s Submitted for the 68th Annual Scientific Meeting of the American College of Gastroenterology October 10-15, 2003, Baltimore, Maryland: CLINICAL VIGNETTES: PDF Only
Introduction: Previous studies have suggested a possible association between Ulcerative Colitis (UC) and non-alcoholic steatohepatitis (NASH). However, this link is controversial since most of these studies have been limited by small sample sizes. We sought to examine the association between UC and NASH using a large population based database. Methods: We queried a commercial database (Explorys Inc., Cleveland, OH), an aggregate of Electronic Health Record (EHR) data from 26 major integrated healthcare systems in the US from 1999 to June 2018. We identified an aggregated patient cohort of eligible patients with diagnoses of Ulcerative Colitis and NASH based on Systemized Nomenclature of Medical terminology (SNOMED-CT) codes, excluding patients with autoimmune liver disease, viral liver disease, and alcoholic liver disease. We calculated the prevalence of NASH in patients with and without UC and performed univariate analyses to assess the prevalence of conditions co-morbid to both UC and NASH. Results: A total of 34,605,400 individuals were included in the study period between June, 2013 and June, 2018. Of these, 129,300 (0.37%) had a diagnosis of UC and 27,170 (0.08%) had a diagnosis of NASH. Of the individuals with UC, 370 also had a diagnosis of NASH (0.29%) [Odds Ratio (OR): 3.7 (P<0.0001)]. Compared to individuals with UC and without NASH, individuals with UC and NASH had higher prevalence rates of HTN, 76% vs 46% (OR 3.6, p<0.0001), HLD 76% vs 38% (OR 5.0, p<0.0001), metabolic disease 97% vs 62% (OR 2.2, p<0.0001), diabetes 59% vs 22% (OR 5.1, p<0.0001), obesity 57% vs 22% (OR 4.8, p<0.0001), and morbid obesity 27% vs 5.8% (OR 6.0; p< 0.0001). UC patients with NASH had increased prevalence of azathioprine use at 11% compared to 6.5% (OR 1.8; p= 0.0008), and TNF-alpha inhibitors at 14% compared to 9% in subjects with UC and without NASH (OR 1.6; p< 0.004). Conclusion: In this large population-based study, the overall prevalence of NASH in UC patients was 0.29% compared to 0.08% in the general population. Patients with UC and NASH had higher rates of metabolic risk factors and higher rates of use of immunomodulators and anti-TNF-alpha agents.855_A Figure 1 No Caption available.855_B Figure 2 No Caption available.
Purpose: Glycogenic Hepatopathy (GH) is an under-recognized pathologic overloading of hepatocytes with glycogen in patients with poorly controlled type I diabetes mellitus. We present a case of GH and discuss its clinical presentation, diagnosis, and management. Case presentation: An 18-year-old woman with Type I diabetes mellitus since age 5 was admitted via the emergency department for worsening nausea, vomiting, right upper quadrant pain, and increased abdominal girth. Physical examination revealed tender hepatomegaly 8 cm below the right costal margin. Laboratory data revealed an AST of 170 U/L, ALT 120 U/L, alkaline phosphatase 181 U/L, total bilirubin 0.8 mg/dl, HbA1C 12.5%. Subsequent laboratory screening for viral hepatitis and autoimmune hepatitis were negative. The patient denied alcohol use. A computed tomography scan of the abdomen revealed significant hepatomegaly without other abnormalities. An abdominal ultrasound revealed a liver measuring 17.5 cm in length with increased echogenic parenchyma suggestive of fatty infiltration. The hepatic vascular indices were normal. A trans-jugular liver biopsy revealed swollen hepatocytes, pale cytoplasm, and numerous glycogenated nuclei. A periodic acid-Schiff stain with and without diastase digestion demonstrated extensive glycogen deposition confirming the diagnosis of GH. Fibrosis, steatosis, and inflammation were absent. With aggressive glycemic control, the patient's abdominal pain, girth, and liver function abnormalities improved and the patient was discharged. Subsequent follow-up laboratory data revealed improved HbA1C and normal liver function tests. Discussion: GH is a complication of uncontrolled type I diabetes mellitus. Patients often present with liver function test abnormalities and abdominal pain, hepatomegaly, nausea, or vomiting. Glycogen is not toxic to hepatocytes and the elevation in liver enzymes is likely secondary to leakage from hepatocyte injury rather that cell death. Many physicans often mistake GH for fatty liver disease. Imaging and laboratory testing cannot effectively distinguish between these two entities. The diagnosis is made by liver biopsy which reveals marked glycogen accumulation in hepatocytes. Unlike steatosis, GH is not known to progress to cirrhosis. Management strategies for GH focus primarily on achieving strict glycemic control.
Introduction: Reactivation of Hepatitis B virus (HBV) infection following the administration of chemotherapy is a potentially lethal complication. Oral HBV antiviral medications are generally very well tolerated and can be used both prior to chemotherapy and to treat the actual reactivation. We report a case of HBV reactivation from chemotherapy and a potentially fatal complication of the treatment. Case Report: A 54 y/o Croatian male with chronic lymphocytic leukemia (CLL) developed severe hepatitis one week after chemotherapy. He had no known history of liver disease, family history of liver disease, alcohol use, or use of other medications. All prior LFTs were normal, with no prior testing for viral hepatitis. Admission examination revealed jaundice. Laboratory data showed a protein 5.4 mg/dL, albumin 2.7 mg/dL, alkaline phosphatase 112 U/L, bilirubin 20.9 mg/dL, AST 2853 U/L, ALT 3521 U/L, and an INR of 1.76. Electrolytes, kidney function, and abdominal ultrasound were all normal. Hepatitis B surface antigen and HBV-DNA were found to be positive. Serologies for other viral infections and autoimmune hepatitis were negative. A diagnosis of HBV reactivation was made, and therapy with entecavir, adefovir, and prednisone was begun. Liver biopsy revealed severe hepatitis, cholestasis, cirrhosis, and positive HBsAg immunostaining. His laboratory values improved, and he was discharged home after a 12 day hospitalization. Ten days later, the patient presented with shortness of breath. He was hypotensive, hypoxic, coagulopathic (INR 4.4), in renal failure, with a profound metabolic lactic acidosis. LFTs revealed bilirubin 32.7 mg/dL, AST 141 U/L, and ALT 264 U/L. There was no clinical evidence of a perforated viscous. He was intubated, dialyzed, given broad spectrum antibiotics, and adefovir and entecavir were discontinued. The patient expired within 24 hours. Autopsy failed to provide any gross explanation for his lactic acidosis, and all growth from blood cultures was negative. Discussion: This case report illustrates that reactivation of HBV after chemotherapy remains a major clinical issue. Prior to chemotherapy, patients should undergo testing for HBV. This case may also illustrate a rare but fatal side effect of HBV nucleoside/nucleotide analogues: lactic acidosis due to mitochondrial toxicity. Clinicians should be aware that significant side effects can occur with oral HBV antiviral agents.
Introduction: Repeat diagnostic paracentesis 48 hours after the initiation of treatment for spontaneous bacterial peritonitis (SBP) is a common practice. An increase in ascites absolute neutrophil count (ANC) indicates treatment failure. However, a less clear scenario is when ANC drops, but still remains > 250. We performed an analysis to review such patients and to determine if different therapeutic approaches affected survival. Methods: This was a retrospective analysis of all patients diagnosed with SBP between 2006 and 2010 at two large, academic medical centers. SBP was defined as ascites ANC > 250 with or without positive cultures. Data collected included antibiotic adjustments and survival. Results: 105 patients were diagnosed with SBP. 68 (65%) of these had a repeat diagnostic paracentesis. 47/68 (69%) had ANC < 250, and 4/68 (6%) had an increase in the ANC and were considered nonresponders and had adjustments in their antibiotics. 17/68 (25%) had a decrease in the ANC (from 4-93% decrease), but remained above 250. Of these 17, six had antibiotic changes and 11 did not. Of these 11 patients, all completed their original antibiotic course, and had no observed complications. Seven of the 11 had repeat diagnostic paracentesis which revealed downward trend in the ascites ANC. 29/37 (78%) of SBP patients who did not get a repeat paracentesis, 41/47 (87%) who had repeat ANC < 250, 3/4 (75%) who had an increase in ANC requiring a change in antibiotic course, 11/11 (100%) who had ANC > 250 on repeat tap but just completed their originally-recommended antibiotics course, and 3/6 (50%) who had ANC on repeat tap and had their antibiotics adjusted survived until hospital discharge. Conclusion: In this study, 25% of SBP patients who had a repeat diagnostic paracentesis had improvement of ANC but still remained > 250. For such patients, completing their originally-prescribed antibiotic course resulted in excellent outcomes with 100% survival observed. Larger prospective studies are needed to evaluate the findings in this small study and determine if these patient can be observed and complete their course of therapy. Also, this study demonstrated that 95/105 (90%) of SBP patients either had no repeat tap or had no change in their antibiotics despite the results of the tap. This calls into question the utility of repeating diagnostic paracentesis in SBP patients in general. This should also be evaluated in larger prospective studies.
Purpose: The JAK2V617F mutation is strongly implicated in the pathogenesis of myeloproliferative disorders (MPD) which account for at least 50% of cases of Budd-Chiari Syndrome (BCS). MPD is a common cause of splanchnic vein thrombosis in young women. Patients with BCS and underlying JAK2 mutation have severe hepatic outflow obstruction with worse Child-Pugh scores, and often require decompressive procedures such as transjugular intrahepatic portosystemic shunts (TIPS) placement or liver transplantation compared to those without the mutation. A 19 year old Caucasian woman with chronic abdominal pain, nausea and vomiting was found to have splenic vein thrombus on ultrasound. An initial hypercoagulable workup was negative. She was instructed to discontinue her oral contraceptives and started on anticoagulation with warfarin. Imaging studies two months later showed resolution of the thrombus. She was noncompliant with her anticoagulation and presented six months later with similar symptoms. A repeat ultrasound of the abdomen showed thrombosis of two of her hepatic veins, right portal vein and splenic vein. She was immediately restarted on anticoagulation. She was noted to have a mildly elevated ALT in the 50-60 range but her other liver function tests remained normal. She also had a normal CBC except for mild anemia and a normal INR. Further workup revealed a positive JAK2 mutation. She was admitted one month later with worsening abdominal pain, new large ascites and occlusion of all three hepatic veins despite anticoagulation. She was diagnosed with acute BCS. Hepatic venography demonstrated “spider web” collaterals of the right and left hepatic veins consistent with BCS. She underwent a large volume paracentesis and successful TIPS placement with decrease in her hepatic venous pressure gradient from 27 to 5 mm Hg. Liver biopsy showed evidence of moderate to severe sinusoidal dilation in zone 3 consistent with BCS. She recovered well with resolution of her ascites and abdominal pain. She was discharged home with the anticipation of lifelong anticoagulation. Patients with newly diagnosed BCS should be routinely screened for JAK2 mutations. Unlike the majority of patients with MPD, this subgroup of patients have normal hemoglobin levels, platelet counts and erythropoietin levels making diagnosis difficult with laboratory values alone. These patients present with severe hepatic outflow obstruction which portends a worse clinical outcome, and thus should be aggressively intervened upon at time of presentation to ensure long-term survival.
Purpose: Cholangiocarcinoma (CCA), a rare malignancy of the biliary duct system, arises from epithelial cells of the intrahepatic or extrahepatic bile ducts. Clinical presentation varies depending on location of tumor, but includes jaundice, pruritus, abdominal pain, weight loss, and fever. Primary sclerosing cholangitis, choledochal cysts, and infection with parasitic liver flukes are risk factors strongly associated with CCA. Hepatitis B virus infection (HBV) is associated with hepatocellular carcinoma, but very rarely with CCA. We present an unusual case of CCA in a patient with chronic HBV infection. Methods: A 38 year old Asian male with chronic untreated HBV infection presented to an outside hospital with fever, fatigue, and right upper quadrant abdominal pain for one week. Imaging studies revealed a right hepatic lobe mass and portal vein thrombosis. Liver biopsy was performed and the patient was referred to our hospital for further management. Physical exam revealed jaundice and hepatomegaly. Hemoglobin was 12.8 g/dl, platelet count 236 × 103/mcL, albumin 3.1 g/dl, bilirubin 0.7 mg/dL, alkaline phosphatase 147 IU/L, aspartate aminotransferase 57 IU/L, alanine aminotransferase 39 IU/L, INR 1.5, alpha-fetoprotein level 114 ng/ml, CA 19-9 of 45 U/ml, and HBV DNA 27,567 IU/ml. Repeat imaging demonstrated a 9.9 × 6.8 cm infiltrating mass extending from the dome inferiorly and invading the gallbladder, as well as portal vein thrombosis. A chest computed tomography (CT) and bone scan were negative for metastatic disease. Liver biopsy of the mass showed moderately differentiated adenocarcinoma and dysplasia of bile ducts. Immunostaining was compatible with CCA. A liver biopsy obtained from the left unaffected lobe revealed HBV hepatitis with early cirrhosis. The patient was not a candidate for liver transplantation. Results: Subsequently, an exploratory laparotomy revealed no obvious peritoneal seeding, thus a right hepatectomy and cholecystectomy were performed. Pathology was consistent with CCA and an abundance of hepatocytes positive for hepatitis B surface antigen. The patient had an uncomplicated postoperative course and was discharged on antiviral HBV medications and follow up with oncology and radiation oncology. Conclusion: We demonstrate a unique, rare case of CCA associated with chronic HBV. It has been proposed that HBV may infect biliary epithelium resulting in an immunologic attack causing inflammation and degenerative changes. More research is needed to evaluate the potential role of HBV in the pathogenesis of CCA, so that we can prevent and control this devastating disease.
Continuing medical education (CME) is essential to increase the knowledge, skills, and professional performance of health care providers. To keep the content of CME relevant and balanced, conflict of interest (COI) determination and mitigation is essential. While the Accreditation Council for Continuing Medical Education provides oversight and guidelines, each organization that sponsors CME programs has its own protocol for COI. To standardize and simplify the American Association for the Study of Liver Diseases' approach to COI, we propose a standardized COI disclosure scoring system for all CME programs to notify the audience of any conflicts and how such conflicts can be mitigated.
