Adam E. Mikolajczyk

Gastrointestinal Manifestations of Autosomal-Dominant Polycystic Kidney Disease

&NA; Autosomal‐dominant polycystic kidney disease (ADPKD) is the most commonly inherited kidney disease, and the fourth most common cause of end‐stage renal disease. ADPKD is a systemic disorder, associated with numerous extrarenal manifestations, including polycystic liver disease, the most common gastrointestinal manifestation, and diverticular disease, inguinal, and ventral hernias, pancreatic cysts, and large bile duct abnormalities. All of these gastrointestinal manifestations play a significant role in disease burden in ADPKD, particularly in the later decades of life. Thus, as ADPKD becomes more recognized, it is important for gastroenterologists to be knowledgeable of this monogenic disorders effects on the digestive system.

Assessment of Tandem Measurements of pH and Total Gut Transit Time in Healthy Volunteers

Objectives:The variation of luminal pH and transit time in an individual is unknown, yet is necessary to interpret single measurements. This study aimed to assess the intrasubject variability of gut pH and transit time in healthy volunteers using SmartPill devices (Covidien, Minneapolis, MN).Methods:Each subject (n=10) ingested two SmartPill devices separated by 24 h. Mean pH values were calculated for 30 min after gastric emptying (AGE), before the ileocecal (BIC) valve, after the ileocecal (AIC) valve, and before body exit (BBE). Intrasubject variability was determined by comparing mean values from both ingestions for an individual subject using standard deviations, 95% limits of agreement, and Bland-Altman plots.Results:Tandem device ingestion occurred without complication. The median (full range) intrasubject standard deviations for pH were 0.02 (0.0002–0.2048) for AGE, 0.06 (0.0002–0.3445) for BIC, 0.14 (0.0018–0.3042) for AIC, and 0.08 (0.0098–0.5202) for BBE. There was a significant change in pH for AIC (mean difference: −0.45±0.31, P=0.0015) observed across all subjects. The mean coefficients of variation for transit time were 12.0±7.4% and 25.8±15.8% for small and large bowels, respectively (P=0.01).Conclusions:This study demonstrates the safety and feasibility of tandem gut transit and pH assessments using the SmartPill device. In healthy individuals and over 24 h, the gut pH profile does not markedly fluctuate in a given region with more variation seen in the colon compared with the small bowel, which has important implications for future physiology and drug delivery studies.

Current Management of Chronic Hepatitis B and C in Chronic Kidney Disease.

The landscape of therapeutic options for hepatitis B and C has changed drastically over the course of 2 decades. There are now novel, effective, well-tolerated, oral antiviral agents being used to successfully control chronic hepatitis B (HBV) infections and cure chronic hepatitis C (HCV) infections. However, patients with CKD were rarely included in the Phase II and III randomized trials for these medications. This paucity of data and the high prevalence of comorbidities associated with CKD pose distinct challenges to physicians treating chronic hepatitis B virus and hepatitis C virus infections in the setting of kidney insufficiency/failure. Thus, this review will attempt to summarize the current data regarding novel antiviral therapies for HBV and HCV in the CKD population.

Sa1213 Assessment of the Degree of Variation of Histologic Inflammation in Ulcerative Colitis

Introduction: Treatment goals in ulcerative colitis (UC) are evolving to more objective measures of mucosal inflammation. This has included endoscopic measures, and more recently, histologic measures. However, adoption of histologic endpoints of mucosal healing is hindered by a lack of evidence guiding interpretation and reproducibility of results. Aim: To characterize intra-segment and inter-segment variation of histologic scores of colonic mucosal inflammation in patients with UC. Methods: We analyzed 1802 biopsy fragments from standard of care colonoscopies in 94 UC patients (88 with pancolitis). The biopsies were scored using a novel, previously validated 6-point histologic inflammatory activity (HIA) scale . Location of the biopsies was described as rectum, left, or right side of colon. Biopsies from unlabeled locations were excluded. Variability was determined using both ordinal and continuous representations of HIA scores. In the ordinal intra-segment analysis, the most frequently observed score and the percentage of biopsies with that score were determined for each segment in a colonoscopy. The ordinal inter-segment analysis also calculated the most frequently observed score and the percentage of biopsies with that score but from across all 3 segments. Mean percentages and 95% confidence intervals were then calculated. The continuous analysis used random or fixed effects regression models in order to determine coefficients of variation (COV = standard deviation/mean HIA score). Results: The HIA scores included in the analyses are shown in Table 1. For the ordinal analysis, the mean percentages of intra-segment biopsies with the same HIA score were: 85.5% (95% CI, 80.9-92.9%) for the rectum, 79.6% (CI, 76.0-87.3%) for the left side, and 82.7% (CI, 79.1-90.0%) for the right side. The mean percentage of inter-segment biopsies with the same HIA score was 70.2% (CI, 65.7-82.5%). The continuous inter-segment analysis revealed a COV of 25.4% for HIA scores in patients with left-sided colitis and 14.7% in patients with pancolitis. Neither of these values was significantly greater than zero, the COV expected if all scores were identical (P=0.15 and 0.07, respectively). Both analyses separately revealed that there was no correlation between the degree of inflammation and the degree of intrasegment variation within scores. Conclusions: This is the first study to analyze the variability of histologic inflammation within individual patients with UC. Using our previously validated scoring system, we have demonstrated minimal variability between biopsies within each colonic segment and among different segments. These findings have significant implications for the use of histology as a clinical trial endpoint in UC. 1. Rubin DT, et al. Clin Gastroenterol Hepatol 2013;11:1601-1608. Distribution of HIA Scores

Massive Hepatic Infarction Caused by HELLP Syndrome

A healthy, 30-year-old woman at 32 weeks gestation presented to the emergency department with sudden-onset headache and abdominal pain. On physical exam, she was hypertensive (188/69 mm Hg) and had mild tenderness to palpation in the right upper quadrant. Initial laboratory studies revealed proteinuria, aspartate aminotransferase at 730 U/L, and alanine aminotransferase at 478 U/L. She was diagnosed with severe preeclampsia, and an emergent cesarean section was performed.

A Diagnosis That Eats at You

Question: A 78-year-old Caucasian man with a 12-year history of extensive ulcerative colitis in stable remission on azathioprine 150 mg/d presented to the emergency department with a 3-day history of fevers and malaise. He had no gastrointestinal symptoms. On physical examination, he had a fever of 40.1 C, was hypotensive (87/51 mmHg), and had a diffuse, lacy, macular rash with scattered petechiae. He also was noted to have an intention tremor and global, symmetric weakness. Azathioprine was discontinued, and an extensive infectious workup, including analysis of cerebral spinal fluid, only revealed elevated cytomegalovirus (CMV) DNA in the serum (39,000 copies/mL). Repeat assessment 24 hours later revealed an increase of serum CMV DNA to 154,000 copies/mL, without evidence of mutations that confer antiviral resistance. Thus, the patient was treated with an induction dose of ganciclovir 2.5 mg/kg every 24 hours. Over the course of several days, the patient developed melenic stool (upper endoscopy findings; Figures A and B), a coagulopathy (International Normalized Ratio, 1.7; partial thromboplastin time, 52.9 seconds), acute renal failure (blood urea nitrogen, 104 mg/dL; creatinine, 4.1 mg/dL), worsening liver injury (aspartate aminotransferase, 205 U/L; alanine aminotransferase, 95 U/L; alkaline phosphatase, 338 U/L), progressive hypoalbuminemia (1.9 g/dL), and pancytopenia (white blood cell count, 2.4 K/mL; hemoglobin, 5.9 g/dL; platelets, 80 K/mL). Ferritin was noted to increase from an initial 7657 ng/mL to 11,217 ng/mL, triglycerides were elevated (319 mg/dL), and fibrinogen was decreased (166 mg/dL). He was also noted to have hepatosplenomegaly on abdominal ultrasonography. In light of all these abnormalities, a biopsy was promptly performed. The pathology is shown Figures C–E. What is the cause of this patient’s physical examination findings, multi-organ dysfunction, and laboratory abnormalities? Look on page 489 for the answer and see the GASTROENTEROLOGY web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Acknowledgments: The authors acknowledge the contributions of Muhammad Mirza MD, PhD in the Section of Hematopathology in the Department of Pathology at the University of Chicago Medicine.

Pro: Patient and allograft survival remain the best metric to gauge successful liver transplantation

Survival is a well-validated, objective, quantifiable metric that can be adjusted across programs and is universally used in research and quality reporting. Program-specific survival reporting has been associated with continually improved outcomes among liver transplant recipients over the past two decades despite a continued increase in transplant volume and recipient medical acuity. Additional metrics, such as wait-list mortality, transplant rate, and recipient quality of life, have been proposed as important measures of program performance, but these metrics are not validated and may lead to unintended consequences for the transplant community.

Calciphylaxis in end-stage liver and renal disease patients before and after transplant

Calciphylaxis is a rare vascular disorder characterized by calcification of arterioles which causes tissue inflammation and necrosis. It is associated with the metabolic disturbances seen in end‐stage renal disease (ESRD) and has also been described in patients with cirrhosis with preserved kidney function. Characteristic calciphylaxis lesions are black eschars surrounded by retiform purpura, and the gold standard for diagnosis is skin biopsy. Reported 1‐year mortality rates range between 45% and 80%. No treatment modality has been evaluated in a prospective randomized trial, and reports of treatment efficacy vary. Kidney transplant has been reported as a successful therapy for calciphylaxis; however, cases exist of the initial onset of calciphylaxis following kidney transplant as well as simultaneous liver‐kidney (SLK) transplant. The decision to maintain a patient with end‐stage renal and liver disease on the waiting list for SLK transplant following the onset of calciphylaxis must consider the high 1‐year mortality associated with this condition. More research is necessary to understand how to allocate donor allografts to manage patients with calciphylaxis and ESRD and/or cirrhosis effectively.

Atypical Acute Liver Failure in Acute Myeloid Leukemia

Gastroent Question: A 65-yearold white womanwith therapy-related acute myeloid leukemia was admitted to the intensive care unit with altered mental status 33 days after completing induction chemotherapy with azacitadine, high-dose cytarabine, and mitoxantrone. She had a history of breast cancer treated 12 years prior with 4 cycles of cyclophosphamide and doxorubicin, local radiation therapy, and tamoxifen, as well as mantle cell lymphoma treated 6 years prior with bendamustine, rituximab, and radiation therapy to a lytic lesion of the L1 vertebrae. On physical examination, she was afebrile, normotensive (133/89 mmHg), but obtunded. She had scleral icterus as well as mild abdominal distension with minimal ascites. There were no recent additions to her medication list; the only potentially hepatotoxic agent present was prophylactic posaconazole, which had been discontinued several days prior. Her laboratory studies revealed neutropenia (absolute neutrophil count, 90 K/mL) and evidence of acute hepatic dysfunction (aspartate aminotransferase [AST], 4,891 U/L; alanine aminotransferase [ALT], 2,070 U/L; International Normalized Ratio [INR], 3.3). The total bilirubin (TB) was 5.4 mg/dL, alkaline phosphatase (AP) 90 U/L, and serum ammonia 61 mg/dL. There was no serologic evidence of acute varicella zoster or hepatitis A, B, C, D, or E infections. Furthermore, polymerase chain reaction assays for herpes simplex virus, Epstein-Barr virus, cytomegalovirus, human herpesvirus 6, and adenovirus were all negative. Thick and thin blood smears ruled out a transfusion-related trypanosomiasis infection; a urine toxicology screen was unremarkable, and a serum acetaminophen level was <3.0 mg/mL. Abdominal ultrasound revealed hepatomegaly (18.7 cm), ascites, a large right pleural effusion and patent hepatic vasculature. A liver biopsy had been deferred given her coagulopathy and persistent thrombocytopenia (<10 K/mL). Thus, the etiology of her acute hepatic dysfunction remained unknown. Thirteen days later, despite improvements in coagulopathy (INR 1.5), aminotransferases (AST, 68 U/L; ALT, 36 U/L) and mental status, she continued to have worsening cholestasis (TB,16.6 mg/dL; conjugated, 12.6 mg/dL; AP, 175 U/L, which peaked at 492 U/L days later). Thus, a liver biopsy was finally obtained (Figure A, B). What was the elusive etiology of this patient’s acute liver failure? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.