Histopathological evaluation of long-term tenofovir disoproxil fumarate treatment in patients with hepatitis be antigen-negative chronic hepatitis B.

BACKGROUND: Hepatitis B virus is a universal health problem. There are approximately 250 million people living with hepatitis B worldwide, and approximately 600000 of these people die every year due to the virus. AIM: To compare the pretreatment and post-treatment histopathological results of patients with hepatitis be antigen (HBeAg)-negative chronic hepatitis B (CHB) who had been receiving tenofovir disoproxil fumarate (TDF) treatment at our clinic for at least 5 years. METHODS: Patients with HBeAg-negative CHB who were being treated with TDF (245 mg/d) were included in the study. Liver biopsies of patients before TDF treatment and liver biopsies after 5 years of TDF treatment were retrospectively compared. RESULTS: A total of 50 HBeAg-negative CHB patients were included in the study (mean age: 47.9 ± 10.4 years, men: 27.54%). Histological improvement was observed in 78% (39) of the patients after 5 years of treatment. After the 5 years of treatment, the mean Ishak score of the patients was 1.3 ± 1.3, and the mean histologic activity index score was 4.1 ± 2.8. A 1.53 point reduction in Ishak fibrosis score was detected after long-term TDF treatment. CONCLUSION: Liver biopsies after 5 years of TDF treatment revealed a significant histological response and a regression of the necroinflammatory score compared to pretreatment liver biopsies. To better understand the effects of antiviral treatments on the improvement of liver histology, long-term studies involving larger numbers of patients are needed.

Peroral endoscopic myotomy as treatment for Zenker's diverticulum (Z-POEM): a multi-center international study.

BACKGROUND: Peroral endoscopic myotomy for the treatment of Zenker's diverticulum (Z-POEM) is a novel technique that has been described in several recent reports. This method utilizes the third space (submucosal layer) to create a tunnel to facilitate complete visualization of the septum and hence cutting it entirely. Conventional endoscopic septotomy carries the risk of recurrence due to incomplete visualization of the septum. While surgical correction is a risky and lengthy procedure in old comorbid patients with Zenker's diverticulum. The aim of this study is to assess the efficacy and safety of Z-POEM. METHODS: The study enrolled 24 patients diagnosed with Zenker's diverticulum (ZD) who underwent Z-POEM at seven independent endoscopy centers in five different countries. RESULTS: Mean patient age ± standard deviation (SD) was 74.3 ± 11 years. Most of the patients were males (n = 20, 83.3%); four (16.7%) were females. More than 50% of the patients (n = 14, 58.3%) had associated comorbidities. The mean size of the diverticula was 4 cm (range 2-7 cm). The Kothari-Haber Score was used to assess clinical symptoms; values ranged from 6 to 14 (median = 9). We achieved 100% technical success with a median procedure time of 61 min and no adverse events. Median hospital stay was 1 day (range 1-5 days). There is a significant reduction in the Kothari-Haber Score after Z-POEM (P < 0.0001). Technical success was achieved in 100% of the patients. Clinical success was achieved in 23/24 (95.8%) of the patients with a median follow-up of 10 months (range 6-24 months). CONCLUSION: Z-POEM is a safe and effective modality for managing ZD.

A Single-Center Experience: The Diagnostic Role of Peritoneoscopy in Patients with Exudative Ascites.

BACKGROUND AND AIM: The causes of exudative and transudative ascites can be detected through noninvasive methods nowadays. In selected cases, peritoneoscopy could be necessary for definitive diagnosis. In this retrospective study, we aimed to present the peritoneal biopsy results of patients who had exudative ascites with unclear etiology. MATERIALS AND METHODS: A retrospective analysis was performed in 86 patients who had exudative ascites of unclear etiology. All the patients showed abnormalities of the peritoneum or greater omentum as determined by abdominal ultrasonography and underwent peritoneoscopy between January 2012 and December 2015. Patient data were obtained from hospital records. RESULTS: Eighty-six patients (male: 22; 25.6%, mean age ± standard deviation: 57.97 ± 15.97) who had exudative ascites of unclear etiology were included to the study. The success rate of the procedures was 100% (86/86). A specific histopathological diagnosis was made in all patients, with an overall diagnostic accuracy of 100%. Among the 86 diagnosed patients, 43 (50%) were peritonitis carcinomatosa, 21 (24.4%) were tuberculous peritonitis, 14 (16.3%) were mesothelioma, 4 (4.7%) were chronical inflammation, and 1 (1.2%) was lymphoma. Three (3.5%) patients had normal peritoneal biopsy findings. DISCUSSION: Peritoneoscopy is a safe and efficient alternative method due to its high diagnostic capacity in selected patients who have exudative ascites of unclear etiology.

Correlation between neutrophil/lymphocyte ratio and Ranson score in acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is characterized by inflammation of the pancreas, elevated pancreatic enzymes, and abdominal pain. The neutrophil to lymphocyte ratio (NLR) is used as a marker of inflammation. In this retrospective study, we aimed to investigate novel early prognostic predictors of AP, such as NLR and its correlation with the Ranson score. METHODS: A total 435 patients (Male: 152; 34.9%, Age: 63.53 ± 17.22 years) were included in the study. Data were collected by two clinicians scanning the registered hospital records. RESULTS: Classification of the patients according to the aetiologies revealed gallstone(s) 58.6% (n = 255), hyperlipidaemia 2.2% (n = 9), viruses 0.7% (n = 3), malignancies 0.5% (n = 2), and alcohol 0.2% (n = 1). No reason was discovered in 37.9% (n = 165) of patients. Age, duration in the intensive care unit, serum aspartate aminotransferase (AST) levels, alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), total bilirubin, direct bilirubin, lactate dehydrogenase (LDH), white blood cell (WBC) count, neutrophil count, lymphocyte count, and the NLR were greater in the group with a Ranson score ≥3 than the group with a Ranson score <3. DISCUSSION: Quick diagnosis is essential in AP. Current scoring systems for AP diagnosis are complicated, whereas NLP is a simple, practical, and effective marker.

Distribution of hepatitis C virus genotypes among intravenous drug users in the Çukurova region of Turkey.

BACKGROUND/AIM: The most common hepatitis C virus (HCV) genotype in Turkey is genotype 1. However, there has not been a study about the distribution of HCV genotypes among intravenous drug users (IVDUs) in the Çukurova region of Turkey. This study was planned to understand if there is a difference between IVDUs and the normal population. MATERIALS AND METHODS: Between May 2010 and May 2014, anti-HCV positive IVDUs who applied to the 6 hospitals in the Çukurova region of Turkey were included in this study. Their HCV genotypes were studied. RESULTS: Ninety-seven anti-HCV positive IVDUs were screened in terms of HCV RNA and genotype. Ten were excluded from the study because their HCV RNA results were negative. Fifty-one of the 87 patients (58.6%) had genotype 3. Genotype 2 was detected in 26 (29.9%) and genotype 1 was detected in 10 (11.5%) patients. CONCLUSION: HCV genotypes seem to be different between the normal population and IVDUs according to studies worldwide. Among IVDUs, we detected a dominance of genotype 3 and genotype 2, which is apparently different from the normal population. The reason for this difference can be simply explained by infection through shared needles. However, there may still be a different immunological response in IVDUs, the investigation of which may lead to further studies.

Prevalence and genotypes of Helicobacter pylori in gastric biopsy specimens from patients with gastroduodenal pathologies in the Cukurova Region of Turkey.

The effects of Helicobacter pylori genotypes on clinical prognosis in the Cukurova region of Turkey were investigated by PCR. The prevalence of type I strains carrying the s1c allele, unlike in neighboring regions and countries, was found to be significantly higher in patients with gastritis and/or gastric ulcers (P = 0.001), and that of type I strains carrying the s1a allele was found to be significantly higher in patients with duodenal ulcers (P < 0.001). The cagA gene was strongly associated with the more virulent vacA genotypes (P < 0.001).

Mean platelet volume is elevated during paroxysmal atrial fibrillation: a marker of increased platelet activation?

Paroxysmal atrial fibrillation might be a risk factor for stroke such as chronic atrial fibrillation. We examined the relation between mean platelet volume and paroxysmal atrial fibrillation to determine the effect of paroxysmal atrial fibrillation on the thrombotic state via elevated mean platelet volume. Mean platelet volume is a marker of platelet size, function, and activation. Increased mean platelet volume reflects active and large platelets that release more thromboxane A2 than smaller ones. We hypothesized that mean platelet volume is elevated in patients with paroxysmal atrial fibrillation. The study population comprised 103 consecutive patients who were detected to have paroxysmal atrial fibrillation by 24-h Holter monitoring and 87 control individuals with normal Holter monitoring. Mean platelet volume and inflammatory parameters were measured. Comprehensive clinical and echocardiographic data were collected. Patients with aortic and mitral stenosis, hyperthyroidism, hypothyroidism, malignancy, infection, and pregnancy were excluded from the study. Mean age of the patients was 63 +/- 11 vs. 45 +/- 14 years (P < 0.001) in paroxysmal atrial fibrillation and control groups, respectively. Fifty-seven patients (55%) in paroxysmal atrial fibrillation and 19 (21%) (P < 0.001) patients in control group were men. Mean platelet volume was significantly higher in the paroxysmal atrial fibrillation group when compared with control group (10.0 +/- 2.0 vs. 8.3 +/- 1.5 fl, respectively; P < 0.001). C-reactive protein (18.5 +/- 28 vs. 3.8 +/- 2 mg/l, respectively; P = 0.004) and erythrocyte sedimentation rate (21 +/- 21 vs. 12 +/- 7 mm/h, respectively; P = 0.01) were also higher in the paroxysmal atrial fibrillation group. There was no difference in white blood cell and platelet counts between groups. In a multivariate analysis, elevated mean platelet volume was associated with the occurrence of paroxysmal atrial fibrillation before and after adjustment for age and sex. Our results indicate that inflammatory markers such as C-reactive protein and erythrocyte sedimentation rate and the marker of platelet size and activity mean platelet volume are elevated in patients with paroxysmal atrial fibrillation.

SEN virus prevalence among non-B and non-C hepatitis patients with high liver function tests in the south of Turkey.

We investigated the characteristics and detection rates of SEN virus (SENV) infection among 100 Turkish patients who had with high alanine aminotransferase (ALT) and aspartate aminotransferase levels but were negative for HBV DNA and HCV RNA and had no history of transfusion. As a control group, we also analyzed 50 healthy individuals who had normal ALT levels, were negative for HBV DNA and HCV RNA, and had no history of transfusion. The serum samples of patient and controls were analyzed by PCR to detect the presence of SENV DNA and its two genotypes (SENV-H and SENV-D). We detected SENV DNA in 13 of 100 (13%) patients. Five of 13 (38.46%) patients were positive for SENV-D and 8 of 13 (61.53%) patients were positive for SENV-H DNA. We also detected SENV DNA in 5 of 50 (10%) patients in the control group. Two of 5 (40%) patients were positive for SENV-D and 3 of 5 (60%) patients were positive for SENV-H DNA in the control group. SENV was detected at almost the same frequency in the patient and control group. SENV did not seem to contribute to the pathogenesis of liver disease (P > 0.05) in this cohort. Our results also showed that SENV transmission was not only associated with blood transfusion but also with some other possible routes.

Genotyping of hepatitis B virus isolated from chronic hepatitis B patients in the south of Turkey by DNA cycle-sequencing method.

The 8 genotypes of hepatitis B virus (HBV A-H) show a distinct geographic distribution and influence the course of disease and the prognosis of treatment. In this study, we have genotyped 50 HBV isolates circulating in the south of Turkey by DNA cycle sequencing, based on their compatibility with reference sequences of a part of S gene. In our cases, all 50 (100%) HBV sequences from the patients demonstrated full compatibility with the sequences of ayw subtype viruses in genotype D. However, we have found some nucleotide sequence variations within genotype D, 47 (94%) of which were related to HBVGEN1 (Z35716 genotype D) and 3 (6%) were related to HBVDNA (X68292, genotype D).

Helicobacter pylori in the etiology of cholesterol gallstones.

GOALS: We aimed to investigate the presence of bacterial structures in cholesterol gallstones and particularly presence of Helicobacter spp/H. pylori in gallstones by microbiologic cultivation, histopathologic staining, and polymerase chain reaction (PCR). BACKGROUND: Many studies suggest that different mechanisms are responsible for the formation of pigmented gallstones and cholesterol gallstones. Recently, studies showed that infection could have an important role in the formation of cholesterol gallbladder stones. STUDY: We examined 77 mixed cholesterol gallstones. After cholecystectomy, gallbladder cultures were done for H. pylori and other bacterium. Gallbladder has also been examined by three histopathologic staining methods (Warthin-Starry, hematoxylin eosin, and gram staining) for Helicobacter spp. In addition, 16S rRNA-PCR amplification was performed for Helicobacter spp in gallstones. Twenty postmortem gallbladders without gallstones were investigated by the same histopathologic and PCR methods for Helicobacter spp. as a control group. RESULTS: Different bacterium were isolated from 22 gallbladder samples (12 Escherichia coli, 8 Pseudomonas, and 2 clostridium) and H. pylori was isolated in 6 gallbladder samples. Helicobacter spp was found in 7 gallstones by PCR amplification. Helicobacter-like organisms were demonstrated in 18 samples by three different histopathologic methods. Helicobacter-like organisms were also found in five samples by the same histopathologic methods (Warthin-Starry, hematoxylin-eosin, and gram staining). Only four samples were found positive for Helicobacter spp/H. pylori by all methods. CONCLUSIONS: Bacterial population including H. pylori could have a possible role in the formation of cholesterol gallstones.

Expression of Fas antigen in liver tissue of patients with chronic hepatitis B and C.

OBJECTIVES: Cells infected with the hepatitis B or C virus can be eliminated by an immune response mediated by cytotoxic T cells. Recently, the Fas Ligand has been detected on the surface of cytotoxic T cells, and is thought to induce cells to apoptosis by adhering to the Fas antigen. METHODS: To evaluate the role of the Fas antigen and apoptosis in chronic hepatitis B or C, we used immunohistochemistry to study Fas antigen expression in liver samples obtained from 30 patients infected with chronic hepatitis B and 32 patients with chronic hepatitis C. RESULTS: In samples from patients with chronic hepatitis C and B, Fas antigen was mainly expressed in the cytoplasm (partly at the membrane) of hepatocytes, and these positive cells were detected especially at the periportal region near 'piecemeal necrosis'. According to Knodell's scoring system for the histological activity index, the scores of periportal inflammation and necrosis were higher in cases that were positive for Fas antigen than in cases that were negative for the antigen (n = 62, P < 0.001) and there was a positive correlation between these scores and the degree of Fas antigen expression (r = 0.621). There was also a positive correlation between the scores of intralobular inflammation and necrosis and the degree of Fas antigen expression (n = 62, r = 0.522, P = 0.001). Fas antigen was not detected in patients without hepatitis infection. CONCLUSIONS: These findings suggest that apoptosis of hepatocytes is induced via the Fas antigen and contributes to the elimination of infected cells.

Serum profile of T helper 1 and T helper 2 cytokines in patients with chronic hepatitis C virus infection.

BACKGROUND/AIMS: T cell immunoregulatory cytokines may play a crucial role in the host response to hepatitis C virus infection. While T-helper type 1 cytokines are required for host antiviral immune responses, T-helper type 2 cytokines can inhibit the development of these effector mechanisms. The aim of the present study was to determine T-helper type 1 and T-helper type 2 cytokine levels in chronic hepatitis C infection. METHODS: Serum levels of T-helper type 1 cytokine, interferon-gamma (IFN-g), and T-helper type 2 cytokines, IL-4 and IL-10 were measured in 30 patients with hepatitis C infection and 25 healthy controls using ELISA. Serum levels of alanine transaminase were also assessed in both patients and controls. Histologic activity score was evaluated in the chronic hepatic C infected patients. RESULTS: Serum levels of IFN-g were 59.03+/-46.24 pg/mL, IL-4 were 213.59+/-135.67 pg/mL and IL-10 were 106.73+/-60.85 pg/mL in hepatitis C infected patients whereas in healthy controls they were found to be 61.84+/-54.87 pg/mL, 67.39+/-59.74 pg/mL and 60.14+/-50.73 pg/mL respectively. Serum levels of IL-4, IL-10 but not IFN-g were found to be significantly increased in chronic HCV patients compared to those of control subjects. CONCLUSIONS: Our findings may suggest the involvement of Th2 cytokines in the pathogenesis of chronic hepatitis C virus liver disease.

Fibromyalgia syndrome in patients with hepatitis C infection.

Fibromyalgia syndrome (FS) is characterized by widespread pain and tenderness at specific anatomic sites. Different theories have been proposed in the etiopathogenesis of this syndrome, and besides genetic, neuroendocrine, psychologic, and traumatic causes, infections have also been reported. The aim of the present study was to evaluate the presence of FS in patients with hepatitis C virus (HCV) infection. Ninety-five patients with chronic HCV infection and 95 healthy controls were enrolled in the study. The 1990 American College of Rheumatology classification criteria were used for the diagnosis of FS. Tender point count, pain intensity, sleep disturbance, stiffness, headache, paresthesia, fatigue, irritable bowel syndrome (IBS), and sicca- and Raynaud-like symptoms were assessed. Fibromyalgia was found in 18.9% of patients and 5.3% of healthy controls. Mean tender point count, pain intensity scored on a visual analog scale (VAS), sleep disturbance, stiffness, paresthesia, and fatigue were higher in the HCV group. No significant relationship was observed between the two groups regarding headache, IBS, and sicca- and Raynaud-like symptoms. In addition, mean tender point count and pain intensity scores were also significantly higher in HCV patients with FS than in control subjects with FS. All of the symptoms except stiffness were not statistically significant between the HCV and control groups with FS. Our results demonstrate a tendency toward higher prevalence of FS in patients with HCV infection. Besides various extrahepatic features, musculoskeletal disorders including fibromyalgia might be expected in the progression of HCV infection. Detailed examination of the patients helps to differentiate FS from other musculoskeletal complications of HCV infection. This will provide appropriate management approaches and better quality of life for them.

Bullous pemphigoid and cholestatic hepatitis associated with Castleman's disease.

The case of a 21-yr-old woman admitted with a two-week history of icterus, fever, multiple peripheral lymphadenopathy and pruritic eruption is presented. A full evaluation including computed tomography, endoscopic retrograde cholangiography, liver, skin and lymph node biopsies and biochemical tests confirmed the diagnosis of multicentric Castleman's disease (angiofollicular lymph node hyperplasia). All symptoms improved within four weeks of commencing prednisone therapy. Castleman's disease should be considered in the differental daignosis of cholestatic hepatitis and bullous pemphigoid.