History Of Esophageal Varices Research Articles

Nasoenteric Tube Placement in Patients with Esophageal Varices: A Review of the Current Evidence and Society Guidelines.

Esophageal varices are a common complication of portal hypertension and variceal bleeding can be associated with significant morbidity and mortality. Hospitalized patients with cirrhosis might require nasoenteric tube (NET) placement, commonly for nutritional support and/or medication administration. However, the fear of causing massive variceal bleeding among clinicians might lead to hesitancy or complete avoidance of NET placement in patients who either have a known history of esophageal varices or are at risk to have them. Several experts and society guidelines addressed this concern with variable recommendations and degrees of evidence. In this article, we present an extensive review of the literature and latest society guidelines that address the safety of NET placement in patients with esophageal varices.

28463 Aprelimast and psoriasis: Significant hemoglobin A1c reduction and improved insulin resistance independent of changes in body mass index

A 46-year-old male with a 25-year history of plaque psoriasis and psoriatic arthritis presented for follow up with uncontrolled disease despite six months of adalimumab. The patient’s past medical history was notable for decompensated cirrhosis due to nonalcoholic steatohepatitis, splenomegaly, esophageal varices, thrombocytopenia, obstructive sleep apnea, obesity, and type 2 diabetes. Given his medical comorbidities, the patient was started on apremilast, reaching goal dose of 30 mg twice daily by four weeks. He achieved total clearance of his psoriasis at four month follow-up. Interestingly, patient’s glucose metabolism and glycemic control had dramatically improved since starting apremilast: hemoglobin A1c dropped from 10.9% at the initiation of therapy to 7.9% at three months and then to 6.6% by six months. His insulin requirement went from 250 units daily to zero by three months. Patient’s BMI, diet, and exercise activity all remained unchanged during this timeframe. No other medication changes were noted except for the addition of low dose propranolol for his history of esophageal varices. The patient continues to remain clear on apremilast after six months with sustained glycemic benefits. This case suggests that apremilast acts as a metabolic modulator of glucose metabolism irrespective of its ability to induce weight loss or reduce BMI. Further studies should investigate the link between proinflammatory chronic conditions, such as psoriasis, and type 2 diabetes. Better understanding of the pathophysiology may help influence therapeutic recommendations, as apremilast could be considered a preferred agent in patients that have psoriasis and concomitant type 2 diabetes or metabolic syndrome.

Entecavir add-on Peg-interferon therapy plays a positive role in reversing hepatic fibrosis in treatment-naïve chronic hepatitis B patients: a prospective and randomized controlled trial.

BackgroundThe efficacy of entecavir (ETV) add-on peg-interferon therapy compared with ETV monotherapy in treatment-naïve hepatitis B virus (HBV) patients remains controversial. We investigated whether adding peg-interferon to ongoing ETV treatment leads to a better curative effect or not.MethodsAll patients have been recruited between August 2013 and January 2015 from the Shanghai Public Health Clinical Center and Zhongshan Hospital (China). Eligible HBV patients (n = 144) were randomly divided (1:1) to receive either ETV monotherapy (n = 70) or peg-interferon add-on therapy from week 26 to 52 (n = 74). Patients were followed-up for at least 2 years. Indexes including hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) seroconversion rate, sustained virologic response, transient elastography value, and histological scores were evaluated every 3 months until the end of the study. The rate of patients with HBsAg loss was defined as the primary endpoint criteria.ResultsAt week 26, no patient achieved HBsAg seroconversion in either group. At week 52, one patient in the monotherapy group was HBsAg-negative but there was none in the combination therapy group. The monotherapy group showed significantly better liver function recovery results than the combination therapy group. At week 78, one patient in the combination group had HBsAg seroconverted. At week 104, only three patients in the combination therapy group were HBsAg-negative compared with one patient in monotherapy. The mean alanine aminotransferase and aspartate aminotransferase levels and transient elastography values decreased significantly compared with baseline. Both groups showed a favorable decrease in alpha-fetoprotein (monotherapy: 4.5 [2.8, 7.1] vs. 2.2 [1.8, 3.1] ng/mL, P < 0.001; combination therapy: 5.7 [3.0, 18.8] vs. 3.2 [2.0, 4.3] ng/mL, P < 0.001) and an improved result of liver biopsy examination scores. The combination group showed a better improvement in histology compared with the monotherapy group (mean transient elastography value 6.6 [4.9, 9.8] vs. 7.8 [5.4, 11.1] kPa, P = 0.028). But there was no significant difference in HBsAg conversion rate (1.8% [1/56] vs. 4.1% [3/73], P = 0.809) and HBeAg conversion rate (12.5% [7/56] vs. 11.0% [8/73], P = 0.787), as well as HBV-DNA, sustained virologic response (93.2% vs. 98.5%, P = 0.150) between the two groups.ConclusionsBoth therapies supported liver function recovery and histology improvement. Combination therapy did not show better anti-viral efficacy in HBsAg or HBeAg seroconversion compared with monotherapy. However, combination therapy played a more positive role in reversing hepatic fibrosis compared with monotherapy.Trial registrationClinicalTrials.gov: NCT02849132; https://clinicaltrials.gov/ct2/show/NCT02849132

1743 From Red to Black: A Deadly Case of Acute Esophageal Necrosis

INTRODUCTION: Black Esophagus, or acute esophageal necrosis (AEN), is a rare but deadly clinical syndrome appearing as diffuse circumferential black necrotic mucosa on esophagogastroduodenoscopy (EGD). It is associated with comorbidities that cause hypoperfusion and ischemia to the esophageal mucosa. It has a reported incidence rate of about 0.001% to 0.2%. We report a case of black esophagus in a patient with fulminant hepatic failure related to nonalcoholic steatohepatitis (NASH) cirrhosis. CASE DESCRIPTION/METHODS: A 75-year-old female with a history of diabetes mellitus, hypertension, gastroesophageal reflux disease, NASH-related cirrhosis, and GI bleeding due to esophageal varices presented to the hospital with altered mental status and increased lethargy of 2 weeks’ duration. Her initial lab workup revealed a calculated MELD score of 36. She was diagnosed with an NSTEMI and hepatic encephalopathy in the setting of fulminant hepatic failure. During her hospital stay, she developed coffee ground emesis and melena with resultant drop in hemoglobin requiring transfusion with multiple units of blood. An EGD performed in order to find the source of her apparent upper GI bleeding revealed diffuse circumferential black discoloration of the mucosa at the middle and inferior third of the esophagus demarcated clearly from the normal-appearing mucosa of the cardia at the gastroesophageal junction (Figure 1). Unfortunately, she developed hepatorenal syndrome due to worsening liver function. Due to the poor prognosis, the patient’s family chose to request “do not resuscitate” (DNR) status. Severe hypoxia failing noninvasive positive-pressure ventilation ultimately led to cardiac arrest and death. DISCUSSION: This case emphasizes the need to include black esophagus on the differential of upper GI bleeding in a patient with a history of esophageal varices and NASH cirrhosis and highlights the high mortality rate, estimated at about 32%, associated with this condition. Documented cases exist of black esophagus in patients with alcohol-related cirrhosis, but we found no others reporting this condition in a patient with NASH-related cirrhosis. There is no direct treatment for black esophagus; recommendations are to treat comorbidities, suppress acid production, and optimize vascular perfusion. Complications include stricture, infection, perforation and death. This case clearly demonstrates that early detection through endoscopy and active management of its underlying cause is critical to improving patient outcomes.

P: 48 Nonselective Beta-blocker Use Is Associated With Increased Hepatic Encephalopathy-Related Readmissions in Patients With Cirrhosis

BACKGROUND: Hepatic Encephalopathy (HE) is a reversible syndrome of impaired brain function that is associated with frequent hospitalizations and decreased survival in cirrhotic patients. Nonselective beta-blockers (NSBB) are the mainstay of pharmacologic treatment for portal hypertension and prevention of variceal bleeding. Due to their effects on hepatic blood flow, we hypothesized that NSBB use would decrease portal flow, leading to increased HE related hospitalizations independent of liver disease severity. This study was done to assess the effect of NSBB use on HE-related readmissions. METHODS: We examined all the patients with cirrhosis admitted at Baylor University Medical Center between January 2013 and July 2018. The outcome measure of HE-related readmissions was analyzed in patients taking NSBB vs. patients not taking NSBB using cox proportional hazard regression model. The model was adjusted for age, sex, Model for End-Stage Liver Disease (MELD) score, selective beta-blocker (SBB) use, ascites, and history of esophageal varices (EV) and transjugular intrahepatic portosystemic shunt (TIPS). The Kaplan-Meier method and log-rank test were used to compare the cumulative incidence of HE-related readmissions between the aforementioned groups. RESULTS: There were 393 patients in this study with a mean age of 58.1 ± 10.2 years and a male predominance. The mean MELD score was 19.6 ± 7.7. The median time between the first admission and future readmission was 1.9 months with interquartile range of 4.8 months. The cumulative incidence of HE-related readmissions was significantly higher in patients taking NSBB compared with patients who were never prescribed NSBB (P &lt; 0.001) (Figure 1). This effect was not seen for patients who were taking SSBs. In multivariate analysis, after adjusting for age, sex, MELD score, SBB use, ascites, history of EV and TIPS, NSBB use was independently associated with increased risk of HE-related re-hospitalizations; Hazard ratio was 2.82 (95% confidence interval: 1.81–4.41). CONCLUSIONS: NSBB use is independently associated with increased HE-related readmissions in patients with cirrhosis, regardless of liver disease severity. Thus, NSBBs should be used cautiously in patients who have experienced a prior HE episode. However, further prospective studies are needed to determine the impact of NSBB on portal hypertension complications.

Rates of Gastrointestinal Bleeding in Cirrhotics Treated With Warfarin

Introduction: It is well accepted that there is an increased risk of bleeding for patients prescribed anticoagulants like warfarin. Moreover, cirrhosis, particularly when associated with portal hypertension, also increases the risk of gastrointestinal bleeding (GIB). However, while there is data on outcomes for cirrhotics treated with anticoagulants for portal vein thrombosis, there is a paucity of data on the risk of GIB in cirrhotics who are treated with anticoagulants like warfarin for other indications. Methods: Retrospective review comparing patients at our local VA prescribed warfarin between 2009 and 2016 who had cirrhosis (cases) or did not have cirrhosis (controls). Patients were enrolled when anticoagulation was begun or when cirrhosis was diagnosed if already on anticoagulation. Controls were required to have a fib-4 score < 1.45. Primary outcome was the rate of GIB at 30 days, 90 days, 1 year, and 2 years. Results: 82 cases and 62 controls were identified. Etiology of cirrhosis for the cases included hepatitis C 49%, alcohol 39%, non-alcoholic steatohepatitis 22%, hepatitis B 2%, and others 17%. 14 (17%) had a history of esophageal varices. >80% of cases and controls were on warfarin for atrial fibrillation or venous thromboembolism (VTE). Charlson comorbidity index and HAS-BLED scores were higher in cases as compared to controls. There were no differences in use of antiplatelet agents, proton pump inhibitors, H2 receptor blockers, or statins. Cases were treated more often with beta-blockers (71% vs 37%, p60% of both cases and controls who experienced GIB presented with supratherapeutic INRs. Rates of GIB trended towards occurring significantly more often for cases (see table). Of the cirrhotics who experienced GIB on warfarin, 5 (25%) were due to portal hypertensive causes. All cause mortality rates were higher for cases as compared to controls, but the difference was not significant. Conclusion: Not unexpectedly, patients with cirrhosis treated with warfarin for common indications like atrial fibrillation or VTE have high rates of GIB with over 10% of patients experiencing GIB after 1 year of therapy. Interestingly, 75% of cirrhotics on warfarin bled from causes other than portal hypertension. This is important information to share with patients when discussing risks and benefits of anticoagulant therapy.556 Figure 1. Baseline demographics and results

The use of nonselective beta blockers is a risk factor for portal vein thrombosis in cirrhotic patients.

Background/Aim:A reduction in portal vein inflow velocity seems to predispose to the emergence of portal vein thrombosis (PVT). Nonselective β-blockers (NSBBs), used to prevent variceal bleeding, may increase the development of PVT by reducing portal vein inflow velocity. In this retrospective case-control study, we evaluated the risk factors and clinical features of a first event of PVT in 130 cirrhotics, 19 (15%) with (PVT group) and 111 (85%) without PVT (non-PVT group).Patients and Methods:Patient evaluation and NNBB treatment were carried out according to the AASLD guidelines.Results:PVT was prevalently partial (84%) and asymptomatic (84%). Patients with PVT were treated with different regimens, and resolution of thrombosis was observed in about 50% of the cases. In both groups, HCV was the most frequent cause of cirrhosis and Child-Pugh score A was prevalent. Ascites and esophageal varices were more frequent in the PVT group (P = 0.05 and <0.000, respectively). Treatment with NSBBs was significantly more frequent in the PVT group than in the non-PVT group (P < 0.000). PVT was associated with higher prevalence of chronic renal disease (P = 0.002), higher PT impairment (P = 0.003) and lower AST and ALT (P = 0.000). At multivariate logistic regression analysis, history of esophageal varices (P = 0.007) and NSBB treatment (P = 0.0003) were independent risk factors significantly associated with PVT.Conclusions:Esophageal varices and NSBB treatment were independent risk factors of PVT. Larger studies should evaluate the risk between variceal bleeding and portal vein thrombosis of using NSBBs, particularly in the prevention of first bleeding in nonadvanced liver cirrhosis.

Impact of Vitamin K Administration on INR Changes and Bleeding Events Among Patients With Cirrhosis.

The efficacy of vitamin K in lowering an elevated INR in the setting of cirrhosis is not well established. The purpose of this investigation is to determine the effect of vitamin K administration on the INR and bleeding eventsamong hospitalized patients with cirrhosis. This is a retrospective investigation of patients hospitalized at an academic institution from 2010 to 2012. Adults with an ICD9 code supporting cirrhosis were segregated into matched cohorts based on provision of vitamin K. Multivariable logistic regression of factors associated with INR decrease and bleeding events was completed. The final matched cohort (n = 276) contained 130 patients who received vitamin K and 146 who did not receive this therapy. ICU care (adjusted odds ratio [AOR] = 2.91; 95% CI = 1.54-5.49; P = 0.01), receipt of a blood product (AOR = 2.40; 95%CI = 1.35-4.24; P = 0.03), and baseline INR > 1.6 (AOR = 1.72; 95% CI = 1.00-2.95; P = 0.05), but not vitamin K administration (AOR = 1.17; 95% CI = 0.66-2.08; P = 0.59), were associated with INR decrease. Bleeding events occurred more frequently among patients with a history of esophageal varices (AOR = 6.35; 95% CI = 1.21-33.4; P = 0.03), but vitamin K administration did not have an impact on these events (AOR = 4.90; 95% CI = 0.56-43.0; P = 0.15). Administration of vitamin K did not affect INR changes or bleeding events in this cohort of hospitalized patients with cirrhosis.

Portal Hypertension and Variceal Hemorrhage

Gastrointestinal bleeding in patients with cirrhosis can occur from a number of different causes, including portal hypertension, gastric antral vascular ectasia, and acute variceal hemorrhage. The management of these conditions involves a combined medical and endoscopic approach, with radiologic and surgical therapies restricted to refractory cases. This review covers the natural history of gastroesophageal varices, portal hypertensive gastropathy, and gastric antral vascular ectasia; diagnostic principles; primary and secondary prophylaxis relating to esophageal variceal hemorrhage; and treatment overviews for gastric variceal hemorrhage, portal hypertensive gastropathy, and gastric antral vascular ectasia. Figures show the pathophysiology of complications of cirrhosis, esophageal varices as seen during an upper endoscopic procedure, natural history of esophageal varices in patients with cirrhosis, portal hypertensive gastropathy, gastric antral vascular ectasia, and management principles for acute variceal hemorrhage, esophageal variceal ligation, and gastric varices. Tables list the prevalence of various etiologies of hemorrhage in patients with cirrhosis, current recommendations for follow-up screening and surveillance of varices, sensitivities and specificities of some noninvasive markers, and principles of initial management of acute variceal hemorrhage. This review contains 8 highly rendered figures, 4 tables, and 44 references.

Factors Affecting Physician Decision to Utilize Prophylactic Anticoagulation in Hospitalized Cirrhotic Patients

Purpose: To investigate which factors are most likely to influence a physician's decision on whether or not to prophylactically anticoagulate a hospitalized cirrhotic patient to protect against venous thromboembolism (VTE), with a secondary aim to determine associated adverse outcomes, including VTE and bleeding events. Methods: This study is a retrospective cohort study of hospitalized cirrhotic patients at one Veterans Affairs Medical Center between 01/01/2005 and 12/31/2011. Data were collected from electronic medical records, and the primary outcome was whether or not anticoagulation was used. Additional data gathered include: etiology of cirrhosis, age, sex, prothrombin time (PT), platelet count, creatinine, bilirubin, albumin, history of esophageal varices, history of previous gastrointestinal bleeding, previous VTE, and active malignancy. Chi-squared testing and logistical regression was used in the analysis, and a p-value <0.05 was considered significant. VTE outcomes with and without anticoagulation and bleeding complications when given anticoagulation were also collected as part of a secondary aim of the study. Results: One hundred twenty-five patient charts were reviewed. 97.6% of patients were men, and the average age was 60. Overall, 53% of the cirrhotic patients received anticoagulation. In univariate analysis, PT, platelet count, albumin, creatinine, and bilirubin all were significantly related to use of anticoagulation. In multivariate analysis, only PT, platelet count, and albumin were independently significantly related to the use of anticoagulation. Anticoagulation use was more likely the higher the platelet count, and the albumin, and the lower the PT. There were no adverse bleeding complications in any patients. There was one incident of deep vein thrombus in a patient receiving anticoagulation. Conclusion: This study demonstrates that the factors most likely to influence a physician to anticoagulate a cirrhotic patient in the hospital are: PT, platelets, and albumin. This finding may aid in better understanding how to utilize low-dose anticoagulation in hospitalized cirrhotic patients, with the goal to minimize VTE outcomes while concurrently minimizing bleeding complications. Currently, there are no guidelines that help to direct use of prophylactic anticoagulation in cirrhotic patients, despite this being a common management dilemma.

Ectopic varices.

Ectopic varices.

Variceal Recurrence, Rebleed Rates, and Alterations in Clinical and Laboratory Parameters Following Post Variceal Obliteration in Cirrhotic Patients

© 2011, INASL 21 Ex-vivo Treatment of Neutrophils with a p38-MAPK Agonist in Patients with Acute and Chronic Liver Failure and Elevated Arterial Ammonia Improves Their Bacteriocidal Capacity A Nishtala, NJ Taylor, RD Abeles, JA Wendon, DL Shawcross Institute of Liver Studies and Transplantation, King’s College London School of Medicine at King’s College Hospital, Denmark Hill, London, UK Background: Ammonia reduces neutrophil phagocytic and bacteriocidal capacity. Neutrophils swell in response to ammonia exposure and activation of the p38-MAPK pathway has been implicated in protecting the neutrophil against osmotic shock and normalizing neutrophil phagocytic dysfunction. In patients with acute (ALF) and chronic liver failure (CLF) with elevated arterial ammonia, we hypothesized that treating neutrophils ex vivo with isoproterenol, a β non-specific adrenergic receptor and p38-MAPK agonist would improve neutrophil bacteriocidal capacity. Aims and Methods: Out of 20 patients (10 ALF and 10 CLF) enrolled in study of neutrophil function encompassing 125 patients, we investigated the role of ex vivo incubation of neutrophils with an exogenous ammonia load, a p38-MAPK agonist (Isoproterenol) and the specific p38-MAPK antagonist SB203580 (Calbiochem) on neutrophil function. Phagocytic capacity in heparinized whole blood was quantitatively determined by flow cytometry using FITC-labelled opsonized Escherichia coli at baseline, and following incubation for 90 minutes with NH4Cl (200 μmol/L), isoproterenol (2 μmol/L) or SB203580 (40 μmol/L) at 37°C. Results: ALF patients had a median SOFA score of 16 and APACHE II score of 22. CLF patients had median MELD score 27. The median arterial ammonia level in ALF group was 88 and CLF group was 62 μmol/L. Baseline bactericidal capacity was 67% in the ALF group and 72% in the CLF group compared to > 85% in healthy controls. The exogenous ammonia load further reduced neutrophil phagocytic capacity by median of 7.3%. The p38-MAPK agonist isoproterenol significantly abrogated the ammonia-induced phagocytic impairment and improved bacteriocidal capacity (p < 0.007). The p38-MAPK antagonist SB203580 however, exacerbated the ammonia-induced reduction in neutrophil phagocytic capacity by median of 5.2%; p = 0.003. Conclusion: Data shows that in patients with liver failure and elevated arterial ammonia that neutrophil bacteriocidal capacity is impaired. Activation of the p38-MAPK pathway serves as an important cellular protective mechanism against ammonia-induced impairment. Conflict of Interest: None Variceal Recurrence, Rebleed Rates, and Alterations in Clinical and Laboratory Parameters Following Post Variceal Obliteration in Cirrhotic Patients K Arun Kumar, B Siva Subramaniam, V Jayanthi Department of Gastroenterology and Hepatology, Stanley Medical College and Hospital, Chennai Background: Band ligation is considered as an effective method for obliteration of esophageal varices. Injection sclerotherapy is an alternative method. Aim: To determine the natural history of esophageal varices after its obliteration following sclerotherapy. Material and Method: Consecutive patients with endoscopic proven varices between June 2006 and May 2007 were registered. All the patients had an elective or an emergency variceal endoscopic injection with 0.5% sodium tetradecyl sulphate at an interval of 3 weeks. The patients were followed-up in the liver clinic for recurrences of varices, variceal rebleed, changes in clinical, laboratory parameters and hemodynamic changes in portal venous system at 3 monthly intervals for the first year and thereafter at 6 monthly intervals until May 2010. Patients who had an EVL or a devascularization procedure were excluded. Results: A total of 104 patients with cirrhosis were registered. Eradication of varices required a mean of 5 sessions. Eighteen patients with cirrhosis liver had recurrence of varices at the end of 3 years. Twenty patients had Gr I varices and the remaining Gr II. The varices appeared after a mean period of 11.4 months. Only 4 patients rebled following reappearance of varices. A significant improvement in laboratory findings was noted in hemoglobin, platelet count, prothrombin time (PT), and INR. There was a significant improvement in ascites and regression of jaundice following endotherapy in GpI patients (P < 0.05). A significant (P < 0.05) number of patients in Gp I reverted from Child’s C to B or A. Conclusion: The rebleed rates and bleed-related death was significantly low in cirrhotic patients with portal hypertension after sclerotherapy. There was a significant improvement in clinical and laboratory findings after obliteration of esophageal varices. A significant number of patients reverted from Child’s C to B or A. Conflict of Interest: None 03_JCEH-Abstract.indd 21 3/18/2011 11:13:04 AM

Chronic Liver Failure and Progressive Neurologic Decline due to Mitochondrial Depletion

Purpose: A 43-year-old African American female presented to the GI Clinic for follow-up of chronic liver disease after a prolonged hospitalization for neurologic complaints of vision disturbance, transient left-sided facial droop, left-sided weakness, and dysphagia. She experienced cognitive deficits, which improved over time. Past medical history includes chronic liver disease with a biopsy in 2002 consistent with small duct sclerosing cholangitis, history of esophageal varices with banding, hepatic and metabolic encephalopathy, achalasia status post multiple Botox injections and Heller Myotomy, chronic pelvic pain, depression. She does not smoke or drink. She has had multiple abdominal surgeries. Family history is outlined in the pedigree as shown in Figure 1. The patient uses a wheelchair and speaks slowly and softly, though coherently. She has external ophthalmoplegia with marked strabismus, as demonstrated in Figure 2. Abdomen reveals multiple healed surgical scars and is diffusely tender to palpation, no ascites. Neurological exam reveals generalized weakness. Pertinent labs include WBC 2.3, Hgb 8.7, Plt 68, T bili 1.6, INR 1.3. Creatinine 0.7. MELD 11. A liver biopsy from 2002 shows features of chronic cholestasis with portal fibrosis, ductal proliferation, periductal fibrosis and loss of some bile ducts. MRCP reveals poor visualization of the intrahepatic ductal system and a 9 mm CBD without filling defect. MRI of the brain reveals Manganese deposition in the basal ganglia, abnormal signal intensity in the splenium of the corpus callosum and minimal gliotic or small vessel chronic ischemic changes involving the cerebral white matter. Genetic studies for mitochondrial disorders detected a heterozygous novel variant in the DNA polymerase gamma 1 gene (POLG1), c.1837C>T (p. H613Y). There were a total of 7 heterozygous DNA polymorphisms identified, including the novel variant, H613Y, in exon 9 of this gene. Family member studies of our patient's sister (her deceased affected nephew's mother) for this variant was negative. Further testing for mitochondrial depletion on repeat liver biopsy were declined by the patient, and no other family members would consent to genetic analysis. This case represents a complicated mixture of chronic liver disease, neurologic manifestations, and a complex family history of liver disease. Genetic testing in this patient's case is abnormal, but not diagnostic. However, the conglomeration of findings including hepatic encephalopathy, liver failure, chronic progressive external ophthalmoplegia, and abnormal neurologic features suggestive of metabolic stroke with an abnormal MRI, are strongly suggestive of a mitochondrial syndrome.

Current status of ectopic varices in Japan: Results of a survey by the Japan Society for Portal Hypertension

The Clinical Research Committee of the Japan Society for Portal Hypertension has conducted a nationwide questionnaire survey to clarify the current status of ectopic varices in Japan. A total of 173 cases of ectopic varices were collected. Duodenal varices were found in 57 cases, and most of them were located in the descending to transverse parts. There were 11 cases of small intestinal varices and 6 cases of colonic varices, whereas 77 patients had rectal varices, accounting for the greatest proportion (44.5%). Other sites of varices were the biliary tract, anastomotic sites, the stoma, and the diaphragm. Liver cirrhosis was the most frequent diseases (80.3%) underlying ectopic varices. It was noted that patients with rectal varices frequently had a history of esophageal varices (94.8%) and received endoscopic treatment (87.0%). The treatments for ectopic varices were as an emergency in 46.5%, elective in 35.4% and prophylactic in 18.2%. In emergency cases, endoscopic therapy was most frequent (67.4%), followed by interventional radiology (IVR; 15.2%), and endoscopy-IVR combination (6.5%). Elective treatment was performed by endoscopy in 34.3%, IVR in 28.6%, combined endoscopy-IVR in 5.7%, and surgical operation in 25.7%. The prophylactic treatment was endoscopic in 50.0%, IVR in 33.3%, combined treatments in 11.1%, and prophylactic surgery in none. The change of ectopic varices after treatment was disappearance in 54.9%, remnant in 35.4% and recurrence in 9.7%. The rate of disappearance was significantly lower in rectal varices (40.8%) than in duodenal varices (73.4%). The patient outcome did not differ among the various sites of the lesion. Conslusions: Current status of ectopic varices in Japan has been clarified by a nationwide questionnaire survey. The authors expect that the pathophysiology of ectopic varices will be further elucidated, and that improved diagnostic modalities and treatment methods are established in the future.

Nasogastric Aspiration and Lavage in Emergency Department Patients with Hematochezia or Melena Without Hematemesis

The utility of nasogastric aspiration and lavage in the emergency management of patients with melena or hematochezia without hematemesis is controversial. This evidence-based emergency medicine review evaluates the following question: does nasogastric aspiration and lavage in patients with melena or hematochezia and no hematemesis differentiate an upper from lower source of gastrointestinal (GI) bleeding? MEDLINE, EMBASE, the Cochrane Library, and other databases were searched. Studies were selected for inclusion in the review if the authors had performed nasogastric aspiration (with or without lavage) in all patients with hematochezia or melena and performed esophagogastroduodenal endoscopy (EGD) in all patients. Studies were excluded if they enrolled patients with history of esophageal varices or included patients with hematemesis or coffee ground emesis (unless the data for patients without hematemesis or coffee ground emesis could be separated out). The outcome was identifying upper GI hemorrhage (active bleeding or high-risk lesions potentially responsible for hemorrhage) and the rate of complications associated with the nasogastric tube insertion. Quality of the included studies was assessed using standard criteria for diagnostic accuracy studies. Three retrospective studies met our inclusion and exclusion criteria. The prevalence of an upper GI source for patients with melena or hematochezia without hematemesis was 32% to 74%. According to the included studies, the diagnostic performance of the nasogastric aspiration and lavage for predicting upper GI bleeding is poor. The sensitivity of this test ranged from 42% to 84%, the specificity from 54% to 91%, and negative likelihood ratios from 0.62 to 0.20. Only one study reported the rate complications associated with nasogastric aspiration and lavage (1.6%). Nasogastric aspiration, with or without lavage, has a low sensitivity and poor negative likelihood ratio, which limits its utility in ruling out an upper GI source of bleeding in patients with melena or hematochezia without hematemesis.

Effect of Balloon-Occluded Retrograde Transvenous Obliteration on the Natural History of Coexisting Esophageal Varices

Balloon-occluded retrograde transvenous obliteration (BRTO) provides an effective mean of controlling gastric variceal (GV) bleeding; however, increased portal pressure after the obliteration of gastrorenal shunts may lead to a worsening and subsequent rupture of esophageal varices (EV). The aim of this study was to determine whether the natural history of coexisting EV is affected by BRTO. Two hundred thirty-seven patients with gastric varices and no history of EV or GV bleeding at the time of diagnosis were included. Clinical, laboratory, and endoscopic features were compared between 25 patients who underwent BRTO due to GV bleeding (BRTO group) and 198 patients who never experience GV bleeding (control group) during follow-up. The incidences of EV bleeding were evaluated and compared between these 2 groups. The BRTO and control groups were not significantly different with respect to baseline characteristics including age, sex, etiologies of cirrhosis, hepatic function, and the classification or extent of EV and GV. During follow-up (median 48 mo), the overall incidence of first EV bleeding in the patients with fundal varices was significantly higher in the BRTO group (P=0.04). The incidences of EV bleeding were not different at 1 or 3 years (10.1% vs. 12.9%, P=0.32 and 39.3% vs. 38.4%, P=0.57), but became significantly higher in the BRTO group at 5 (72.2% vs. 48.5%, P=0.02) and 7 years (90.7% vs. 50.6%, P<0.01). BRTO increased the bleeding rate of coexisting EV in the long term. Close monitoring and prophylaxis of EV bleeding may be warranted after BRTO.

Delayed puberty in girls having biliary atresia

Biliary atresia patients have several problems even after undergoing successful Kasai operation. Fourteen female patients have been followed for over 12 years after successful Kasai original portoenterostomy procedures. The oldest patient is 21 years of age. All patients are jaundice-free, but 10 patients have a history of esophageal varices and/or hypersplenism. Five patients complain of menstrual disorders. The average age of menarche was delayed 1 year, 9 months, compared with Japanese controls. Two cases of 11 (18.2%) presented primary amenorrhea after 14 years, 6 months, which is mean + 2SD of Japanese controls. Four cases of 11 (36.4%) showed secondary amenorrhea. Unestablished menstrual cycles after 2 years of menarche were observed in two patients of nine (22.2%). Four cases had regular menstruation. Five patients showed delay in the development of pubic hair and breasts. Six patients showed atypical body height velocity pattern that showed no peaking, and one patient showed no growth spurt. All the patients with amenorrhea had portal hypertension. In hormonal evaluation, the patients with menstruation showed normal or slightly good reaction of luteinizing hormone and follicle stimulating hormone in the luteinizing hormone-releasing hormone test, having normal to high estradiol levels. The patients with menstrual abnormality showed overreaction of LH, having normal estradiol levels.