appearances and clinical and biochemical features related to pheochromocytomas were recorded. RESULTS: One chart was not available for review. In the 52 cases analyzed, 40 of the patients had symptoms: 31 patients had hypertension; 10 had the triad of palpitations, diaphoresis, and headaches; and all had elevated urinary metanephrine concentrations. Seven patients had a familial syndrome, and five had bilateral pheochromocytomas. One patient had an extraadrenal pheochromocytoma, and five had malignant tumors. The mean size of pheochromocytomas was 4.0 cm. Most pheochromocytomas were heterogeneous (CT, 56%; MRI, 65%; ultrasound, 45%) and were MIBG positive (90%). Eleven of 34 (32%) pheochromocytomas had T2 signal intensity greater than that of the spleen. Most pheochromocytomas were less enhancing than the spleen (CT, 85%; MRI, 71%). Contrast-enhanced CT was performed on 33 tumors, of which 20 enhanced less than the spleen and 8 showed similar enhancement to the spleen; contrast-enhanced MRI was performed on 24 tumors, of which 12 enhanced less than the spleen and 5 showed similar enhancement to the spleen. Predominant cystic change was found in 4 of 20 (20%) ultrasound, 9 of 41 (22%) CT, and 11 of 34 (32%) MRI examinations. Eight of 34 (24%) pheochromocytomas were hemorrhagic, two (5%) had calcifications, and three of six were PET positive. Two cystic pheochromocytomas and one lipid-containing pheochromocytoma were misdiagnosed as adrenal adenomas. CONCLUSION: Most pheochromocytomas were heterogeneous at imaging, were MIBG positive, accompanied elevated urinary metanephrine concentrations, and were symptomatic. High T2 signal intensity was found in approximately one third of solid tumors. Atypical imaging features included homogeneity, cystic change, hemorrhage, intense enhancement, calcifications, intracellular lipid, bilaterality, and malignancy.

Changes in Gastric Pathology after H. pylori Treatment in Community-Driven Research Aimed at Gastric Cancer Prevention.

Community-driven projects have characterized Helicobacter pylori (Hp) infection in Indigenous communities in the Northwest Territories (NT) and Yukon (YT), Canada. These projects address concerns about the frequent diagnosis of Hp infection among community members and its relation to gastric cancer deaths, perceived to occur with alarming frequency in this region. Projects included breath-test screening for Hp infection, gastroscopy with gastric biopsies, and treatment to eliminate Hp infection. Previous project results showed a high prevalence of stomach pathologies associated with increased cancer risk among Hp-positive participants at baseline. This analysis describes changes in precancerous gastric pathologies in project participants who had gastroscopy before baseline treatment during 2008-2013 and again in 2017. Throughout the study period, the same pathologist graded Hp density, active gastritis, chronic gastritis, atrophic gastritis, and intestinal metaplasia using the updated Sydney System. Of 310 participants from three communities with baseline pathology data, 69 had follow-up pathology data. Relative to baseline, the prevalence of Hp infection and precancerous gastric pathology was substantially lower at follow-up; most participants who were Hp-positive at baseline and Hp-negative at follow-up had reduced severity of active, chronic, and/or atrophic gastritis at follow-up. Though follow-up numbers are small, these results yield evidence that successful Hp treatment has the potential to reduce the risk of gastric cancer in Arctic Indigenous communities.

Acute hepatitis following mRNA BNT162b2 COVID-19 vaccination.

BACKGROUND: Widespread administration of COVID-19 vaccinations have led to reports of rare but potentially serious side effects. METHODS: We present two cases of acute hepatitis following mRNA BNT162b2 (Comirnaty, Pfizer-BioNTech) vaccination. RESULTS: A 25-year-old male presented to hospital with progressive jaundice 5 days following his second dose of Comirnaty. Initial bloodwork revealed severe hepatocellular enzyme elevation and conjugated hyperbilirubinemia with preserved INR. Extensive serologic workup was negative, with normal imaging. Percutaneous liver biopsy was performed and revealed acute cholestatic hepatitis possibly related to drug-induced liver injury. He was started on prednisone 40 mg daily with good initial response but had a second flare; a biopsy was repeated which showed near-identical findings. Steroids were discontinued given non-response and the patient had gradual near complete resolution of liver enzymes and hyperbilirubinemia. A 32-year-old male presented with a 4-week history of nausea followed by progressive choluria, jaundice, and pruritis. He received his second dose of Comirnaty vaccination two weeks prior to presentation. Initial bloodwork showed mixed enzyme elevation with hyperbilirubinemia. Serological workup and imaging were unrevealing. He underwent liver biopsy which showed severe intrahepatic cholestasis, with drug-induced liver injury being suggested as most likely cause. His course was self-limited with resolution of serological abnormalities and symptoms. CONCLUSIONS: While overwhelmingly safe on a population level, our case series illustrate two cases of acute icteric hepatitis following mRNA BNT162b2 vaccination. Clinicians should be aware of this association with hepatic inflammation and consider vaccine history an important component of evaluating patients with acute liver injury.

Abnormal Gastrointestinal Histopathology in Children With Autism Spectrum Disorders.

OBJECTIVES:: The significance of the association between many gastrointestinal (GI) pathologies and autism has yet to be discovered. The aim of the present study was to review available evidence documenting any link between autism and GI histopathology in children. MATERIALS AND METHODS:: In a systematic review, the following sources were searched: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1980-August week 2, 2009), EMBASE (1980-August week 2, 2009), PubMed (last 180 days), Web of Science, and Scopus, using the terms "autism" or "autistic spectrum disorder" and "intestinal" or "gastrointestinal" or "colitis." In addition, relevant studies were identified through browsing the reference lists of the included articles for relevant citations. All children younger than 18 years old with autistic spectrum disorder who were examined for abnormal GI histopathology were included. Cohort studies published in the English language, reporting GI histopathological examination findings in children with autism, were included. Two independent authors performed data extraction. The methodological quality of each trial was assessed. RESULTS:: Eight studies have reported the histopathological features of the GI tract in children with autism and fulfilled inclusion criteria. In general, none of these trials appeared to be of high quality. Apart from intestinal lymphonodular hyperplasia, the majority of these findings were not consistent. CONCLUSIONS:: GI pathological findings in children with autism have been inconsistent. The present available evidence does not support or refute a link between GI histopathology and autism in children. The significance of intestinal lymphonodular hyperplasia in these children is unknown. Large properly designed prospective controlled trials addressing this issue are required.

Community-driven research in the canadian arctic: dietary exposure to methylmercury and gastric health outcomes.

Indigenous Arctic Canadians have a higher prevalence of gastric neoplasms relative to North Americans of European ancestry. We investigated the hypothesis that low-dose methylmercury exposure from eating fish/whale increases the risk of gastric cancer in Arctic communities. We used intermediate endpoints from an established model of gastric carcinogenesis: intestinal metaplasia, atrophy, and severe chronic gastritis. During 2008-2012, we obtained gastric biopsies from participants of community-driven projects in 3 communities. In 2016, we collected hair samples to measure methylmercury levels and interviewed them about diet. In cross-sectional analysis, logistic regression estimated odds ratios for the estimated effect of hair-methylmercury concentration on the prevalence of each pathology outcome stratified by selenium intake. Among 80 participants, prevalence of intestinal metaplasia, atrophy and severe chronic gastritis was 17, 29 and 38%, respectively. Adjusted Odds of severe chronic gastritis and atrophy were highest at hair-methylmercury concentrations ≥1µg/g when estimated selenium intake was 0, and approached 0 for all methylmercury levels as estimated selenium intake increased. Gastric pathology increased with methylmercury exposure when selenium intake was low. Though limited by small numbers, these findings suggest selenium ingested by eating fish/whale may counter harmful effects of methylmercury exposure in Arctic populations.

Epidemiological and Clinical Characteristics of Alveolar Echinococcosis: An Emerging Infectious Disease in Alberta, Canada.

Human alveolar echinococcosis (AE) is a zoonotic cestode infection which is usually fatal in the absence of treatment. Treatment involves major surgery or indefinite antiparasitic therapy. The incidence is rising in Europe and Asia, with an increased risk observed in immunocompromised individuals. Previously, AE acquisition in North America was extremely rare, except for one remote Alaskan Island. Recent studies have demonstrated a new European-like strain of Echinococcus multilocularis (Em) in wildlife and in human AE in western Canada. We report the experience of all AE patients diagnosed in Alberta. Each was diagnosed by histopathology, serology, and PCR-confirmed by a reference laboratory. Seventeen cases of human AE, aged 19-78 years, nine females, were diagnosed between 2013 and 2020: all definitely or probably acquired in Alberta. Six lived in urban areas, and 14 had kept dogs. In eight, the lesions were found incidentally on abdominal imaging performed for other indications. Six were immunocompromised to varying degrees. Six were first diagnosed at surgery. All have been recommended benzimidazole therapy. One died of surgical complications. Clinicians should be aware of this diagnostic possibility in patients presenting with focal nonmalignant hepatic mass lesions. Greater urbanization of coyotes, the predominant definitive host of Em in Alberta, and growing numbers of immune suppressed individuals in the human population may lead to increasing recognition of AE in North America.

The impact of sirolimus on hepatocyte proliferation after living donor liver transplantation.

BACKGROUND: There is a lack of data on the use of sirolimus after partial liver transplantation, especially regarding its impact on post-transplant regeneration. METHODS: We reviewed adult living donor transplantations, with de novo sirolimus (n = 7) and without sirolimus (n = 21). Liver biopsies were stained for KI-67, a proliferation marker. Controls included specimens with normal liver parenchyma (n = 13). RESULTS: Both groups had similar demographics, graft and patient survival and complication rates. During the first six wk and over the whole first year post-transplant, the use of sirolimus was associated with lower levels of hepatocyte proliferation compared to sirolimus-free patients, (overall, 0.3 [0-7.2] vs. 3 [0-49] KI-67 positive hepatocytes per high power field, p ≤ 0.05). The levels observed in the sirolimus group were similar to those seen in non-transplanted control patients with normal parenchyma (0.2 [0-1.3], p = NS). Post-transplant hepatocyte proliferation correlated with the serum levels of sirolimus (p ≤ 0.05), but not with those of tacrolimus or with the dose of mycophenolate mofetil (p = 0.9 and 0.3, respectively). CONCLUSIONS: These data suggest that sirolimus is associated with decreased post-transplant hepatocyte proliferation. The clinical significance of this observation remains to be fully determined.

Childhood autism and eosinophilic colitis.

BACKGROUND/AIMS: The significance of the association between many gastrointestinal pathologies and autism is yet to be discovered. The aim of this report is to highlight an association between autism and microscopic eosinophilic colitis in 2 children. The possible mechanisms that may connect these two conditions are discussed. METHODS AND RESULTS: A rare association between autism and microscopic eosinophilic colitis in 2 children is reported through retrospective chart review. Common causes of secondary eosinophilic colitis were excluded. CONCLUSION: This report suggests the possibility of either impaired intestinal barrier function or an aberrant immune system that predisposes autistic children to sensitization to environmental antigens. Large controlled studies are needed to examine this hypothesis.

Microscopic colitis in children.

BACKGROUND: Microscopic colitis typically presents with chronic watery nonbloody diarrhea with normal endoscopy findings but abnormal inflammatory histopathological findings. As it is mainly a condition of the elderly, pediatric data is scarce. AIMS: To describe and characterize children with microscopic colitis. METHODS: The pathology database at the University of Alberta Hospital together with the pediatric inflammatory bowel disease database at the Stollery Children's Hospital were both searched from September 1996 to May 2008. Charts of all children under the age of 17 years who fulfilled the diagnostic criteria of microscopic colitis were examined. RESULTS: Eleven children (four girls, mean age at diagnosis 11.2 years, +/- 4.4 years) fulfilled the inclusion criteria. The patients were followed up for a mean of 24.8 months (standard deviation, SD 15.2 months). Two patients were on proton pump inhibitors, two had stool organisms, and two had immunodeficiency. All patients had normal endoscopy and colonoscopy on visualization. Five patients were diagnosed with lymphocytic colitis and the rest had nonspecific/eosinophilic microscopic colitis. The majority of children responded to mesalazine. One patient with immunodeficiency was difficult to manage. CONCLUSIONS: Microscopic colitis is rare in children. Microscopic eosinophilic colitis is an underdescribed variant of microscopic colitis. The majority of children with microscopic colitis respond well to aminosalicylic acid (5-ASA) medications. Microscopic colitis associated with immunodeficiency can be very challenging to manage. Large multicenter pediatric trials with long-term follow-up are needed to allow investigators to have a better understanding of this rare condition in children.