Objective:To investigate the correlation between serum ferritin (SF) level and liver damage in the acute stage of dengue fever.Methods:A retrospective study was conducted to analyze 171 cases diagnosed with dengue fever as dengue fever group and 130 healthy patients as control group in Hangzhou 3A grade hospital from July to December 2017. Clinical data, SF and liver function related indicators were collected from both groups: alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) to analyze the correlation between liver damage and SF in patients with dengue fever.Results:ALT, AST, and SF levels were significantly higher in the dengue fever group than those in the healthy control group ( Z = 11.553, 15.054 and 15.163, P < 0.001). SF levels were higher in the dengue fever combined with liver damage group than those without the liver damage group ( z = 6.930, P < 0.001). However, there was no statistically significant differences in age, gender, peak body temperature, and history of liver disease ( P > 0.05). In addition, Spearman’s correlation analysis showed that SF was positively correlated with ALT, AST, and TBIL ( r = 0.464, 0.531 and 0.315, P < 0.001). Among dengue patients with different SF levels, there were significant difference in ALT, AST levels and incidence of liver damage ( H = 14.240 and 17.584, χ2 = 49.547, P < 0.001). Patients with higher SF levels had higher ALT, AST levels and incidence of liver damage. Binary logistic regression analysis showed that hyperferritinemia (SF≥500 ng/ml) was the risk factor for dengue fever combined with liver damage ( OR = 8.120, P < 0.001). Furthermore, ROC curve analysis showed that the AUC for SF to judge dengue fever combined liver damage was 0.846 (95% CI: 0.785-0.908), and the sensitivity and specificity when the SF cut-off value was 1 506 ng/ml were 74.8% and 83.3%. Conclusion:There is a certain correlation between the SF level and the degree of liver damage in acute stage of dengue fever patients, and hyperferritinemia is a risk factor for dengue fever combined with liver damage.

Immune checkpoint inhibitor (ICI) has been emerged as a major breakthrough in tumor immunotherapy, but its unique mechanism of action has also led to a number of immune-related adverse events (irAE). Type 1 diabetes mellitus (T1DM) is one of the rarest irAEs. This paper reports a case of advanced malignant liver tumor-induced T1DM who received second-line anti-PD-1 therapy and showed initial symptoms of hyperosmolar coma and hyperglycemia. In addition, the relevant literature at home and abroad was collected and reviewed, and the clinical characteristics of T1DM induced by anti-PD-1 therapy were summarized with a view to achieve early detection, diagnosis and treatment.

Objective: We aimed, in our prospective study, to assess the predictive value of serum non-invasive and biochemical markers for clinical diagnosis of significant fibrosis (including early stages). Methods: We measured sH2a levels in serum, comparing with routine liver function markers. We compared blindly pretreatment serum samples from a cohort of hepatitis B patients without non-alcoholic fatty liver disease(NAFLD), which had histological grades of liver fibrosis, with NAFLD individuals and CHB with NAFLD patients. Statistical analysis was by Student′s t test, and receiver-operating characteristic (ROC) curves were drawn. Results: ROC curves showed that serum sH2a had greater diagnostic performance than routine liver function markers compared with histological grades of liver fibrosis(S0, S1-2, S3-4). ROC curves showed that using a sH2a cut-off point of 0.79 was with highest sensitivity as 63% and highest specificity as 80%. And sensitivity as 96.7% and specificity as 75.5% when using a sH2a cut-off point of 0.77. Conclusions sH2a has the potential to be a uniquely sensitive and specific novel marker for liver fibrosis and function.

Objective: Study the clinical significance of HBX gene detection, sequence analysis in peripheral blood mononuclear cell(PBMC) of chronic hepatitis B(CHB) patients with serum HBV DNA negative conversion after treatment by nucleoside analogues(NAs). Methods: Detected and analyzed the HBX gene sequence by real time PCR in PBMC of 60 patients with CHB including some with cirrhosis or hepatocellular carcinoma(HCC), all the serum HBV DNA had turned negative after treatment by NAs, and explore the clinical significance of the HBX gene. Results: HBX genes were detected in 37 cases(61.67%, 37/60). HBX positive rates of PBMC in HCC and cirrhosis patients were higher than that of CHB patients(P=0.000, P=0.010). HBX △120, HBX△129, HBX△131 truncations were detected in two HCC and one CHB cases. Two hotspot mutation including A389T/G391A, T380C had been found, and A389T/G391A double mutation in HCC patients was significantly higher than that in CHB patients(P=0.021). In cirrhosis and HCC patients, T380C mutation rate in HBeAg(-) cases was higher than that in HBeAg(+ ) cases(P=0.035). Conclusions In patients with serum HBV DNA negative conversion after treatment by NAs, PBMC HBX gene positive rates in cirrhosis or HCC cases are higher than that in CHB cases. A389T/G391A double mutation rate in HCC cases is significantly higher than that in CHB cases. In cirrhosis and HCC patients, T380C mutation rate in HBeAg(-) cases is higher than that in HBeAg(+ ) cases.

Objective: To investigate the value of 1H-magnetic resonance spectroscopy (¹H-MRS) in determining the content of liver triglyceride in patients with fatty liver disease (FLD), as well as its influencing factors. Methods: A total of 124 patients with nonalcoholic fatty liver disease (NAFLD), chronic hepatitis B (CHB), or hepatitis B complicated by FLD who underwent liver biopsy in the Affiliated Hospital of Hangzhou Normal University were enrolled, and the clinical data, serological markers, FibroScan results, and ¹H-MRS results were collected. A correlation analysis was performed with the results of liver biopsy as the gold standard, and the influence of factors including hepatitic B virus (HBV) infection and obesity on accuracy was analyzed. A one-way analysis of variance was used for comparison of means between the three groups, and the LSD or SNK test (for homogeneity of variance) or the Tamhane’s or Dunnett’s test (heterogeneity of variance) was used for comparison between any two groups. The t-test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data. The MRS-PDFF receiver operating characteristic (ROC) curve was plotted, the area under the ROC curve (AUC) was calculated, the optimal cut-off points for the diagnosis of NAFLD were estimated, and sensitivity and specificity were calculated. Results: The NAFLD group (42 patients) and the CHB + NAFLD group (40 patients) had a significantly higher proton density fat fraction (PDFF, the content of triglyceride in the liver) than the CHB group (42 patients) (16.84±9.76/9.39 ± 5.50 vs 3.45 ± 1.63, P < 0.001). The results were significantly correlated with the degree of steatosis confirmed by liver biopsy (P < 0.001), but it was not significantly correlated with inflammation or fibrosis grade. The correlation analysis showed that the MRS-PDFF value measured by 1H-MRS was significantly correlated with body mass index (BMI), blood lipids, alkaline phosphatase, and blood glucose, while it was not significantly correlated with age, sex, or the presence or absence of hepatitis B. The ROC curve analysis showed that the AUCs of PDFF measured by 1H-MRS were 0.93, 0.974, and 0.976, respectively, for the diagnosis of steatosis S1(≥5%), S2(≥34%), and S3(≥66%), and the corresponding optimal thresholds were 5.14%, 11.16%, and 16.7%, respectively. Conclusion 1H-MRS has a high diagnostic value in quantitative evaluation of the degree of liver steatosis in patients with FLD and is not affected by the factors such as HBV infection, age, and sex, while it is correlated with BMI and lipid metabolism.

OBJECTIVETo study the clinical significance of hepatitis B surface antigen (HBsAg) levels and HBsAg/hepatitis B virus (HBV) DNA ratio in relation to liver inflammation in HBeAg-positive chronic hepatitis B (CHB).

METHODSOne hundred and fifty-three Chinese patients with chronic HBV infection with HBeAg-positive status were enrolled in the study.Quantitative measurements were made for HBsAg levels by immunoassay (Architect HBsAg QT by Abbott Diagnostic) and HBV DNA by real-time fluorescence quantitative PCR.Levels of liver function markers were measured by standard methods.Liver biopsy specimens were obtained from all patients and used to score the histology (liver inflammation) activity index (HAI) and grade (G) the extent of necroinflammation.Statistical correlation analysis was performed to determine the association of HBsAg titre or HBsAg/HBV DNA ratio with the various parameters of liver injury.

RESULTSHBsAg titre and HBsAg/HBV DNA ratio were significantly correlated (r =0.578, P less than 0.0001).A significant positive correlation (r =0.642, P less than 0.0001) was found between HBsAg titre and HBV DNA load, and a significant negative correlation was found between the HAI and HBsAg (r =-0.389, P less than 0.0001) and HBsAg/HBV DNA ratio (r =-0.307, P=0.000l).A significant positive correlation was found between alanine aminotransferase (ALT) level and the HAI (r =0.480, P less than 0.0001).Patients with G less than 2 necroinflammation had significantly higher HBsAg titre and HBsAg/HBV DNA ratio than patients with G more than or equal to 2 necroinflammation (both P less than 0.01) but similar levels ofHBV DNA.Generation of a receiver operating characteristic curve using G more than or equal to 2 as the positive index provided the following area under the curve (AUC) values:HBsAg titre, 0.700; HBsAg/HBV DNA ratio, 0.672; ALT level, 0.713.When the random chance AUC was 0.5, all levels of AUC were statistically significant (Pless than 0.001).HBsAg titre (sensitivity =76.92%) was more sensitive than ALT level (sensitivity =76.92%), and HBsAg/HBV DNA ratio (specificity =81.33%) was more specific than ALT level (specificity =81.33%).Youden's index for comprehensive evaluation using ALT was higher than those for HBsAg titre or HBsAg/HBV DNA ratio.When HBsAg and ALT were considered in parallel, the sensitivity increased to 94.08% and specificity rose to 85.60%.

CONCLUSIONHBsAg titre, HBsAg/HBV DNA ratio and ALT levels can be used as the index for judging the degree of liver inflammation in HBeAg-positive CHB patients.Higher sensitivity and specificity are attained when HBsAg and ALT are used in series or parallel.

Alanine Transaminase ; Area Under Curve ; Biomarkers ; DNA, Viral ; Hepatitis B e Antigens ; Hepatitis B virus ; Hepatitis B, Chronic ; Humans ; Inflammation ; ROC Curve ; Real-Time Polymerase Chain Reaction ; Serologic Tests

Objective To evulate the effection of HBV on controlled attenuation parameters(CAP)measurement of fatty liver using FibroScan(R).Methods Patients with only non alcohol fatty liverdisease (NAFLD),only chronic hepatitis B(CHB)and CHB combining with NAFLD (CHB + NAFLD) were complete the CAP measurement with FibroScan-502.Results 579 patients with CHB,624 patients with NAFLD and 124 patients with CHB + NAFLD were recruited.CAP values of CHB was 218.90 ±56.40 dB/m,significantly lower than that of NAFLD (290.85 ± 61.46 dB/m,P =0.00) and that of CHB + NAFLD (284.93 ±64.70 dB/m,P =0.00).It is no difference between CAP values of CHB + NAFLD and NAFLD (P =0.55).It is no difference between CAP values of high load of HBVDNA group and the low,high load of HBsAg group and the low,and HBeAg positive group and the negative (P =0.73,0.93,0.55).Conclusion HBV infection does not effect on CAP values of FibroScan(R).

Objective A study on the loci variation characteristics of polymerase on area RT and it's clinical significance while a failure using Adefovir monotherapy antiviral treatment,by analyzing the HBV polymerase reverse transcription (RT) gene sequence of the serum from the chronic hepatitis B patients.Method By using retrospective analysis on the loci variation characteristics,clinical significance of polymerase on area RT and follow-up data from the 44 patients identified genetic mutations through the gene sequence of the HBV polymerase area RT,who had a virus re-activation after getting ADV mono therapy antiviral treatment.Result The 44 patients with Adefovir mono therapy,who had the mutation in area RT with the shortest treatment time eight months,up to five years,an average of(32.2 ± 6.7) months.The level fluctuations of the virus is between 103 copies/ml-108 copies/ml.After virological breakthrough,in these 44 cases,11 as A181T (25.0％),8 as A181V (18.2％),10 as 181T/N236T(22.7％),6 as A181V/N236T (13.6％),9 as N236T(20.4％); 40 cases (90.9％) appeared a biochemistry breakthrough,alanine aminotransferase index fluctuation during 37 IU/L-946 IU/L; Remedial treatment using combination lamivudine 23 cases,6 patients with jointing entecavir,than,1 case for jointing telbivudine,change single drug lamivudine in 4 cases,10 cases of single drug entecavir.Prognosis of severe disease (3 cases),and through the remedial treatment,42 cases was recovered.Conclusion ① RT area A181T (A181T/ N236T) variation accounted about a half of total(47.7％),after the drug resistance of the adefovir,2 years of follow-up,the incidence of liver cancer shows a higher trend than patients without A181T.②Conditions allowed,strong inhibitory effect medicines during tinitial therapy should be preferred,to low the incidence of drug-resistant HBV drug,avoid adverse events.

Objective To compare the efficacy and safety of lamivudine and adefovir combined with entecavir initial monotherapy in the treatment of chronic hepatitis B for 144 weeks.Methods Collected 120 patients with chronic hepatitis initial treatment,which adefovir + lamivudine (LAM + ADV) initial combination group and entecavir (ETV) monotherapy treatment group for 144 weeks,60 cases respectively.Results After treated for 144 weeks LAM + ADV group beneath the 300copy/ml detection rate,HBeAg serum conversion rate and conversion rates were higher than ETV treatment group (P ＜ 0.05),viral breakthrough rate was lower than the ETV group (P ＜ 0.05),HBV-DNA and HBsAg compared with baseline decline in absolute terms and ALT normalization had no statistical difference between the two groups (P ＞ 0.05),serum creatinine in two groups had no statistical difference,serum creatinine increased compared with baseline and differences were not statistically (P ＞ 0.05).Conclusions Lamivudine and adefovir in the initial joint sustained virologic response,reducing HBV-DNA,HBeAg seroconversion and combined response rate was superior to entecavir monotherapy,both are similar in terms of renal safety.