Cryptogenic liver cirrhosis and hepatitis E virus (HEV): Are they related?

INTRODUCTION AND OBJECTIVES: Hepatitis E virus (HEV) is one of the most common causes of acute hepatitis. In recent years, its role in the development of chronic hepatitis and cirrhosis especially in immunosuppressed patients and its wide range of extrahepatic involvement have increased the amount of research on HEV. In this study we aimed to investigate the presence of HEV infection in individuals with cryptogenic cirrhosis. MATERIALS AND METHODS: HEV antibodies were analysed using the Anti HEV enzyme-linked immunosorbent assay (ELISA) kit (anti-HEV ELISA; Diapro Prodiagnostic Bioprobes, Milan, Italy). HEV RNA was isolated with using QIAMP Viral RNA mini kit (QIAGEN, Hilden, Germany). The HEV RNA titre was detected with the Rotor Gene 3000 real time polymerase chain reaction (PCR) system using GenoSen's HEV (Rotor Gene) Quantitative Real Time PCR Kit (Genome Diagnostics Private Limited, the Netherlands). RESULTS: Our study included 21 healthy volunteers (12 males) and 35 cryptogenic cirrhosis patients (19 males). The ages of the patients and the controls were similar (46±12.1 vs. 37.5±9.7years). The mean Child-Pugh score was 8±2.5. The anti HEV immunoglobulin G(IgG) positivity rate was 9.5% and 25.7% in the control and patient groups respectively (p>0.05). HEV RNA positivity was not detected in the control group, but 3 cases (8.6%) in the patient group were positive (p>0.05). The HEV RNA, aspartate aminotransferase (AST) and alanine aminotransferase(ALT) levels for these 3 cases were 326.461copies/mL, 91IU/L and 67IU/L; 480copies/mL, 68IU/L and 36IU/L and 72copies/mL, 42IU/L and 24IU/L respectively. There were positive correlations between HEV RNA levels and AST and ALT levels (p<0.05). CONCLUSIONS: Anti HEVIgG and HEV RNA positivity rates are high in cryptogenic cirrhosis although it is not statistically significant and there is a positive correlation between HEV RNA and aminotransferases.

Isolated hepatic tuberculosis: a rare cause of hepatic mass lesions.

Hepatic tuberculosis usually accompanies pulmonary and extrapulmonary tuberculosis. Although isolated hepatic tuberculosis is a very rare condition, it should be considered in the differential diagnosis of a hepatic mass. Here, we report a 42-year-old woman presenting with weight loss, fever, night sweats, and a hepatic mass on the abdominal ultrasonography and magnetic resonance imaging (MRI). Ultrasonography-guided percutaneous needle biopsy demonstrated a caseating granuloma with epithelioid histiocytes and giant cells compatible with the diagnosis of tuberculosis. The patient was treated with four anti-tuberculous drugs for 1 year. She recovered clinically, and her post-treatment abdominal MRI was normal.

Foreign material in the gastrointestinal tract: cocaine packets.

Smuggling drugs by swallowing or inserting into a body cavity is not only a serious and growing international crime, but can also lead to lethal medical complications. The most common cause of death in 'body packers', people transporting drugs by ingesting a packet into the gastrointestinal tract, is acute drug toxicity from a ruptured packet. However, more than 30 years after the initial report of body packing, there is still no definitive treatment protocol for the management of this patient group. The treatment strategy is determined according to the particular condition of the patient and the clinical experience of the treatment center. Surgical intervention is also less common now, due to both the use of improved packaging materials among smugglers and a shift towards a more conservative medical approach. Herein, we report a case of toxicity from ingested packets of cocaine that leaked and, despite surgery, resulted in exitus of the patient.

Association of the MEFV gene variations with inflammatory bowel disease in Turkey.

BACKGROUND: Association of NOD2 (CARD15) gene mutations with inflammatory bowel diseases (IBD) is well known. We herein aimed to investigate the role of familial Mediterranean fever-associated MEFV variations in IBD patients as additional regional-specific risk factor. STUDY: One hundred thirty-seven (78 female, 56.9%) IBD patients [62 Crohn's disease (CD), 75 ulcerative colitis (UC)] were enrolled into the study. The diagnosis of all patients was confirmed by colonoscopy, histopathology, and the clinical findings. One hundred one healthy donors' samples were used as healthy controls. All patients were genotyped for the most common E148Q, M608I, M694V, and V726A variations of the MEFV and R702W, G908R, and 1007fs of the NOD2. RESULTS: The overall MEFV variation frequency was found to be higher in the IBD (25.5%) patients (28% in UC, 22.6% in CD) compared with controls (9.9%, P=0.006). This association was stronger with the penetrant exon 10 variations (M694V, M680I, V726A; odds ratio =4.5, P=0.001). Contribution of M694V was higher compared with the other variations (14.5% in CD, 17.3% in UC and 3% in controls, odds ratio =6.039, 95% confidence intervals, 1.7-20.7, P=0.002). The overall frequency of 3 NOD2 variants in the IBD group was not different from that of controls. CONCLUSIONS: The results of this study suggest that the MEFV variations may be an additional susceptibility factor for IBD in certain parts of the world where the carrier rate is high, and the genetic background of the IBD patients may show regional changes.

Etiological factors of duodenal and gastric ulcers.

BACKGROUND/AIMS: We aimed to determine the etiology of patients with duodenal and gastric ulcers. METHODS: 140 patients diagnosed with peptic ulcer between April 2002-2009 were enrolled in this prospective study. Two biopsy specimens were collected from the antrum and corpus for histology and one for rapid urease testing, and stool samples were analyzed for Helicobacter pylori antigen. Serum calcium and gastrin levels were also analyzed. RESULTS: 82 (58%) patients were male, with a median age of 47.70±15.03 years (range: 16-92). The ulcer was located in the duodenum in 96 patients, stomach in 40, and both duodenum and stomach in 4. The rates of patients positive for Helicobacter pylori antigen in stool, positive in urease testing and positive for Helicobacter pylori presence in antral and corpus samples were 48%, 52%, 67%, and 60%, respectively. 107 (76%) patients were positive for Helicobacter pylori in one of the test methods. 64 (46%) patients had a history of nonsteroidal antiinflammatory drug use within the last month. Mean levels of calcium and gastrin were 9.29±0.40 (7.90-10.20) and 73.96±89.88 (12.86-562.50), respectively. Gastrin level was correlated to inflammatory activity (p<0.05). 19 (13.6%) of the patients were negative for Helicobacter pylori, nonsteroidal anti- inflammatory drug use and hypersecretory illness, and were classified as idiopathic. CONCLUSIONS: The most common cause of duodenal and gastric ulcer was Helicobacter pylori, and it was responsible for three-fourths of the cases. About half of the patients had a history of nonsteroidal antiinflammatory drug use, and nonsteroidal antiinflammatory drug and Helicobacter pylori were both responsible for the ulcer in three-fourths of these patients. In about one-tenth of the patients, nonsteroidal antiinflammatory drug use was the cause of ulcer alone, and about one-tenth of the ulcers were classified as idiopathic.

Acute pancreatitis associated with H1N1 influenza during 2009 pandemic: a case report.

The relationship between viral infections and acute pancreatitis (AP) is not well-defined and universally accepted. Although an association is debated due to lack of solid evidence, a vast number of case reports suggest a possible interrelation. Influenza A virus is one of the most common infectious pathogens in humans but the incidence of subclinical or overt AP during the course of flu is unknown. We report a case of AP, which occurs shortly after a H1N1 infection during the pandemic in 2009.

Effect of proton pump inhibitor (PPI) treatment in obstructive sleep apnea syndrome: an esophageal impedance-pHmetry study.

BACKGROUND/AIMS: There is an increasing interest for a link between gastroesophageal reflux (GER) and obstructive sleep apnea syndrome (OSAS). There is no study in the literature which examines the relationship between OSAS and esophageal functions in adults with impedance. We first evaluated the role of reflux in OSAS with simultaneous polysomnography and impedance-pHmetry and then investigated whether the effect of proton pump inhibitor (PPI) treatment changes in these parameters. METHODOLOGY: Twenty two OSAS patients who had applied to sleep laboratory between September 2007 and May 2008 were consecutively enrolled to the study. Twenty four hours esophageal impedance study was performed during polysomnographic recording. At least 50% of all apneas in patients must proceed with a reflux event in 2 minute intervals in order to be considered reflux related apnea patient. RESULTS: Pathologic reflux episodes were determined in 20 patients (8 were weakly acidic, 12 were acidic). Reflux dependent apnea was found in 6 patients. There was endoscopically esophagitis in all reflux related apnea patients. There was a negative correlation between initial mean SaO2 and gas reflux events at night (p=0.004, r =-0.588) and mixed reflux events at night (p=0.02, r=0.493). There was a statistically significant regression of AHI (apnea hypopnea index) after 3-months PPI treatment (p=0.012). CONCLUSIONS: Reflux may trigger apnea in some of the OSAS patients. Therefore, each OSAS patient must be inquired about esophageal and extraesophageal symptoms of reflux.

Anticoagulant therapy and Budd-Chiari syndrome: is it successful?

BACKGROUND/AIMS: Anticoagulant therapy is an accepted treatment for Budd-Chiari syndrome (BCS). However, the natural course of untreated patients is unclear. We aimed to evaluate the efficacy of anticoagulant therapy on survival in BCS. METHODOLOGY: Between 1995 and 2007, 45 patients diagnosed with BCS based on the clinical, biochemical, radiological and histological findings were retrospectively evaluated with respect to underlying disease, therapeutic interventions, complications and overall outcome. Complications and survival during the follow-up period were compared in between anticoagulant treated and untreated cases. RESULTS: Mean patient age was 34.4 +/- 11.8 years and 46.7% (21) of them were male. Median followup time was 24 months (6-132); 8.9% of patients were diagnosed as acute, 31.1% as subacute and 60% as chronic BCS according to disease duration. Centrilobular necrosis was found in 16 of 36 biopsy performed patients. Etiological factors were detected in 60% of patients and 40% of them were cryptogenic. Twenty four of them received anticoagulant therapy, the remaining 21 were followed-up with supportive medical therapy. Five patients who had shunt operation were excluded for survival analyses. Complications were similar between treated and untreated cases (p>0.05). There was a positive correlation between survival and centrilobular necrosis (r=0.376, p=0.037). The mean survival periods were 95.5 months (%95 CI 73-117 months) and 72.5 months (%95 CI 42-103 months) in anticoagulant treated and untreated patients, respectively (p>0.246). CONCLUSION: Most patients with BCS are admitted to hospital at the chronic stage and more than half of them have underlying thrombotic risk factor. In our study, no beneficial effects of anticoagulant therapy were observed on the survival and complications of liver disease.

Is portal hypertensive enteropathy an important additional cause of blood loss in portal hypertensive patients?

OBJECTIVE: Recently, mucosal changes of small bowel were defined by developing new imaging techniques including capsule endoscopy (CE) in portal hypertensive patients. However, the clinical impact of these changes is unknown. In this study, we aimed to determine the additional cause of blood loss in portal hypertensive patients. MATERIAL AND METHODS: A total of 444 portal hypertensive patients, hospitalized in our clinic between 2005 and 2007, were evaluated. Patients with obscure bleeding were enrolled to this prospective case-control study. CE was performed in 21 patients who met inclusion criteria. Gastroscopy, colonoscopy and computerized tomography/small bowel enema were performed in all patients. RESULTS: Fourteen cirrhotic and seven noncirrhotic portal hypertensive patients were enrolled to this study. Mean age of patients was 47.9±15.6 years, and 13 of 21 were male. Small bowel varices were found in 7 patients (1 active bleeding) and other mucosal abnormalities in 10 patients (vascular ectasia, erosion and edema, 1 active bleeding). Although two of them were normal, jejunal malignant mass was found in two patients (1 active bleeding). Of 21 patients, 19 (90.5%) patients had portal hypertensive abnormalities (including varices). However, ileal varices rate was 57.1% (4 patients) in noncirrhotic portal hypertensive patients and 21.4% (3 patients) in cirrhotics. CONCLUSION: Ninety percent of patients had portal hypertensive abnormalities in small bowel and one-third of them had small bowel varices. Small bowel varices and vascular ectasia were the main causes of obscure bleeding in portal hypertensive patients.

Electron microscopic findings in non-alcoholic fatty liver disease: is there a difference between hepatosteatosis and steatohepatitis?

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease has long been accepted as benign; however, recent evidence suggests that the disease may progress to cirrhosis and hepatocellular carcinoma, although the natural course of the disease is still unclear. This study was designed to comparatively evaluate electron microscopic features of non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). METHODS: Quantitative and semi-quantitative ultrastructural evaluations were performed on liver biopsies from 23 patients, 10 with NAFL and 13 with NASH. RESULTS: No statistically significant difference was noted between NAFL and NASH patients in ultrastructural features of hepatocytes including megamitochondria, intramitochondrial crystalline inclusions, mitochondrial matrix granules, foamy cytoplasmic appearance, electron-lucent and glycogen-containing nuclear regions, lipofuscin granules, or an increased frequency of vesicles containing electron-dense material in peribiliary Golgi zone; however, the mitochondrial diameter was significantly higher in the NASH patients. Intercellular distance and microvilli between hepatocytes, collagen and electron-dense material accumulation in the space of Disse, electron-dense material accumulation and microvillus density in bile canaliculi did not differ significantly between the groups. CONCLUSIONS: Our data show that, although NAFL and NASH can be distinguished by their distinct light microscopic features, ultrastructural characteristics are similar, which suggests that NAFL may also have the potential to progress to fibrosis and cirrhosis like NASH.

Decreased prohepcidin levels in patients with HBV-related liver disease: relation with ferritin levels.

BACKGROUND: Levels of prohepcidin, a homeostatic regulator of iron absorption, are altered in chronic hepatitis C and liver cirrhosis. However, data on the potential alterations of prohepcidin in patients with HBV-related liver disease are scarce. We investigated whether serum prohepcidin is related to iron overload and perenchymal dysfuction in HBV-related liver disease. METHODS: Three groups of subjects were studied: 66 patients with chronic hepatitis B, 32 patients with HBV-related cirrhosis, and 42 healthy controls without evidence of liver disease. Serum levels of prohepcidin were determined by enzyme-linked immunosorbent assay. RESULTS: Serum prohepcidin levels were significantly lower in patients with HBV-related cirrhosis (175.85 ± 71.5 ng/ml) than in patients with chronic hepatitis B (209.02 ± 62.7 ng/ml P < 0.05) and controls (222.4 ± 128.4 ng/ml, P < 0.05). After adjustment for potential confounders, prohepcidin was found to be an independent predictor of ferritin levels in multiple linear regression analysis (ß = -1.10, t = -3.11, P < 0.01). CONCLUSION: These results demonstrate that prohepcidin levels are reduced in patients with HBV-related cirrhosis and are an independent correlate of serum ferritin.

Are acquired hepatocerebral degeneration and hepatic myelopathy reversible?

BACKGROUND: Acquired hepatocerebral degeneration (AHD) and hepatic myelopathy (HM) are rare complications of chronic liver disease and are usually resistant to medical therapy. MATERIALS AND METHODS: The clinical and laboratory findings of 14 male and 2 female patients with AHD or HM were evaluated. RESULTS: The prevalence of AHD and HM was 2% inpatient case series in the last 10 years. The median age of the patients (5 Child's B and 11 Child's C) was 48.7 years (28 to 66 y), and the mean known duration of the liver disease was 75 months (24 to 194 mo). The median time of onset of neurologic findings after diagnosis of the liver disease was 14.5 months. Eight patients who had marked spastic paraparesis or tetraparesis were included in the HM group and all others had AHD group. Sixty-nine percent of the patients had a spontaneous or surgical portosystemic shunts, and the remaining dense retroperitoneal collaterals. During the follow-up period of median 29 months (4 to 72 mo), 12 patients died while waiting for liver transplantation, and these patients suffered from the several complications of chronic liver disease more than the living patients. A marked improvement was observed in 2 of the patients (1 with AHD and the other with HM) at 6 and 8 months after the liver transplantation, respectively. CONCLUSIONS: Our data suggest that liver transplantation had an important effect on the improvement in these patients.

Intestinal metaplasia in portal hypertensive gastropathy: a frequent pathology.

OBJECTIVE: To compare the frequency of intestinal metaplasia (IM) in patients with portal hypertensive gastropathy (PHG) to the control group with functional dyspepsia. METHODS: Two-hundred and eighty-nine cases were prospectively evaluated in three groups (controls:group I--123 patients; cirrhotics: group II--135 patients; noncirrhotic portal hypertensives: group III--31 patients). Mucosal biopsies (three antrum, one angulus, two corpus) were taken and examined for atrophy, IM, dysplasia, Helicobacter pylori (Hp) and histologic PHG. RESULTS: Frequencies of IM in groups I, II and III were 17.1% (type I, 3.3%; type II, 10.6%; type III, 3.3%), 34.3% (type I, 9.6%; type II, 17%; type III, 6.7%) and 33.3% (type I, 9.7%; type II, 12.9%; type III, 9.7%), respectively. In patients with PHG, frequency of IM was significantly higher than in control group (P<0.05) and correlated with the severity of PHG (P<0.05). The frequency of type III IM was not statistically different among the three groups. Frequency of atrophy in cirrhotic patients was higher than in control group (17.9% in group I, 32.6% in group II, 25.8% in group III; P<0.05). In the control group, Hp prevalence was significantly higher than in patients with PHG (P<0.05) and there was a positive correlation between Hp and atrophy (P<0.05). In multivariate analysis, PHG and age were found as independent predictors for IM; PHG, age and Hp for atrophy. CONCLUSION: Frequencies of atrophy and IM are higher in patients with PHG. PHG is a reliable marker for IM and atrophy in gastric mucosa.

Rapidly progressive HCV cirrhosis in a hypogammaglobulinemic patient.

Contrary to the widely known view of the insidious, slowly progressive pattern of hepatitis C, a rapidly progressive cirrhotic form can develop in immunodeficient conditions. Hepatitis C leads to cirrhosis in immunocompetent hosts after 20 years of infection however in hypogammaglobulinemic patients disease progresses faster, leading to cirrhosis and death within 10 years of diagnosis and frequently earlier. Here we present a 57-year-old woman with common variable immunodeficiency infected with hepatitis C after antral and duodenal resection and gastrojejunostomy operation in another hospital for lymphoma mimicking duodenal nodular hyperplasia which then rapidly progressed to decompensated cirrhosis in less than two years.

Response to hepatitis B vaccination in patients with celiac disease.

Abnormal immune response to gliadin, genetic, and environmental factors play a role in the pathogenesis of celiac disease (CD). Non-responsiveness to hepatitis B virus (HBV) vaccination is related to genetic features. Certain human leukocyte antigen (HLA) genotypes are more prevalent among non-responders to HBV vaccination. There is also a strong relationship between CD and these HLA genotypes. This study investigates the relationship between CD and non-responsiveness to HBV vaccination, with an emphasis on genotypic co-incidence. No statistically significant difference was noted between the ages and gender of CD patients and control subjects. Baseline serum IgA, IgM, and IgG levels of all CD patients were normal. Responsiveness to HBV vaccination was observed in 17 (68%) CD patients and all (100%) control subjects (P = 0.006). In conclusion, CD should also be sought in unresponders to HBV vaccine who are not immunosuppressed.

What is the reason of elevated alanine aminotransferase level in HBeAg negative patients with low viremia: NAFLD or chronic hepatitis?

BACKGROUND AND STUDY AIMS: Increased alanine aminotransferase (ALT) levels with negative hepatitis B virus (HBV) DNA by hybridization is a common problem in Turkey where is a mild endemic region. We aimed to evaluate the causes of elevated ALT levels in patients who are negative for hepatitis B e antigen (HBeAg) and HBV DNA (by hybridization) for at least 6 months. PATIENTS-METHODS: Forty-nine patients were enrolled in this study. Histological changes [histological activity index (HAI), and the extent of fibrosis] were assessed according to the Knodell scoring system and steatosis were graded by Brunt's classification for NAFLD in all patients. RESULTS: A mean age of the patients was 34.9 +/- 12.1 years (16-70). 43 (87.8%) of them were male. Mean ALT level was 95 +/- 39.7 IU/L (50- 258). Hyperglycemia (>100 mg/dL) and hyperlipidemia were found in 12 and 24 patients, respectively. Hepatic steatosis (7 patients grade 1; 5 patients grade 2; and 7 patients grade 3), ground-glass hepatocyte, chronic hepatitis, and Wilson disease were found in liver biopsy in 38.8%, 32.6%, 26.6%, 2%, respectively. Mean HAI was 6.5 +/- 3.6 (4-12) in chronic hepatitis. Seven patients (53.9%) were in stage 1 and 2 while 6 patients (46.1%) were in stage 3 and 4. CONCLUSIONS: Nonalcoholic fatty liver disease is the most common cause of elevated ALT levels in HBeAg negative/HBV DNA negative patients. Chronic hepatitis B was found in 26.6% of these patients.

The effects of rosiglitazone, metformin, and diet with exercise in nonalcoholic fatty liver disease.

Our aim was to evaluate effects of metformin, rosiglitazone, and diet with exercise in nonalcoholic fatty liver disease. Forty-seven patients (mean age, 44+/-10 years; 17 female) whose ALT levels had been high for at least 6 months and with hepatosteatosis detected by liver biopsy and/or USG were enrolled in this study. Of these, 12 were treated with 850 mg/day metformin (group 1), 11 with 4 mg/day rosiglitazone (group 2), and 24 with diet and exercise (group 3) for 1 year. ALT normalization at months 6 and 12 was accepted as treatment response. Liver biopsy was performed in all patients in groups 1 and 2 before treatment and 12 patients (4 in group 1, 8 in group 2) after treatment; but in group 3 it was performed only in patients who approved this procedure (12 patients). Body mass index did not change in groups 1 and 2, but it decreased significantly in group 3 (30+/-3 to 28+/-2 kg/m(2)) at month 12. Treatment response rate was 33.3, 54.5, and 54.2% in groups 1, 2, and 3, respectively, at month 6. This rate was 22.2, 37.5, and 41.2 in groups 1, 2, and 3, respectively, at month 12. Rate of steatosis and stage of fibrosis did not change after treatment. Diet with exercise seems to be superior to metformin and rosiglitazone. Decreasing treatment response at month 12 compared to month 6 may be due to fluctuations of ALT levels. Treatment response should be evaluated histologically.

Pneumatic balloon dilatation in primary achalasia: the long-term follow-up results.

BACKGROUND/AIMS: Pneumatic dilatation is a safe and most effective treatment for achalasia. We analyzed the long-term results of pneumatic dilatation in primary achalasia by objective and subjective findings. METHODOLOGY: Pneumatic dilatation was performed in patients that were diagnosed with primary achalasia in our manometry laboratory between 1993-1999 years. We evaluated patients with clinical, radiologic, endoscopic and manometric results before treatment. Mean esophageal diameters on the level of the lower esophageal sphincter and middle esophagus were measured by barium esophagograms. The patients were clinically reevaluated after one week and barium esophagograms were repeated one month later after dilatation. Clinical examination, endoscopy and manometry were done at 1, 3, 6 and 12 months and repeated yearly for follow-up period. A statistical comparison of pre- and posttreatment on the frequency of dysphagia, radiological diameter of the esophagus and manometric data was performed using unpaired t tests and chi2 tests. RESULTS: Pneumatic dilatation was performed on 50 adult patients with a mean age 41.42+/-18.07 years. A single dilatation was successful in forty patients (80%) and two to three dilatations were performed in ten (20%) patients. The median number of dilatations was 1.26. In the postdilatation period, mean short-term (< 1 year) and long-term (2-7 years) clinical improvement was 82.8% and 66.85% respectively. The mean diameter of the esophagus was regressed to 26.51+/-7.69 mm from 36.66+/-11.23 mm (p<0.001) and the mean diameter of the lower esophageal sphincter was increased to 8.38+/-3.12 mm from 2.58+/-1.13 mm (p<0.001) with pneumatic dilatation. The mean pretreatment pressure of lower esophageal sphincter was 41.14+/-11.34 mmHg and these values were 18.79+/-7.85 mmHg (p<0.001), 13.18+/-9.53 mmHg (p<0.001) in the 1st, and 5th years of the posttreatment period, respectively. The mean pressure of the lower esophageal sphincter was 31.78+/-8.91 mmHg in nonresponder patients during the posttreatment period; there was no significant difference prior to pneumatic dilatation (p>0.1). Surgical operation was performed on 5 patients (10%), who had no benefit from pneumatic dilatation. CONCLUSIONS: Pneumatic dilatation is an effective procedure in the treatment of primary achalasia during the short- and long-term period. Treatment evaluation can possibly be made objectively with radiographic and manometric alterations of esophagus that occurred after pneumatic dilatation.