Prospective study of hepatitis B and D epidemiology and risk factors in Romania:A 10-year update

BACKGROUND The global burden of hepatitis D virus(HDV)infection represents a major medical challenge and a public health crisis worldwide.However,there is a lack of accurate data on the epidemiology and risk factors for HDV.Hepatitis B virus(HBV)and HDV coinfection causes the most severe form of viral hepatitis,leading to a higher cumulative incidence of liver-related events compared with HBV monoinfection,including the need for liver transplantation and death.AIM To investigate the epidemiology,natural history,risk factors and clinical management of HBV and HDV coinfection in Romanian patients.METHODS This prospective study was conducted between January and July 2022 in six tertiary gastroenterology and hepatology referral centres in Romania.All consecutive adults admitted for any gastroenterology diagnosis who were HBV-positive were enrolled.Patients with acute hepatitis or incomplete data were excluded.Of the 25390 individuals who presented with any type of gastroenterology diagnosis during the study period,963 met the inclusion criteria.Testing for anti-HDV antibodies and HDV RNA was performed for all participants.Demographic and risk factor data were collected by investigators using medical charts and patient questionnaires.All data were stored in an anonymized online database during the study.RESULTS The prevalence of HBV was 3.8%;among these patients,the prevalence of HBV/HDV coinfection was 33.1%.The median age of the study population was 54.0 years,and it consisted of 55.1%men.A higher prevalence of HBV/HDV coinfection was observed in patients 50–69 years old.Patients with HBV/HDV coinfection were significantly older than those with HBV monoinfection(P=0.03).Multivariate multiple regression analysis identified female gender(P=0.0006),imprisonment(P<0.0001),older age at diagnosis(P=0.01)and sexual contact with persons with known viral hepatitis(P=0.0003)as significant risk factors for HDV.CONCLUSION This study shows that HDV infection among those with HBV remains endemic in Romania and updates our understanding of HDV epidemiology and associated risk factors.It emphasizes the need for systematic screening for HDV infection and collaborative initiatives for controlling and preventing HBV and HDV infection.

Nonalcoholic fatty liver disease, metabolic risk factors, and hepatocellular carcinoma: An open question

Non-alcoholic liver disease(NAFLD) defines liver abnormalities ranging from simple steatosis to nonalcoholic steatohepatitis with or without cirrhosis development, occurring in the absence of significant alcohol consumption, use of teratogenic medication, or hereditary disorders.The association between NAFLD and metabolic syndrome is well documented and widely recognized.Obesity, type 2 diabetes mellitus(T2DM), and dyslipidemia are the most common metabolic risk factors associated with NAFLD.Among the components of metabolic syndrome, current evidence strongly indicates obesity and diabetes as hepatocellular carcinoma(HCC) risk factors.There is also growing evidence that suggests an increased risk of HCC in NAFLD patients, even surpassing other etiologies in some high-income countries.Epidemiologic data demonstrate a parallel rise in prevalence of obesity, diabetes, NAFLD, and HCC.As obesity and its related diseases have steadily afflicted larger populations, HCC incidence is expected to increase in the future.Pathophysiologic mechanisms that underlie NAFLD development and subsequent progression to nonalcoholic steatohepatitis and cirrhosis(insulin resistance and hyperinsulinemia, oxidative stress, hepatic stellate cell activation, cytokine/adipocytokine signaling pathways, and genetic and environmental factors) appear to play a significant role in the development of NAFLD-related HCC.However, a comprehensive view of molecular mechanisms linking obesity, T2 DM, and NAFLD-related HCC, as well as the exact sequence of molecular events, is still not understood in its entirety.Good-quality data are still necessary, and efforts should continue towards better understanding the underlying carcinogenic mechanisms of NAFLD-related HCC.In this paper, we aimed to centralize the most important links supporting these relationships, focusing on obesity, T2 DM, and NAFLD-related HCC, as well as point out the major gaps in knowledge regarding the underlying molecular mechanisms behind them.

Hybrid ultrasound imaging techniques(fusion imaging)

Visualization of tumor angiogenesis can facilitate noninvasive evaluation of tumor vascular characteristics to supplement the conventional diagnostic imaging goals of depicting tumor location,size,and morphology.Hybrid imaging techniques combine anatomic [ultrasound,computed tomography(CT),and/or magnetic resonance imaging(MRI)] and molecular(single photon emission CT and positron emission tomography) imaging modalities.One example is real-time virtual sonography,which combines ultrasound(grayscale,colour Doppler,or dynamic contrast harmonic imaging) with contrast-enhanced CT/MRI.The benefits of fusion imaging include an increased diagnostic confidence,direct comparison of the lesions using different imaging modalities,more precise monitoring of interventional procedures,and reduced radiation exposure.

Role of intrahepatic innervation in regulating the activity of liver cells

Liver innervation comprises sympathetic,parasympathetic and peptidergic nerve fibers,organized as either afferent or efferent nerves with different origins and roles.Their anatomy and physiology have been studied in the past 30 years,with different results published over time.Hepatocytes are the main cell population of the liver,making up almost 80%of the total liver volume.The interaction between hepatocytes and nerve fibers is accomplished through a wealth of neurotransmitters and signaling pathways.In this short review,we have taken the task of condensing the most important data related to how the nervous system interacts with the liver and especially with the hepatocyte population,how it influences their metabolism and functions,and how different receptors and transmitters are involved in this complex process.

Contrast-enhanced ultrasonography parameters in neural network diagnosis of liver tumors

AIM:To study the role of time-intensity curve(TIC) analysis parameters in a complex system of neural networks designed to classify liver tumors.METHODS:We prospectively included 112 patients with hepatocellular carcinoma(HCC)(n = 41),hypervascular(n = 20) and hypovascular(n = 12) liver metastases,hepatic hemangiomas(n = 16) or focal fatty changes(n = 23) who underwent contrast-enhanced ultrasonography in the Research Center of Gastroenterology and Hepatology,Craiova,Romania.We recorded full length movies of all contrast uptake phases and post-processed them offline by selecting two areas of interest(one for the tumor and one for the healthy surrounding parenchyma) and consecutive TIC analysis.The difference in maximum intensities,the time to reaching them and the aspect of the late/portal phase,as quantified by the neural network and a ratio between median intensities of the central and peripheral areas were analyzed by a feed forward back propagation multi-layer neural network which was trained to classify data into five distinct classes,corresponding to each type of liver lesion.RESULTS:The neural network had 94.45% training accuracy(95% CI:89.31%-97.21%) and 87.12% testing accuracy(95% CI:86.83%-93.17%).The automatic classification process registered 93.2% sensitivity,89.7% specificity,94.42% positive predictive value and 87.57% negative predictive value.The artificial neural networks(ANN) incorrectly classified as hemangyomas three HCC cases and two hypervascular metastases,while in turn misclassifying four liver hemangyomas as HCC(one case) and hypervascular metastases(three cases).Comparatively,human interpretation of TICs showed 94.1% sensitivity,90.7% specificity,95.11% positive predictive value and 88.89% negative predictive value.The accuracy and specificity of the ANN diagnosis system was similar to that of human interpretation of the TICs(P = 0.225 and P = 0.451,respectively).Hepatocellular carcinoma cases showed contrast uptake during the arterial phase followed by wash-out in the portal and first seconds of the late phases.For the hypovascular metastases did not show significant contrast uptake during the arterial phase,which resulted in negative differences between the maximum intensities.We registered wash-out in the late phase for most of the hypervascular metastases.Liver hemangiomas had contrast uptake in the arterial phase without agent wash-out in the portallate phases.The focal fatty changes did not show any differences from surrounding liver parenchyma,resulting in similar TIC patterns and extracted parameters.CONCLUSION:Neural network analysis of contrastenhanced ultrasonography-obtained TICs seems a promising field of development for future techniques,providing fast and reliable diagnostic aid for the clinician.

B2 adrenergic receptors and morphological changes of the enteric nervous system in colorectal adenocarcinoma

AIM To study the morphology of the enteric nervous system and the expression of beta-2 adrenergic(B2A) receptors in primary colorectal cancer.METHODS In this study, we included forty-eight patients with primary colorectal cancer and nine patients for control tissue from the excision of a colonic segment for benign conditions. We determined the clinicopathological features and evaluated the immunohistochemical expression pattern of B2 A receptors as well as the morphological changes of the enteric nervous system(ENS). In order to assess statistical differences, we used the student t-test for comparing the means of two groups and one-way analysis of variance with Bonferroni's post hoc analysis for comparing the means of more than two groups. Correlations were assessed using the Pearson's correlation coefficient.RESULTS B2 A receptors were significantly associated with tumor grading, tumor size, tumor invasion, lymph node metastasis(P < 0.05), while there were no statistically significant associations with gender, CRC location and gross appearance(P > 0.05). We observed, on one hand, a decrease of the relative area for both Auerbach and Meissner plexuses with the increase of the tumor grading, and on the other hand, an increase of the relative area of other nervous elements not in the Meissner plexus or in the Auerbach plexus with the tumor grading. For G1 tumors we found that epithelial B2 A area showed an inverse correlation with the Auerbach plexus areas [r(14) =-0.531, P < 0.05], while for G2 tumors, epithelial B2 A areas showed an indirect variation with both the Auerbach plexus areas [r(14) =-0.453, P < 0.05] and the Meissner areas [r(14) =-0.825, P < 0.01]. For G3 tumors, the inverse dependence increased for both Auerbach [r(14) =-0.587, P < 0.05] and Meissner [r(14) =-0.934, P < 0.05] plexuses.CONCLUSION B2 A receptors play an important role in colorectal carcinogenesis and can be utilized as prognostic factors. Furthermore, study of the ENS in colorectal cancer may lead to targeted molecular therapies.