[Significance of histological assessment in drug-induced liver injury].

Liver histological assessment is of great clinical significance for the diagnosis, classification, and prognosis prediction of drug-induced liver injury (DILI). Liver histological evaluation can effectively supplement RUCAM. The clinical phenotypes of DILI are complex and diverse, including acute, chronic and severe hepatic injury. DILI has multiple insult-targets, including hepatocytes, cholangiocytes, and vascular endothelial cells and others. The pathological damage patterns are similar to many types of non-DILI liver diseases, therefore making differential diagnosis difficult. New anti-tumor drugs such as immune checkpoints inhibitors and targeted therapy are widely used in clinical antineoplastic practice, thus the growing incidence of related liver injury occurs. Liver histological examination can effectively assess the pathological phenotypes and severity of DILI, so as to guide treatment. In uncommon conditions such as special types of DILI (such as hepatic vascular disease), DILI with other competitive etiology overlapping, chronic DILI, and DILI induced liver failure, liver histological assessment can provide strong support for identifying the cause, rational treatment, and prognosis. Currently, the histological evaluation system for drug-induced liver injury seems to be a lack of consensus, and the diagnosis of DILI is short of highly specific and sensitive serological markers. All in all, liver histological assessment plays a crucial role in the diagnosis and differential diagnosis of DILI.

[Intrahepatic and extrahepatic clinical manifestations and treatment progress for hepatitis type E].

Hepatitis type E virus (HEV) is one of the main causes of acute hepatitis globally and has thus gained attention as a public health issue. The diverse clinical manifestations of hepatitis type E are typically acute and self-limiting with mild symptoms, but populations with underlying liver disease or immunocompromised patients can have severe and chronic symptoms. Severity and chronicity can arise and manifest as fulminant hepatitis, chronic hepatitis, or even hepatic failure. HEV infection-induced hepatic failure (acute-on-chronic liver failure), based on the different backgrounds of chronic liver disease, is a clinical phenotype of severe HEV infection that requires attention. In addition, HEV infection can exhibit extrahepatic clinical manifestations of multi-system and organ involvement like neurological diseases (Guillain-Barré syndrome), renal diseases (membranous/membranous proliferative glomerulonephritis, cryoglobulinemia), and blood diseases (thrombocytopenia). At home or abroad, there are no antiviral drugs approved, particularly for HE treatment. Since most acute HE can resolve spontaneously, no special treatment is required clinically. However, in patients with severe or chronic HE, ribavirin (RBV) monotherapy and/or pegylated interferon-combination therapy have achieved certain antiviral effects. Combined small-molecule drugs and RBV have been attempted to treat HEV, but high-level evidence-based treatment is still lacking. Thus, new, highly effective anti-HEV drugs are clinical priorities to address these concerns. Severe and chronic HEV infections' clinical phenotype, early detection, mechanism, intervention, and outcome need additional study.

[Effect of the nomenclature of non-alcoholic fatty liver disease on diagnosis and treatment of fatty liver disease concomitant with other liver diseases].

Fatty liver disease (FLD) is one of the major causes of chronic liver disease worldwide. With the increasing incidence of obesity and metabolic syndrome worldwide, FLD concomitant with other liver diseases is becoming more common, and multiple etiological overlap is associated with poor disease prognosis. Therefore, FLD concomitant with other liver diseases is a clinical concerning issue. Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of disease continuum from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH), and relative end stage liver disease, excluding other factors that may lead to fatty liver disease such as excessive alcohol consumption et. al. Following the nomenclature of NAFLD with metabolic associated fatty liver disease (MAFLD), an international panel of experts proposed a new name in June 2023 as Metabolic dysfunction - associated steatotic liver disease (MASLD), replacing the word "fatty" with "steatotic," The effect of lipid toxicity on FLD progression was highlighted. Compared with the concept of MAFLD, the disease spectrum of MASLD is broader, and the etiology and mechanism are more clear. The nomenclature of FLD brings some influence to the diagnosis and treatment of chronic liver diseases concomitant with FLD, including chronic hepatitis B, alcoholic fatty liver disease and genetic metabolic diseases. This article reviews the influence of renaming FLD on the diagnosis and treatment of FLD concomitant with other etiologies caused liver diseases.

[Analysis of clinical characteristics and risk factors of hepatic fibrosis in children with chronic hepatitis B combined with metabolic-related fatty liver disease].

Objective: To compare the clinical and pathological features of children with chronic viral hepatitis B combined with metabolic-associated fatty liver disease (CHB-MAFLD) and chronic viral hepatitis B alone (CHB alone), and to further explore the effect of MAFLD on the progression of hepatic fibrosis in CHB. Methods: 701 initially treated CHB children confirmed by liver biopsy admitted to the Fifth Medical Center of the PLA General Hospital from January 2010 to December 2021 were collected continuously. They were divided into CHB-MAFLD and CHB-alone groups according to whether they were combined with MAFLD. A retrospective case-control study was conducted. CHB-MAFLD was used as the case group, and 1:2 propensity score matching was performed with the CHB alone group according to age and gender, including 56 cases in the CHB-MAFLD group and 112 cases in the CHB alone group. The body mass index (BMI), metabolic complications, laboratory indicators, and pathological characteristics of liver tissue were compared between the two groups. The related factors affecting liver disease progression in CHB were analyzed by a binary logistic regression model. The measurement data between groups were compared using the t-test and rank sum test. The χ (2) test was used for the comparison of categorical data between groups. Results: Alanine aminotransferase (ALT, P = 0.032) and aspartate aminotransferase (AST, P = 0.003) levels were lower in the CHB-MAFLD group than those in the CHB alone group, while BMI (P < 0.001), triglyceride (TG, P < 0.001), total cholesterol (P = 0.016) and the incidence of metabolic syndrome (P < 0.001) were higher in the CHB alone group. There were no statistically significant differences in HBsAg quantification or HBV DNA load between the two groups (P > 0.05). Histologically, the proportion of significant liver fibrosis (S2-S4) was higher in the CHB-MAFLD group than that in the CHB alone group (67.9% vs. 49.1%, χ (2) = 5.311, P = 0.021). Multivariate regression results showed that BMI (OR = 1.258, 95% CI: 1.145 ~ 1.381, P = 0.001) and TG (OR = 12.334, 95% CI: 3.973 ~ 38.286, P < 0.001) were the risk factors for hepatic steatosis occurrence in children with CHB. MAFLD (OR = 4.104, 95% CI: 1.703 ~ 9.889, P = 0.002), liver inflammation (OR = 3.557, 95% CI: 1.553 ~ 8.144, P = 0.003), and γ-glutamyl transferase (OR = 1.019, 95% CI: 1.001 to 1.038, P = 0.038) were independent risk factors for significant hepatic fibrosis in children with CH. Conclusion: MAFLD occurrence is related to metabolic factors in children with CHB. Additionally, the combination of MAFLD may promote liver fibrosis progression in CHB patients.

[A preliminary discussion on carnosine dipeptidase 1 as a potential novel biomarker for the diagnostic and prognostic evaluation of hepatocellular carcinoma].

Objective: To explore carnosine dipeptidase 1 (CNDP1) potential value as a diagnostic and prognostic evaluator of hepatocellular carcinoma (HCC). Methods: A gene chip and GO analysis were used to screen the candidate marker molecule CNDP1 for HCC diagnosis. 125 cases of HCC cancer tissues, 85 cases of paracancerous tissues, 125 cases of liver cirrhosis tissues, 32 cases of relatively normal liver tissue at the extreme end of hepatic hemangioma, 66 cases from serum samples of HCC, and 82 cases of non-HCC were collected. Real-time fluorescent quantitative PCR, immunohistochemistry, western blot, and enzyme-linked immunosorbent assay were used to detect the differences in mRNA and protein expression levels of CNDP1 in HCC tissue and serum. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival were used to analyze and evaluate the value of CNDP1 in the diagnosis and prognosis of HCC patients. Results: The expression level of CNDP1 was significantly reduced in HCC cancer tissues. The levels of CNDP1 were significantly lower in the cancer tissues and serum of HCC patients than those in liver cirrhosis patients and normal controls. ROC curve analysis showed that the area under the curve of serum CNDP1 in the diagnosis of HCC patients was 0.753 2 (95% CI 0.676-0.830 5), and the sensitivity and specificity were 78.79% and 62.5%, respectively. The combined detection of serum CNDP1 and serum alpha-fetoprotein (AFP) significantly improved the diagnostic accuracy (AUC = 0.820 6, 95% CI 0.753 5-0.887 8). The diagnostic sensitivity and specificity of serum CNDP1 for AFP-negative HCC patients were 73.68% and 68.75% (AUC = 0.793 1, 95% CI 0.708 8-0.877 4), respectively. In addition, the level of serum CNDP1 distinguished small liver cancer (tumor diameter < 3 cm) (AUC = 0.757 1, 95% CI 0.637 4-0.876 8). Kaplan-Meier survival analysis showed that CNDP1 was associated with a poor prognosis in HCC patients. Conclusion: CNDP1 may be a potential biomarker for the diagnostic and prognostic evaluation of HCC, and it has certain complementarity with serum AFP.

Mating-Type Genes Control Sexual Reproduction, Conidial Germination, and Virulence in Cochliobolus lunatus.

Cochliobolus lunatus (anamorph: Curvularia lunata) is a major pathogenic fungus that causes the Curvularia leaf spot of maize. ClMAT1-1-1 and ClMAT1-2-1, the C. lunatus orthologs of C. heterostrophus ChMAT1-1-1 and ChMAT1-2-1, were investigated in the present study to uncover their functions in C. lunatus. Southern blot analysis showed that these mating-type MAT genes exist in the C. lunatus genome as a single copy. ClMAT1-1-1 and ClMAT1-2-1 were knocked out and complemented to generate ΔClmat1-1-1 and ΔClmat1-2-1 and ΔClmat1-1-1-C and ΔClmat1-2-1-C, respectively. The mutant strains had defective sexual development and failed to produce pseudothecia. There were no significant differences in growth rate or conidia production between the mutant and wild-type strains. However, the aerial mycelia and mycelial dry weight of ΔClmat1-1-1 and ΔClmat1-2-1 were lower than those of wild type, suggesting that MAT genes affect asexual development. ClMAT genes were involved in the responses to cell wall integrity and osmotic adaptation. ΔClmat1-2-1 had a lower conidial germination rate than the wild-type strain CX-3. The virulence of ΔClmat1-2-1 and ΔClmat1-1-1 was also reduced compared with the wild-type. Complementary strains could restore all the phenotypes.

[Natural history and disease progression of chronic hepatitis B virus infection].

OBJECTIVE: To better understand and revise the natural history and disease progression of chronic hepatitis B virus (HBV) infection through analysis of a single-center large-scale cohort of indivi-duals with chronic HBV infection. METHODS: Patients with chronic HBV infection who had undergone liver biopsy in the Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital from January 2014 to October 2020 were retrospectively recruited. Based on patient's hepatitis B e antigen (HBeAg) states and pathologic diagnosis, they were categorized into four disease progression statuses (or phases according to the old-terminology in the updated guidelines of chronic hepatitis B (CHB), such as European Association for the Study of the Liver (EASL) 2017, Clinical Practice Guidelines on the Management of Hepatitis B Virus Infection: HBeAg-positive chronic HBV infection (immune tolerance), HBeAg-positive CHB (immune active HBeAg positive), HBeAg-negative chronic HBV infection (inactive carrier), and HBeAg-negative CHB (immune reactive HBeAg negative). Then the demographic, laboratory tests and liver histological results of the patients in different disease progression stages were compared. Age differences between the two groups were evaluated using Mann-Whitney U test. RESULTS: A total of 760 eligible patients with a median age of 29 (interquartile range: 16-39) years were enrolled. Among them, 197 were underage individuals (age < 18 years) and 563 were adults; and 456 were males and 304 females. According to the pathological diagnosis, the patients were classified, and in each of the above four natural disease phases there were 173, 329, 95, and 163 individuals, respectively. Further comparison of the ages of the patients of the four disease progression statuses revealed that patients of HBeAg-negative CHB had a median age at 37 years, which was reasonably higher than those with HBeAg-positive CHB in immune active phase (37 vs. 24 years, P < 0.001), but was relatively younger than those with HBeAg-negative chronic HBV infection (37 vs. 39 years, P= 0.240). CONCLUSION: According to this study, it could be speculated that HBeAg-negative CHB patients probably not all reactivate from individuals of HBeAg-negative chronic HBV infection. Instead, certain HBeAg-negative CHB patients may also come from HBeAg-positive CHB patients who have undergone HBeAg clearance or seroconversion and still remain in the immune active state.

[The companion diagnostics of targeted therapy and immunotherapy for hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) has a high incidence and low five-year survival rate in China. There is a lack of effective therapeutic approaches available for unresectable patients with advanced HCC. Recently, the development of targeted and immunotherapy agents and their application in the therapy of various solid tumors have brought new options and benefits to patients with advanced HCC. Companion diagnostics (CDx) emerged with the development of targeted agents, and its roles in selecting eligible patients for specific targeted/immunotherapy agents and improving prognosis are getting more prominent. This article focuses on the CDx technologies and applications related to HCC targeting and immunotherapy, in order to provide inspiration for the precise diagnosis and treatment of HCC.

Accuracy of Nolla Method for Age Estimation of Northern Chinese Han Children.

ABSTRACT: Objective To study the accuracy of Nolla method for age estimation of Northern Chinese Han children aged between 5.00 and 14.99 years based on original transformation tables and multiple regression model. Methods A total of 2 000 orthopantomographs （OPGs） were collected from the Hospital of Stomatology, Xi'an Jiaotong University, including 1 000 males and 1 000 females. Development stage of 7 left mandibular permanent teeth （except third molars） was assessed based on Nolla method, then age estimation was conducted through transformation tables and multiple regression model, respectively. Firstly, the development stage results of 7 permanent teeth were added up and the estimated age was obtained through the original transformation tables. Secondly, 80% of the samples （80 males and 80 females in each age group） were randomly selected from 2 000 OPGs as the train set. The chronological age of the selected patients was taken as the dependent variable, while gender and the development stage results of 7 permanent teeth were taken as the independent variable to establish multiple regression model. The remaining 20% of the samples were substituted into the model as the test set, to verify the accuracy of age estimation by multiple regression model. Results Mean chronological ages of males and females were 10.03±0.09 years and 10.01±0.09 years, respectively. The age estimated by original transformation tables showed an overestimation for males （0.18 years on average） and an underestimation for females （0.02 years on average）, with mean absolute error （MAE） of 0.94 years and 0.97 years, respectively. While the results by multiple regression model showed that males were overestimated by 0.06 years on average and females were underestimated by 0.02 years on average. The MAE was 0.66 years and 0.77 years, respectively. Conclusion The Nolla method is suitable for age estimation of Northern Chinese Han children. Compared with the original transformation tables method, the multiple regression model is more accurate for age estimation.

[Research progress on application of laboratory indicators detection of COVID-19].

The outbreak of corona virus disease-19 (corona virus disease-19, COVID-19) caused a huge human disaster from the end of 2019 which is caused by SARS-CoV-2. It will cause damage to multiple organs function in the disease occurrence and development, viral nucleic acid, antibody and serological biochemical immune indicators are mainly indicators of clinical laboratory. The results of these indicators can reflect the organs function of patients and further guide clinical treatment. In this paper, the detection and clinical application of COVID-19 laboratory indicators are reviewed.

[Diagnostic value of liver stiffness measurement for the evaluation of liver fibrosis in nonalcoholic fatty liver].

Objective: To investigate the clinical and diagnostic value of liver stiffness measurement (LSM) for the evaluation and comparison of aspartate aminotransferas/platelet ratio index (APRI), fibrosis 4 indexes (FIB-4) and NAFLD fibrosis score (NFS) with liver fibrosis staging in relation to nonalcoholic fatty liver disease (NAFLD). Methods: 103 cases with NAFLD who met the inclusion criteria confirmed by liver biopsy were selected for retrospective analysis. The results of serological tests and LSM were recorded. The APRI, FIB-4 and NFS were calculated. The accuracy and applicability of four liver fibrosis models in the diagnosis of liver fibrosis in NAFLD patients were compared with the receiver operating characteristic curve (ROC), and the diagnostic cut-off value of LSM was established. Results: Varying degrees of LSM, APRI, FIB-4 and NFS had shown positive correlations with the increasing degree of liver fibrosis. Among them, LSM was positively correlated with the degree of liver fibrosis, and the correlation coefficient was r = 0.727, P < 0.0001. Consistent with this, the area under the receiver operating characteristic curve, sensitivity, and specificity of LSM diagnosis of liver fibrosis in different stages was significantly higher than APRI, FIB-4 and NFS. Area under receiver operating characteristic curve of LSM was 0.862 and 0.928 for significant liver fibrosis (f ≥ 2), and advanced liver fibrosis (f ≥ 3). Conclusion: LSM has a good diagnostic exclusion value for NAFLD-induced fibrosis, and its sensitivity and specificity are better than APRI, FIB-4 and NFS.

[Establishment and preliminary application of serum Golgi protein 73 based noninvasive diagnostic model for compensated stage hepatitis B cirrhosis].

Objective: To establish and evaluate diagnostic efficacy and applicability of serum Golgi protein (GP) 73 based non-invasive diagnostic model with other conventional serological indicators for compensated stage hepatitis B cirrhosis. Methods: 666 cases with chronic hepatitis B (CHB) who had visited to the Fifth Medical Center of People's Liberation Army General Hospital from January 2010 to December 2017 were selected as the study subjects, and were classified according to compensated stage cirrhosis into clinical and pathological diagnosis group based on whether or not the liver histological examination was performed. A diagnostic model of compensated stage hepatitis B cirrhosis in the clinical diagnosis group was established. The current clinically used diagnostic model of liver cirrhosis, aspartate aminotransferase/platelet ratio index (APRI), fibrosis index (FIB)-4 and liver stiffness measurement (LSM) were compared. Eventually, the diagnostic model was verified step by step by pathological diagnosis group. Results: The area under the receiver operating characteristic curve (AUC) of GP73 and APRI, FIB-4, and LSM for cirrhosis patients in the clinical diagnosis group were 0.842, 0.857, 0.864, and 0.832, respectively. The diagnostic efficiency of the four indicators were of similar (P value > 0.05). A diagnostic model of compensated stage hepatitis B cirrhosis (GAPA) using logistic regression analysis was established: LogitP = 1/ [1 + exp (1.614-0.054 × GP73-0.045 × Age + 0.030 × PLT-0.015 × ALP)]. The AUC of the model was as high as 0.940 and the optimal cut-off value were 0.41. The corresponding diagnostic sensitivity and specificity were 0.92 and 0.82, respectively. The diagnostic efficiency was better than that of APRI, FIB-4, LSM and GP73 alone (P < 0.05). The AUC of GAPA was 0.877 in the pathological diagnosis group, which was similar to the diagnostic efficacy of LSM (0.891) and FIB-4 (0.847) (P > 0.1), but still superior to that of APRI (0.811) and GP73 alone (0.780) (P < 0.001). Conclusion: GAPA, a diagnostic model for compensated stage hepatitis B cirrhosis established in this study, has a good diagnostic efficacy in both the clinical and pathological diagnosis group, and has certain auxiliary diagnostic value in the areas where resources are relatively scarce or where LSM has not been developed.

[Research Progress and Prospect of Facial Reconstruction in Forensic Science].

ABSTRACT: Facial reconstruction is a way to recover facial morphology by restoring soft tissues based on unidentified skulls using the knowledge of anatomy, anthropology, aesthetics, and computer science. It is applied in forensic science, oral plastic surgery and archeology, and especially plays an important role in the identification of the origin of the unknown corpses in forensic science. Facial reconstruction is the supplementary means of identification when other approaches （such as DNA comparison, imaging matching, dental records comparison, etc.） cannot identify individual identity. Facial soft tissue thickness （FSTT） is the basis of facial reconstruction and with the development of imaging and computer science, the techniques for measuring FSTT are improving rapidly and many related researches have appeared. This paper summarizes the application of facial reconstruction in forensic science, the accuracy of different methods and the research progress of this field to provide reference to this field.

Temperature-dependent optical constants of highly transparent solids determined by the combined double optical pathlength transmission-ellipsometry method.

The optical constants of five highly transparent substrates (polycrystalline BaF2, CaF2, MgF2, ZnSe, and ZnS) were experimentally determined based on a combined technique using both the double optical pathlength transmission method and the ellipsometry method within temperature range 20°C-350°C in the ultraviolet-infrared region (0.2-20 µm). The results show that the refractive index spectra of polycrystalline BaF2, CaF2, and MgF2 are similar, but differ from that of polycrystalline ZnSe and ZnS. The thermo-optic coefficient of these highly transparent substrates increases with increasing temperature. The absorption indices show a significant temperature-dependent behavior, which increases with increasing temperature from 20°C to 350°C over the transparent region. For the sake of application, the fitted formulas of the refractive index of the five highly transparent substrates as a function of wavelength and temperature are presented.

Long non-coding RNA PICART1 suppresses proliferation and promotes apoptosis in lung cancer cells by inhibiting JAK2/STAT3 signaling.

Lung cancer remains the most common cause of tumor-related death worldwide. Recent studies have revealed that long non-coding RNAs (lncRNAs) are involved in the development of various cancers, including lung cancer. This study aimed to investigate the effect and the molecular basis of lncRNA PICART1 on lung cancer. We first assessed the PICART1 expression in lung cancer in vitro and vivo by qRT-PCR. Then the expression of PICART1 in SPC-A-1 and NCI-H1975 cell lines was inhibited and overexpressed by transient transfections. Thereafter, cell viability, cell cycle, migration and apoptosis were respectively measured by MTT, Transwell and flow cytometry assay. Furthermore, qRT-PCR and western blot analysis were mainly performed to assess the expression levels of apoptosis- and migration-related proteins and JAK2/STAT3 pathway proteins. Tumor formation was measured by xenograft tumor model assay in vivo. PICART1 expression was down-regulated in human lung cancer tissues and cell lines. Knockdown of PICART1 increased cell viability of lung cancer cell lines. However, PICART1 overexpression inhibited cell cycle progression and promoted apoptosis in SPC-A-1 and NCI-H1975 cell lines. PICART1 overexpression also inhibited migration, as evidenced by up-regulation of E-cadherin, and down-regulation of Twist1, MMP2 and MMP9. Furthermore, we found PICART1 inhibition may regulate cell apoptosis and migration through activating JAK2/STAT3 pathway. In vivo experiments revealed that PICART1 knockdown significantly promoted tumor formation. This study demonstrates that PICART1 overexpression represents an anti-growth and anti-metastasis role in lung cancer cells. Additionally, PICART1 acts as a tumor suppressor may be via regulation of JAK2/STAT3 pathway.

[Histological evaluation of liver in chronic hepatitis C after direct-acting antiviral agents treatment].

The histological assessment of liver biopsy in chronic hepatitis C patients after direct-acting antiviral agents(DAAs) treatment plays a key role in evaluation of response to therapy. Liver necro-inflammation gradually subsides in patients who achieved sustained virologic response after DAAs treatment, thus the histological assessment focus on evaluating remission of liver fibrosis and other lesions. However, the evaluation of liver inflammation and fibrosis are usually inconsistent when the histological scoring systems are recommended by the clinical practice guidelines and applied in chronic hepatitis C patients who achieved viral clearance after DAAs therapy. Therefore, an immunohistochemical staining of α-smooth muscle actin is recommended to evaluate the activity of liver fibrosis. The gold standard for determining the complete clearance of virus after DAAs treatment is detection of HCV RNA in liver tissues. RNAscope technology and RT-PCR technique and other technologies are the powerful means of detecting HCV RNA in liver tissues. The implementation of non-invasive diagnostic techniques in clinic for the screening of liver fibrosis after DAAs therapy is problematic.

[The clinical practice of improvement the "Volume and Quality" of functional liver in autologous liver transplantation for the patients with alveolar echinococcosis].

Objective: To investigate the clinical significance of accurate assessment of "volume and quality" of functional liver in Autologous liver transplantation (ALT) in the treatment of the advanced hepatic alveolar echinococcosis (HAE). Methods: The clinical data of 12 patients with advanced HAE who underwent ALT at the First Affiliated Hospital of Xinjiang Medical University from May 2015 to July 2016 were retrospectively analyzed. Results: The preoperative hepatic functions of 12 patients were 8 Child-Pugh Grade A, 1 Grade B, and 3 Grade C. Three of the patients had moderate or severe jaundice. Three of the patients calculated functional liver graft volume (GV) and standard liver volume (SLV) ratio (GV/SLV) were <30%. After the protection of liver function, anti-infection, percutaneous transhepatic cholangiography drainage (PTCD), selective portal vein embolization (PVE), and staging liver resection, liver function Child-Pugh grade of 11 patients was raised to A grade, and the other patient was B grade, meanwhile the bilirubin was reduced to 2 times the normal value. The GV/SLV ratios of 3 patients with low GV/SLV ratio had reached 44.4%, 47.2% and 56.2% respectively. In this study, the GV/SLV ratios of the 12 patients were between 73.2% and 40.8% with an average of 55.6%. Operation time was 11.5-20.5 h, with an average of 12.3 h. Anhepatic phase time was 193-375 min with median 253.5 min. The red blood cell suspension was 0-6 U during the operation. The average hospitalization was 10-42 d, with the average 22.7 d. Total hospital costs were 121 600-434 800 Yuan, with the median cost of 174 400 Yuan. One patient died of septic shock a week after surgery. Conclusion: (1)ALT may provide feasibility for the advanced HAE. (2)Accurate assessment of functional liver "volume and quality" appeared as the key points to the ALT. (3)Precise surgery and individualized treatment could improve and protect the functional liver "volume and quality" .

[The potential use of serum HBV RNA to guide the functional cure of chronic hepatitis B].

Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) in infected hepatocytes is the main cause of off-therapy viral rebound. The half-life of cccDNA is only 33-50 days, so the conversion of newly synthesized rcDNA to cccDNA in the nucleus is essential for the maintenance of cccDNA pool in infected hepatocytes. Though not directly targeting the existing cccDNA, current nucleos(t)ide analogues (NAs) may exhaust the cccDNA reservoir by blocking the rcDNA formation. Indeed, a prolonged consolidation therapy post loss of serum HBV DNA can achieve sustained remission and thus safe drug discontinuation in a small proportion of chronic hepatitis B (CHB) patients. In recent studies, we and others have demonstrated that it is the serum HBV RNA that reflects the cccDNA activity in infected hepatocytes, particularly among the patients on NAs. Here we suggest that instead of measuring serum HBV DNA only, simultaneous measurement of both viral DNA and RNA would improve the accuracy to reflect the cccDNA activity; therefore, the virological response should be redefined as consistent loss (less than the lower limit of detection) of both serum HBV DNA and RNA, which indicates the safety of drug discontinuation. Accumulating evidence has suggested that for the CHB patients with lower serum HBsAg, switch-to or add-on pegylated interferon (Peg-IFN) treatment would result in loss of serum HBsAg in a relatively large proportion of CHB patients. Since serum HBV RNA is an ideal biomarker to reflect the intrahepatic cccDNA activity, for the patients with a serum HBsAg level lower than 1 500 IU/ml after long-term NAs treatment, the serum HBV RNA should be measured. If serum HBV RNA is detected, peg-IFN should be added on; if serum HBV RNA is not detected, NAs treatment should be switched to peg-IFN treatment. We believe the therapy based on serum HBV RNA would make the functional cure of CHB (serum HBsAg loss or even conversion to anti-HBs) more efficient.

Ex Vivo Liver Resection and Autotransplantation for End-Stage Alveolar Echinococcosis: A Case Series.

The role of autotransplantation in end-stage hepatic alveolar echinococcosis (AE) is unclear. We aimed to present our 15-case experience and propose selection criteria for autotransplantation. All patients were considered to have unresectable hepatic AE by conventional resection due to critical invasion to retrohepatic vena cava, hepatocaval region along with three hepatic veins, and the tertiary portal and arterial branches. All patients successfully underwent ex vivo extended right hepatectomy and autotransplantation without intraoperative mortality. The median autograft weight was 706 g (380-1000 g); operative time was 15.5 hours (11.5-20.5 hours); and anhepatic time was 283.8 minutes (180-435 min). Postoperative hospital stay was 32.3 days (12-60 days). Postoperative complication Clavien-Dindo grade IIIa or higher occurred in three patients including one death that occurred 12 days after the surgery due to acute liver failure. One patient was lost to follow-up after the sixth month. Thirteen patients were followed for a median of 21.6 months with no relapse. This is the largest reported series of patients with end-stage hepatic AE treated with liver autotransplantation. The technique requires neither organ donor nor postoperative immunosuppressant. The early postoperative mortality was low with acceptable morbidity. Preoperative precise assessment and strict patient selection are of utmost importance.