OBJECTIVES: Long-term hepatitis B virus (HBV) infection can cause recurrent inflammation in the liver, and then develop into liver fibrosis, cirrhosis, and liver cancer. The hepatic pathological change is one of the important criteria for guiding antiviral therapy in patients with chronic hepatitis B (CHB). Due to the limitations of liver biopsy, it is necessary to find valuable non-invasive indicators to evaluate the hepatic pathological changes in CHB patients and guide the antiviral therapy. This study aims to analyze the clinical characteristics of different pathological changes in CHB patients, and to explore the factors influnencing the degree of liver inflammation and fibrosis in CHB patients with normal alanine aminotransferase (ALT). METHODS: This retrospective study was conducted on 310 CHB patients. Liver biopsy was performed in all these patients. The clinical data of the patients were collected. The liver biopsy pathological results were used as the gold standard to analyze the relationship between clinical indicators and liver pathological changes. Then CHB patients with normal ALT were screened, and the independent factors influencing the degree of liver inflammation and fibrosis were explored. RESULTS: Among the 310 patients with CHB, there were 249 (80.3%) patients with significant liver inflammation [liver inflammation grade (G) ≥2] and 119 (38.4%) patients with significant liver fibrosis [liver fibrosis stage (S) ≥2]. The results of univariate analysis of total samples showed that the ALT, γ-glutamyl transferase, alkaline phosphatase, and HBV DNA were related to the significant liver pathological changes. Among the 132 CHB patients with normal ALT, the patients with liver pathology G/S≥2, G≥2, and S≥2 were 80.3% (106/132), 68.2% (90/132), and 43.2% (57/132), respectively. The results showed that the independent influencing factor of significant liver inflammation was HBV DNA>2 000 U/mL (OR=3.592, 95% CI 1.534 to 8.409), and the independent influencing factors of significant liver fibrosis were elevated alkaline phosphatase level (OR=1.022, 95% CI 1.002 to 1.043), decreased platelet count (OR=0.990, 95% CI 0.982 to 0.998), and positive in hepatitis B e antigen (HBeAg) (OR=14.845, 95% CI 4.898 to 44.995). According to the multivariate analysis, a diagnostic model for significant liver fibrosis in CHB patients with normal ALT was established, and the area under the receiver operating characteristic curve was 0.844 (95% CI 0.779 to 0.910). CONCLUSIONS The liver pathological changes should be evaluated in combination with different clinical indicators. A considerable number of CHB patients with normal ALT still have significant liver pathological changes, which need to be identified and treated with antiviral therapy in time. Among them, HBV DNA>2 000 U/mL suggests the significant liver inflammation, and the diagnostic model for significant liver fibrosis based on alkaline phosphatase, platelet count, and HBeAg can help to evaluate the degree of liver fibrosis.
Humans ; Hepatitis B, Chronic/complications* ; Hepatitis B e Antigens/therapeutic use* ; Alkaline Phosphatase ; DNA, Viral ; Retrospective Studies ; Fibrosis ; Hepatitis B virus/genetics* ; Liver Cirrhosis/etiology* ; Inflammation/drug therapy* ; Antiviral Agents/therapeutic use* ; Alanine Transaminase

Objective: To analyze the occurrence of recompensation conditions in patients with chronic hepatitis B virus-related decompensated cirrhosis after entecavir antiviral therapy. Methods: Patients with hepatitis B virus-related decompensated cirrhosis with ascites as the initial manifestation were prospectively enrolled. Patients who received entecavir treatment for 120 weeks and were followed up every 24 weeks (including clinical endpoint events, hematological and imaging indicators, and others) were calculated for recompensation rates according to the Baveno VII criteria. Measurement data were compared using the Student t-test or Mann-Whitney U test between groups. Categorical data were compared by the χ (2) test or Fisher's exact probability method between groups. Results: 283 of the 320 enrolled cases completed the 120-week follow-up, and 92.2% (261/283) achieved a virological response (HBV DNA 20 IU/ml). Child-Pugh and MELD scores were significantly improved after treatment (8.33 ± 1.90 vs. 5.77 ± 1.37, t = 12.70, P < 0.001; 13.37 ± 4.44 vs. 10.45 ± 4.58, t = 5.963, P < 0.001). During the 120-week follow-up period, 14 cases died, two received liver transplants, 19 developed hepatocellular cancer, 11 developed gastroesophageal variceal bleeding, and four developed hepatic encephalopathy. 60.4% (171/283) (no decompensation events occurred for 12 months) and 56.2% (159/283) (no decompensation events occurred for 12 months and improved liver function) of the patients had achieved clinical recompensation within 120 weeks. Patients with baseline MELD scores > 15 after active antiviral therapy achieved higher recompensation than patients with baseline MELD scores ≤15 [50/74 (67.6%) vs. 109/209 (52.2%), χ (2) = 5.275, P = 0.029]. Conclusion: Antiviral therapy can significantly improve the prognosis of patients with hepatitis B virus-related decompensated cirrhosis. The majority of patients (56.2%) had achieved recompensation. Patients with severe disease did not have a lower probability of recompensation at baseline than other patients.
Humans ; Hepatitis B virus/genetics* ; Hepatitis B, Chronic/drug therapy* ; Antiviral Agents/adverse effects* ; Esophageal and Gastric Varices/complications* ; Liver Cirrhosis/complications* ; Treatment Outcome ; Gastrointestinal Hemorrhage/complications* ; Hepatitis B/drug therapy*

Objective: To explore the efficacy of entecavir antiviral therapy on the degree of liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) combined with chronic hepatitis B (CHB) in Tibet region. Methods: HBeAg-positive CHB patients who were treated with entecavir in the outpatient and inpatient Department of Infectious Diseases of the Tibet Autonomous Region people's Hospital between January 2018 to December 2019 were retrospectively analyzed. Among the 140 subjects with CHB, 95 cases were CHB alone, and the other 45 cases were diagnosed as CHB combined with NAFLD by ultrasound. All patients were given entecavir 0.5 mg orally once daily on an empty stomach for 48 weeks. HBeAg negative conversion rate, blood glucose, blood lipid, liver function and the degree of liver fibrosis were compared between the two groups at the 12th, 24th and 48th weeks of treatment to evaluate the virological response. SPSS 19.0 statistical software was used to process the data. Measurement data were expressed as mean ± standard deviation (x¯±s). Descriptive statistical analysis was used for t-test, and the categorical variables were expressed as percentage (%) and χ² test. A p-value < 0.05 was considered as statistically significant. Results: After 48 weeks of treatment, the HBeAg and HBV DNA negative conversion rate were significantly better in patients with CHB alone (group B) than CHB combined with NAFLD (group A), that is to say, HBeAg negative conversion rate in group A and B patients were 28.90% and 40%, respectively, and group B was better than group A. HBV DNA negative conversion rate was significantly elevated in group B (83.2%) than group A (64.4%), with statistical significance (P<0.05), and the difference between the both groups was statistically significant. Alanine aminotransferase level was significantly decreased in patients with CHB alone than patients with CHB combined with NAFLD. Aspartate aminotransferase/platelet ratio index was significantly decreased after treatment than before treatment in both group of patients, and the depletion was more pronounced in CHB alone group. Liver stiffness values were significantly decreased in patients with CHB combined with NAFLD than CHB alone group. Moreover, liver stiffness values was higher in group A than group B before treatment under the influence of fat attenuation factors, and the differences before treatment and after treatment were 3.50±4.66 and 2.05±2.53, respectively; however, group B was not affected by fat attenuation factors, so LSM value reduction in group A was more obvious, and the differences were statistically significant. There was no statistically significant difference in blood glucose and blood lipids levels before and after treatment between the two groups. Conclusion: NAFLD has a certain effect on antiviral therapy and liver fibrosis in patients with CHB, i.e., the effect of antiviral therapy in patients with CHB alone is better than patients with CHB combined with NAFLD. Patients with CHB combined with NAFLD when treated with antiviral therapy had a significantly greater degree of liver stiffness reduction than patients with CHB alone. Therefore, it is necessary to actively intervene the risk factors associated with NAFLD according to the actual situation of different individuals to improve clinical efficacy of antiviral therapy.
Antiviral Agents/therapeutic use* ; DNA, Viral ; Guanine/analogs & derivatives* ; Hepatitis B e Antigens ; Hepatitis B, Chronic/drug therapy* ; Humans ; Liver Cirrhosis/complications* ; Non-alcoholic Fatty Liver Disease/drug therapy* ; Retrospective Studies ; Tibet ; Treatment Outcome

Objective: To evaluate the real-world efficacy and safety of sofosbuvir and velpatasvir (SOF/VEL) tablets in the treatment of Chinese patients with chronic HCV infection. Methods: An open-label, single-center, prospective clinical study was conducted in a county in northern China. A total of 299 cases were enrolled. Of these, 161 cases with chronic hepatitis C and 73 cases with compensated cirrhosis received SOF/VEL for 12 weeks. 65 cases with decompensated cirrhosis received SOF/VEL combined with ribavirin for 12 weeks (22 cases) or SOF/VEL for 24 weeks (43 cases). Virological indicators, liver and renal function indexes, and liver stiffness measurement were detected at baseline, the fourth week of treatment, the end of treatment, and the 12-weeks of follow-up. Adverse reactions and laboratory abnormalities were observed during the course of treatment . The primary endpoint was undetectable rate of HCV RNA (SVR12) at 12 weeks of follow-up with the use of modified intention-to-treat (mITT) approach. Measurement data between two groups were compared using t-test. One Way ANOVA was used for comparison between multiple groups. Enumeration data were analyzed by chi-square test or Fisher's exact test. Results: 291 cases had completed treatment. HCV RNA was undetectable after 12 weeks of follow-up, and the SVR12 rate was 97.3% (95% confidence interval: 95.4%-99.3%). Among them, 97.4% of genotype 1b, 96.4% of genotype 2a, and 100% of those with undetected genotype achieved SVR12. The SVR12 rates in patients with chronic hepatitis C, compensated and decompensated liver cirrhosis were 98.1%, 98.6% and 93.8%, respectively. An improvement in alanine aminotransferase, aspartate aminotransferase and other liver biochemical indicators accompanied with virological clearance and reduced liver stiffness measurement was observed in patients with compensated cirrhosis, with statistically significant difference. There was no significant abnormality in renal function before and after treatment. The most common adverse reactions were fatigue, headache, epigastric discomfort and mild diarrhea. The overall adverse reactions were mild. One patient died of decompensated liver cirrhosis combined with massive upper gastrointestinal bleeding, which was unrelated to antiviral treatment. Four patients discontinued treatment prematurely due to adverse events. Relapse was occurred in four cases, and drug-resistance related mutations were detected in three cases. Conclusion: Sofosbuvir and velpatasvir tablets in Chinese HCV-infected patients with different genotypes, different clinical stages or previously treated with pegylated interferon combined with ribavirin resulted in higher SVR12, indicating that the treatment safety profile is good.
Antiviral Agents/therapeutic use* ; Carbamates ; Drug Therapy, Combination ; Genotype ; Hepacivirus/genetics* ; Hepatitis C/drug therapy* ; Hepatitis C, Chronic/drug therapy* ; Heterocyclic Compounds, 4 or More Rings ; Humans ; Liver Cirrhosis/complications* ; Prospective Studies ; RNA ; Ribavirin/therapeutic use* ; Sofosbuvir/adverse effects* ; Sustained Virologic Response ; Treatment Outcome

Aim: To identify the key risk factors of intrauterine hepatitis B virus transmission (HBV) and its effect on the placenta and fetus. Methods: 425 infants born to hepatitis B surface antigen (HBsAg)-positive pregnant women who received combined immunization with hepatitis B immunoglobulin and hepatitis B vaccine between 2009 to 2015 were prospectively enrolled in this study. The intrauterine transmission situation was assessed by dynamic monitoring of infants HBV DNA load and quantitative HBsAg. Univariate and multivariate regression analysis was used to determine the high risk factors for intrauterine transmission. Stratified analysis was used to determine the relationship between maternal HBV DNA load and fetal distress. Transmission electron microscopy was used to observe HBV Effects on placental tissue. Results: HBV intrauterine infection rate was 2.6% (11/425). Multivariate analysis result showed that the maternal HBV DNA load was an independent risk factor for intrauterine infection among infants (P=0.011). Intrauterine infection and distress rate was significantly higher in infants with with maternal HBV DNA>10⁶ IU/ml than those with HBV DNA <10⁶ IU/ml (12.2% vs. 1.8%; χ²=11.275, P=0.006), and (24.4% vs. 16.0%, χ²=3.993, P=0.046). Transmission electron microscopy showed that mitochondrial edema, endoplasmic reticulum expansion and thicker basement membrane were apparent when the maternal HBV DNA>10⁶ IU/ml than that of maternal HBV DNA<10⁶ IU/ml (960 nm vs. 214 nm, Z=-2.782, P=0.005) in the placental tissue. Conclusion: Maternal HBV DNA>10⁶ IU/ml is associated not only with intrauterine infection, but also with increased incidence of intrauterine distress and placental sub-microstructural changes, providing strong clinical and histological evidence for pregnancy avoidance and treatment in this population.
DNA, Viral ; Female ; Fetal Distress/drug therapy* ; Hepatitis B/prevention & control* ; Hepatitis B Surface Antigens ; Hepatitis B Vaccines/therapeutic use* ; Hepatitis B virus/genetics* ; Humans ; Immunoglobulins/therapeutic use* ; Infant ; Infectious Disease Transmission, Vertical/prevention & control* ; Placenta ; Pregnancy ; Pregnancy Complications, Infectious

We described two patients who were successfully resuscitated from out-of-hospital cardiac arrest. Their ECGs showed ST elevations in V1 and aVR, as well as diffuse ST depression. Their ST elevation in V1 was noted to be greater than in aVR. While one patient was found to have an occlusion of the right ventricular (RV) branch of the right coronary artery, the other was found to have an occlusion of a proximal non-dominant right coronary artery supplying the RV branch. Successful primary percutaneous coronary intervention was performed for each patient with angioplasty and implantation of a drug-eluting stent. Both patients made good physical and neurological recovery.
Adult ; Angioplasty ; Angioplasty, Balloon, Coronary ; Cardiopulmonary Resuscitation ; Coronary Vessels ; physiopathology ; Defibrillators ; Drug-Eluting Stents ; Electrocardiography ; Heart Ventricles ; physiopathology ; Hepatitis B ; complications ; Humans ; Male ; Myocardial Infarction ; diagnosis ; physiopathology ; Out-of-Hospital Cardiac Arrest ; therapy ; Percutaneous Coronary Intervention ; Resuscitation ; Singapore

Adult ; Cytomegalovirus ; Cytomegalovirus Infections ; complications ; Drug Hypersensitivity Syndrome ; complications ; virology ; Eosinophilia ; complications ; virology ; Fatal Outcome ; Female ; Gout ; drug therapy ; Hepatitis ; complications ; virology ; Humans ; Liver ; physiopathology ; Viremia

BACKGROUNDThe long-term outcomes of patients with autoimmune hepatitis (AIH) given the immunosuppressive treatment are considered to be preferable. However, little is known about the response of AIH patients with cirrhosis to immunosuppressive treatment. We assessed the effects of immunosuppressive therapy in Chinese AIH patients with cirrhosis from a tertiary hospital.

METHODSPatients with a clinical diagnosis of AIH January 2000 and December 2015 were retrospectively reviewed. Two-hundred and fourteen patients who were followed up and satisfied the simplified AIH criteria were included in the study. Among these patients, 87 presented with cirrhosis when initially diagnosed for AIH. Immunosuppressive treatments were employed in 57 AIH patients who did not present with cirrhosis and 39 patients who presented with cirrhosis. Initial responses to immunosuppressive treatment of patients with and without cirrhosis were analyzed. Independent risk factors were assessed for predicting the prognosis of patients. The t-test and Cox regression statistical analysis were used.

RESULTSIn total, 96 AIH patients including 39 with cirrhosis and 57 without cirrhosis underwent immunosuppressive therapy. The overall complete remission after initial immunosuppressive treatment was achieved in 81/96 patients (84.4%), whereas 9/96 (9.4%) achieved incomplete response, and 6/96 (6.3%) occurred treatment failure. Compared to noncirrhotic patients, patients who presented with cirrhosis responded to treatment to a comparable extent regarding complete response (noncirrhosis 50/57 [87.7%] vs. cirrhosis 31/39 [79.5%], P = 0.275), incomplete remission (noncirrhosis 4/57 [7.0%] vs. cirrhosis 5/39 [12.8%], P = 0.338), and treatment failure (noncirrhosis 3/57 [5.3%] vs. cirrhosis 3/39 [7.7%], P = 0.629). Importantly, the remission rate was comparable (54/57 [94.7%] and 36/39 [92.3%], P = 0.629) for noncirrhotic and cirrhotic patients after immunosuppressive therapy. Compared to patients who maintained remission (n = 19) after drug withdrawal, patients who experienced relapse (n = 17) had significantly higher levels of serum immunoglobulin G at entry (15.0 ± 6.5 g/L vs. 22.3 ± 5.8 g/L, t = 2.814, P = 0.004). Moreover, cirrhosis at presentation significantly increased the risk of disease exacerbation (hazard ratio [HR]: 4.603; P = 0.002). The treatment of immunosuppressant (HR: 0.058; P = 0.005) and the level of aspartate aminotransferase at presentation (HR: 1.002; P = 0.017) also increased the risk of disease progression.

CONCLUSIONSThe efficacy of initial immunosuppressive treatment in AIH patients with cirrhosis is comparable to that in those without cirrhosis. Cirrhotic patients not treated by immunosuppressants have poor long-term outcomes.

Aged ; Asian Continental Ancestry Group ; Azathioprine ; therapeutic use ; Female ; Hepatitis, Autoimmune ; complications ; drug therapy ; Humans ; Immunosuppressive Agents ; therapeutic use ; Liver Cirrhosis ; drug therapy ; etiology ; Male ; Middle Aged ; Multivariate Analysis ; Prednisolone ; therapeutic use ; Proportional Hazards Models ; Retrospective Studies ; Treatment Outcome

A high maternal viral load is the most important factor affecting immunoprophylaxis against mother-infant transmission of HBV. The application of antiviral drugs in pregnant women with a high serum HBV DNA level (>10(6)~10(7) IU/ml) during the second and third trimesters can reduce the prenatal serum HBV DNA level and significantly increase the success rate of blocking mother-infant transmission in neonates. This article interprets the contents related to antiviral therapy for pregnant women carrying HBV with the purpose of blocking mother-infant transmission of HBV in the guidelines published by Asian Pacific Association for the Study of the Liver, European Association for the Study of the Liver, National Institute for Health and Care Excellence, Korean Association for the Study of the Liver, and World Health Organization.
Antiviral Agents ; therapeutic use ; DNA, Viral ; blood ; Female ; Hepatitis B ; drug therapy ; prevention & control ; Humans ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; prevention & control ; Nucleosides ; therapeutic use ; Nucleotides ; therapeutic use ; Practice Guidelines as Topic ; Pregnancy ; Pregnancy Complications, Infectious ; virology ; Viral Load

OBJECTIVETo evaluate the clinical efficacy and safety of Yinchen Zhufu Decoction (, YCZFD) in the treatment of acute-on-chronic liver failure caused by hepatitis B virus (HBV-ACLF) with cold pattern in Chinese medicine (CM).

METHODSThis is a multi-center randomized controlled trial of integrative treatment of CM and Western medicine (WM) for the management of HBV-ACLF patients. A total of 200 HBV-ACLF patients with cold pattern were equally randomly assigned to receive YCZFD and WM (integrative treatment) or WM conventional therapy alone respectively for 4 weeks. The primary end point was the mortality for HBV-ACLF patients. Secondary outcome measures included Model for End-Stage Liver disease (MELD) score, liver biochemical function, coagulation function and complications. Adverse events during treatment were reported.

RESULTSThe mortality was decreased 14.28% in the integrative treatment group compared with WM group (χ(2) =6.156, P=0.013). The integrative treatment was found to signifificantly improve the MELD score (t=2.353, P=0.020). There were statistically signifificant differences in aspartate transaminase, total bilirubin, indirect bilirubin, direct bilirubin and prothrombin time between the two groups (P<0.05 or P<0.01). The complications of ascites (χ(2)=9.033, P=0.003) and spontaneous bacteria peritonitis (χ(2)=4.194, P=0.041) were improved signifificantly in the integrative treatment group. No serious adverse event was reported.

CONCLUSIONSThe integrative treatment of CM and WM was effective and safe for HBV-ACLF patients with cold pattern in CM. The Chinese therapeutic principle "treating cold pattern with hot herbs" remains valuable to the clinical therapy. (Trial registration No. ChiCTR-TRC-10000766).

Acute-On-Chronic Liver Failure ; complications ; drug therapy ; mortality ; virology ; Adult ; Ascites ; complications ; Demography ; Drugs, Chinese Herbal ; adverse effects ; pharmacology ; therapeutic use ; Electrolytes ; Female ; Hepatitis B ; complications ; drug therapy ; mortality ; physiopathology ; Hepatitis B virus ; physiology ; Humans ; Integrative Medicine ; Liver ; drug effects ; pathology ; physiopathology ; virology ; Liver Function Tests ; Male ; Peritonitis ; complications ; Time Factors ; Treatment Outcome