NGF (-198C > T, Ala35Val) and p75NTR (Ser205Leu) gene mutations are associated with liver function in different histopathological profiles of the patients with chronic viral hepatitis in the Brazilian Amazon.

BACKGROUNDS: Neural growth factor (NGF) is a neurotrophin that can interact with the p75NTR receptor and initiate a cascade of reactions that determines cell survival or death, and both are associated with the physiology of liver tissue. Single nucleotide polymorphisms (SNPs) in the NGF and p75NTR genes have been investigated in different pathologies; however, there are no studies that have analyzed their biological roles in the hepatic microenvironment. In the present study, we evaluated the impact of SNPs in these genes on the maintenance of liver function at different stages of inflammation and fibrosis in patients with chronic viral liver disease in the Brazilian Amazon. METHODS: The SNPs -198C > T, Arg80Gln, Val72Met, Ala35Val, Ala18Ala and Ser205Leu were genotyped by real-time PCR in samples from patients with chronic viral hepatitis stratified by stage of inflammation and liver fibrosis. Histopathological, viral load (VL), liver enzyme and comorbidities data were obtained from updated medical records. Other aspects were highlighted by applied epidemiological questionnaires. RESULTS: The -198C/T and Ala35Val polymorphisms in NGF were associated with changes in histopathological profiles, VL and liver enzymes. Ser205Leu polymorphism in p75NTR was associated only with changes in VL and liver enzymes. Polymorphic frequencies were variable among different ethnic populations, mainly for biologically relevant polymorphisms. A multifactorial network of interactions has been established based on genetic, virological, behavioral and biochemical aspects. CONCLUSION: Mutations in the NGF (-198C > T, Ala35Val) and p75NTR (Ser205Leu) genes, within the list of multifactorial aspects, are associated with liver function in different histopathological profiles of patients with chronic viral liver disease in the Brazilian Amazon.

Mechanisms of kidney dysfunction in the cirrhotic patient: Non-hepatorenal acute-on-chronic kidney damage considerations.

Renal dysfunction is a common finding in cirrhotic patients and has a great physiologic, and therefore, prognostic relevance. The combination of liver disease and renal dysfunction can occur as a result of systemic conditions that affect both the liver and the kidney, although primary disorders of the liver complicated by renal dysfunction are much more common. As most of the renal dysfunction scenarios in cirrhotic patients correspond to either prerenal azotemia or hepatorenal syndrome (HRS), physicians tend to conceive renal dysfunction in cirrhotic patients as mainly HRS. However, there are many systemic conditions that may cause both a "baseline" chronic kidney damage and a superimposed kidney dysfunction when this systemic condition worsens. The main aim of this article is to review some of the most important non prerenal non-HRS considerations regarding acute on chronic kidney dysfunction in cirrhotic patients, including renal manifestation of related to non-alcoholic steatohepatitis (NASH) viral hepatitis, the effect of cardiorenal syndrome in cirrhotics and corticosteroid-deficiency associated renal dysfunction.

Electrocardiographic Changes in Liver Cirrhosis-Clues for Cirrhotic Cardiomyopathy.

Background and Objectives: Cirrhotic cardiomyopathy is a chronic cardiac dysfunction associated with liver cirrhosis, in patients without previous heart disease, irrespective of the etiology of cirrhosis. Electrocardiography (ECG) is an important way to evaluate patients with cirrhosis and may reveal significant changes associated with liver disease. Our study aimed to evaluate ECG changes in patients with diagnosed liver cirrhosis and compare them to patients with chronic hepatitis. Materials and Methods: We evaluated laboratory findings and ECG tracings in 63 patients with cirrhosis and 54 patients with chronic hepatitis of viral etiology. The end points of the study were prolonged QT interval, QRS hypovoltage and T-peak-to-T-end decrease. We confirmed the diagnosis of cirrhotic cardiomyopathy using echocardiography data. Results: Advanced liver disease was associated with prolonged QT intervals. Also, QRS amplitude was lower in patients with decompensated cirrhosis than in patients with compensated liver disease. We found an accentuated deceleration of the T wave in patients with cirrhosis. These findings correlated to serum levels of albumin, cholesterol and ammonia. Conclusions: ECG changes in liver cirrhosis are frequently encountered and are important noninvasive markers for the presence of cirrhotic cardiomyopathy.

Evolutionary biology of human hepatitis viruses.

Hepatitis viruses are major threats to human health. During the last decade, highly diverse viruses related to human hepatitis viruses were found in animals other than primates. Herein, we describe both surprising conservation and striking differences of the unique biological properties and infection patterns of human hepatitis viruses and their animal homologues, including transmission routes, liver tropism, oncogenesis, chronicity, pathogenesis and envelopment. We discuss the potential for translation of newly discovered hepatitis viruses into preclinical animal models for drug testing, studies on pathogenesis and vaccine development. Finally, we re-evaluate the evolutionary origins of human hepatitis viruses and discuss the past and present zoonotic potential of their animal homologues.

Liver disease in pregnancy: Medical aspects and their implications for mother and child.

Liver disease during pregnancy is more common than expected and may require specialized intervention. It is important to determine if changes in liver physiology may develop into liver disease, to assure early diagnosis. For adequate surveillance of mother-fetus health outcome, liver disease during pregnancy might require intervention from a hepatologist. Liver diseases have a prevalence of at least 3% of all pregnancies in developed countries, and they are classified into two main categories: related to pregnancy; and those non- related that are present de novo or are preexisting chronic liver diseases. In this review we describe and discuss the main characteristics of those liver diseases associated with pregnancy and only some frequent pre-existing and co-incidental in pregnancy are considered. In addition to the literature review, we compiled the data of liver disease occurring during pregnancies attended at the National Institute of Perinatology in Mexico City in a three-year period. In our tertiary referral women hospital, liver disease was present in 11.24 % of all pregnancies. Associated liver disease was found in 10.8% of all pregnancies, mainly those related to pre-eclampsia (9.9% of pregnancies). Only 0.56% was due to liver disease that was co-incidental or preexisting; the acute or chronic hepatitis C virus was the most frequent in this group (0.12%). When managing pregnancy in referral hospitals in Latin America, it is important to discard liver alterations early for adequate follow up of the disease and to prevent adverse consequences for the mother and child.

Viral hepatitis.

Hepatitis viruses A to E can cause abnormal liver function tests in children. Although, overall, they are relatively uncommon in children in Australia, epidemiology diagnosis and treatment modalities for these viruses have evolved over the last decade. This review provides an update on the diagnosis and treatment of viral hepatitis in children.

Diseases of the Liver.

IMPAIRED LIVER function affects every aspect of the body's physiology. Diseases of the liver have more widespread and life-threatening impacts than malfunctioning of any of the body's other conditions. accessory organs. Non-alcoholic fatty Liver disease rates are soaring, concurrent with the obesity epidemic and increasing rates of type 2 diabetes. Alcoholic liver disease and viral hepatitis also contribute to high rates of liver damage in the population, making liver disease one of the commonest causes premature death. Liver transplants, hepatocellular carcinomas, and deaths from Liver disease are increasingly due to preventable or treatable liver conditions. Understanding normal liver function allows nurses to predict the impact of Liver disease on their patients' health and well-being. Knowledge of underlying causes of impaired liver function enhances our ability to support and counsel those who are at risk of, or have been diagnosed with liver disease.

Prediction of portal pressure from intraoperative ultrasonography.

BACKGROUND: Portal hypertension is a major risk factor for hepatic failure or bleeding in patients who have undergone hepatectomy, but it cannot be measured indirectly. We attempted to evaluate the intraoperative ultrasonography parameters that correlate with portal pressure (PP) in patients undergoing hepatectomy. METHODS: We examined 30 patients in whom PP was directly measured during surgery. The background liver conditions included chronic viral liver disease in seven patients, chemotherapy-associated steatohepatitis in four patients, fatty liver in one patient, hepatolithiasis in one patient, obstructive jaundice in one patient, and a normal liver in 16 patients. A multivariate logistic analysis and linear regression analysis were conducted to develop a predictive formula for PP. RESULTS: The mean PP was 10.4 ± 4.1 mm Hg. The PP tended to be increased in patients with chronic viral hepatitis. A univariate analysis identified the association of the six following parameters with PP: the platelet count and the maximum (max), minimum (min), endo-diastolic, peak-systolic, and mean velocity in the portal vein (PV) flow. Using multiple linear regression analysis, the predictive formula using the PV max and min was as follows: Y (estimated PP) = 18.235-0.120 × (PV max.[m/s])-0.364 × (PV min). The calculated PP (10.44 ± 2.61 mm Hg) was nearly the same as the actual PP (10.43 ± 4.07 mm Hg). However, there was no significant relationship between the calculated PP and the intraoperative blood loss and post hepatectomy morbidity. CONCLUSIONS: This formula, which uses ultrasonographic Doppler flow parameters, appears to be useful for predicting PP.

[Features of structural and functional changes of the myocardium in patients with chronic viral hepatitis].

OBJECTIVE: Our aim was to evaluate the characteristics of structural and functional changes of the heart in patients with chronic viral hepatitis. METHODS: The study included 123 patients - 17 patients with aviraemnia after antiviral therapy (group 1), 38 patients with laboratory inactive hepatitis (group 2), 68 patients with biochemical active hepatitis (group 3). All patients had standard echocardiography, Doppler sonography and tissue Doppler echocardiography. RESULTS: Patients with chronic viral hepatitis were revealed to develop changes in the geometry of the left ventricle (increase in the wall thickness). Patients with active hepatitis had increase in the left atrium, the right ventricle and indexed left ventricular mass of the heart. Significant morphological changes were not confirmed statistically in patients after "therapy". Pulmonary hypertension was revealed in 19% of cases, mitral valve prolapse was confirmed in 48%, with the detection rates being not dependent on hepatitis activity. Abnormal left ventricular remodeling was identified in 45% of patients, in patients with active hepatitis more frequently. Compliance dysfunction of both right and left ventricles was detected, it depends on the activity of the inflammatory process in the liver. This disorder partially persists after antiviral treatment. CONCLUSION: Specifics of the structural and functional changes of the heart in patients with chronic viral hepatitis is the development of left ventricular hypertrophy, and in the presence of laboratory activity hepatitis - relative dilatation of the right heart and ventricular diastolic dysfunction of the heart. Carrying out specific antiviral therapy has a beneficial effect on cardiac hemodynamics parameters. Method of tissue Doppler echocardiography was efficient in evaluation of early disorders of diastolic function in patients with chronic viral hepatitis.

Urinary potassium loss in children with acute liver failure and acute viral hepatitis.

OBJECTIVES: The aim of the present study was to determine urinary potassium (K⁺) loss (as measured by fractional excretion of K⁺ [FEK] and transtubular K⁺ gradient [TTKG]) in children with acute liver failure (ALF) and acute viral hepatitis (AVH) at the time of presentation to the hospital and day 45 of follow-up. METHODS: Twenty-five patients with ALF and 84 patients with AVH were worked up for clinical features, liver function tests, and hepatitis viral infections and monitored for outcome. All of the patients with ALF were hospitalized. FEK and TTKG were estimated on the day patients were first seen in the hospital or hospitalized and later on day 45 of follow-up. RESULTS: Sixty percent (15/25) of patients with ALF were hypokalemic (serum K⁺ <3.5 mEq/L) as compared with only 12% (10/84) in the AVH group (P = 0.000) at the time of presentation in the hospital. Inappropriate kaliuresis was present in 80% to 100% of hypokalemic children compared with 0% to 30% of normokalemic individuals at the time of first contact in either the ALF or AVH group. Inappropriate urinary K⁺ loss and serum K⁺ levels in the hypokalemic individuals improved as the hepatic functions recovered by day 45 of follow-up (P = 0.014-0.000). No significant change in kaliuresis was observed among normokalemic subjects between first contact and later on day 45 of follow-up (P = 0.991-0.228). Despite different physiologic mechanisms, appropriateness of kaliuresis measured by FEK and TTKG showed results in the same direction. CONCLUSIONS: Hypokalemia and inappropriate kaliuresis observed during the acute phase of ALF and AVH reversed with clinical and biochemical recovery. In the absence of major gastrointestinal losses and renal abnormalities, there is need to investigate the contributory role of factors like hyperaldosteronism and food intake, which may have therapeutic implications.

Role of integrins in fibrosing liver diseases.

Integrins and other cell adhesion molecules regulate numerous physiological and pathological mechanisms by mediating the interaction between cells and their extracellular environment. Although the significance of integrins in the evolution and progression of certain cancers is well recognized, their involvement in nonmalignant processes, such as organ fibrosis or inflammation, is only beginning to emerge. However, accumulating evidence points to an instrumental role of integrin-mediated signaling in a variety of chronic and acute noncancerous diseases, particularly of the liver.

Viral hepatitis infection and insulin resistance: a review of the pathophysiological mechanisms.

Viral hepatitis is a common cause of morbidity in Mexico. Insulin resistance (IR) is related to the liver damage caused by some viral infections, especially chronic infections. Chronic viral infection is an important risk factor for the development of type 2 diabetes mellitus, disease that is currently among the 10 main causes of morbidity and the most common cause of mortality. Although several studies have reported an association between IR and hepatitis B virus or hepatitis C virus (HCV) infection, the pathophysiology has been studied thoroughly only for the association between IR and HCV infection. It is thought that HCV infection causes direct damage through the action of the core proteins, which induces an inflammatory state characterized by secretion of proinflammatory cytokines that interfere with normal insulin signaling and disturb glucose, lipid and protein metabolism. This review summarizes the mechanisms by which viral infection is thought to induce IR.

[Role of autophagy in the pathogenesis of liver diseases]. / Az autophagia szerepe a májbetegségek kialakulásában.

Autophagy is a self-digestion process that plays an important role in the development, differentiation and homeostasis of cells, helping their survival during starvation and hypoxia. Accumulated mutant proteins in the endoplasmic reticulum can be degraded by autophagy in alpha-1 antitrypsin deficiency. Hepatitis C and B virus may exploit the autophagy pathway to escape the innate immune response and to promote their own replication. Autophagy is decreased in response to chronic alcohol consumption, likely due to a decrease in 5'-adenosine monophosphate-activated protein kinase, increase in mTOR activity and due to an alteration in vesicle transport in hepatocytes. In obesity and alcoholic liver disease the decreased function of autophagy causes formation of Mallory-Denk bodies and cell death. The deficient autophagy can contribute to liver steatosis, to endoplasmic reticulum stress, and to progression of liver disease. Autophagy defect in hepatocellular carcinoma suggests that it can serve a tumor-suppressor function. The autophagy protein Beclin-1 levels have prognostic significance in liver tumors. Understanding of the molecular mechanism and the role of autophagy may lead to more effective therapeutic strategies in liver diseases in the future.

Capacity building of healthcare workers: Key step towards elimination of viral hepatitis in developing countries.

BACKGROUND: Lack of awareness about viral hepatitis (VH) potentially predisposes the healthcare workers (HCWs) to a higher risk of infection and may in turn increase the risk of transmission of the infection to their families and in the community. Thus, combating VH, requires adequate and updated training to the HCWs. With this objective, Project PRAKASH designed a meticulously planned training program, aimed to assess the effect of a one-day training on VH among in-service nurses. METHODS AND MATERIAL: The content and schedule of scientific sessions of the training program were decided by subject experts to improve knowledge, attitude and practice(KAP) related to VH among in-service nurses. A 54-item questionnaire divided into four domains: Transmission and Risk Factors; Prevention; Treatment; Pathophysiology and Disease Progression were used to assess the KAP related to VH. The questionnaire consisted of four sections: demographic details, knowledge(30-items), attitude(12-items) and practice(12-itmes) with a total score of 30, 60 and 24 respectively in each section. The pre-post knowledge assessment was done and impact assessment survey was undertaken among the participants who completed six months post-training period. Paired-t-test was used to assess the effect of training on knowledge using SPSSv-22. RESULTS: A total of 5253 HCWs were trained through 32 one-day trainings, however data for 4474 HCWs was included in final pre-post knowledge analysis after removing the missing/incomplete data. Mean age of participants was 33.7±8.4 with median experience of 8(IQR: 3-13). Mean improvement in knowledge score was found to be significant (p<0.001) with mean knowledge score of 19.3±4.4 in pre-test and 25.7±3.9 in the post-test out of 30. Impact assessment survey suggested change in attitude and practice of HCWs. CONCLUSION: The one-day training programs helped the in-service nurses to enhance their knowledge related to viral hepatitis. The study provided a roadmap to combating viral hepatitis through health education among HCWs about viral hepatitis.

Autophagy in liver diseases.

Autophagy, or cellular self-digestion, is a cellular pathway crucial for development, differentiation, survival, and homeostasis. Its implication in human diseases has been highlighted during the last decade. Recent data show that autophagy is involved in major fields of hepatology. In liver ischemia reperfusion injury, autophagy mainly has a prosurvival activity allowing the cell for coping with nutrient starvation and anoxia. During hepatitis B or C infection, autophagy is also increased but subverted by viruses for their own benefit. In hepatocellular carcinoma, the autophagy level is decreased. In this context, autophagy has an anti-tumor role and therapeutic strategies increasing autophagy, as rapamycin, have a beneficial effect in patients. Moreover, in hepatocellular carcinoma, Beclin-1 level, an autophagy protein, has a prognostic significance. In α-1-antitrypsin deficiency, the aggregation-prone ATZ protein accumulates in the endoplasmic reticulum. This activates the autophagic response which aims at degrading mutant ATZ. Some FDA-approved drugs which enhance autophagy and the disposal of aggregation-prone proteins may be useful in α-1-antitrypsin deficiency. Following alcohol consumption, autophagy is decreased in liver cells, likely due to a decrease in intracellular 5'-AMP-activated protein kinase (AMPk) and due to an alteration in vesicle transport in hepatocytes. This decrease in autophagy contributes to the formation of Mallory-Denk bodies and to liver cell death. Hepatic autophagy is defective in the liver in obesity and its upregulation improves insulin sensitivity.

Adipokines in liver diseases.

Adipokines are polypeptides secreted in the adipose tissue in a regulated manner. While some of these molecules are expressed only by adipocytes, resident and infiltrating macrophages and components of the vascular stroma markedly contribute to expression of other adipokines. As a result, adipose tissue inflammation is associated with a modification in the pattern of adipokine secretion. Leptin, adiponectin, and resistin are the best-studied molecules in this class, but cytokines such as tumor necrosis factor or interleukin-6 are also secreted at high levels by the adipose tissue. Several other molecules have been recently identified and are actively investigated. Adipokines interfere with hepatic injury associated with fatty infiltration, differentially modulating steatosis, inflammation, and fibrosis. Several studies have investigated plasma levels of adiponectin in patients with nonalcoholic fatty liver disease, to establish correlations with the underlying state of insulin resistance and with the type and severity of hepatic damage. Hepatitis C is another disease where adipokines may represent a link between viral infection, steatosis, and metabolic disturbances. Identification of the mediators secreted by expanded adipose tissue and their pathogenic role is pivotal in consideration of the alarming increase in the prevalence of obesity and of the detrimental role that this condition exerts on the course of liver diseases.

Comparison of modes of prothrombin time reporting in patients with advanced liver disease associated with viral hepatitis.

BACKGROUND: Prothrombin time is widely utilized for evaluation of liver disease severity. However, its standardization of modes of reporting is not established for universal purpose. Variability in thromboplastin reagents leads to large intralaboratory and interlaboratory differences in PT results. OBJECTIVE: The aim of this study was to establish standardization of modes of PT reporting by the interchangeability analysis of prothrombin time in patients with advanced liver disease associated with viral hepatitis measured with different thromboplastin reagents by the use of various methods of expression, i.e. prothrombin time (PTs), prothrombin activity percentage (PTp), prothrombin time ratio (PTr) and International Normalized Ratio (INR). METHODS: we prospectively collected blood samples from 61 patients with advanced liver disease associated with viral hepatitis, control patients were on warfarin (n = 20). PT was measured on a STA-R with six thromboplastin reagents. PT was expressed in PTs, PTr, PTp, and INR. Neoplastin was selected as reference reagent for comparison of methods of reporting. RESULTS: The study revealed the closest agreement of the results in study population between Neoplastin and the other five reagents, and the regression lines of these reagents were close to each other, when the results were expressed in PTp while INR, PTs and PTr is not valid for comparison of patients with liver disease. In patients on oral anticoagulant therapy, only INR standardize PT results. CONCLUSION: we conclude that, in patients with liver disease, only activity percentage expression may provide a common international scale of PT reporting.

[Plasma levels of D-dimer and von Willebrand factor and the therapeutic effect of compound glycyrrhizin in children with cytomegalovirus hepatitis].

OBJECTIVE: To study the significance of plasma D-dimer and von Willebrand factor (vWF) and the therapeutic effect of compound glycyrrhizin in children with cytomegalovirus (CMV) hepatitis. METHODS: Twenty healthy children, 16 asymptomatic cases with CMV infection and 52 cases of CMV hepatitis (21 cholestatic and 31 non-cholestatic) were enrolled. The 52 children with CMV hepatitis were randomly administered with conventional treatment alone or conventional treatment plus compound glycyrrhizin treatment. Plasma D-dimer and vWF levels were measured before and after treatment. RESULTS: Plasma D-dimer and vWF levels in the CMV hepatitis group were markedly higher than those in the healthy control and asymptomatic CMV infection groups (P<0.01). The cholestatic hepatitis group had more increased plasma D-dimer and vWF levels compared with the non-cholestatic hepatitis group (P<0.01). Plasma D-dimer and vWF levels in the CMV hepatitis group were markedly reduced after conventional or compound glycyrrhizin treatment (P<0.01). Compound glycyrrhizin treatment decreased more significantly plasma D-dimer and vWF levels compared with the conventional treatment in children with CMV hepatitis (P<0.01). CONCLUSIONS: The detection of plasma D-dimer and vWF is useful in the early assessment of liver damage in children with CMV hepatitis. Compound glycyrrhizin can decrease obviously plasma D-dimer and vWF levels and might thus provide protective effects against liver damage.

New aspects of the development of liver diseases ­ with special regard to the role of autophagy and microRNA / A májbetegségek kialakulásának új szempontjai - különös tekintettel az autophagiára és a mikro-RNS szerepére.

Autophagy plays an important role in the homeostasis of the cells and it may be upregulated in response to several types of stresses. Deregulation of autophagy is a key mechanism in the pathogenesis and progression of several liver diseases. Deficient autophagy can contribute to liver steatosis, to endoplasmic reticulum stress and to the progression of non-alcoholic fatty liver disease. Chronic alcohol consumption inhibits autophagy. The accumulated mutant protein in the endoplasmic reticulum can be degraded by autophagy in alpha-1-antitrypsin deficiency. Hepatitis C and B viruses may exploit the autophagy pathway to promote the own replication. Hepatitis C virus non-structural protein 5A and 5B have roles in the induction of autophagosomes. MicroRNAs regulate multiple physiological, pathological functions and autophagy through the modulation of gene expression. MicroRNA-122 is involved in HCV replication. In HBV-infected livers, the microRNA pathways related to cell death, DNA damage, recombination and signal transduction were activated. MicroRNA-122 effects multiple important factors which regulate the lipid and carbohydrate metabolisms in human non-alcoholic fatty liver disease. Oxidative stress and free oxygen radicals generation involved in alcoholic liver diseases development are regulated by microRNAs through different pathways. MicroRNAs control autophagy process and autophagy regulates the expression of microRNA-s. The exploration of their interactions contributes to understanding the development of liver diseases. Orv Hetil. 2020; 161(35): 1499-1455.