Hepatic steatosis: quantification by proton density fat fraction with MR imaging versus liver biopsy.

PURPOSE: To determine utility of proton density fat fraction (PDFF) measurements for quantifying the liver fat content in patients with nonalcoholic fatty liver disease (NAFLD), and compare these results with liver biopsy findings. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board with waivers of informed consent. Between June 2010 and April 2011, 86 patients received a diagnosis of NAFLD. Ten patients did not accept liver biopsy and six patients had contraindications for magnetic resonance (MR) imaging. Seventy patients were included in this study. Seventy patients with NAFLD (40 men, 30 women; mean age, 44.7 years; range, 16-69 years) underwent T1-independent volumetric multiecho gradient-echo imaging with T2* correction and spectral fat modeling. Median time interval between MR imaging and liver biopsy was 14.5 days (range, 0-259 days). MR examinations were performed with a 1.5-T MR imaging system. Complex-based PDFF measurements were performed by placing regions of interest in Couinaud system segments V-VI and all liver segments from I to VIII. All liver biopsy specimens were retrieved from archives and evaluated by one pathologist for hepatic steatosis according to criteria from a previous study. Pearson correlation coefficient, receiver operating characteristics, and linear regression analyses were used for statistical analyses. RESULTS: Mean PDFF calculated with MR imaging was 18.1% ± 9.5 (standard deviation). Close correlation for quantification of hepatic steatosis was observed between PDFF and liver biopsy (r = 0.82). PDFF was effective in discriminating moderate or severe hepatic steatosis from mild or no hepatic steatosis, with area under the curve of 0.95. The correlation between biopsy and PDFF-determined steatosis was less pronounced when fibrosis was present (r = 0.60) than when fibrosis was absent (r = 0.86; P = .02). CONCLUSION: PDFF measurement by MR imaging provided a noninvasive, accurate estimation of the presence and grading of hepatic steatosis in patients with NAFLD. Hepatic fibrosis reduced the correlation between biopsy results and PDFF.

The characteristics and clinical outcome of drug-induced liver injury: a single-center experience.

BACKGROUND AND GOALS: The aim of this cohort study was to determine the characteristics and clinical outcome of 170 patients with drug-induced liver injury (DILI) in a single center. STUDY: Between January 2001 and June 2007, a total of 170 individuals who were diagnosed with DILI were retrospectively analyzed. The median follow-up period was 110.0 days. RESULTS: During the study period, a total of 5471 new patients were assessed for liver test abnormalities. Of those, 170 patients (3.1%) fulfilled the criteria of DILI. A total of 83 different drugs were considered to be related to the hepatotoxicity; a single drug was suspected in 57.6% of individuals. The median interval between the suspicious drug intake and DILI recognition was 15.0 days. Hepatocellular pattern was observed in 50.0% of patients with a mean alanine aminotransferase level of 952.2+/-907.0 U/L. The main causative group of drugs was antibiotics. Sixty-two patients required hospitalization; acute liver failure developed in 14 (8.2%), chronicity was observed in 19 (11.2%), and 7 died (4.1%). Overall, complete recovery occurred in 82% of patients. The presence of jaundice on admission and shorter interval period between drug intake and DILI recognition were identified as risk factors for the development of acute liver failure. CONCLUSIONS: DILI is an important cause of liver test abnormalities in outpatient clinics, and antibiotics represent the most common drug group. Overall, complete recovery after the withdrawal of the suspicious drug occurred in the majority of patients, but DILI may progress to acute liver failure, chronicity, and death.

Obstructive jaundice: an unusual initial manifestation of intra-abdominal non-Hodgkin lymphoma in a child.

Obstructive jaundice is an unusual manifestation of non-Hodgkin lymphomas in children. Although surgical drainage is one of the initial treatment choices in some cases, usually lymphomatous masses rapidly response to chemotherapy and jaundice decreases due to regression of the mass, without any surgical procedure. The authors report the case of a 16-year-old girl who presented with biliary obstruction due to a neoplasm involving the duodenum. Histological examination of the specimen, which was taken from the mass by endoscopic biopsy, revealed Burkitt lymphoma infiltrating the duodenum. Chemotherapy including cyclophosphamide was started immediately. In a few days, jaundice decreased rapidly by the shrinkage of the mass. Neither surgery nor percutaneous drainage were needed. In conclusion, biliary tract obstruction due to non-Hodgkin lymphoma can be effectively treated with chemotherapy alone without any surgical procedure.

Thrombophilic gene mutations in cirrhotic patients with portal vein thrombosis.

OBJECTIVE: Thrombophilic gene mutations have been reported to be associated with the formation of portal vein thrombosis (PVT). This study aimed to investigate the role of thrombophilic gene mutations in cirrhotic patients with PVT. PATIENTS AND METHODS: A total of 74 cirrhotic patients (17 with PVT, 57 without PVT), and 19 non-cirrhotic patients with PVT and 80 healthy controls were included. Factor V Leiden G1691A, prothrombin G20210A and methylenetetrahydrofolate reductase C677T mutations were analysed by restriction fragment length polymorphism. RESULTS: Aetiologies and Child-Pugh distribution of cirrhotic patients with and without PVT were similar. Five of 17 (29%) of cirrhotic patients with PVT but only two of 57 (3.5%) of cirrhotics without PVT, five of 80 (6%) of controls and none of the 19 non-cirrhotic patients with PVT had factor V Leiden G1691A mutation (P<0.05). Prothrombin G20210A mutation was found in five (29%) cirrhotic patients with PVT while only two (3.5%) cirrhotic patients without PVT, one (5%) non-cirrhotic patient with PVT and two (2.5%) controls had this mutation (P<0.05). The frequency of the homozygote methylenetetrahydrofolate reductase 677C-T mutation was similar in all four groups. CONCLUSIONS: Inherited thrombophilic gene mutations appear to increase the risk of PVT formation in cirrhotic patients but not in patients without liver disease in a cohort of Turkish patients.

Diagnosis of hepatocellular carcinoma by fine needle aspiration cytology. Cellular features.

OBJECTIVE: To evaluate the importance of fine needle aspiration cytology (FNAC) in the diagnosis of hepatocellular carcinoma (HCC). STUDY DESIGN: We analyzed 17 cytologic and 5 architectural features in a series of 320 FNACs from HCC and compared them with 73 FNACs from benign lesions and with 705 FNACs from metastatic carcinomas. One thousand ninety-eight patients who were diagnosed by liver FNAC between December 1988 and July 1998 and had adequate follow-up were included in the study. The specimens were evaluated according to the presence or absence of the cytologic features and cellular arrangement. A stepwise logistic regression analysis was performed on the data to determine the variables predictive of HCC. RESULTS: Multinucleated tumor giant cells, cytoplasmic hyaline and central sinusoidal pattern were selected as the 3 most predictive parameters for differentiated reactive hepatocytes from HCC (P < .0001), while bile, centrally located nucleus in an atypical cell and intranuclear inclusion were selected as the 3 most predictive parameters for differentiated metastatic carcinoma from HCC (P < .0001-< .001) by stepwise logistic regression analysis. CONCLUSION: In the 1,098 patients suspected of having hepatic malignancy, a correct diagnosis was made by a combination of the above features. The sensitivity of this procedure for hepatic malignancy was 99.5%, and the specificity was 100%.

The value of fine needle aspiration biopsy in the diagnosis of metastatic liver tumours.

BACKGROUND/AIMS: Fine needle aspiration biopsy is a useful tool in the diagnosis of primary malignancies and metastatic lesions of the liver. The aim of this study was to determine the types and features of tumors diagnosed by this method and the difficulties in differential diagnosis. METHODS: Fine needle aspiration biopsy smears from 704 patients with metastatic liver lesions were reviewed. RESULTS: Among the metastastatic carcinomas in which their primary origin was identified, pulmonary carcinomas were the largest group. While colon adenocarcinoma was most prevalent (21.65%) where the primary origin of metastatic tumors was identified, followed by breast carcinoma (20.10%) and gastric adenocarcinoma (19.59%). The cases which cannot be differentiated from hepatocellular carcinoma in cytologic examination are invasive ductal carcinoma, renal cell carcinoma and squamous cell carcinoma. CONCLUSIONS: Pulmonary and colon carcinomas are the common metastatic tumors of the liver.

Percutaneous transhepatic venoplasty: an alternative treatment for Budd-Chiari syndrome.

BACKGROUND/AIMS: In patients with Budd-Chiari syndrome due to short segment hepatic vein stenosis where percutaenous transluminal venoplasty is not successful, percutaneous transhepatic balloon venoplasty may be a valid treatment option. The aim of this prospective study was to evaluate the effects of this procedure for the treatment of patients with Budd-Chiari syndrome, in whom transluminal cannulation was unsuccessful. METHODS: Ten patients with short segment occlusion of the hepatic veins were treated by percutaneous transhepatic balloon venoplasty between January 1997 and January 2000. The median follow-up period of these patients was 20 months (2-33 months). RESULTS: The procedure was unsuccessful in two patients. Eight patients (five men, three women) with a median age of 28 (range, 15-61) years were treated by percutaneous transhepatic balloon venoplasty and in seven of them, clinical symptoms including abdominal distension and ascites, resolved completely. Long term anticoagulation therapy was not given to the patients. One patient with advanced stage liver disease died of variceal bleeding two months after the procedure. During follow-up, symptomatic reocclusion requiring dilatation occurred in three patients. CONCLUSIONS: Percutaneous transhepatic balloon venoplasty is an alternative treatment option for selected patients with Budd-Chiari syndrome when transluminal cannulation of the hepatic veins is not possible. Long term anticoagulation therapy seems to be necessary in these patients.

Endoscopic treatment of biliary complications following liver transplantation.

BACKGROUND/AIMS: The aims of the present study were to review biliary complications following liver transplantation in a single-center experience, to identify the factors associated with biliary complications, and to evaluate the success of endoscopic and percutaneous treatment in such patients. MATERIALS AND METHODS: Between January 1994 and June 2010, a total of 176 patients with liver disease underwent liver transplantation; 119 recipients were included in this retrospective analysis. Median posttransplant follow-up period was 49 months. RESULTS: Mean age was 43.0±12.7 years. Living donor liver transplantation (LDLT) and deceased-donor liver transplantation (DDLT) were performed in 71 and 48 patients, respectively. Duct-to-duct anastomosis and Roux-en-Y hepaticojejunostomy were performed in 68 and 51 patients, respectively. The overall incidence of posttransplant biliary complications was 36%; anastomotic biliary strictures were the most common biliary complications (42%), followed by biliary leakage (28%). On logistic regression analysis, duct-duct anastomosis was the only risk factor associated with the development of biliary complications (Odds ratio (OR), 3.346; p=0.005). Endoscopic and percutaneous treatment was successful in the majority of patients (81%), and the remaining 19% recipients underwent surgery for biliary repair. Endoscopic retrograde cholangiopancreatography (ERCP) guided drainage and balloon dilatation with stent placement were the most common treatment modalities. CONCLUSION: Biliary complications were most frequent after liver transplantation; biliary strictures were the most commonly seen. The use of duct-to-duct anastomosis for biliary reconstruction is a risk factor for the development of biliary complications. Endoscopic and percutaneous treatment was successful in the majority of these patients.

Manometric assessment of esophageal motor function in patients with primary biliary cirrhosis.

INTRODUCTION/AIM: Primary biliary cirrhosis is associated with other autoimmune diseases including Sjögren's syndrome, and scleroderma. Esophageal dysmotility is well known in scleroderma, and Sjögren's syndrome. The aim of this study is to investigate whether any esophageal motor dysfunction exists in patients with primary biliary cirrhosis. METHOD: The study was performed in 37 patients (36 women, mean age: 56.29 ± 10.01 years) who met diagnostic criteria for primary biliary cirrhosis. Thirty-seven functional dyspepsia patients, were also included as a control group. Patients entering the study were asked to complete a symptom questionnaire. Distal esophageal contraction amplitude, and lower esophageal sphincter resting pressure were assessed. RESULTS: Manometric findings in primary biliary cirrhosis patients vs. controls were as follows: Median lower esophageal sphincter resting pressure (mmHg): (24 vs 20, p=0.033); median esophageal contraction amplitude (mmHg): (71 vs 56, p=0.050); mean lower esophageal sphincter relaxation duration (sc, x ± SD): (6.10 ± 1.18 vs 8.29 ± 1.92, p<0.001); and median lower esophageal sphincter relaxation (%) (96 vs 98, p=0.019); respectively. No significant differences were evident in median peak velocity (sc) (3.20 vs 3.02, p=0.778) between patients with primary biliary cirrhosis and the functional dyspepsia patients. Esophageal dysmotility was found in 17 (45.9%) primary biliary cirrhosis patients (non-specific esophageal motor disorder in ten patients, hypomotility of esophagus in five patients, nutcracker esophagus in one patient and hypertensive lower esophageal sphincter in one patient). CONCLUSION: Esophageal dysmotility was detected in 45.9% of patients. The study suggests that subclinic esophageal dysmotility is frequent in patients with primary biliary cirrhosis.

A rare cause of massive ascites: familial Mediterranean fever.

Familial Mediterranean fever is an autosomal recessive disease characterized by recurrent fever and peritoneal and pleural inflammation. It is an inherited disorder commonly found in Armenians, Turks, Arabs, Balkans, and Jews originating from North African countries. A small amount of peritoneal fluid collection can be observed during peritoneal attacks in patients with Familial Mediterranean fever, but chronic ascites has been described rarely in these patients. A 42-year-old female patient was admitted to our clinic in June 2010 with fever, severe abdominal pain and abdominal distention that had continued for one month. There was no family history of periodic fevers or abdominal pain. We could not find any cause for ascites, including tuberculosis. A diagnosis of Familial Mediterranean fever was suspected based on the clinical findings and her family history. She was screened for mutations causing Familial Mediterranean fever, and when found to be homozygous for M694V, treatment with colchicine was initiated. After treatment, the amount of ascites decreased, and relief of symptoms was confirmed during a follow-up. In conclusion, because Familial Mediterranean fever is common in our country, it should be considered in the differential diagnosis of patients with ascites of unknown etiology in populations where hereditary inflammatory disease is endemic.

Effects of Helicobacter pylori infection and long-term proton pump inhibitor use on enterochromaffin-like cells.

BACKGROUND: Excessive release of gastrin leads to hypertrophy and hyperplasia of enterochromaffin-like cells (ECL) and prolonged stimulation of these cells causes functional impairment. The purpose of this study was to investigate the effect of Helicobacter pylori (H. pylori) infection and long-term proton pump inhibitors (PPI) use on ECL cells. METHODS: Fifteen patients who underwent endoscopy because of dyspeptic symptoms were enrolled in the present study. Biopsies were taken from corpus and antrum and existence of H. pylori was investigated with culture, cytology and CLOtest. The patients were divided into 3 groups. Group-A: H. pylori-negative, never treated previously with PPI; Group-B: H. pylori-positive, never treated previously with PPI; and group-C: H. pylori-negative and continuously treated with PPI for more than 6 months before the subject recruitment period. The features of ECL cell in oxyntic glands were examined with electron microscopy on biopsy specimens. RESULTS: ECL cells were completely normal in Group A. In group B, moderate hyperplasia and vacuolization was seen in ECL cells. In group C, ECL cell hyperplasia was observed and vacuoles with greater amounts of granules in enlarged vesicles were found more intensely in cytoplasm. CONCLUSION: The use of PPI for a long period of time and presence of H. pylori infection are risk factors for ECL hyperplasia.

The efficacy and safety of colonoscopy preparation with oral sodium phosphate in elderly patients.

BACKGROUND/AIMS: Oral sodium phosphate is an agent used commonly in our country for cleaning the intestines before colonoscopy. Our aim was to compare the safety, tolerability and efficiency of oral sodium phosphate solution used in colonoscopy preparation in patients over 70 years of age. METHODS: This study was carried out in Ankara University School of Medicine Cebeci Hospital Endoscopy Center between August 2008 and March 2009. The extent of colon cleanliness was scored in the colonoscopy procedure. The data from the two groups were compared. RESULTS: In our study, 55 patients were divided into two groups according to their age, as over 70 years (n: 25) and under 70 years (n: 30). The average age of the group under 70 years was 49.4±9.8 and of the group over 70 years was 71.4±1.2 (p=0.04). Among the patients included in this study, 59.1% were female (n: 28) and 50.9% were male (n: 27). In the over 70 years group, the intestinal cleanliness was poor-fair in 2 patients, acceptable in 7 patients and excellent in 16 patients. In the below 70 years group, the intestinal cleanliness was poor in 2 patients, acceptable in 9 patients, good in 13 patients, and excellent in 6 patients. In the statistical evaluation, it was determined that there was no statistical difference between the over- and below 70 years of age groups regarding good-excellent intestinal cleanliness and poor-medium intestinal cleanliness (p=0.109). There was no statistical difference between the groups with regard to the adverse effects. The sodium, potassium and creatinine levels were assessed on the procedure day in 5 patients with clinical side effects (abdominal pain, nausea, vomiting, dizziness, hypotension) in the elderly group. No electrolyte imbalance or renal function impairment was observed in these patients. CONCLUSIONS: In the group of patients over 70 years old, a special patient group without comorbid diseases, oral sodium phosphate solution used for colon preparation was effective and well-tolerated with a low adverse effect rate. In spite of this safe profile, since serum creatinine levels and electrolyte imbalance were assessed in only a limited number of patients, the relationship reported in the literature between oral sodium phosphate and electrolyte imbalance and renal function impairment should be kept in mind.

Sequential therapy for Helicobacter pylori eradication.

BACKGROUND AND AIMS: The success of Helicobacter pylori eradication using triple eradication therapy declines over time. In this prospective study, we have compared a group of naive H. pylori-positive patients receiving sequential therapy with our previously published naive H. pylori-positive control group who received ranitidine bismuth citrate-clarithromycin-amoxicillin eradication treatment. Moreover, the eradication success of these two treatment protocols was compared with that of recent standard triple eradication treatment results for the naive patients in our country and western communities. METHODS: We performed invasive tests for H. pylori in naive patients who underwent gastroduodenoscopy in the Endoscopy Unit, Ankara University, Faculty of Medicine, and patients who were diagnosed as H. pylori-positive by these tests were rechecked by the same invasive tests one month after the completion of eradication treatment. The group receiving sequential therapy was given pantoprazole + amoxicillin during the first seven days and pantoprazole + metronidazole + tetracycline during the second seven days. These patients were compared with the H. pylori-positive naive control group patients, who were given ranitidine bismuth citrate + clarithromycin + amoxicillin. The patients in whom eradication was achieved in the 4th week with sequential therapy were reevaluated one year later regarding the success of eradication with the H. pylori stool antigen test. RESULTS: The average age of the 108 patients who received the sequential therapy was 45.2±12.5 years. The average age of the 75 patients who received ranitidine bismuth citrate treatment was 41.2±12.6 years. Six (5%) patients in the consecutive treatment group developed deterioration in taste in the mouth and 10 (9%) developed diarrhea. However, no side effects severe enough to require discontinuation of the treatments were observed in either treatment group. The results of the invasive tests were evaluated by the end of the first month, and revealed an eradication rate of 88% in the sequential treatment group versus 95% in the ranitidine bismuth citrate treatment group. Sixty-eight of 94 patients in whom eradication was achieved by sequential therapy were reevaluated with H. pylori stool antigen test in one year, and eradication was found to persist in 52 (77%) of these 68 patients. CONCLUSIONS: High rates of eradication were achieved in both groups in the 4th week evaluation. It was observed at the follow-up performed one year later that the eradication achieved with sequential therapy persisted in 77% of the patients treated.

Mitochondrial neurogastrointestinal encephalomyopathy: diagnostic features of two patients.

Mitochondrial neurogastrointestinal encephalomyopathy is a rare, multisystem disorder characterized by gastrointestinal dysmotility, ptosis, neurologic findings (e.g., peripheral neuropathy), leukoencephalopathy, and thin body habitus. Gastrointestinal motility studies and skeletal muscle biopsy are recommended diagnostic tools. We report two patients that highlight the diagnostic characteristics of this rare entity.

Bronchoalveolar lavage fluid analysis in individuals with chronic hepatitis C.

A number of disorders for which an association with hepatitis C virus infection exist. These disorders include essential mixed cryoglobulinemia, membranoproliferative glomerulonephritis, and idiopathic pulmonary fibrosis. This study was initiated to investigate the cellular content and lymphocyte subpopulations of bronchoalveolar lavage fluid obtained from individuals with chronic hepatitis C and to compare the results to those of controls. Eighteen patients with chronic hepatitis C (male/female, 6/12) and 14 healthy volunteers (male/female, 6/8), were studied. Bronchoalveolar lavage fluid was obtained from each; and the lymphocyte subtypes and the presence of HCV-RNA in the bronchoalveolar lavage fluid were determined. All anti-HCV positive subjects were HCV-RNA positive in serum. One (5.6%) had a HCV-RNA positive bronchoalveolar lavage. The total cell and neutrophil counts of the bronchoalveolar lavage fluid were significantly greater in patients with chronic hepatitis C as compared to controls (5,799.6 +/- 957.4 x 10(3)/ml vs. 1,835.7 +/- 447.8 x 10(3)/ml, P = 0.001; 1,175.8 +/- 634.7 x 10(3)/ml vs. 53.1 +/- 28.1 x 10(3)/ml, P = 0.029). In contrast, the lymphocyte, macrophage and eosinophil counts did not differ. No difference in the percentage, median or range of individual T cell subsets or B cell numbers in the bronchoalveolar lavage fluid existed between the groups. It is concluded that hepatitis C virus infection may be associated with an occult pulmonary inflammatory reaction manifested by an increased number of polymorphonuclear neutrophils in bronchoalveolar lavage fluid. This finding may contribute to the process that leads to idiopathic pulmonary fibrosis seen in a minority of cases of chronic hepatitis C.