Acute Exacerbation Of Chronic Hepatitis Research Articles

Versatile performance edges of HBsAg Next assay in diagnosis and therapeutic monitoring of HBV infection.

HBsAg Next assay (HBsAgNx) claims improved detection of HBsAg. The aim was to investigate its performance in ascertaining HBsAg loss, ability to detect HBsAg in various phases of HBV infection, specificity and its amenability to in-house neutralization. Analytical sensitivity was investigated using NIBSC standard (3rd WHO-IS). For clinical performance, out of 91,962 samples tested for HBsAg (Qual-II), 512 samples consisting of 170 cases with evidence of HBsAg loss during treatment (n=116) and without treatment (n=54), acute-hepatitis B (n=90) and acute exacerbation of chronic-hepatitis B (n=41), acute-hepatitis A (n=24) and acute-hepatitis E (n=9) positive, HIV-1 positive (n=20), non-HBV, HAV and HEV related acute-hepatitis (n=81) and HBsAg prozone (n=14) as well as in-house neutralization (n=63) were included. The calculated limit of detection (LOD) was 0.004IU/mL. Of the 170 patients with apparent HBsAg loss, 18/116 (15.5%) among treated and 15/54 (27.7%) with spontaneous clearance were positive in HBsAgNx (p<0.0001). Additionally, it detected HBsAg in 12/95 (12.6%) and 6/34 (17.6%) patients who were HBV DNA negative in treatment experienced and spontaneous clearance groups respectively (p<0.001). The specificity of HBsAgNx was comparable to HBsAg Qual-II. The signal-intensity of HBsAgNx was significantly higher than HBsAg Qual-II across various phases of HBV infection and prozone samples. HBsAgNx significantly enhanced the accuracy of HBsAg detection without compromising the specificity in ascertaining HBsAg loss. The performance was superior in various phases of HBV infection including samples that exhibited prozone effect. Furthermore, it is amenable to cost-effective in-house neutralization to confirm low HBsAg levels.

Therapeutic Effects of Plasmapheresis on Acute Exacerbations of Chronic Hepatitis B Infection.

ObjectiveIn this study, we aimed to demonstrate the effectiveness of plasmapheresis therapy in patients with acute exacerbation of chronic Hepatitis B (CHB) infection.MethodsWe selected 48 patients with acute exacerbation of CHB infection who were treated by plasmapheresis in our intensive care unit between 2009 and 2016. The patients' demographic characteristics and biochemical and hematological parameters, which were recorded before and after plasmapheresis, were assessed, and the effect of plasmapheresis on the course of patients' treatment was examined. The patients were also divided into three groups according to their clinical course (discharged: 24; transplanted: six; exitus: eight). The patients were further divided into four groups and compared based on the underlying causes that led to the exacerbation (spontaneous exacerbation: 25; caused by immunosuppressive drugs: nine; hepatotoxic drugs: six; other agents: eight).ResultsWe observed significant improvements in terms of international normalized ratio (INR), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), total bilirubin, direct bilirubin, blood urea nitrogen (BUN), ammonia, and the Model for End-Stage Liver Disease (MELD) score after plasmapheresis therapy. However, there was no significant improvement in hemoglobin (Hb), white blood cell (WBC) count, platelets, albumin, and lactate values. Also, INR, ALP, and ALT values were found to be significantly correlated with transplants and exitus in patients.ConclusionPlasmapheresis therapy is a reliable treatment method that provides clinical recovery and improvement in laboratory parameters in patients with exacerbation of CHB infection.

Inappropriate cessation of nucleos(t)ide analog associated with reduced liver transplant-free survival in patients with HBV-related acute on chronic liver failure

The inappropriate cessation of nucleos(t)ide analog (NA) therapy may lead to acute exacerbations of chronic hepatitis B virus (HBV) infection, acute-on-chronic liver failure (ACLF), and even death. This study aims to elucidate the association between inappropriate NA cessation and prognosis in patients with HBV-ACLF. A total of 901 patients with ACLF were enrolled and stratified into inappropriate NA cessation and non-NA cessation group. Clinical characteristics and prognosis between the two groups were compared. The association between inappropriate NA cessation and the prognosis of patients with HBV-ACLF was evaluated using Cox proportional hazard models after propensity score matching (PSM). NA cessation was identified in 132 patients (NA cessation group), while 769 patients were triggered by other factors (non-NA cessation group). The 28- and 90-day liver transplant-free survival rates were higher in patients with non-NA cessation than in those with NAs cessation (78.3 % vs. 62.1 %, P < 0.001; 62.8 % vs. 44.7 %, P < 0.001). The need for liver transplantation was significantly higher in the NA cessation group compared with the non-NAs cessation group (21.2 % vs. 7.0 %, P < 0.001). The Kaplan-Meier curve showed that inappropriate NA therapy discontinuation had reduced 28- and 90-day live transplant-free survival compared with other precipitating events prior to PSM (all P < 0.001). After matching, the 28- and 90-day transplantation-free survival was also significantly lower in the NA cessation group vs. the non-NA cessation group (P = 0.012 and P = 0.022). In conclusion, the inappropriate cessation of NA therapy is associated with reduced liver transplant-free survival in patients with HBV-related ACLF.

Early, short-term, low-dose glucocorticoid therapy effectively blocks progression of severe acute exacerbation of chronic hepatitis B to liver failure

ObjectiveTo determine whether early, short-term, low-dose glucocorticoid treatment prevents the progression of severe acute exacerbation of chronic hepatitis B to liver failure. MethodsWe prospectively enrolled 125 patients with severe acute exacerbation of chronic hepatitis B from the Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University between September 2013 and March 2016. The patients were randomized to a hormone group (3-day, low-dose glucocorticoid treatment plus conventional treatment; 63 patients) and a control group (conventional treatment only; 62 patients). We analyzed markers of liver function, complications, mortality rates, and duration and cost of hospitalization. ResultsSerum alanine transaminase levels were significantly lower in the hormone group than in the control group at 3 days (P = 0.009) and 1 week (P = 0.018) after treatment. The decrease in this level from the baseline value on day 3 was greater in the hormone group than in the control group (P = 0.023). The trend of the changes in this level significantly differed between the two groups (P = 0.008). The incidence of liver failure (8.06% vs. 30.16%; P = 0.002) and the duration of hospitalization (23.79 vs. 31.79 days; P = 0.031) were significantly lower in the hormone group than in the control group. ConclusionLow-dose, short-term glucocorticoid treatment early in the course of severe acute exacerbation of chronic hepatitis B along with conventional treatment significantly reduced the risk of progression to liver failure and shortened the duration of hospitalization, without increasing the complication rate.

A Brief Analysis of Mesenchymal Stem Cells as Biological Drugs for the Treatment of Acute-on-Chronic Liver Failure (ACLF): Safety and Potency.

Acute-on-Chronic Liver Failure (ACLF) is characterized by acute exacerbation of chronic hepatitis, organ failure, high mortality, and poor prognosis. At present, the clinical methods of treatment include comprehensive treatment with medicines, artificial liver system, and Orthotopic Liver Transplantation (OLT), and of these, OLT is considered the most effective treatment for ACLF. However, it is difficult for ACLF patients to benefit from OLT due to the shortage of liver donors, high cost, unpredictable postoperative complications, and long-term use of immunosuppressive drugs; therefore, it is important to explore a new treatment option. With the development of stem cell transplantation technology in recent years, several studies have shown that treatment of ACLF with Mesenchymal Stem Cells (MSCs) leads to higher survival rates, and has good tolerance and safety rates, thereby improving the liver function and quality of life of patients; it has also become one of the popular research topics in clinical trials. This paper summarizes the current clinical interventions and treatments of ACLF, including the clinical trials, therapeutic mechanisms, and research progress on MSC application in the treatment of ACLF. The problems and challenges of the development of MSC-based therapy in the future are also discussed.

The dilemma of differentiating between acute hepatitis B and chronic hepatitis B with acute exacerbation: Is quantitative serology the answer?

Background/AimsAcute exacerbations of chronic hepatitis B (CHB-AEs) are common in endemic areas and are often presumed to be acute hepatitis B (AHB) due to their similarities in clinical and serological pictures, presenting a major diagnostic dilemma. This study aimed to identify laboratory markers for differentiating between the two groups, and to establish the cut-off value for significant markers.MethodsA retrospective analysis of records was conducted for patients who presented with clinical features of acute hepatitis along with hepatitis B surface antigen (HBsAg) and IgM antibody to hepatitis B core antigen (IgM anti-HBc) positivity from May 2015 to May 2017. A total of 172 patients were enrolled and grouped as AHB (n=89) and CHB-AE (n=83) based on their history of hepatitis B virus infection and duration of HBsAg persistence. Virological and biochemical parameters were analyzed and compared. Cut-off values, sensitivity, and specificity of the variables were calculated.ResultsThe median value of signal by cut-off (S/Co) ratio for IgM anti-HBc was significantly higher in AHB group (30.44) compared to CHB-AE group (8.63) with a sensitivity and specificity of 97% and 84%, respectively, at a cut-off of 20.5 (P<0.01). The mean international normalized ratio (INR) was significantly greater in CHB-AE (1.88±1.24) group compared to AHB group (1.62±0.17) with a sensitivity and specificity of 57.9% and 45.1%, respectively, at a cut-off value of 1.27.ConclusionsA value of 20.5 S/Co of IgM anti-HBc and 1.27 INR could be helpful in differentiating between AHB and CHB-AE. (Clin Mol Hepatol 2020;26:187-195)

Spontaneous Flares of Chronic Hepatitis B Virus in Hepatitis Be Antigen Negative Carriers Who Subsequently Clear Hepatitis B Surface Antigen.

Acute exacerbations of chronic hepatitis B virus (HBV) infections can occur in HBV-infected, hepatitis e antigen (HBeAg)-negative patients in the absence of recent withdrawal of antiviral or immunosuppressive therapies. Whether these spontaneous "flares" predict subsequent loss of hepatitis B surface antigen (HBsAg) has yet to be determined. To document the percent of patients who experience spontaneous HBV flares and severity of the flares in chronic HBeAg-negative carriers. A retrospective review of an HBV database identified and followed HBeAg-negative patients for biochemical evidence of flares (ALT > 5× normal) and subsequent HBsAg status. Patients that subsequently cleared HBsAg were matched 1:1 with those who remained HBsAg positive. Of 1299 HBeAg-negative patients followed for 10.2 ± 6.1years, 88 (6.8%) developed spontaneous HBV flares. Flares occurred in 14/115 (12.2%) patients who subsequently cleared HBsAg and 4/111 (3.6%) matched patients who remained HBsAg positive (p = 0.025). The severity of flares was similar in the two study cohorts. Following multivariate analyses, only low HBV-DNA levels at baseline identified patients likely to subsequently clear HBsAg. Although more common in patients who subsequently clear HBsAg, spontaneous HBV flares do not predict subsequent HBsAg clearance.

Risk factors for progression to acute-on-chronic liver failure during severe acute exacerbation of chronic hepatitis B virus infection.

BACKGROUNDAcute exacerbation in patients with chronic hepatitis B virus (HBV) infection results in different severities of liver injury. The risk factors related to progression to hepatic decompensation (HD) and acute-on-chronic liver failure (ACLF) in patients with severe acute exacerbation (SAE) of chronic HBV infection remain unknown.AIMTo identify risk factors related to progression to HD and ACLF in compensated patients with SAE of chronic HBV infection.METHODSThe baseline characteristics of 164 patients with SAE of chronic HBV infection were retrospectively reviewed. Independent risk factors associated with progression to HD and ACLF were identified. The predictive values of our previously established prediction model in patients with acute exacerbation (AE model) and the model for end-stage liver disease (MELD) score in predicting the development of ACLF were evaluated.RESULTSAmong 164 patients with SAE, 83 (50.6%) had compensated liver cirrhosis (LC), 43 had progression to HD without ACLF, and 29 had progression to ACLF within 28 d after admission. Independent risk factors associated with progression to HD were LC and low alanine aminotransferase. Independent risk factors for progression to ACLF were LC, high MELD score, high aspartate aminotransferase (AST) levels, and low prothrombin activity (PTA). The area under the receiver operating characteristic of the AE model [0.844, 95% confidence interval (CI): 0.779-0.896] was significantly higher than that of MELD score (0.690, 95%CI: 0.613-0.760, P < 0.05) in predicting the development of ACLF.CONCLUSIONIn patients with SAE of chronic HBV infection, LC is an independent risk factor for progression to both HD and ACLF. High MELD score, high AST, and low PTA are associated with progression to ACLF. The AE model is a better predictor of ACLF development in patients with SAE than MELD score.

THU-057-The homeostasis imbalance of autophagy in acute-on-chronic liver failure patients caused by acute exacerbation of chronic hepatitis B

THU-057-The homeostasis imbalance of autophagy in acute-on-chronic liver failure patients caused by acute exacerbation of chronic hepatitis B

Intrahepatic diffuse periportal enhancement patterns on hepatobiliary phase gadoxetate disodium-enhanced liver MR images: Do they correspond to periportal hyperintense patterns on T2-weighted images?

The purpose of this study was to investigate the findings of diffuse periportal enhancement in the liver on hepatobiliary phase gadoxetate disodium-enhanced magnetic resonance images by comparing with the finding of periportal hyperintensity on T2-weighted images and to reveal their clinical significance.Nineteen consecutive patients with diffuse periportal enhancement on hepatobiliary phase images constituted the study population. The intrahepatic diffuse periportal enhancement finding was assessed on whether it corresponded to periportal hyperintense patterns on T2-weighted images or not in the location, and the cases were classified into 2 groups according to this characteristic. Signal intensities at the periportal areas were also assessed on T1-, T2-, diffusion-weighted and dynamic images. Furthermore, possible associations between these image findings and the final diagnoses were explored.In 7 of the 19 patients, periportal enhancement area corresponded with the periportal hyperintensity area on T2-weighted images. In the remaining 12 patients, the finding of periportal T2-hyperintensity was absent or the periportal enhancement differed from the periportal T2-hyperintensity in the location. Diseases of the former group comprised autoimmune hepatitis, acute exacerbation of chronic hepatitis and acute alcoholic steatohepatitis, and those of the latter group primary sclerosing cholangitis, autoimmune hepatitis-primary biliary cirrhosis overlap syndrome, and liver cirrhosis with miscellaneous etiology.Diffuse periportal enhancement during the hepatobiliary phase did not always correspond to periportal hyperintensity on T2-weighted images. In the classification based on whether enhancement area corresponded or not, each enhancement pattern appeared in different groups of liver diseases. Specifically, the former (corresponding) was associated with active inflammation such as hepatitis and the latter (not corresponding) was predominantly associated with a chronic change such as cirrhosis. Appropriate recognition of these periportal enhancement patterns may contribute to the improved diagnosis of diffuse liver diseases.

Development and validation of a scoring system to predict progression to acute-on-chronic liver failure in patients with acute exacerbation of chronic hepatitis B.

The aim of this study was to develop and validate a scoring system to predict the progression to acute-on-chronic liver failure (ACLF) in patients with acute exacerbation (AE) of chronic hepatitis B (CHB). The baseline characteristics of 474 patients with AE of CHB were retrospectively reviewed; 280 and 194 patients were randomly assigned to the derivation and validation cohorts, respectively. Univariate risk factors associated with ACLF development were entered into a multivariate logistic regression. The score model was established, and its predictive value was evaluated by the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUROC). Hepatitis B virus (HBV) DNA, international normalized ratio (INR) of prothrombin time, and patient age were identified as independent risk factors associated with progressing to ACLF. The prediction model was established as R = -13.323 + 0.553 × log HBV-DNA (copies/mL) + 3.631× INR + 0.053 × age. The AUROCs of our prediction model were higher than those of the Model for End-stage Liver Disease (MELD) and MELD-sodium (Na) for both cohorts. At the cut-off value of -2.43, our prediction model had higher sensitivity (87.5%), specificity (73.6%), positive predictive value (23.0%), positive likelihood ratio (3.30), and lower negative likelihood ratio (0.17) in the validation cohort than those of MELD and MELD-Na. The independent risk factors associated with progressing to ACLF in patients with AE of CHB are HBV-DNA, INR, and age. Our risk prediction model is useful for predicting the development of ACLF.

Clinical application of mesenchymal stem cells in treatment of acute-on-chronic liver failure and related research advances

Acute-on-chronic liver failure is a syndrome characterized by acute exacerbation of chronic hepatitis, organ failure, and high mortality. Clinical treatment of acute-on-chronic liver failure included comprehensive medical treatment, artificial liver support system, and liver transplantation, but such methods have their own shortcomings and patients tend to have a poor prognosis. Mesenchymal stem cells (MSCs), as a new type of cell therapy, have wide sources and are easy to extract and culture. Many studies have shown that MSC treatment not only helps to achieve a high survival rate, but also has good tolerability and safety; therefore, the clinical value of MSCs has become a hot research topic. This article reviews the clinical studies on acute-on-chronic liver failure, related mechanisms, and research advances, in order to provide a reference for future clinical trials and application.

Genome-wide association study identifies HLA-DR variants conferring risk of HBV-related acute-on-chronic liver failure

ObjectiveAcute-on-chronic liver failure (ACLF) is an extreme condition after severe acute exacerbation of chronic hepatitis B; however, the underlying genetic factors involved in its onset and progression are currently unclear.DesignWe...

The Hepatitis B Flare That Wasn't

Background: Acute exacerbation of chronic hepatitis B virus occurs as either a flare of HBV in immune clearance phase or as a reactivation of HBV in patients with inactive or resolved HBV infection. In rare situations, HBV causes systemic autoimmunity that improves with antiviral therapy. However, in certain patients, puritan forms of autoimmune hepatitis develop independent of HBV that requires immunosuppressive therapy. Report: We present the case of a religious nun, who presented with suspected reactivation of HBV leading to jaundice and grade 2 hepatic encephalopathy not responding to 3 weeks of antiviral therapy with fluctuating jaundice and elevated transaminases. A timely liver biopsy based on a strong clinical suspicion led to a final diagnosis. We also briefly discuss the importance of liver biopsy in this scenario. Conclusion: We present the case of a patient who was incidentally detected to have HBV infection during work up of a flare of AIH. Treating physicians must be astute in analysing blood tests in the light of clinical symptoms and signs for comprehensive diagnosis of multiple insults that could occur in the liver.

Prevention of hepatitis B virus-associated liver diseases by antiviral therapy

Hepatitis B virus (HBV) is a major cause of acute and chronic hepatitis, cirrhosis and hepatocellular carcinoma, particularly in Asia-Pacific countries. The major complications in HBV carriers are hepatocellular carcinoma (HCC), liver failure and esophageal varices following the progression to cirrhosis, while some develop HCC without cirrhosis. The progression to liver fibrosis and these other complications could be prevented by treatment with nucleos(t)ide analogues (NUCs); however, NUCs must be continuously administered for a long time. Peginterferon could lead to HBV surface antigen loss. It is difficult to use peginterferon in HBV-infected patients with decompensated cirrhosis. Acute liver failure due to HBV infection and acute exacerbation of chronic hepatitis B could be treated by NUCs. Universal vaccination programs against HBV could prevent new HBV infections globally. Here, we review the currently available treatments for HBV infection.

Acute hepatitis B virus infection or acute exacerbation of chronic hepatitis B infection: the differential serological diagnosis.

Acute exacerbations of chronic hepatitis B are common, and may even be the first presentation of hepatitis B virus (HBV) infection. Sometimes, patients involved in these scenarios may have mistaken diagnosis of acute hepatitis B. The reason for the confusion is that the two forms of infection manifestation resemble remarkably in clinical, biochemical, and serological features, such as apparent rapid onset of severe disease, advanced grades of encephalopathy, high aminotransferases and prolonged international normalized ratios (INRs), as well as positivity for HBsAg and for IgM anti-HBc antibodies and DNA detection. Therefore, these two entities cannot be distinguished easily without historical information of HBV-associated chronic infection or recent HBV exposure, information that is often inaccurate. Considering the different prognoses, treatment strategies, and the epidemiological impact in the public health context, the correct diagnosis is extremely important. Despite the lack of effective and reliable tests to differentiate between acute infection and acute exacerbation of chronic HBV infection, the expression and kinetic evaluation of viral markers present in the circulation of individuals infected, the observation of physical-chemical properties of specific antibodies, and the combination of these findings represent some strategies in serology that could assist in differentiating between the two entities, or at least in the guidance for the correct diagnosis.

Causes of Acute Exacerbation of Chronic Hepatitis B Infection: A Report of Case Series

Causes of Acute Exacerbation of Chronic Hepatitis B Infection: A Report of Case Series

The dysregulation of endoplasmic reticulum stress response in acute-on-chronic liver failure patients caused by acute exacerbation of chronic hepatitis B.

Although endoplasmic reticulum (ER) stress is critical in various liver diseases, its role in acute-on-chronic liver failure (AoCLF) caused by acute exacerbation of chronic hepatitis B (CHB) is still elusive. This study aimed to analyse ER stress responses in the progression of HBV-related AoCLF. Normal liver tissues (n = 10), liver tissues of CHB (n = 12) and HBV-related patients with AoCLF (n = 19) were used. Electron microscopy of the ultrastructure of the ER was carried out on liver specimens. The gene and protein expression levels of ER stress-related genes were measured. We further analysed the correlation between the expression levels of ER stress-related molecules and liver injury. Electron microscopy identified typical features of the ER microstructure in AoCLF subjects. Among the three pathways of unfolded protein responses, the PKR-like ER kinase and inositol-requiring enzyme 1 signalling pathway were activated in CHB subjects and inactivated in AoCLF subjects, while the activating transcription factor 6 signalling pathway was sustained in the activated form during the progression of AoCLF; the expression of glucose-regulated protein (Grp)78 and Grp94 was gradually decreased in AoCLF subjects compared to healthy individuals and CHB subjects, showing a negative correlation with serum ALT, AST and TBIL; moreover, the ER stress-related apoptosis molecules were activated in the progression of acute exacerbation of CHB. The dysregulated ER stress response may play a complicated role in the pathogenesis of AoCLF, and a severe ER stress response may predict the occurrence of AoCLF caused by acute exacerbation of CHB.

Severe endoplasmic reticulum stress response predicts the occurrence of acute-on-chronic liver failure caused by acute exacerbation of chronic hepatitis B

Severe endoplasmic reticulum stress response predicts the occurrence of acute-on-chronic liver failure caused by acute exacerbation of chronic hepatitis B

Prevention of acute exacerbation of chronic hepatitis B infection in cancer patients receiving chemotherapy in a hepatitis B virus endemic area.

Reactivation of hepatitis B viral (HBV) infection in cancer patients undergoing chemotherapy may cause interruption of chemotherapy and lead to liver failure and death. In our institute, a computerized order entry-based alert system was introduced in September 2011 to remind healthcare providers of HBV testing when prescribing chemotherapy. Since August 2012, an order entry-based therapeutic control system has been applied to ensure HBV prophylaxis during chemotherapy. This retrospective cohort study included cancer patients receiving chemotherapy in the Kaohsiung Veterans General Hospital from November 2009 to June 2013. The prechemotherapy HBV screening rate, HBV prophylactic rate, and severe HBV acute exacerbation rate were compared between stages with different order systems. Newly diagnosed cancer patients (n = 2512) were included. The HBV testing rate in the screening reminder stage was higher than that in the educational stage (93.5% versus 40.2%, P < 0.001), whereas the adequate HBV prophylactic rates in the two order entry-based stages were comparable (41.1% versus 39.2%). Patients in the order entry-based therapeutic control stage had a higher HBV screening rate (99.3% versus 40.2%, P < 0.001) and a higher HBV prophylactic rate (95.8% versus 39.2%, P < 0.001) than those in the educational stage. Additionally, the severe HBV acute exacerbation rate in the therapeutic control stage was lower than those in the educational and screening reminder stages (0% versus 1.2% and 1.2%, respectively; both P < 0.01). A computerized order entry-based therapeutic control system can provide excellent prechemotherapy HBV screening for cancer patients undergoing chemotherapy and can effectively prevent severe acute exacerbation of HBV infection in hospitals among HBV endemic areas.