Epidemiology of hepatitis D virus infection in Europe: Is it vanishing?

Co-infection with hepatitis delta virus (HDV) is a challenging health care problem worldwide, estimated to occur in approximately 5%-10% of patients with chronic hepatitis B virus (HBV) infection. While HBV prevalence is decreasing globally, the prevalence of HDV infection is rising in some parts mainly due to injection drug use, sexual transmission and immigration from high endemicity areas. Eastern Europe and the Mediterranean are among the regions with high rates of endemicity for HDV and the immigration from high endemicity areas to Central and Western Europe has changed the HDV epidemiology. We aimed to review the prevalence of HDV infection in Europe. A paucity of publication appears in many European countries. Prevalence studies from some countries are old dated and some other countries did not report any prevalence studies. The studies are accumulated in few countries. Anti-HDV prevalence is high in Greenland, Norway, Romania, Sweden and Italy. Belgium, France, Germany, Spain, Switzerland, Turkey and United Kingdom reported decreasing prevalences. Among cirrhotic HBV patients, Germany, Italy and Turkey reported higher rates of HDV. The studies including centres across the Europe reported that HIV-HBV coinfected individuals have higher prevalence of HDV infection. The immigrants contribute the HDV infection burden in Greece, Italy, and Spain in an increasing rate. Previous studies revealed extremely high rates of HDV infection in Germany, Greece, Italy and Sweden. The studies report a remarkably high prevalence of hepatitis delta among HIV/HBV-coinfected individuals, individuals who inject drugs, immigrants and severe HBV infected patients across Europe. The HDV infection burden still appears to be significant. In the lack of an effective HDV therapy, prevention strategies and active screening of HBV/HDV appear as the most critical interventions for reducing the burden of liver disease related to HDV infection in Europe.

Safety of anticoagulation use for treatment of portal vein thrombosis in liver cirrhosis and its effect on hospital-based outcomes: an insight from a US nationwide database.

BACKGROUND AND AIM: Anticoagulation use for portal vein thrombosis (PVT) in patients with advanced liver disease is controversial. We investigated the effect of anticoagulation on outcomes in patients with PVT with cirrhosis. METHODS: We reviewed National Inpatient Sample data from 2016 to 2018 to identify patients with PVT. Our outcomes were in-hospital mortality, variceal bleeding, hepatic encephalopathy, acute kidney injury (AKI), hepatorenal syndrome (HRS), spontaneous bacterial peritonitis (SBP), sepsis and hospital resource utilisation. RESULTS: We included 60 505 patients with PVT, out of whom 6.63% (4015) were on anticoagulation. The overall mortality in the anticoagulation group was 2.12% compared with 9.72% in the no anticoagulation group. The adjusted odds of mortality were low in the anticoagulation group (adjusted OR (AOR) 0.27, 95% CI 0.15 to 0.46, p<0.001). Patients on anticoagulation had 29% lower odds of variceal bleeding (AOR 0.71, 95% CI 0.53 to 0.96, p=0.03). Lower odds of HRS (AOR 0.56, 95% CI 0.37 to 0.85, p=0.01) and AKI (AOR 0.57, 95% CI 0.48 to 0.69, p<0.001) were also seen in the anticoagulation group. Patients in the anticoagulation group also showed lower odds of SBP (AOR 0.62, 95% CI 0.43 to 0.89, p=0.01) and sepsis (AOR 0.57, 95% CI 0.35 to 0.93, p=0.03). Anticoagulation use resulted in shorter hospital stay by 1.15 days (adjusted length of stay -1.15, 95% CI -1.51 to -0.79, p<0.001). The mean difference in total hospital charges between the anticoagulation and the no anticoagulation group was -$20 034 (95% CI -$27 077 to -$12 991, p<0.001). CONCLUSION: Our analysis found that anticoagulation use is safe and associated with better outcomes in patients with PVT with advanced liver disease.

Improved Detection of Circulating Epithelial Cells in Patients with Intraductal Papillary Mucinous Neoplasms.

BACKGROUND: Recent work has demonstrated early shedding of circulating epithelial cells (CECs) from premalignant intraductal papillary mucinous neoplasms (IPMNs). However, the potential use of CECs as a "liquid biopsy" for patients with IPMNs has been limited by antigen dependence of CEC isolation devices and the lack of robust detection biomarkers across CEC phenotypes. MATERIALS AND METHODS: We utilized a negative depletion microfluidic platform to purify CECs from contaminating leukocytes and coupled this platform with immunofluorescence, RNA in situ hybridization, and RNA sequencing (RNA-seq) detection and enumeration. RESULTS: Using established protein (EpCAM, cytokeratins) and novel noncoding RNA (HSATII, cytokeratins) biomarkers, we detected CECs in 88% of patients bearing IPMN lesions. RNA-seq analysis for MUC genes confirm the likely origin of these CECs from pancreatic lesions. CONCLUSION: Our findings increase the sensitivity of detection of these cells and therefore could have clinical implications for cancer risk stratification. IMPLICATIONS FOR PRACTICE: This work describes a high-sensitivity platform for detection of epithelial cells shed from preneoplastic lesions at high risk of malignant transformation. Further research efforts are underway to define the transcriptional programs that might allow discrimination between circulating cells released from tumors that will become malignant and cells released from tumors that will not. After further refinement, this combination of technologies could be deployed for monitoring and early detection of patients at high risk for developing new or recurrent pancreatic malignancies.

Feasibility and safety of microforceps biopsy in the diagnosis of pancreatic cysts.

BACKGROUND AND AIMS: The tissue acquisition and diagnostic yield of cyst fluid cytology is low-to-moderate and rarely provides a specific diagnosis. The aim of this study was to compare the tissue acquisition and diagnostic tissue yield of microforceps biopsy (MFB) with cyst fluid cytology. METHODS: In this multicenter study, data of 42 patients who had cysts both aspirated by EUS-guided FNA (EUS-FNA) and biopsy specimens were then obtained with an MFB device, were collected. Cytology analysis of cyst fluid and histologic analysis of biopsy specimens were done. Acquisition yield was defined as percentage of patients with tissue present in the aspirate or biopsy. Diagnostic tissue yield was evaluated at 3 levels: the ability of differentiation between mucinous and/or nonmucinous cysts, detection of high risk for malignancy, and specific cyst type diagnosis. RESULTS: The mean patient age was 69 years. Sixteen pancreatic cysts (38.1%) were located in the head, 17 (40.5%) in the body, and 9 (21.4%) in the tail. The mean cyst size was 28.2 mm (12-60 mm); 25 of 42 (60%) were septated. The EUS-FNA tissue (fluid) acquisition yield was 88.1% (37/42). The MFB tissue acquisition yield was 90.4% (38/42). The diagnostic cytology yield to differentiate between mucinous and/or nonmucinous cysts was 47.6% (20/42), and the MFB histologic yield to differentiate between mucinous and/or nonmucinous cysts was 61.9% (26/42) (P = .188). The percentage of cysts at high risk for malignancy by cytology was 54.7% (23/42), and MFB was 71.5% (30/42) (P = .113). However, the ability of MFB to provide a specific cyst type diagnosis was 35.7% (15/42), and that for cytology was 4.8% (2/42) (P = .001). Surgical histology was concordant with that of MFB in 6 of 7 patients (85%), and with that of cytology in 1 of 7 patients (15%). CONCLUSION: The cyst tissue acquisition yield for MFBs was 90%. Although cytology of cyst fluid and MFB were comparable in distinguishing mucinous and nonmucinous cysts and detecting cysts at high risk for malignancy, MFB was far superior to cytology for providing a specific cyst diagnosis.

Needle-Based Confocal Laser Endomicroscopy for Evaluation of Cystic Neoplasms of the Pancreas.

BACKGROUND: The accurate diagnosis of cystic neoplasms of the pancreas (CNP) with current diagnostic methods is limited. Endoscopic ultrasound (EUS)-guided needle-based confocal laser endomicroscopy (nCLE) is a new technique which can obtain images from the cyst wall during EUS-fine needle aspiration (EUS-FNA). The aim of this study was to assess the safety, feasibility, and diagnostic value of nCLE for CNP. METHODS: Patients who underwent EUS-FNA to evaluate a CNP larger than 2 cm were enrolled. The cyst was punctured with 19-G FNA needle preloaded with an nCLE probe. The images from different areas of the cyst wall were recorded. Using the final diagnosis defined by surgery or EUS-FNA cyst fluid analysis, the accuracy of the confocal images was defined. RESULTS: The procedure and image acquisition was successful in 18 of the 20 patients. Predefined typical structures for mucinous cysts were visualized in 8 of 12 (66%) cysts but none of the non-mucinous cysts. The superficial vascular network which is a typical finding of serous cysts was observed in 2 of 3 patients. The sensitivity, specificity, and diagnostic accuracy of the findings of epithelial structures by nCLE were 66, 100, and 80%, respectively, for a mucinous cyst diagnosis. All patients tolerated the procedure well, and no adverse effects were determined. CONCLUSION: nCLE was found to be safe and feasible with high technical success, in this pilot study. With an overall accuracy of 80%, it has the potential to contribute to the diagnosis of CNP with specific imaging.

Mean platelet volume could be possible biomarker in early diagnosis and monitoring of gastric cancer.

Gastric cancer is the fourth most frequent cancer and the second cause of cancer-related deaths worldwide. The early diagnosis of gastric cancer is fundamental in decreasing the mortality rates. It has been shown that MPV level is a sign of inflammation in hepatocellular carcinoma and pancreatic adenocarcinoma. The aim of this study is to examine whether MPV would be a useful inflammatory marker for differentiating gastric cancer patients from healthy controls. Thirty-one gastric cancer patients and 31 age-sexes matched healthy subjects included into the study. Patients with hypertension, hematological and renal disease, heart failure, chronic infection, hepatic disorder and other cancer were excluded from the study. MPV level was significantly higher in pre-operative gastric cancer patients compared to healthy subjects (8.31 fL vs. 7.85; p: 0.007). ROC analysis suggested 8.25 fL as the cut-off value for MPV (AUC: 0.717, sensitivity: 61%, specificity: 81%). Surgical tumor resection resulted in a significant decrease in MPV level (8.31 fL vs. 7.55 fL; p: 0.001). No significant difference was found in MPV level between the post-operative group and control subjects. We did not find statistically significant difference between MPV and TNM stages. In conclusion, changes in MPV values may be used as an easily available biomarker for monitoring the healthy patients for GC risk and may prompt physicians to make an early diagnosis of GC.

Long-term efficacy and safety of lamivudine, entecavir, and tenofovir for treatment of hepatitis B virus-related cirrhosis.

BACKGROUND & AIMS: Data are limited on the efficacy and safety of tenofovir and entecavir when given for more than 1 year to patients with hepatitis B-related cirrhosis. We investigated the long-term safety and efficacy of these antiviral drugs in patients with chronic hepatitis B virus (HBV) infection, with compensated or decompensated cirrhosis, and compared results with those from lamivudine. METHODS: We performed a retrospective analysis of data from 227 adult patients with chronic HBV infection who were diagnosed with cirrhosis, beginning in 2005, at 18 centers throughout Turkey. There were 104 patients who had decompensated cirrhosis, and 197 patients were treatment naive before. Seventy-two patients received tenofovir (followed up for 21.4 ± 9.7 mo), 77 patients received entecavir (followed up for 24.0 ± 13.3 mo), and 74 patients received lamivudine (followed up for 36.5 ± 24.1 mo). We collected data on patient demographics and baseline characteristics. Laboratory test results, clinical outcomes, and drug-related adverse events were compared among groups. RESULTS: Levels of HBV DNA less than 400 copies/mL were achieved in 91.5%, 92.5%, and 77% of patients receiving tenofovir, entecavir, or lamivudine, respectively. Levels of alanine aminotransferase normalized in 86.8%, 92.1%, and 71.8% of patients who received tenofovir, entecavir, and lamivudine, respectively. Child-Turcotte-Pugh scores increased among 8.5% of patients who received tenofovir, 15.6% who received entecavir, and 27.4% who received lamivudine. Frequencies of complications from cirrhosis, including hepatic encephalopathy, variceal bleeding, hepatocellular carcinoma, and mortality, were similar among groups. Lamivudine had to be changed to another drug for 32.4% of the patients. CONCLUSIONS: Tenofovir and entecavir are effective and safe for long-term use in patients with compensated or decompensated cirrhosis from HBV infection.

Lamivudine treatment failure risks in chronic hepatitis B patients with low viral load.

AIM: To analyze the risk factors of lamivudine treatment failure (LTF) for the long-term use in patients with low viral load (LVL). MATERIAL AND METHODS: In this multicenter study, 548 antiviral naïve noncirrhotic adult patients with LVL (for HBeAg+ patients HBV DNA <10 9 copies/ml and for HBeAg­patients HBV DNA <10 7 copies/ml) were enrolled. As a control group, 46 lamivudine-initiated patients with high viral load (HVL) were included. Primary outcome was switching to or adding on another antiviral drug as a consequence of primary nonresponse, partial response, viral breakthrough or adverse events. Secondary outcomes included LTF rates at 1, 2, 3, 4 and 5 years and LTF-related viral and host factors. RESULTS: Among 594 patients, 294 had to change lamivudine at the follow-up. Primary nonresponse, partial response, viral breakthrough or adverse events frequencies were 6.8, 1.6, 64.5 and 0.1%, respectively. Five-year LTF rates were 61.3 and 84.2% in patients with LVL and HVL, respectively. Among patients with LVL, patients with <100,000 copies/ml and ≥ 100,000 copies/ ml had 54.8 and 67.3% LTF rates at the end of the 5th year, respectively. Logistic regression analysis of risk factors showed HBeAg+, hepatic activity index, HBV DNA, virological response at 6 months and duration of follow-up were independent predictors for LTF (p values were 0.001, 0.008, 0.003, 0.020 and 0.003, respectively). CONCLUSION: Similar to patients with HVL, first-line lamivudine therapy is not efficient for long-term use in patients with LVL. LTF risk is so high even in the absence of worse predictive factors.

Adding pineapple juice to a polyethylene glycol-based bowel cleansing regime improved the quality of colon cleaning.

BACKGROUND/AIMS: An unsuccessful colonoscopy procedure is often related to inadequate bowel cleansing. It is difficult for patients to finish the whole 4 liters of polyethylene glycol-electrolyte lavage (PEG-EL) because of its salty taste and the large quantity. Pineapple juice has been shown to be an effective agent in the dissolution of undigested food in the stomach. This study assessed the effectiveness of both 2 and 4 liters of PEG-EL in precolonoscopic bowel cleansing and the quality of colonoscopic cleaning by adding 1 liter of pineapple juice to a reduced-volume PEG-based regime. METHODS: The patients were chosen from those undergoing a colonoscopic procedure. A total of 126 patients were randomized into 3 groups receiving 3 different PEG-EL (Golytely®) regimes, i.e. 4 liters of PEG-EL (group 1, n = 44), 2 liters of PEG-EL (group 2, n = 39) or 2 liters of PEG-EL with 1 liter of pineapple juice (Dimes® 100%; group 3, n = 43). RESULTS: Both the 4- and 2-liter PEG-EL regimes resulted in similar bowel cleansing scores in all parts of the colonic segments. However, adding 1 liter of pineapple juice to the reduced-volume PEG-EL regime improved the quality of the cleansing on the right side of the colon and in the transverse colon. Adequate bowel cleansing was achieved in 68.1% of the patients in group 1, 63.9% in group 2 and 80% in group 3 (the lowest score in one of the segments). On the other hand, the tolerability of the regimes was similar in all 3 groups (p = 0.509). CONCLUSIONS: Reduced PEG-EL (2 rather than 4 liters) may be sufficient for precolonoscopic bowel cleansing in the Turkish population. Administration of pineapple juice in the reduced-dose preparation regime may improve the quality of the bowel cleaning.

Non-Alcoholic Fatty Pancreas Disease: The Unsung Disease.

Non-alcoholic fatty pancreas disease (NAFPD) is a relatively new and emerging disease that is increasingly diagnosed yearly, like non-alcoholic fatty liver disease (NAFLD). It is associated especially with metabolic syndrome and obesity. As awareness of pancreatic steatosis and its clinical implications increase, it is diagnosed more frequently. The researchers have explained the clinical importance of NAFPD and the diseases it causes, such as pancreatitis, pancreatic insufficiency, and pancreatic cancer. Although the definitive treatment is not yet established, the primary treatment approach is weight loss since NAFPD is associated with metabolic syndrome as well as obesity. Although pharmacological agents, such as oral hypoglycemic agents, have been investigated in animal experiments, studies on humans have not been conducted. Since the research on NAFPD is still insufficient, it is a subject that needs to be investigated, and further studies are needed to explore its pathophysiology, clinical impact, and its management.

Lymphocytic Esophagitis: A Case Series of Esophageal Disease with Increasing Frequency.

BACKGROUND: Lymphocytic esophagitis (LE) is a poorly understood clinical finding that has been increasingly identified in the last decade. Previous studies proposed increased frequency of LE in elderly females, as well as associations with smoking and pediatric Crohn's disease. OBJECTIVE: We aimed to determine the patient characteristics and clinical features of our adult LE patients. As inflammation in the esophagus has been linked to cancer, this review also describes this association. However, there are no reported cases of malignant transformation in those with underlying lymphocytic esophagitis. METHODS: We retrospectively reviewed records for patients at the University of Missouri Hospital- Columbia (located in the USA) who had a histopathological diagnosis of LE. Cases of LE were identified using the pathology reporting system at the University of Missouri Hospital for esophageal biopsy specimens for the above-mentioned period. RESULTS: The data of a total of 20 adult cases with esophageal biopsy specimens consistent with LE were included. CONCLUSION: LE seems to be a benign but disturbing clinical problem and should be remembered in elderly females complaining of dysphagia or refractory reflux symptoms. It has similar endoscopic findings of eosinophilic esophagitis with rings and esophagitis. Smoking and hiatal hernia are common risk factors. The majority of LE patients can respond to proton pump inhibitor (PPI) therapy. Endoscopic dilations and steroid therapy should be considered for PPI nonresponder LE patients.

A novel appetite peptide, nesfatin-1 in patients with non-alcoholic fatty liver disease.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver pathology worldwide and is strongly associated with obesity and insulin-resistance and food intake. Nesfatin-1 is a new peptide that controls appetite and food intake. The objective of this research was to examine the serum concentrations of nesfatin-1 in NAFLD. MATERIAL AND METHODS: Thirty NAFLD patients who had elevated liver enzymes and 40 age- and sex-matched healthy subjects were included in this study. NAFLD was diagnosed and graded with the findings of liver ultrasound scan. Nesfatin-1 concentrations were measured using an ELISA method and the relationship between nesfatin-1 and metabolic parameters were investigated. The subjects were divided into two groups according to their body mass index (≥ 30 and < 30) and nesfatin-1 concentrations were examined between both groups. RESULTS: Serum nesfatin-1 concentrations in NAFLD patients were lower than healthy controls (0.26 ± 0.14 ng/ml, 0.38 ± 0.18 ng/ml, respectively, and p = 0.008). We found a negative correlation between nesfatin-1 and fasting glucose and body mass index. In obese subjects, serum nesfatin-1 concentrations were significantly lower when compared with non-obese subjects (0.26 ± 0.12 ng/ml, 0.37 ± 0.19 ng/ml, respectively; p = 0.014). In addition, we showed that nesfatin-1 concentrations in subjects with insulin resistance were significantly lower in comparison with insulin-sensitive ones (0.27 ± 0.17 ng/ml, 0.38 ± 0.17 ng/ml, respectively; p = 0.015). CONCLUSION: Our study has shown that nesfatin-1 concentrations were reduced in NAFLD. The results of this study indicate that nesfatin-1 may have a significant role in NAFLD.

Evaluation of serum TWEAK concentration in patients with acute pancreatitis.

BACKGROUND AND AIM: Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis factor super family of structurally-related cytokines. The aim of this study was to determine the diagnostic and prognostic role of serum TWEAK concentration in patients with acute pancreatitis. METHODS: Twenty four patients with acute pancreatitis and 24 consecutive healthy age- and sex-matched control subjects were included in the study. The serum concentrations of TWEAK were measured at admission and then at remission. The average time between admission and remission was 7-10 days. RESULTS: At admission, TWEAK concentration was significantly lower in patients with acute pancreatitis compared to control subjects (p < 0.001). Serum TWEAK concentrations were elevated after the remission period, however the differences were not statistically significant. In addition, serum TWEAK concentration showed a significant, inverse correlation with amylase, lipase, CRP, AST, fibrinogen, LDH and a positive correlation with calcium, albumin and platelet count. CONCLUSIONS: Patients with acute pancreatitis have lower serum TWEAK concentration than healthy subjects. These results suggest that serum TWEAK concentration could be a potential biomarker of acute pancreatitis.

Is there an association between the measurement of qualitative HBsAg and virologic response in chronic HBV infection?

BACKGROUND: In the follow up of chronic hepatitis B infection (HBV), a significant correlation between quantitative HBsAg titer measurement and HBV DNA level, and moreover with intrahepatic covalently closed circular DNA was already shown. However, besides their impact on long-term follow up, they are really expensive methods, and not available widespread. We aimed to investigate the utility of qualitative measurement of HBsAg titer in prediction of virologic response at the end of the first year of anti-viral treatment in chronic HBV infection. MATERIAL AND METHODS: A total of 70 patients receiving anti-viral therapies for chronic HBV infection were included into the study. The patients were evaluated according to Hbe Ag status and response to treatment. The determinations used in the study (biochemical, virologic responses, primary non-response) were accepted as it was described in AASLD. RESULTS: Qualitative HBsAg titer increased significantly in both HBeAg positive and negative patients (p values 0.002 and < 0.000). Increasing of HBsAg titer in first three months is more dramatic in responder group, however the difference was disappeared at the sixth and twelve moths on follow up. Similarly, a fast increasing in anti-HBe titer in HBeAg negative chronic HBV patients was related with higher response at the end of first year therapy. However, the changings at the 12th month of anti-viral treatment were similar in both responder and non-responder groups. CONCLUSION: In conclusion, the fast increase in qualitative measurement of HBsAg titer seemed to be a predictor of higher anti-viral medication success in chronic HBV patients. However, this meaningful increasing was disappeared on the follow up, particularly after the six months examination.

Pancreatic Cystic Neoplasms.

Early detection of high-risk pancreatic cystic lesions enables potentially curative surgical resection, and early detection of lesions without worrisome features may lead to appropriate surveillance. Regrettably, differentiating premalignant and malignant cysts from nonmalignant ones remains challenging. However, emerging additional diagnostic tools, including the needle biopsy with microforceps and needle-based confocal laser endomicroscopy, are of exciting potential along with cyst fluid analysis".

Peripheral arthritis in the course of inflammatory bowel diseases.

BACKGROUND: Musculoskeletal disorders are well-defined extra-intestinal manifestations of inflammatory bowel diseases (IBD). There is little data regarding the frequencies of IBD and extra-intestinal manifestations from Central and East Europe and Middle Eastern countries. AIMS: To determine the prevalence of peripheral arthritis in IBD and to document the relationship to other extra-intestinal manifestations. METHODS: Enrolled in the study were 357 patients who were diagnosed with IBD from December 2002 through January 2008. All of the patients underwent a detailed whole-body examination by a gastroenterologist and rheumatologist. RESULTS: IBD-related peripheral arthritis (IBDPA) was found in 66 (18.5%) of the 357 patients (28.3% Crohn's disease, 13.5% ulcerative colitis; p=0.001 χ=11.62). IBDPA was more frequent in female patients (60.6 vs. 39.4%, p=0.000, χ=11.12). In eight (12.1%) cases, IBDPA occurred before the onset of IBD. Acute self-limiting episodes, recurrences of the attacks, and persistent symptoms of arthritis were present in 40 (60.6%), 26 (39.3%), and 29 (45.7%) patients, respectively. Arthritis was symmetrical in 33 (50%) cases. Knees (65.2%) and ankles (62.1%) were the most commonly affected joints. Erythema nodosum and pyoderma gangrenosum were more common among patients with IBDPA than patients without it (p=0.001, χ=10.49, and p=0.000 χ=25.77, respectively). CONCLUSIONS: IBDPA is a frequent extra-intestinal complication of IBD. Those of female gender and the presence of Crohn's disease, erythema nodosum and pyoderma gangrenosum have a higher risk to develop IBDPA.