Oxidized Regenerated Cellulose can be a Cause of False Tumor Recurrence on PET/CT in Patients with Lung Cancer Treated Surgically.

Objectives: Regular follow-up of patients with lung cancer treated surgically is crucial to detect local recurrence or distant metastasis of the tumor. Postoperative follow-ups are performed with thorax computed tomography (CT) and, if necessary, positron emission tomography (PET)/CT. Sometimes, inflammatory tissue reactions due to the materials used during the surgery for hemostasis may cause the appearance of tumor recurrence in imaging modalities. In this study, we presented that oxidized regenerated cellulose (ORC) used intraoperatively may cause false tumor recurrence on PET/CT. Methods: The records of patients who had local tumor recurrence after lung cancer surgery was reviewed retrospectively. Inclusion criteria were the presence of local recurrence of cancer on PET/CT, specification of using ORC in the surgical notes, and histopathological diagnosis of the recurrence site of tumor was reported as a foreign body reaction. Data of patients were collected according to age, gender, surgery performed, adjuvant therapy status, resolution status and time ORC, and standard uptake value of 18F-fluorodeoxyglucose on PET/CT. Results: Eleven patients (1 female, 10 males) who met the criteria were included in the study. The median age was 64. Histopathological results of all patients were reported as foreign body reactions. The median detection time of PET/CT positivity after surgery was 139 days (range: 52-208 days). False tumor recurrence was resolved in 8 patients (72.7%) in their control radiological examinations and median resolution time was 334 days (range: 222-762 days). The median maximum standard uptake value of the lesions was 6.2 (1.7-11) on the PET/CT. Conclusion: ORC used intraoperatively in patients undergoing surgery for lung cancer may cause false tumor recurrence in imaging modalities in postsurgical follow-ups. When tumor recurrence is suspected in the follow-up of these patients, histopathological confirmation is necessary to prevent unnecessary operations and treatments.

The Relationship Between Plexin C1 Overexpression and Survival in Hepatocellular Carcinoma: a Turkish Oncology Group (TOG) Study.

PURPOSE: Plexin C1 is a transmembrane receptor and plexin C1 overexpression might have role in carcinogenesis. Hepatocellular carcinoma (HCC) has poor prognosis because of its aggressive behavior and limited treatment options, especially in advanced stage. We recently documented that Plexin C1 was overexpressed in HCC. We aimed to evaluate the prognostic significance of Plexin C1 overexpression in HCC in the present study. METHODS: Plexin C1 overexpression was evaluated immunohistochemically on paraffin-embedded blocks of the HCC patients. Plexin C1 immunohistochemical staining was scored. Plexin C1 overexpression staining intensity and prevalence were used for plexin scale staining evaluation and plexin scores were estimated according this staining scale. Plexin C1 score and its association with survival and clinicopathological features was assessed. RESULTS: Sixty-seven HCC patients with adequate tissue for pathological evaluation were included. Median age was 63 years with male predominance (male to female ratio was 4.75 (n 57/12). Well-differentiated HCC (53.7%) patients had higher plexin C1 overexpression (p < 0.05). Median OS was 22.1 months. Patients with lower plexin C1 score (< 12) had shorter OS (17.5 vs 30.1 months, p = 0.036). Neutrophil count, GGT, and PNR (platelet/neutrophil ratio) had prognostic significance (p = 0.047, p = 0.018, and p = 0.045). CONCLUSION: Plexin C1 overexpression is inversely correlated with grade in HCC. The patients with lower rate of Plexin C1 overexpression have worse survival outcome. It might be a prognostic factor in HCC.

Hepatocellular adenomas in the Turkish population: reclassification according to updated World Health Organization criteria.

AIMS: Hepatocellular adenoma (HCA) is an uncommon liver neoplasm, and studies of HCA subtypes have been primarily limited to France, the USA, and Japan. The aim of this study was to describe the clinicopathological features of HCA subtypes in Turkey. METHODS AND RESULTS: The resection specimens of 59 cases diagnosed as 'hepatocellular adenoma' collected from 15 institutions were reviewed to confirm the diagnosis and to classify them according to the current World Health Organization 2019 classification. Immunostaining for glutamine synthetase, liver fatty acid-binding protein, C-reactive protein, ß-catenin and reticulin was performed. Of the 59 cases, 48 (81%) were diagnosed as HCA. We identified 24 (50%) hepatocyte nuclear factor 1α (HNF1α)-inactivated HCAs, five (10%) inflammatory HCAs, 15 (32%) ß-catenin-activated HCAs, three (6%) ß-catenin-activated inflammatory HCAs, and one (2%) unclassified HCA. HCA patients were predominantly female (female/male ratio of 5:1); they had a median age of 34 years and a median tumour diameter of 60 mm. In the ß-catenin-activated HCA group, nine cases (19%) showed cytoarchitectural atypia, and were also referred to as atypical hepatocellular neoplasms. In the ß-catenin-activated HCA group, three cases (6%) showed focal areas supportive of transition to HCA. The original diagnosis of HCA was changed to well-differentiated hepatocellular carcinoma in nine cases and to focal nodular hyperplasia in two cases. CONCLUSION: In our series, the major HCA subtype was HNF1α-inactivated HCA. We found a low incidence of inflammatory-type HCA. Our data also showed that ß-catenin-activated hepatocellular neoplasms, including cases with atypical histology, constituted a relatively high proportion of the cases. These findings are in contrast to those of most other studies of HCA subtypes.

A Retrospective Evaluation of the Epithelial Changes/Lesions and Neoplasms of the Gallbladder in Turkey and a Review of the Existing Sampling Methods: A Multicentre Study.

OBJECTIVE: As there is continuing disagreement among the observers on the differential diagnosis between the epithelial changes/lesions and neoplasms of the gallbladder, this multicentre study was planned in order to assess the rate of the epithelial gallbladder lesions in Turkey and to propose microscopy and macroscopy protocols. MATERIAL AND METHOD: With the participation of 22 institutions around Turkey that were included in the Hepato-Pancreato-Biliary Study Group, 89,324 cholecystectomy specimens sampled from 2003 to 2016 were retrospectively evaluated. The numbers of adenocarcinomas, dysplasias, intracholecystic neoplasms/adenomas, intestinal metaplasias and reactive atypia were identified with the review of pathology reports and the regional and countrywide incidence rates were presented in percentages. RESULTS: Epithelial changes/lesions were reported in 6% of cholecystectomy materials. Of these epithelial lesions, 7% were reported as adenocarcinoma, 0.9% as high-grade dysplasia, 4% as low-grade dysplasia, 7.8% as reactive/regenerative atypia, 1.7% as neoplastic polyp, and 15.6% as intestinal metaplasia. The remaining lesions (63%) primarily included non-neoplastic polypoids/hyperplastic lesions and antral/pyloric metaplasia. There were also differences between pathology laboratories. CONCLUSION: The major causes of the difference in reporting these epithelial changes/lesions and neoplasms include the differences related to the institute's oncological surgery frequency, sampling protocols, geographical dissimilarities, and differences in the diagnoses/interpretations of the pathologists. It seems that the diagnosis may change if new sections are taken from the specimen when any epithelial abnormality is seen during microscopic examination of the cholecystectomy materials.

Fibrinogen Gamma Chain Mutations Provoke Fibrinogen and Apolipoprotein B Plasma Deficiency and Liver Storage.

p.R375W (Fibrinogen Aguadilla) is one out of seven identified mutations (Brescia, Aguadilla, Angers, Al du Pont, Pisa, Beograd, and Ankara) causing hepatic storage of the mutant fibrinogen γ. The Aguadilla mutation has been reported in children from the Caribbean, Europe, Japan, Saudi Arabia, Turkey, and China. All reported children presented with a variable degree of histologically proven chronic liver disease and low plasma fibrinogen levels. In addition, one Japanese and one Turkish child had concomitant hypo-APOB-lipoproteinemia of unknown origin. We report here on an additional child from Turkey with hypofibrinogenemia due to the Aguadilla mutation, massive hepatic storage of the mutant protein, and severe hypo-APOB-lipoproteinemia. The liver biopsy of the patient was studied by light microscopy, electron microscopy (EM), and immunohistochemistry. The investigation included the DNA sequencing of the three fibrinogen and APOB-lipoprotein regulatory genes and the analysis of the encoded protein structures. Six additional Fibrinogen Storage Disease (FSD) patients with either the Aguadilla, Ankara, or Brescia mutations were investigated with the same methodology. A molecular analysis revealed the fibrinogen gamma p.R375W mutation (Aguadilla) but no changes in the APOB and MTTP genes. APOB and MTTP genes showed no abnormalities in the other study cases. Light microscopy and EM studies of liver tissue samples from the child led to the demonstration of the simultaneous accumulation of both fibrinogen and APOB in the same inclusions. Interestingly enough, APOB-containing lipid droplets were entrapped within the fibrinogen inclusions in the hepatocytic Endoplasmic Reticulum (ER). Similar histological, immunohistochemical, EM, and molecular genetics findings were found in the other six FSD cases associated with the Aguadilla, as well as with the Ankara and Brescia mutations. The simultaneous retention of fibrinogen and APOB-lipoproteins in FSD can be detected in routinely stained histological sections. The analysis of protein structures unraveled the pathomorphogenesis of this unexpected phenomenon. Fibrinogen gamma chain mutations provoke conformational changes in the region of the globular domain involved in the "end-to-end" interaction, thus impairing the D-dimer formation. Each monomeric fibrinogen gamma chain is left with an abnormal exposure of hydrophobic patches that become available for interactions with APOB and lipids, causing their intracellular retention and impairment of export as a secondary unavoidable phenomenon.

Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.

UNLABELLED: Despite advances in the diagnosis and management of idiopathic noncirrhotic portal hypertension, its pathogenesis remains elusive. Insight may be gained from study of early-onset familial idiopathic noncirrhotic portal hypertension, in which Mendelian mutations may account for disease. We performed exome sequencing of eight subjects from six kindreds with onset of portal hypertension of indeterminate etiology during infancy or childhood. Three subjects from two consanguineous families shared the identical rare homozygous p.N46S mutation in DGUOK, a deoxyguanosine kinase required for mitochondrial DNA replication; haplotype sharing demonstrated that the mutation in the two families was inherited from a remote common ancestor. All three affected subjects had stable portal hypertension with noncirrhotic liver disease for 6-16 years of follow-up. This mutation impairs adenosine triphosphate binding and reduces catalytic activity. Loss-of-function mutations in DGUOK have previously been implicated in cirrhosis and liver failure but not in isolated portal hypertension. Interestingly, treatment of patients with human immunodeficiency viral infection with the nucleoside analogue didanosine is known to cause portal hypertension in a subset of patients and lowers deoxyguanosine kinase levels in vitro; the current findings implicate these effects on deoxyguanosine kinase in the causal mechanism. CONCLUSION: Our findings provide new insight into the mechanisms mediating inherited and acquired noncirrhotic portal hypertension, expand the phenotypic spectrum of DGUOK deficiency, and provide a new genetic test for a specific cause of idiopathic noncirrhotic portal hypertension. (Hepatology 2016;63:1977-1986).

Fibrinogen storage disease and cirrhosis associated with hypobetalipoproteinemia owing to fibrinogen Aguadilla in a Turkish child.

BACKGROUND AND AIMS: Fibrinogen gene mutations can rarely result in hepatic fibrinogen storage disease (HFSD). Herein, we report on the first Turkish family carrying the mutation p.Arg375Trp (fibrinogen Aguadilla) in the γ-chain of the fibrinogen (FGG) gene. METHODS: Clinical, laboratory and histopathological findings of the patient were documented. Molecular study of fibrinogen gene was performed in the patient and her family members. RESULTS: The proband was 5 years old girl presenting with advanced liver fibrosis of unknown origin. The child had very low plasma levels of fibrinogen and hypobetalipoproteinemia. Immunomorphologic and electron microscopic studies showed selective and exclusive accumulation of fibrinogen within the endoplasmic reticulum in liver biopsy of the patient. Patient, mother, two sisters and one brother carried p.Arg375Trp mutation (fibrinogen Aguadilla) in FGG gene. The patient was treated with ursodeoxycholic acid and carbamazepine. After 3 months, carbamazepine was suspended upon family decision and unresponsiveness of carbamazepine. CONCLUSIONS: HFSD is characterized by hypofibrinogenemia and accumulation of abnormal fibrinogen within hepatocytes. In addition, hypofibrinogenemia is associated with hypobetalipoproteinemia in Aguadilla mutation.

Investigation of diagnostic utility and expression profiles of stem cell markers (CD133 and CD90) in hepatocellular carcinoma, small cell dysplasia, and cirrhosis.

The aim of this study was to investigate the expression rates of CD133 and CD90 in cirrhosis-dysplastic nodule-HCC (Crh-DN-HCC) sequence related to the etiologic background. Thirty-five HCC, 8 small cell dysplasia (SCD), and 63 cases of cirrhosis having different etiologies were collected. Immunohistochemical expressions of CD133 and CD90 were evaluated. CD133 positivity was higher in HCC cases with chronic hepatitis B and CD90 with chronic hepatitis C. The highest staining rate was seen in poorly differentiated HCC cases. Only one SCD case and almost half of the cirrhotic cases which were stained for CD133 were associated with hepatitis B; none was stained for CD90. Increased CD133 expression indicated a significantly shorter overall survival rate. No significant relationship was detected between the expression rates of CD133 or CD90 and other parameters. In this study, which investigates the immunohistochemical expression profiles of CD133 and CD90 through Crh-DN-HCC sequence, the highest staining rate was detected in HCC. It is rational to try to elucidate the earliest events in hepatocarcinogenesis by studying SCD. It is important to be aware of this issue in daily practice, which will provide a deeper insight into the understanding of the effects of CSCs in the progression and management of HCC.

Successful multimodal treatment for aggressive metastatic and recurrent fibrolamellar hepatocellular carcinoma in a child.

Fibrolamellar variant of hepatocellular carcinoma (FLHCC) does not have a favorable prognosis than conventional HCC, and there is no difference regarding the response to chemotherapy and the degree of surgical resectability. FLHCC commonly recurs after complete surgical resection, and there is a high rate of lymph node metastases. Herein, we report a 12-year-old girl with metastatic FLHCC with multiple recurrences aggressively treated with surgery, chemotherapy, and antiangiogenic agents. She is in complete remission after 4 years and 2 months after the diagnosis of metastatic FLHCC. The standard treatment of FLHCC is excision of the primary tumor and its metastases. Chemotherapy for FLHCC is controversial, and it has been suggested that cytoreductive chemotherapy was ineffective and adjuvant chemotherapy did not improve survival. Our patient with multiple recurrences was successfully treated with surgery, first-line chemotherapy with cisplatin and doxorubicin, second-line chemotherapy with 5-fluorouracil/interferon-α combination, and adjuvant antiangiogenic agents like cyclophosphamide and thalidomide. As FLHCC patients have no underlying liver disease, they can tolerate higher doses of chemotherapy compared with conventional HCC patients. We support the use of repeated aggressive surgery with adjuvant chemotherapy and antiangiogenic therapy, which provided complete remission in our patient with metastatic and recurrent FLHCC.

The relationship between advanced oxidation protein products (AOPP) and biochemical and histopathological findings in patients with nonalcoholic steatohepatitis.

OBJECTIVE: To investigate the correlation between advanced oxidation protein products (AOPP) levels and biochemical and histopathological findings in patients with nonalcoholic steatohepatitis (NASH). METHODS: Sixty biopsy-proven NASH patients and 60 individuals with ultrasonographically healthy liver (the control group) were included in the study. AOPP levels were determined in all the participants and liver histopathological examination based on liver biopsy was performed in NASH patients. The NASH activity score (NAS), hepatosteatosis, liver inflammation and fibrosis were evaluated. RESULTS: Serum AOPP level was significantly higher in the NASH group than that in the control group (461.8 ± 201.9 µmol/L vs 191.7 ± 152.5 µmol/L, P < 0.001). The receiver operating characteristic (ROC) curve revealed a sensitivity of 73.3% and a specificity of 88.3% for the diagnosis of NASH with an AOPP cut-off value of 332 µmol/L (the area under ROC curve 0.88, 95% confidence interval 0.82-0.94, P < 0.01). AOPP levels were positively correlated with NAS (r = 0.27, P = 0.035), fibrosis (r = 0.27, P = 0.037) and inflammation (r = 0.34, P = 0.008), but not the grade of steatosis (r = 0.02, P = 0.83) or ballooning (r = 0.02, P = 0.55). CONCLUSIONS: AOPP levels are significantly higher in patients with NASH than in those with ultrasonographically healthy liver. AOPP levels are positively correlated with biochemical and histopathological findings (NAS, liver inflammation and fibrosis), indicating that AOPP may play a role in the development of liver fibrosis and inflammation and may predict liver histopathology in NASH.

The role of interleukin-6 and interleukin-8 gene polymorphisms in non-alcoholic steatohepatitis.

BACKGROUND: Genetic polymorphisms may play role in the pathophysiology of nonalcoholic steatohepatitis (NASH). OBJECTIVES: We purposed to assess the role of interleukin 6 (IL 6) and interleukin 8 (IL 8) gene polymorphisms in the pathogenesis of NASH. PATIENTS AND METHODS: Consecutive patients with biopsy proven NASH and age- and gender-matched healthy individuals with normal liver function tests and normal ultrasonography were enrolled in the study. Histopathological findings were recorded according to nonalcoholic fatty liver disease activity score (NAS). Patients were classified according to fibrosis scores as fibrosis score < 2 (mild fibrosis group) and fibrosis score ≥ 2 (significant fibrosis group). Blood samples were collected and genomic DNA isolation kit was used to evaluate genetic polymorphisms. RESULTS: Of thirty-eight patients, 27 (71%) were in mild fibrosis group and 11 (29%) in significant fibrosis group. Thirty-eight age- and gender-matched healthy controls were enrolled in the study. The frequencies of genotypes G/C and G/G of IL 6 among the NASH group and healthy controls were 39.5% and 60.5% vs. 53.6% and 46.4%, respectively (P = 0.32). The frequencies of the genotypes of IL 8 among the NASH group were 47.2%, 44.6%, and 8.2% for T/T, A/T, and A/A, and in healthy controls were 50%, 28.6% and 21.4%, respectively, (P = 0.568). The differences between IL 8 gene T/A and T/T genotypes were not significant statistically (P > 0.05). However, the frequency of A/A genotype in significant fibrosis group was higher than the mild fibrosis group (P = 0.0016). The differences of -251 A/T polymorphism in the IL 8 and -174 C/G polymorphism in the IL 6 were not statistically significant between fibrosis groups (P > 0.05). CONCLUSIONS: IL6 and IL8 gene polymorphisms have no role in NASH pathogenesis and liver fibrosis process, but presence of the A/A genotype in the IL8 gene is associated with disease progression.

Is increased red cell distribution width an indicating marker of nonalcoholic steatohepatitis and fibrotic stage?

AIM: To evaluate the red cell distribution width (RDW) as an indicator of the presence of non-alcoholic steatohepatitis (NASH) and its association with fibrotic scores. METHODS: A retrospective study was carried out that included sixty-two biopsy proven NASH, 32 simple steatosis patients and 30 healthy controls. The correlation between the clinical and histopathological features of NASH patients and RDW values was evaluated. Liver fibrosis scores were measured using a 0 to 4 point scale and were divided in to two groups; fibrosis scores 0-1 were termed mild and fibrosis scores 2-4 were termed advanced fibrosis. RDW values were compared between NASH, simple steatosis and healthy controls. Univariate and multivariate analyses were performed to evaluate the independent predicting factors for the presence of liver fibrosis caused by NASH. RESULTS: Patients with NASH had higher RDW values compared with simple steatosis and healthy control groups [14.28% ± 0.25% vs 13.37% ± 0.12%, 12.96% ± 0.14% (P < 0.01), respectively]. Patients with advanced fibrosis had higher RDW values than the mild fibrosis group (15.86% ± 0.4% vs 13.63% ± 0.67%, P < 0.01, respectively). RDW also correlated with fibrotic scores (r = 0.579 and P < 0.01). The variables that were significant in the univariate analysis were evaluated in multivariate logistic regression analysis, and RDW was an independent predicting factor of NASH (OR = 1.75, 95%CI: 1.129-2.711, P < 0.05). CONCLUSION: RDW a new non-invasive marker that can be used to demonstrate the presence of NASH and indicate advanced fibrotic scores.

Colonic lymphoid nodular hyperplasia in childhood: causes of familial Mediterranean fever need extra attention.

OBJECTIVES: The clinical importance and etiology of colonic lymphoid nodular hyperplasia (LNH) are not clear. It has been considered a response to some antigenic stimuli. Although food allergies, infections, inflammatory bowel diseases, and immunodeficiencies may be listed in the etiology of colonic LNH, the etiology has remained unclear in many cases. This study investigated the etiology of colonic LNH and its relation to familial Mediterranean fever (FMF) in children. FMF as an etiologic factor for colonic LNH has not been reported before in the literature. METHODS: Medical files of patients who underwent colonoscopy between 2007 and 2011 were examined retrospectively. Demographic features, presenting symptoms, colonoscopy indications, colonoscopic findings, and final diagnoses of patients were evaluated. According to etiologies, patients with colonic LNH were divided into 2 groups: group A consisted of patients with FMF and group B consisted of diseases other than FMF. RESULTS: A total of 311 patients were included in the study. Forty (12.6%) patients had isolated colonic LNH. In 23 (57.5%) patients, isolated LNH was observed in some colonic segments and total colonic LNH was noted in 17 (42.5%) patients. FMF was the etiologic factor in 6 (15%) patients. Thirty-four patients (85%) had etiologic factors other than FMF. We did not find any etiologic factor for LNH in 3.53% (11/311) of patients. CONCLUSIONS: FMF may be an etiologic factor for colonic LNH in children besides food allergies, infections, inflammatory bowel diseases, and immunodeficiencies.

Lack of association of hepatic estrogen receptor-alpha expression with histopathological and biochemical findings in chronic hepatitis C.

Estrogens exert a protective effect against hepatic steatosis and fibrosis. Loss of estrogen receptor-alpha (ER-α) in the liver is associated with hepatic steatosis and inflammation in animal models. We conducted a study in order to investigate the presence and extent of ER-α expression in HCV infection, and its relationship with histological and biochemical findings. Ninety biopsy-proven chronic hepatitis C (CHC) patients were enrolled in the study. Liver biopsy specimens were immunohistochemically stained for ER-α expression. Nuclear ER-α expression percentage was calculated. ER-α was positive in 69 of the patients (76%). ER-α positive and negative groups were not significantly different in terms of age, gender, necroinflammatory activity, fibrosis, steatosis, serum levels of AST, ALT, ALP, GGT, and bilirubin. ER-α expression percentage was not correlated with fibrosis, steatosis, necroinflammatory activity and biochemical findings. Although estrogens are known to be protective against fibrosis and steatosis in animal models, we did not find any significant correlation between ER-α expression and histopathological and biochemical findings in CHC patients. These findings should be verified in further large scale studies.

Presence and extent of estrogen receptor-alpha expression in patients with simple steatosis and NASH.

Loss of estrogen receptor-alpha (ER-α) in the liver is associated with hepatic steatosis and inflammation. We conducted a study in order to investigate the presence and extent of ER-α expression in NASH, and its relationship with histological findings. Fifty-four patients with histologically confirmed NASH, 12 patients with simple steatosis (SS), and 6 patients with normal liver tissue (NLT) were included. NASH activity score and fibrosis score were calculated according to biopsy findings. Liver biopsy specimens were immunohistochemically stained for ER-α expression. Nuclear ER-α expression percentage (staining index) was calculated. Mean staining index was significantly different across the NASH, SS, and NLT groups (6.3±9.9 vs. 22.1±26.4 vs. 44.2±24.8, respectively, p<0.001 for all comparisons). Staining index was significantly higher in women than in men (19.4±22.2 vs. 7.9±15.3, respectively, p=0.003). Staining index negatively correlated with serum ALT (r=-0.240; p=0.04), fasting plasma glucose (r=-0.261; p=0.027), and fibrosis score (r=-0.312; p=0.011). As a conclusion, hepatic nuclear ER-α expression percentage (staining index) is lower in patients with NASH when compared to SS and NLT groups. Staining index is negatively correlated with serum ALT levels, plasma glucose, and fibrosis score. Further studies are required to clarify the significance of ER-α expression in NASH.

Diagnostic potential of serum direct markers and non-invasive fibrosis models in patients with chronic hepatitis B.

AIM: Liver biopsy is recommended in the majority of patients with chronic viral hepatitis for fibrosis evaluation. Because of the disadvantages of liver biopsy, many studies related to non-invasive biomarkers and scores have been performed. In this study, we aimed to assess the diagnostic value of serum direct markers and non-invasive fibrosis models to predict liver fibrosis in the treatment-naive chronic hepatitis B (CHB) patients and to compare their diagnostic performance. METHODS: This study included 58 patients with a diagnosis of CHB virus infection and 30 healthy controls. Hyaluronic acid, tissue inhibitor of matrix metalloproteinase 1 and amino-terminal propeptide of type III procollagen were measured by enzyme-linked immunosorbent assay; and the Original European Liver Fibrosis panel, the Enhanced Liver Fibrosis (ELF) panel, PP score, aspartate aminotransferase to platelet ratio index (APRI) and FIB-4 indexes were calculated using the formulas taken from previous publications. Fibrosis stage was determined using Ishak's scoring system. RESULTS: The fibrosis stages identified upon liver biopsy was F0 in 12 patients (20.7%), F1-2 in 36 (62.1%) and F3-5 in 10 (17.2%). The diagnostic value of all the non-invasive indices was low to detect mild fibrosis. We demonstrated that the diagnostic accuracy of HA is the best for predicting fibrosis of F3 or more (area under the receiver-operator curve, 0.902). In our study, the results from a combination of tests showed that ELF and APRI had the highest diagnostic value sensitivity of 90%, specificity of 100%, positive predictive value of 100% and negative predictive value of 96.4% for detection of fibrosis of F3 or more. CONCLUSION: In CHB patients, combination of ELF and APRI has a better diagnostic value in predicting fibrosis of F3 or more.

Hepatoportal sclerosis in childhood: some presenting with cholestatic features (a re-evaluation of 12 children).

Hepatoportal sclerosis (HPS) is a syndrome of obscure etiology, and is one of the causes of noncirrhotic portal hypertension (PH). We aimed to investigate this heterogeneous group of patients whose presentation showed cholestatic features, histopathologically. Between 1999 and 2009, 12 children diagnosed with HPS were retrospectively evaluated. HPS was diagnosed with evidence of PH, noncirrhotic liver biopsy with typical histopathologic findings, and exclusion of other possible causes of PH. The data was obtained from pathology reports and microscopic slides. In histopathological re-evaluation fibrosis state, aberrant portal vessels, portal tract dilation and inflammation, ductular reaction, regenerative nodular hyperplasia, acinar transformation, presence of bile pigment, and cholangitis were noted. Serum alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl, alkaline phosphatase, bilirubin, and albumin levels, presentation patterns, and radiologic findings were assessed. Familial relationship degrees were also investigated. Twelve patients (9 boys, 3 girls; 3-180 months) were re-evaluated. Two pairs of the patients were siblings. Parents of 7 patients were consanguine. The most common presenting symptom was abdominal distension. Histopathologically, all patients had hepatoportal sclerosis/intimal fibrous thickening of portal vein and periportal fibrosis, acinar transformation, and regenerative nodules not surrounded by fibrous septae. Eight patients had vascular aberrations, 7 had ductular reaction, 1 showed mild cholangitis, and 1 had canalicular bile pigment. We conclude that genetic predisposition might be a possible factor for HPS development in Turkish patients and it should be kept in mind that cholestatic features noticed in histopathological evaluation may represent a variant group in the spectrum of HPS.

Serum levels of advanced oxidation protein products, malonyldialdehyde, and total radical trapping antioxidant parameter in patients with chronic hepatitis C.

BACKGROUND/AIMS: Oxidative stress increases in chronic hepatitis C, and antioxidant defense mechanisms are impaired. The aims of this study were to compare chronic hepatitis C patients and healthy subjects according to oxidative stress and antioxidant system markers, and to determine the relationship between oxidative stress and hepatosteatosis. METHODS: This is an observational study in a tertiary center. Twenty-nine biopsy-proven chronic hepatitis C patients, with no prior anti-viral treatment and persistently elevated serum transaminase levels for 6 months, were included. The control group included 46 healthy subjects. Advanced oxidation protein products and malonyldialdehyde levels were measured. Total radical-trapping antioxidant parameter was calculated. RESULTS: Baseline characteristics were similar in the patient and control groups. In chronic hepatitis C patients, serum levels of advanced oxidation protein products were significantly higher than in the control group (235.0±142.8 vs 116.7±79.5, p<0.001). Serum levels of malonyldialdehyde were also significantly higher than in the control group (9.3±2.1 vs 6.5±1.1, p<0.001). However, there was no significant difference in total radical-trapping antioxidant parameter. The total radical-trapping antioxidant parameter/advanced oxidation protein products index was significantly lower in chronic hepatitis C patients than in healthy controls (p<0.05). There was no significant correlation between advanced oxidation protein products and malonyldialdehyde and hepatosteatosis. CONCLUSIONS: We conclude that oxidative stress occurs in chronic hepatitis C, and antioxidant defense mechanisms are inadequate. Serum levels of advanced oxidation protein products and malonyldialdehyde are higher in chronic hepatitis C patients when compared to healthy individuals, and may be useful markers in chronic hepatitis C.

Effects of verapamil, sodium nitroprusside and glutathione addition into perfusion/preservation solutions on preservation-related ICAM-1 molecule expression in rat liver.

BACKGROUND/AIMS: During cold preservation of liver grafts, expression of tissue adhesion molecules has been reported as a factor indicative of preservation injury. Some biochemical agents as well as increased levels of intracellular calcium also play important roles in preservation injury during cold storage. In the current study, we aimed to test if the addition of a calcium channel blocker, sodium nitroprusside, or glutathione into preservation solution would reduce upregulation of adhesion molecules, thus leading to decreased preservation injury in the rat liver. METHODS: Fifty Albino Wistar rats, weighing 200+/-50 g, were divided into 1 control (perfused with Wisconsin solution, without preservation) and 4 study groups of rat livers (10 livers each). Livers in study groups were harvested, perfused, and preserved for 16 hours in 4 different solutions (Wisconsin solution alone, Wisconsin solution+verapamil, Wisconsin solution+ sodium nitroprusside and Wisconsin solution+glutathione). At the end of the preservation time, levels of graft tissue adhesion molecule (ICAM-1) expression were analyzed. RESULTS: Preservation for 16 hours with Wisconsin solution alone and Wisconsin solution+verapamil perfusates caused significantly more ICAM-1 expression than did preservation for 16 hours with Wisconsin solution+sodium nitroprusside and Wisconsin solution+ glutathione perfusates (p=0.010). No significant difference was found in ICAM-1 expression between the Wisconsin solution+ sodium nitroprusside and Wisconsin solution+glutathione groups. In the control group, perfusion with Wisconsin solution alone, without preservation, represented minimal ICAM-1 expression, reflecting minimum preservation injury (p=0.0003). CONCLUSIONS: Addition of sodium nitroprusside and glutathione into the Wisconsin solution decreased levels of ICAM-1 molecule expression, which reflects lower levels of preservation injury. In this study, the addition of verapamil to the perfusate/preservation solution for reducing the intracellular calcium accumulation had no effect on tissue ICAM-1 molecule expression.