Entecavir vs lamivudine therapy for na?ve patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure

AIM:To investigate the short-term and long-term efficacy of entecavir versus lamivudine in patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure(ACLF).METHODS:This was a single center,prospective cohort study.Eligible,consecutive hospitalized patients received either entecavir 0.5 mg/d or lamivudine 100mg/d.All patients were given standard comprehensive internal medicine.The primary endpoint was survival rate at day 60,and secondary endpoints were reduction in hepatitis B virus(HBV)DNA and alanine aminotransferase(ALT)levels,and improvement in Child-Turcotte-Pugh(CTP)and model for end-stage liver disease(MELD)scores at day 60 and survival rate at week 52.RESULTS:One hundred and nineteen eligible subjects were recruited from 176 patients with severe acute exacerbation of chronic hepatitis B:65 were included in the entecavir group and 54 in the lamivudine group(full analysis set).No significant differences were found in patient baseline clinical parameters.At day 60,entecavir did not improve the probability of survival(P=0.066),despite resulting in faster virological suppression(P<0.001),higher rates of virological response(P<0.05)and greater reductions in the CTP and MELD scores(all P<0.05)than lamivudine.Intriguingly,at week 52,the probability of survival was higher in the entecavir group than in the lamivudine group[42/65(64.6%)vs 26/54(48.1%),respectively;P=0.038].The pretreatment MELD score(B,1.357;95%Cl:2.138-7.062;P=0.000)and virological response at day30(B,1.556;95%Cl:1.811-12.411;P=0.002),were found to be good predictors for 52-wk survival.CONCLUSION:Entecavir significantly reduced HBV DNA levels,decreased the CTP and MELD scores,and thereby improved the long-term survival rate in patients with spontaneous reactivation of hepatitis B presenting as ACLF.

Improved prescription of taohechengqi-tang alleviates D-galactosamine acute liver failure in rats

AIM: To investigate the hepatoprotective effect of improved prescription of Taohechengqi-tang (IPTT) against acute liver failure (ALF) in rats.METHODS: Seventy specific pathogen free male Wistar rats were randomly divided into four groups: control group (normal rats, n = 10), ALF group (ALF model, n = 20), Stronger Neo-Minophagen C (SNMC) group (ALF model + SNMC, n = 20), and IPTT group (ALF model + IPTT, n = 20). The ALF model group was administered an intraperitoneal injection of D-galactosamine (1.4 g/kg), and the control group received normal saline intraperitoneally. The SNMC and IPTT groups were treated with SMMC (15.6 mg/kg) or IPTT (28.6 g/kg) by gavage at 24 h intervals, and the ALF and control groups were treated with normal saline. At 36 h after injection, serum alanine aminotransferase, aspartate aminotransferase, total bilirubin, albumin, and cholinesterase and prothrombin time were determined, and liver histopathological scores were observed by microscopy after hematoxylin and eosin staining. mRNA expression of high mobility group box (HMGB) 1, toll-like receptor (TLR) 4, nuclear factor kappa B (NF-&#x003ba;B) and caspase-3 were analyzed via fluorescence quantitative reverse transcriptase polymerase chain reaction. Proliferating cell nuclear antigen (PCNA) immunohistochemistry in liver tissue was also performed.RESULTS: D-galactosamine notably decreased the biochemical and coagulation profiles in serum. IPTT not only improved liver function and histopathology but also normalized the gene expression levels in liver tissue. Compared with the model group, in the IPTT and SNMC groups, HMGB1 mRNA/&#x003b2;-actin (0.06 &#x000b1; 0.03, 0.11 &#x000b1; 0.04 vs 0.25 &#x000b1; 0.04, P &#x0003c; 0.05); TLR4 mRNA/&#x003b2;-actin (0.07 &#x000b1; 0.02, 0.22 &#x000b1; 0.08 vs 0.41 &#x000b1; 0.22, P &#x0003c; 0.05); NF-&#x003ba;B mRNA/&#x003b2;-actin (0.74 &#x000b1; 0.41, 1.78 &#x000b1; 0.64 vs 2.68 &#x000b1; 1.35, P &#x0003c; 0.05); and caspase-3 mRNA/&#x003b2;-actin levels were all significantly reduced (1.61 &#x000b1; 0.45, 2.57 &#x000b1; 1.04 vs 3.41 &#x000b1; 0.85, P &#x0003c; 0.05). The gene expression levels were significantly lower in the IPTT group than in the SNMC group (P &#x0003c; 0.05). Compared with the model group, the PCNA expression in liver tissue was significantly enhanced in the IPTT and SNMC groups (36.34 &#x000b1; 4.91, 25.57 &#x000b1; 2.94 vs 17.55 &#x000b1; 2.40, P &#x0003c; 0.05).CONCLUSION: IPTT attenuates inflammation in ALF via inhibition of HMGB1 production, which may contribute to limited liver regeneration.

Pelvic Exenteration for Recurrent and Persistent Cervical Cancer

Background： Pelvic exenteration （PE） for primary and recurrent cervical cancer has resulted in favorable survival outcomes, but there are controversies about specific prognosis factors, and up to now, there have been no published reports from China. This study aimed to share our experiences of PE, which were performed in a single institution. Methods： Frorn January 2009 to January 2016, 38 patients with recurrent or persistent cervical cancer were included in the study, and they were followed up until January 2017. Epidemiological and clinicopathological characteristics of patients were compared for survival outcornes in univariate and Cox hazard regression analysis. Results： There were thirty-one and seven patients with recurrent and persistent cervical cancer, respectively. The median age of patients was 45 years （range 29 65 years）. Total, anterior, and posterior PE consisted of 52.6%, 28.9%, and 18.4% of cases, respectively. Early and late complications occurred in 21 （55.3%） patients and 15 （39.5%） patients, respectively. Two （5.3%） patients died due to complications related to surgeries within 3 months after PE. The median overall survival （OS） and disease-free survival （DFS） were 28.5 months （range 9-96 months） and 23 rnonths （range 4.-96 months）, respectively, and 5-year OS and DFS were 48% and 40%, respectively. Cox hazard regression analysis showed that, the margin status of the incision and mesorectal lymph node status were independent risk factors liar OS and DFS. Conclusion： In our patients with rect.rrent and persistent cervical cancer, the practice of PE might achieve favorable survival outcomes. Trial Registration： ClinicalTrials.gov, NCT03291275; https：//clinicaltrials.gov/ct2/show/NCT03291275？term-NCT03291275＆rank = 1.

Distribution of Traditional Chinese Medicine patterns in 324 cases with hepatitis B-related acute-on-chronic liver failure:a prospective,cross-sectional survey

OBJECTIVE： To determine the distribution of Tradi- tional Chinese Medicine （TCM） patterns in hepatitis B-related acute-on-chronic liver failure （HB-ACLF） in different stages for guiding clinical prescriptions and treatments. METHODS： A prospective, cross-sectional survey method was used in this study. A total of 324 cases with HB-ACLF in China were involved. RESULTS： The general frequency of TCM patterns in HB-ACLF were as follows： Heat Toxin Stagnation Pattern （134/324, 41.36%）, Damp-heat Obstruction Pattern （66/324, 20.37% ）, Yong Qi Deficiency Pat- tern （52/324, 16.05%）, and Liver and Kidney Yin De- ficiency Pattern （26/324, 8.02%）. In the early stage of HB-ACLE there was a remarkably higher percent- age of excessive patterns than those in the middle and late stage. The incidence of Heat Toxin Stagna- tion reached 58.57% （82/140） in the early stage, while it was 33.96% （36/106） in the middle stage and 20.51% （16/78） in the late stage. In the early stage of HB-ACLF, excessive patterns, such as the Heat Toxin Stagnation Pattern, were more preva- lent than those in the middle and late stages （P〈a＇= 0.003）. However, in the late stage of HB-ACLE defi- cient patterns, such as the Yang Qi Deficiency Pat- tern, were more prevalent than those in the early and middle stages. The Yang Qi Deficiency Pattern had a higher rate of 41.03% （32/78） in the late stage compared with that of 20.75% （22/106） in the middle stage and 8.57% （12/140, P〈a＇ =0.003） in the early stage. The distribution of the other pat- terns was not significant between the three stages （P〉0.003）. CONCLUSIONS： There are four major patterns of HI3-ACLF, including the Heat Toxin Stagnation Pat- tern, the Damp-heat Obstruction Pattern, the Yang Qi Deficiency Pattern, and the Liver and Kidney Yin Deficiency Pattern. The Heat Toxin Stagnation and Yang Qi Deficiency Patterns are the representative patterns in the early and late stages of HB-ACLF. In the middle stage of HB-ACLF, the TCM patterns vary in a complicated manner, with no significant differ- ence among the patterns. Treatment for HB-ACLF should vary with the different representative pat- terns in the early and late stages.

Comparison of screening strategies for Lynch syndrome in patients with newly diagnosed endometrial cancer:a prospective cohort study in China

Background: The prevalence of Lynch syndrome and screening strategies for this disorder in Chinese patients with endometrial cancer have seldom been investigated. Such data would be essential for the screening, prevention, genetic counseling, and treatment of Lynch syndrome. The purpose of this prospective study was to determine the accuracy of the mismatch repair (MMR) protein immunohistochemistry (IHC), microsatellite instability (MSI) test, and clinical diagnostic criteria in screening for Lynch syndrome-associated endometrial cancer (LS-EC) in a prospective Chinese cohort. Methods: All patients with newly diagnosed endometrial cancer (EC) were evaluated using clinical diagnostic criteria (Amsterdam II criteria and the revised Bethesda guidelines), MSI test, and IHC of MMR proteins in tumor tissues. For all patients, the screening results were compared with results of germline sequencing for pathogenic variants of MMR genes. Results: Between December 2017 and August 2018, a total of 111 unselected patients with newly diagnosed EC were enrolled. Six patients (5.4%) harbored a pathogenic germline mutation of MMR genes: 1 had a mutation in MutL homolog 1 (MLH1), 2 in MutS homolog 2 (MSH2), and 3 in MutS homolog 6 (MSH6). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for identifying LS-EC were 33.3%, 88.6%, 14.3%, and 95.9%, for the clinical criteria, 66.7%, 75.0%, 14.3%, and 97.3% for IHC of MMR proteins, 100%, 89.9%, 33.3%, and 100% for MSI test, and 100%, 72.4%, 20.0% and 100% for combined IHC and MSI test, respectively. The combination of IHC and MSI test had higher sensitivity and PPV than the clinical criteria (p = 0.030). MSI test and IHC were highly concordant for LS-EC screening (73/77, 94.8%). Conclusion: The accuracy of the combination of IHC of MMR proteins and MSI test for screening LS among Chinese patients with EC was superior to that of the clinical criteria.