Berna Savas

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.

Effect of astaxanthin on hepatocellular injury following ischemia/reperfusion

This study investigated the effect of astaxanthin (ASX; 3,3-dihydroxybeta, beta-carotene-4,4-dione), a water-dispersible synthetic carotenoid, on liver ischemia-reperfusion (IR) injury. Astaxanthin (5 mg/kg/day) or olive oil was administered to rats via intragastric intubation for 14 consecutive days before the induction of hepatic IR. On the 15th day, blood vessels supplying the median and left lateral hepatic lobes were occluded with an arterial clamp for 60 min, followed by 60 min reperfusion. At the end of the experimental period, blood samples were obtained from the right ventricule to determine plasma alanine aminotransferase (ALT) and xanthine oxidase (XO) activities and animals were sacrificed to obtain samples of nonischemic and postischemic liver tissue. The effects of ASX on IR injury were evaluated by assessing hepatic ultrastructure via transmission electron microscopy and by histopathological scoring. Hepatic conversion of xanthine dehygrogenase (XDH) to XO, total GSH and protein carbonyl levels were also measured as markers of oxidative stress. Expression of NOS2 was determined by immunohistochemistry and Western blot analysis while nitrate/nitrite levels were measured via spectral analysis. Total histopathological scoring of cellular damage was significantly decreased in hepatic IR injury following ASX treatment. Electron microscopy of postischemic tissue demonstrated parenchymal cell damage, swelling of mitochondria, disarrangement of rough endoplasmatic reticulum which was also partially reduced by ASX treatment. Astaxanthine treatment significantly decreased hepatic conversion of XDH to XO and tissue protein carbonyl levels following IR injury. The current results suggest that the mechanisms of action by which ASX reduces IR damage may include antioxidant protection against oxidative injury.

Serrated polyps of the colon: how reproducible is their classification?

For several years, the lack of consensus on definition, nomenclature, natural history, and biology of serrated polyps (SPs) of the colon has created considerable confusion among pathologists. According to the latest WHO classification, the family of SPs comprises hyperplastic polyps (HPs), sessile serrated adenomas/polyps (SSA/Ps), and traditional serrated adenomas (TSAs). The term SSA/P with dysplasia has replaced the category of mixed hyperplastic/adenomatous polyps (MPs). The present study aimed to evaluate the reproducibility of the diagnosis of SPs based on currently available diagnostic criteria and interactive consensus development. In an initial round, H&E slides of 70 cases of SPs were circulated among participating pathologists across Europe. This round was followed by a consensus discussion on diagnostic criteria. A second round was performed on the same 70 cases using the revised criteria and definitions according to the recent WHO classification. Data were evaluated for inter-observer agreement using Kappa statistics. In the initial round, for the total of 70 cases, a fair overall kappa value of 0.318 was reached, while in the second round overall kappa value improved to moderate (kappa = 0.557; p < 0.001). Overall kappa values for each diagnostic category also significantly improved in the final round, reaching 0.977 for HP, 0.912 for SSA/P, and 0.845 for TSA (p < 0.001). The diagnostic reproducibility of SPs improves when strictly defined, standardized diagnostic criteria adopted by consensus are applied.

An unusual presentation of helicobacter pylori infection: so-called “Russell body gastritis”

Helicobacter pylori (H. pylori) is a “slow” bacterial pathogen, which induces several gastroduodenal diseases. Varying degrees of inflammation can be present in the gastric mucosa of patients infected with H. pylori. The case presented here is a male patient suffering from dyspepsia and nausea. His upper gastrointestinal endoscopy revealed pan gastritis. Histological examination of multiple gastric biopsies taken from the body and antrum showed a rare morphological expression of H. pylori gastritis characterized by diffuse plasma cell infiltration with extensive Russell body formation. Diffuse infiltration of plasma cells with Russell bodies in gastric mucosa can cause difficulties in differentiation from neoplastic processes. However, immunohistochemically, the infiltrating cells in the gastric mucosa stained negatively with cytokeratins while they expressed both kappa and lambda light chains showing their polyclonal nature. The presence of diffuse plasma cells with Russell bodies in the gastric mucosa may represent a different presentation of H. pylori gastritis. There are only two case reports of similar presentation and both have been called “Russell body gastritis”.

A comparison of liver fat content as determined by magnetic resonance imaging-proton density fat fraction and MRS versus liver histology in non-alcoholic fatty liver disease:

Background Many imaging methods have been defined for quantification of hepatic steatosis in non-alcoholic fatty liver disease (NAFLD). However, studies comparing the efficiency of magnetic resonance imaging-proton density fat fraction (MRI-PDFF), magnetic resonance spectroscopy (MRS), and liver histology for quantification of liver fat content are limited. Purpose To compare the efficiency of MRI-PDFF and MRS in the quantification of liver fat content in individuals with NAFLD. Material and Methods A total of 19 NAFLD patients underwent MRI-PDFF, MRS, and liver biopsy for quantification of liver fat content. The MR examinations were performed on a 1.5 HDx MRI system. The MRI protocol included T1-independent volumetric multi-echo gradient-echo imaging with T2* correction and spectral fat modeling and MRS with STEAM technique. Results A close correlation was observed between liver MRI-PDFF- and histology- determined steatosis (r = 0.743, P < 0.001) and between liver MRS- and histology-determined steatosis (r = 0.712, P < 0.001), with no superiority between them (ƶ = 0.19, P = 0.849). For quantification of hepatic steatosis, a high correlation was observed between the two MRI methods (r = 0.986, P < 0.001). MRI-PDFF and MRS accurately differentiated moderate/severe steatosis from mild/no hepatic steatosis (P = 0.007 and 0.013, respectively), with no superiority between them (AUCMRI-PDFF = 0.881 ± 0.0856 versus AUCMRS = 0.857 ± 0.0924, P = 0.461). Conclusion Both MRI-PDFF and MRS can be used for accurate quantification of hepatic steatosis.

Entecavir Treatment of Chronic Hepatitis D

BACKGROUND Hepatitis D virus (HDV) requires hepatitis B surface antigen (HBsAg) to propagate infection and cause disease. Entecavir is a nucleoside analog with potent antiviral efficacy, and in the woodchuck animal model it also decreased hepatitis B virus (HBV) cccDNA and woodchuck surface antigen. The aim of this study was to investigate the efficacy of entecavir in chronic hepatitis D (CHD). METHODS This single-center study was conducted in patients with compensated liver disease. All patients had to have detectable hepatitis HDV RNA and elevated levels of alanine aminotransferase (ALT). Entecavir was given at a dosage of 1 mg/d for 1 year. The primary end point was achievement of undetectable HDV RNA at the end of treatment. RESULTS Thirteen consecutive patients were assessed. All patients had detectable HDV RNA, and 8 had detectable HBV DNA at baseline. At the end of treatment, HBV DNA became undetectable in all patients (P = .001). No significant decline in HDV RNA, ALT, or quantitative HBsAg levels was observed. The primary end point of undetectable HDV RNA at the end of treatment was achieved in 3 patients who had significantly lower baseline HDV RNA levels than nonresponders (2.99 log(10) copies/mL ± .70 vs 4.68 ± .97; P = .0185). In all 3 patients, ALT levels were also normal at the end of treatment. CONCLUSIONS One year of entecavir treatment is ineffective in CHD. Any generalized beneficial effect of nucleoside/nucleotide analog treatment may necessitate prolonged treatment. Patients with CHD with HBV dominance, which is likely to occur in the later phases of CHD, may be a reasonable patient cohort in which to target nucleoside/nucleotide analog therapy.

Rapid early HDV RNA decline in the peripheral blood but prolonged intrahepatic hepatitis delta antigen persistence after liver transplantation

BACKGROUND & AIMS Chronic HDV infection is an inflammatory liver disease and liver transplantation (LTX) remains the only curative treatment option for most patients. The hepatitis D virus (HDV) uses HBsAg as its surface protein, however, it is controversial to what extend HDV may be detected independently of HBsAg in blood and liver after LTX. The aims of this study were to investigate kinetics of HDV RNA and HBsAg early after LTX, to apply the data to a mathematical model and to study long-term persistence of HDV after LTX. METHODS We retrospectively analyzed 26 patients with chronic hepatitis delta who underwent LTX between 1994 and 2009. Blood samples were obtained every 1-3 days during the first 14 days after LTX. Data were applied to a mathematical model to study viral kinetics. Available liver biopsy samples were stained for HBV and HDV viral antigens and tested for HBV DNA/cccDNA. RESULTS HBsAg and HDV RNA became negative after a median of 5 days (range 1-13) and 4 days (range 1-10), respectively. Early HDV RNA and HBsAg decline paralleled almost exactly in all patients; however the mathematical model showed a high variability of virion death. HDAg stained positive in transplanted livers in six patients in the absence of liver HBV DNA/cccDNA, serum-HBsAg, and HDV RNA for up to 19 months after LTX. CONCLUSIONS HDV RNA and HBsAg decline follow almost identical kinetic patterns within the first days after LTX. Nevertheless, intrahepatic latency of HDAg has to be considered when exploring novel concepts to withdraw HBIG.

MTA-1 expression is associated with metastasis and epithelial to mesenchymal transition in colorectal cancer cells

Although metastasis associated protein 1 (MTA1) has been widely linked to tumor metastasis, the relevant mechanisms remain to be elucidated, especially in colorectal cancer (CRC). Here, we have investigated the link between MTA1, metastasis and epithelial–mesenchymal transition (EMT) in CRC. Eighteen normal colon tissues and 91 resected tumor samples were analyzed for MTA1 expression by immunohistochemistry (IHC). IHC indicated low or no nuclear MTA1 expression in the normal tissues and significantly higher expression in Grade II, Grade III and liver metastasis tumors. No statistically significant difference was observed in MTA1 expression between Grade III and liver metastatic tumors. To demonstrate the functional importance of MTA1 in vitro, the gene was silenced in HCT-116 cells and LoVo cells and overexpressed in HCT-116 cells. MTA1 overexpression in HCT-116 cells enhanced proliferation, adhesion to fibronectin, motility, migration, invasion through Matrigel, anchorage-independent growth, neoangiogenesis and induced a loss of apoptosis. Silencing of MTA1 resulted in a reversal of all of these features. Mechanistically, MTA1 silencing caused an increase in the epithelial markers E-cadherin and ZO-1 and a decrease in the mesenchymal marker vimentin while MTA1 overexpression caused an increase in vimentin expression. Moreover, MTA1 enhanced the expression of Snai1 and Slug; silencing of MTA1 reduced their recruitment to the promoter of E-cadherin, thereby leading to its expression. MTA1 is highly expressed in higher grade tumors and is important in the orchestration of various phenotypic changes in CRC, most likely by inducing EMT. This further corroborates its role as a master regulator in tumorigenesis.

Spinal Intradural-Intramedullary Cavernous Malformation

Cavernous angiomas or cavernomas are uncommon vascular malformations of the central nervous system and spinal involvement is much rarer especially in pediatric patients. We report a case of spinal intradural-intramedullary cavernous angioma in a 14-year-old male child. The cavernoma was located at the level of C6–C7 at the dorsal part of the spinal cord. The diagnosis was made with MRI and the patient underwent surgical treatment. The cavernoma was totally removed with laminotomy and microsurgical techniques. Somatosensory evoked potential monitoring was also used peroperatively. The clinical, radiological and surgical features of this rare case were presented and discussed with reference to the literature.

The usefulness of chromoendoscopy with methylene blue in Barrett’s metaplasia and early esophageal carcinoma

BackgroundBarrett’s esophagus is a condition that is premalignant for adenocarcinoma of the esophagus and the esophagogastric junction. Early detection of Barrett’s metaplasia and dysplasia is very important to decrease the mortality and morbidity from esophageal adenocarcinoma cancer. This study aimed to evaluate the effectiveness of methylene blue–targeted biopsies in the differential diagnosis of intestinal metaplasia, dysplasia, and superficial esophageal carcinoma.MethodsA total of 109 patients (43 women and 66 men; average age, 62.32 ± 10.61 years; range, 33–82 years) were enrolled for the study. Four groups were designed before endoscopic examinations. The patients for these groups were selected at the conventional endoscopy, and then chromoendoscopy was performed. The esophagus was stained with methylene blue, after which six biopsies were taken from stained and unstained areas.ResultsConventional and chromoendoscopic assessments were compared with histopathologic examination. The sensitivity of chromoendoscopy for Barrett’s epithelium was superior to that of conventional endoscopy (p < 0.05). However, there was no statistical difference between the two methods in the diagnosis of esophagitis or esophageal carcinoma (p > 0.05). Stained biopsies were superior to unstained biopsies in terms of sensitivity for Barrett’s epithelium and esophageal carcinoma (p < 0.001).ConclusionChromoendoscopy is useful for delineating Barrett’s epithelium and for indicating the correct location for securing biopsies where dysplasia or early esophageal cancer is suspected.