Mild Chronic Hepatitis Research Articles

Chloride intercellular channel 3 suppression‐mediated macrophage polarization: a potential indicator of poor prognosis of hepatitis B virus‐related acute‐on‐chronic liver failure

Patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) are characterized by immune paralysis and susceptibility to infections. Macrophages are important mediators of immune responses can be subclassified into two main phenotypes: classically activated and alternatively activated. However, few studies have investigated changes to macrophage polarization in HBV-related liver diseases. Therefore, we investigated the functional status of monocyte-derived macrophages (MDMs) from patients with mild chronic hepatitis B (n = 226), HBV-related compensated cirrhosis (n = 36), HBV-related decompensated cirrhosis (n = 40), HBV-ACLF (n = 62) and healthy controls (n = 10), as well as Kupffer cells (KCs) from patients with HBV-ACLF (n = 3). We found that during the progression of HBV-related liver diseases, the percentage of CD163+ CD206+ macrophages increased, while the percentage of CD80+ human leukocyte antigen-DR+ macrophages decreased significantly. MDMs and KCs mainly exhibited high CD163+ CD206+ expression in patients with HBV-ACLF, which predicted poor clinical outcome and higher liver transplantation rate. Transcriptome sequencing analysis revealed that chloride intracellular channel-3 (CLIC3) was reduced in patients with HBV-ACLF, indicating a poor prognosis. To further study the effect of CLIC3 on macrophage polarization, human monocytic THP-1 cell-derived macrophages were used. We found that classical and alternative macrophage activation occurred through nuclear factor kappa B (NF-κB) and phosphoinositide 3-kinase/protein kinase B pathways, respectively. CLIC3 suppression inhibited NF-κB activation and promoted the alternative activation. In conclusion, macrophage polarization gradually changed from classically activated to alternatively activated as HBV-related liver diseases progressed. Both CLIC3 suppression and increased alternatively activated macrophage percentage were potential indicators of the poor prognosis of patients with HBV-ACLF.

S3675 Azithromycin-Induced Acute Liver Injury

Introduction: Idiosyncratic drug-induced liver injury (DILI) is a subtype of drug-induced liver injury that is typically variable in presentation and independent of medication dose or duration. A great number of commonly used medications and herbal supplements have been associated with idiosyncratic drug-induced liver injury. DILI is of clinical significance due to the potential for progression to chronic liver disease or acute liver failure, and may be caused by drugs not commonly associated with liver injury. Case Description/Methods: A 60 year old female was admitted after presenting with sore throat, fever, cough, diarrhea, rash and generalized malaise for 4 days prior to admission. Her past medical history was significant for mixed connective tissue disease, rheumatoid arthritis, and a remote history of alcohol abuse. She was on day two of an outpatient Azithromycin course prescribed for community acquired pneumonia. Physical exam showed diffuse, blanching, maculopapular rash along chest wall and dorsum of her upper extremities. Hepatic panel showed AST 64, ALT 42, Total bilirubin 1.1, and alkaline phosphatase of 68. Liver chemistries peaked during admission to AST 607, ALT 936, Total Bilirubin 20.8, ALP 739. MRCP demonstrated gallbladder adenomyomatosis and multiple simple hepatic cysts. Azithromycin was discontinued, and patient was started on N-acetylcysteine infusion. Workup for viral hepatitis was negative, as were EBV, CMV, HSV and HIV serologies. Immunologic workup showed positive ANA with chromatin of 6.5, SMRNP >8, and RNP of 8. AMA and ASMA were < 1:20. Given rising liver chemistries and history of autoimmune disease, a liver biopsy was obtained and revealed mild chronic hepatitis with minimal periportal activity, moderate bile duct injury with marked cholestasis, pseudoxanthomatous degeneration, and mild anisonucleosis consistent with DILI. Liver chemistries began improving on day 11 of admission. Patient’s maculopapular rash was largely cleared prior to discharge. Discussion: Azithromycin is recognized as a common agent in DILI. In this case, Azithromycin was recognized early as a potential cause of the patient’s worsening liver chemistries. Cessation of the offending agent will resolve most cases of DILI. This case demonstrates how a commonly prescribed medication may cause DILI with risk of progression to acute liver failure. Medications not typically associated with hepatic injury should be assessed when considering DILI.Figure 1.: Portal area with reactive atypia in bile ducts consistent with cholestasis. Mixed inflammatory infiltrate surrounding portal area.

Hepatic pathological features in naïve patients with chronic hepatitis C who have developed thyroid disorder.

Knowing the hepatic pathological features encountered in patients with chronic hepatitis C (CHC) and the fact that extrahepatic manifestations occur only in people with certain characteristics of the immune system, we tried to evaluate, qualitatively and semi-quantitatively, the liver pathological aspects encountered in 96 patients with CHC, previously untreated with Interferon (naïve), who showed or did not show signs of thyroid disorder (TD), hospitalized in the 2nd Medical Clinic of the Emergency County Hospital, Craiova, Romania, within a period of five years (2007–2012). Following hormonal, immunological, and thyroid ultrasound investigations, 14 (14.58%) of the 96 patients showed signs of TD. The main clinical forms of TD in the studied patients with CHC were autoimmune thyroiditis and subclinical hypothyroidism. In the patients with CHC with TD, we found mild chronic hepatitis in 14.28% of cases, the appearance of moderate chronic hepatitis was found in 71.42% patients, and the appearance of severe chronic hepatitis was found in 14.28% patients, while in the patients with CHC without TD we found chronic mild hepatitis in 62.19% of cases, the appearance of moderate chronic hepatitis was met in 32.92% patients, and the appearance of severe chronic hepatitis was found in 4.87% of patients. Mild and moderate fibrosis were found only in CHC patients without TD in a percentage of 25.6% and 65.85%, respectively, while severe fibrosis was found at 12.19% among CHC patients without TD and 92.85% among CHC patients with TD. The pathological aspect of liver cirrhosis was found only in those with TD (7.14%). In conclusion, the pathological features which define the liver necroinflammatory process, as encountered at the pathological examination in CHC patients with TD are the same as in any active chronic hepatitis, the differences being represented by the higher percentage of the periportal and the preseptal necrosis (piecemeal necrosis), as well as by the higher score of portal inflammation. In addition, the severe hepatic fibrosis and the histopathological appearance of the liver cirrhosis have only defined the cases of CHC with TD.

Changes in thyroid function in patients with liver failure and their clinical significance: A clinical study of non-thyroidal illness syndrome in patients with liver failure

BackgroundNon-thyroidal illness syndrome (NTIS) develops in a large proportion of critically ill patients and is associated with high risk for death. We aimed to investigate the correlation between NTIS and liver failure, and the short-term mortality of patients with these conditions. MethodsThe clinical data of 87 patients with liver failure were collected retrospectively, 73 of them were randomly selected for an observational study and to establish prognostic models, and 14 for model validation. Another 73 sex- and age-matched patients with mild chronic hepatitis were randomly selected as a control group. Serum free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) were measured. The clinical characteristics of patients with liver failure and NTIS were analyzed. The follow-up of patients lasted for 3 months. Additionally, the values for predicting short-term mortality of model for end-stage liver disease (MELD), Child-Turcotte-Pugh (CTP), chronic liver failure-sequential organ failure assessment (CLIF-SOFA) scores, FT3-MELD model, and FT3 were evaluated. ResultsThe observation group had significantly lower FT3 (2.79 ± 0.71 vs. 4.43 ± 0.75 pmol/L, P < 0.001) and TSH [0.618 (0.186-1.185) vs. 1.800 (1.570-2.590) mIU/L, P < 0.001], and higher FT4 (19.51 ± 6.26 vs. 14.47 ± 2.19 pmol/L, P < 0.001) than the control group. NTIS was diagnosed in 49 of the patients with liver failure (67.12%). In the observation group, patients with NTIS had a higher mortality rate than those without (63.27% vs. 25.00%, P = 0.002). Across the whole cohort, the 3-month mortality was 50.68%. The international normalized ratios (INR) were 2.40 ± 1.41 in survivors and 3.53 ± 1.81 in deaths (P = 0.004), the creatinine (Cr) concentrations were 73.27 ± 36.94 µmol/L and 117.08 ± 87.98 µmol/L (P = 0.008), the FT3 concentrations were 3.13 ± 0.59 pmol/L and 2.47 ± 0.68 pmol/L (P < 0.001), the MELD scores were 22.19 ± 6.64 and 29.57 ± 7.99 (P < 0.001), the CTP scores were 10.67 ± 1.53 and 11.78 ± 1.25 (P = 0.001), and the CLIF-SOFA scores were 8.42 ± 1.68 and 10.16 ± 2.03 (P < 0.001), respectively. FT3 was negatively correlated with MELD score (r = −0.430, P < 0.001). An FT3-MELD model was established by subjecting FT3 concentration and MELD score to logistic regression analysis using the following formula: Logit(P) = −1.337 × FT3+0.114 × MELD+0.880. The area under the receiver operating characteristic (ROC) curve was 0.827 and the optimal cut-off value was 0.4523. The corresponding sensitivity and specificity were 67.6% and 91.7%. The areas under the ROC curve for FT3 concentration, MELD score, CTP score, and CLIF-SOFA score were 0.809, 0.779, 0.699, and 0.737, respectively. ConclusionsPatients with liver failure often develop NTIS. FT3-MELD score perform better than CTP and CLIF-SOFA scores in predicting mortality in patients with liver failure. Thus, the FT3-MELD model could be of great value for the evaluation of the short-term mortality of such patients.

CLIC3 Suppression-Mediated Macrophage Polarization Predicts the Prognosis of HBV-Related Acute-on-Chronic Liver Failure

Background: Patients with HBV-related acute-on-chronic liver failure (HBV-ACLF) are characterized by immune paralysis and susceptibility to infections. Macrophages are reported to polarize to proinflammatory or anti-inflammatory functional states in different morbid states. However, the molecular mechanisms of macrophage polarization in the disease progression of HBV-ACLF have not yet been elucidated. Aims: To investigate the dynamic macrophage polarization changes in different stages of HBV-related liver disease and explore the potential mechanism of macrophage polarization during HBV-ACLF. Methods: The functional status of peripheral blood mononuclear cells derived from macrophages from patients with mild chronic hepatitis B, HBV-related compensated liver cirrhosis, HBV-related decompensated liver cirrhosis, HBV-ACLF and healthy controls was determined. A transcriptome sequencing analysis was performed to investigate the pathways involved in macrophage polarization in HBV-ACLF. The chloride intracellular channel-3 (CLIC3) gene expression was suppressed in the human monocytic THP-1-derived macrophages to study its role in macrophage polarization. Results: Macrophages exhibited different functional statuses in different stages of HBV-related liver disease. Macrophages were mainly exhibiting an anti-inflammatory phenotype and functional characteristics in patients with HBV-ACLF, which was predictive of a poor clinical outcome. The expression of CLIC3, which is involved in immunological diseases, was reduced in HBV-ACLF patients, indicating a poor prognosis. In addition, CLIC3 could regulate proinflammatory macrophage polarization through the NF-κB and Akt pathways. Conclusion: Macrophage polarization changes dynamically in HBV-related liver diseases. CLIC3 suppression-mediated anti-inflammatory macrophage polarization plays an important role in the progression of HBV-ACLF, and CLIC3 expression is a potential indicator of the prognosis of HBV-ACLF patients. Funding Statement: Supported by the Guangzhou City Science and Technology Project (No. 201607010064), the Natural Fund of Guangdong Province (No. 2016A030313237), the National Science and Technology Major Project (2018ZX10302204) and The National Natural Science Foundation of China (81672701). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: This study was approved by the Third Affiliated Hospital of Sun Yat-Sen University Ethics Committee ([2018]02-432-01). If patients were unable to provide consent, informed consent was obtained from the next of kin.

The safety and efficacy of open bedside tracheotomy: A retrospective analysis of 1000 patients.

To evaluate the safety/efficacy of performing open bedside tracheotomy (OBT) in intensive care unit (ICU) patients and identify predictive factors for outcomes. This is a retrospective cohort study. We identified 1000 consecutive patients undergoing OBT at a single university hospital starting from August 1, 2007. Complication rate, 30-day mortality, decannulation rate, time to surgery (TTS) from initial consult, and ICU length of stay were analyzed. Multivariate analysis was performed to identify predictors of complication rate, 30-day mortality, and decannulation rate. Mean TTS was 1.80 days. Major complication rate was 1%. No intraoperative deaths were caused by tracheotomy although two deaths resulted from late tracheotomy-related complications. Thirty-day mortality was 26.6%. The only significant predictor for overall complications was mild chronic hepatitis (OR = 2.355). Predictors for 30-day mortality included platelet count <50,000 (OR = 2.125) and vasopressor use (OR = 3.51). Each additional year of age was associated with decreased decannulation rate (OR = 0.972). This study demonstrates the safety and efficacy of starting an OBT program in a highly comorbid population without strict selection criteria. Safety of OBT was supported by minimal major complication rates and no intraoperative tracheotomy-related deaths in our cohort. These complication rates were comparable to, or lower than, published studies of open and percutaneous techniques. Predictive factors for decannulation, complication, and mortality were identified to help determine which patients would benefit from OBT. 4 Laryngoscope, 130:1263-1269, 2020.

T cell receptor rearrangement excision circles (TRECs) and CD31+ regulatory T cells for assessing recent thymic output in patients with chronic hepatitis B

Objective To evaluate the clinical value of combined detection of T cell receptor rearrangement excision circles (TRECs) and CD31+ regulatory T (Treg) cells for accessing the recent thymic output in patients with chronic hepatitis B. Methods Four groups involving 135 subjects were set up in this study as follows: mild chronic hepatitis B (Mild CHB, n=35), moderate chronic hepatitis B (Moderate CHB, n=35), severe chronic hepatitis B (Severe CHB, n=35) and healthy control (HCs, n=30) groups. CD4+ CD25+ Treg cells in these subjects were sorted out using magnetic cell separation. The ratio of peripheral CD31+ Treg cells to Treg cells in each group was analyzed by flow cytometry. Real-time PCR was performed to detect TRECs in CD4+ CD25+ Treg cells. The percentages of CD3+ , CD4+ and CD8+ T cell subsets were also measured. Results The ratios of CD31+ Treg/Treg cells and the numbers of TRECs in peripheral blood of the Moderate CHB and Severe CHB groups were significantly lower than those of the Mild CHB and HCs groups (P 0.05). No significant difference in the percentages of CD3+ , CD4+ or CD8+ T cell subsets was observed between the four groups (P>0.05). CD31+ Treg/Treg cell ratio had a positive correlation with the number of TRECs (r=0.551, P=0.014). Conclusions Both CD31+ Treg/Treg cell ratio and the number of TRECs were reduced in the peripheral blood of patients with moderate or severe CHB. CD31+ Treg/Treg cell ratio and the number of TRECs were positively correlated and could be used as new indices to evaluate recent thymus output. Key words: Chronic hepatitis B; CD4+ CD25+ regulatory T cell; CD31+ regulatory T cell; T cell receptor rearrangement excision circles

Polarization to Anti-Inflammatory Status of Macrophages Predicts Poor Prognosis of HBV-Related Acute-on-Chronic Liver Failure Patients via Chloride Intercellular Channel 3 Suppression

Background: Patients with HBV-related acute-on-chronic liver failure (HBV-ACLF) are characterized by immune paralysis and susceptibility to sepsis. Macrophages are central mediators of immunoreaction, and reported to polarize to pro-inflammatory or anti-inflammatory functional status in different morbid states. The role of chloride intercellular channel 3 (CLIC3) in immune function is little known. Aims: To investigate the dynamic changes of macrophage polarization in different stages of HBV-related liver diseases, explore the role of CLIC3 in macrophage polarization and its mechanism. Methods: Peripheral blood mononuclear cells derived macrophages from healthy controls (n=10), mild chronic hepatitis B patients (n=226), HBV-related compensated cirrhosis patients (n=36), HBV-related decompensated liver cirrhosis patients (n=40) and HBV-related acute-on-chronic failure patients (n=62) were collected to analyze the macrophage polarization using flowcytometry. Transcriptome sequencing analysis was performed for better understanding the roles of macrophages in HBV-ACLF. Virto cell experiments were used to investigate the role of CLIC3 in macrophage polarization. Results: The anti-inflammatory, CD163+CD206+ macrophages, significantly increased in HBV-ACLF patients, which predicted a poor clinical outcome. Transcriptome sequencing analysis indicated, CLIC3 was declined in HBV-ACLF patients, negatively related with V-set and immunoglobulin domain containing 4, involving in immunological disease, organismal injury and abnormalities. Virto cell experiments showed CLIC3 regulated macrophage polarization through NF-kB and AKT pathway. And CLIC3 suppression in macrophages promoted anti-inflammatory polarization and aggravated the impair of hepatocytes. Conclusion: Polarization to anti-inflammatory status of macrophages predicts poor prognosis of HBV-ACLF patients. And CLIC3 plays a vital role in macrophage polarization in HBV-ACLF progression. Funding Statement: This study was supported by the Guangzhou city science and technology project (No. 201607010064), and the Natural Fund of Guangdong Province (No. 2016A030313237 and 2015A030313172). Third Affiliated Hospital of Sun Yat-Sen University Five-Fiver Project (No. k00005). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: This study was approved by the Third Affiliated Hospital of Sun Yat-Sen University ethics committee ([2018]02-432-01). If patients were unable to provide consent, informed consent was obtained by the next of kin.

THU-200-The Real-Eorld Israeli experience of treating mild and severe chronic hepatitis C patients with elbasvir/grazoprevir: A large multi-center cohort study

THU-200-The Real-Eorld Israeli experience of treating mild and severe chronic hepatitis C patients with elbasvir/grazoprevir: A large multi-center cohort study

Simplified follow-up of patients with mild chronic hepatitis C in areas with limited access to antiviral therapy

Background and aimsIn some areas of the world, antiviral therapy for chronic hepatitis C (CHC) is not available for all patients. The optimal interval for liver stiffness measures (LSM) and noninvasive scores to assess fibrosis progression has not been studied. We evaluated the usefulness of consecutive LSM, APRI, FIB-4 and Forns scores to predict disease progression. MethodsPatients with CHC and at least two annual LSM within 3 years were followed for a minimum of 5 years. Noninvasive scores were assessed. Evolution of LSM and scores were expressed as change/year (Delta). Results623 non-cirrhotic patients were included. Median baseline LSM was 6.6 kPa (IQR 5.4–8.4). During a median follow-up of 6 years, 61(9.7%) patients developed cirrhosis. Baseline LSM ≥ F2 and Forns ≥ 6.9 were the main predictors of cirrhosis (C-index 0.97). The addition of Delta variables did not improve its prediction. In patients with mild fibrosis (F0-1), progression to ≥F2 occurred in 80 (23%) within the first 3 years. Baseline BMI ≥ 24 kg/m2 and LSM ≥ 5.9 kPa were associated to progression. ConclusionsBaseline LSM and Forns are highly predictive of cirrhosis development. In patients with mild CHC, BMI < 24 and LSM < 5.9, the likelihood of progression is very low, allowing for a significant spacing of noninvasive assessments over time.

Control of progression towards liver fibrosis and hepatocellular carcinoma by SOCS3 polymorphisms in chronic HCV-infected patients

Background & aimsChronic Hepatitis C is one of the most important risk factors of liver cirrhosis and hepatocellular carcinoma. Before reaching these ultimate steps, insulin resistance triggered by hepatitis C virus infection is known to participate in the progression of liver disease. The present study aims to investigate the influence of two functional polymorphisms on SOCS3 mRNA expression and on the outcomes of CHC progression in a North African context. Patients & methodsIn this case-control study, 601 Moroccan subjects composed of 200 healthy controls, 101 resolvers and 300 patients with persistent HCV infection including 95 mild chronic hepatitis, 131 Advanced Liver Diseases and 74 HCC were enrolled. They were genotyped for the 4874 A/G (rs4969170) and A + 930– > G (rs4969168) SOCS3 variants using TaqMan SNPs assays. SOCS3 mRNA expression was assessed using Real Time PCR technique. ResultsLogistic regression analysis showed that variation at rs4969168 was associated with spontaneous clearance of HCV (P < 0.05). In addition, minor allele frequencies were significantly higher in AdLD patients when compared to the mCHC group both for rs4969168 (P = 7.0 E-04) and rs4969170 (P = 4.0 E-05). A significant association between haplotype and liver disease progression was also found. Moreover, SOCS3 mRNA was significantly more expressed in peripheral leukocytes from patients with HCC than in those from mCHC. Finally, rs4969170 was significantly associated with LDL-lipoprotein (P = 0.04), total cholesterol (P = 5.0 E-04), and higher fasting glucose levels (P = 0.005) in patients with persistent HCV infection. ConclusionsOur results underline the importance of the functional SOCS3 polymorphisms in the modulation of CHC progression and suggest their contribution to HCC development by affecting its mRNA expression and perturbing key metabolic parameters.

Diagnostic Value of Hepatic Vein Ultrasound in Early Detection of Liver Cirrhosis.

Background: Cirrhosis is a common disease that destroys liver cells, and it has various etiologies. The early diagnosis of cirrhosis can be effective in improving prognosis. Considering the availability and affordability of ultrasound devices throughout the world, in this study we evaluated the diagnostic value of hepatic vein ultrasound examination in the early detection of liver cirrhosis. Materials and Methods: In this study, 45 patients referred to the radiology department of Ghaem Hospital for liver biopsy were evaluated for changes in the hepatic veins under ultrasound with a transducer of 5-7MHz. One piece of the hepatic vein was selected for ultrasound, and the wall of hepatic veins was examined for straightness and uniformity of echogenicity. Subsequently, patients underwent biopsy by ultrasound guide. Of all the study subjects, eight patients presented mild chronic hepatitis without fibrosis, four patients were diagnosed with fatty liver, and 33 patients had severe cirrhosis or chronic hepatitis with fibrosis. Results: Our results showed that hepatitis patients with or without fibrosis had irregular and wavy hepatic vein wall (impairment in straightness) with non-uniform echo (impairment in uniformity of echogenicity). While patients without hepatitis and cirrhosis, but diagnosed with fatty liver, had a smooth and regular hepatic vein wall with a uniform echo. Conclusion: The present study showed that hepatic vein examination in terms of echogenicity and straightness could be used to diagnose hepatitis, its severity as well as its course towards fibrosis and cirrhosis.

Diagnostic Value of Hepatic Vein Ultrasound in Early Detection of Liver Cirrhosis

Background: Cirrhosis is a common disease that destroys liver cells, and it has various etiologies. The early diagnosis of cirrhosis can be effective in improving prognosis.Considering the availability and affordability of ultrasound devices throughout the world, in this study we evaluated the diagnostic value of hepatic vein ultrasound examination in the early detection of liver cirrhosis.Materials and Methods: In this study, 45 patients referred to the radiology department of Ghaem Hospital for liver biopsy were evaluated for changes in the hepatic veins under ultrasound with a transducer of 5-7MHz. One piece of the hepatic vein was selected for ultrasound, and the wall of hepatic veins was examined for straightness and uniformity of echogenicity. Subsequently, patients underwent biopsy by ultrasound guide. Of all the study subjects, eight patients presented mild chronic hepatitis without fibrosis, four patients were diagnosed with fatty liver, and 33 patients had severe cirrhosis or chronic hepatitis with fibrosis.Results: Our results showed that hepatitis patients with or without fibrosis had irregular and wavy hepatic vein wall (impairment in straightness) with non-uniform echo (impairment in uniformity of echogenicity). While patients without hepatitis and cirrhosis, but diagnosed with fatty liver, had a smooth and regular hepatic vein wall with a uniform echo.Conclusion: The present study showed that hepatic vein examination in terms of echogenicity and straightness could be used to diagnose hepatitis, its severity as well as its course towards fibrosis and cirrhosis. [GMJ.2018;7:e1140]

Diagnostic Value of Hepatic Vein Ultrasound in Early Detection of Liver Cirrhosis

Background: Cirrhosis is a common disease that destroys liver cells, and it has various etiologies. The early diagnosis of cirrhosis can be effective in improving prognosis.&#x0D; Considering the availability and affordability of ultrasound devices throughout the world, in this study we evaluated the diagnostic value of hepatic vein ultrasound examination in the early detection of liver cirrhosis.&#x0D; Materials and Methods: In this study, 45 patients referred to the radiology department of Ghaem Hospital for liver biopsy were evaluated for changes in the hepatic veins under ultrasound with a transducer of 5-7MHz. One piece of the hepatic vein was selected for ultrasound, and the wall of hepatic veins was examined for straightness and uniformity of echogenicity. Subsequently, patients underwent biopsy by ultrasound guide. Of all the study subjects, eight patients presented mild chronic hepatitis without fibrosis, four patients were diagnosed with fatty liver, and 33 patients had severe cirrhosis or chronic hepatitis with fibrosis.&#x0D; Results: Our results showed that hepatitis patients with or without fibrosis had irregular and wavy hepatic vein wall (impairment in straightness) with non-uniform echo (impairment in uniformity of echogenicity). While patients without hepatitis and cirrhosis, but diagnosed with fatty liver, had a smooth and regular hepatic vein wall with a uniform echo.&#x0D; Conclusion: The present study showed that hepatic vein examination in terms of echogenicity and straightness could be used to diagnose hepatitis, its severity as well as its course towards fibrosis and cirrhosis. [GMJ.2018;7:e1140]

FRI-393 - A cost-effectiveness analysis of shortened direct-acting antiviral treatment for mild chronic hepatitis C virus

FRI-393 - A cost-effectiveness analysis of shortened direct-acting antiviral treatment for mild chronic hepatitis C virus

The Research of Mild, Moderate, and Severe Chronic Hepatitis B Symptoms Group of Distribution Based on Association Rules

The Research of Mild, Moderate, and Severe Chronic Hepatitis B Symptoms Group of Distribution Based on Association Rules

Expression and clinical significance of serum interleukin-33 in patients with chronic severe hepatitis B

Objective To explore the changes of interleukin-33 in serum of patients with chronic severe hepatitis B. Methods 25 patients with mild chronic hepatitis B(MCHB group) and 25 patients with severe chronic hepatitis B(SCHB group) were collected. 18 healthy people were collected as control(HC group). ELISA method was used to detect IL-33 level in peripheral blood. Results The IL-33 levels in MCHB and SCHB group were(11.7±6.9)ng/L and (16.5±9.1)ng/L, respectively, which were significantly higher than(5.1±2.9)ng/L in HC group(t=4.037, 5.434, P=0.000, 0.000). The IL-33 level in MCHB group was lower than that in SCHB group(t=2.108, P=0.040). The IL-33 level was positively correlated with ALT, AST and HBV DNA(r=0.526, 0.568, 0.285, P=0.000, 0.000, 0.045). Conclusion IL-33 is involved in the pathogenesis of hepatitis B. IL-33 plays an important role in HBV-relate injury. Key words: Hepatitis B; Interleukin

Clinical and virological implications of A1846T and C1913A/G mutations of hepatitis B virus genome in severe liver diseases

Objective: Mutations occurring within different genes of hepatitis B virus (HBV) genome may have different clinical implications. This study aimed to observe the clinical and virological implications of the A1846T and C1913A/G mutations of HBV genome in the development and treatment outcome of severe liver diseases, which has not been previously determined.Materials and methods: A total of 438 cases of patients with liver diseases were retrospectively reviewed, including 146 with mild chronic hepatitis B infection (CHB-M), 146 with severe chronic hepatitis B infection (CHB-S), and 146 with acute-on-chronic liver failure (ACLF). Partial or full-length HBV genome was directly sequenced. Replicons containing A1846T, C1913A or other mutant sequences, or the wild-type counterparts were constructed respectively, and then transfected into HepG2 cells for phenotype analysis.Results: There was significant difference in the detection rates of A1846T (30.82%, 40.41% and 55.48%, respectively) and C1913A/G (15.52%, 28.77%, and 35.62%, respectively) among patients with CHB-M, those with CHB-S, and those with ACLF (p < .01). A1846T was significantly associated with the mortality of ACLF patients within six months after the disease onset (OR 1.704, p = .041). In vitro experiment revealed that A1846T mutant resulted in 3.20-fold and 1.85-fold increase of replication capacity and promoter activity, respectively compared with wild type counterpart (p < .001), while C1913A led to a significant decrease of core protein expression (p < .05).Conclusion: Occurrence of A1846T and C1913A is positively associated with clinical presentations of severe liver disease. A1846T mutation is significantly associated with poor prognosis of ACLF.

Endoplasmic reticulum stress induced LOX-1+ CD15+ polymorphonuclear myeloid-derived suppressor cells in hepatocellular carcinoma.

A recent study indicated that Lectin-type oxidized LDL receptor-1 (LOX-1) was a distinct surface marker for human polymorphisms myeloid-derived suppressor cells (PMN-MDSC). The present study was aimed to investigate the existence LOX-1 PMN-MDSC in hepatocellular carcinoma (HCC) patients. One hundred and twenty-seven HCC patients, 10 patients with mild active chronic hepatitis B, 10 liver cirrhosis due to hepatitis B, 10 liver dysplastic node with hepatitis B and 50 health control were included. LOX-1+ CD15+ PMN-MDSC were significantly elevated in HCC patients compared with healthy control and patients with benign diseases. LOX-1+ CD15+ PMN-MDSC in circulation were positively associated with those in HCC tissues. LOX-1+ CD15+ PMN-MDSCs significantly reduced proliferation and IFN-γ production of T cells with a dosage dependent manner with LOX-1- CD15+ PMNs reached negative results. The suppression on T cell proliferation and IFN-γ production was reversed by ROS inhibitor and Arginase inhibitor. ROS level and activity of arginase of LOX-1+ CD15+ PMN were higher in LOX-1+ CD15+ PMN-MDSCs than LOX-1- CD15+ PMNs, as well as the expression of the NADPH oxidase NOX2 and arginase I. RNA sequence revealed that LOX-1+ CD15+ PMN-MDSCs displayed significantly higher expression of spliced X-box -binding protein 1 (sXBP1), an endoplasmic reticulum (ER) stress marker. ER stress inducer induced LOX-1 expression and suppressive function for CD15+ PMN from health donor. For HCC patients, LOX-1+ CD15+ PMN-MDSCs were positively related to overall survival. Above all, LOX-1+ CD15+ PMN-MDSC were elevated in HCC patients and suppressed T cell proliferation through ROS/Arg I pathway induced by ER stress. They presented positive association with the prognosis of HCC patients.

Antiviral treatment of mild chronic hepatitis B patients with tuberculosis: A controlled study

Antiviral treatment of mild chronic hepatitis B patients with tuberculosis: A controlled study