Pegylated interferon α-2b （PEG-IFN-α-2b） is currently a first-line drug for the treatment of chronic hepatitis B virus infection and is widely used in clinical practice. This drug has multiple effects of inhibiting viral replication， regulating immunity， and improving liver function， and some patients can achieve clinical cure. However， it often causes various adverse reactions during treatment， which are important factors for compromising treatment compliance and efficacy. This article systematically reviews the adverse reactions and their mechanisms during PEG-IFN-α-2b therapy for chronic hepatitis B， including influenza-like symptoms， peripheral blood cytopenia， thyroid dysfunction， and neuropsychiatric symptoms， and it also summarizes the monitoring and management strategies for these adverse reactions， in order to provide evidence-based guidance for clinical decision-making and emphasize the importance of individualized treatment.

Primary hepatic carcinoma（PHC）is the second leading cancer that caused death in the world. The morbidity of PHC is increasing year by year,which threaten people's lives and health. Chronic hepatitis B is considered to be an independent risk factor for PHC,and the incidence of PHC is higher in patients who have progressed to liver cirrhosis. We reviewed the domestic and abroad literatures about the risk factors for hepatitis B cirrhosis progressing to PHC from the year of 1992 to 2018,and concluded that HBV-DNA,HBsAg,HBeAg expression,antiviral treatment time,different antiviral drugs,degree of cirrhosis,alanine transaminase and family history were related to the development of PHC from cirrhosis.

Objective To investigate the histological injury as well as the risk factors for the course of HBeAg-negative chronic hep-atitis B virus( HBV)-infected patients with persistently normal alanine aminotransferase ( ALT) levels ( PNAL) . Methods Ninty four patients of HBeAg-negative chronic HBV-infected with PNAL were performed liver puncturing. The ALT, HBV markers, and liver histo-logical changes were detected. The gender, age, family history, HBV-DNA and HBsAg levels were compared between different patients with liver inflammation and fibrosis. And the Logistic model was used during the analysis of independent risk factor. Results Among 94 cases, patients with inflammatory necrosis classification≥G2 accounted for 74. 5%, fibrosis grading≥S2 accounted for 27. 7%. Patients in the group of inflammatory necrosis classification≥G2 was older than the group of < G2, and the ALT level of≥G2 group was higher, as well as a higher HBV-DNA. What is more,Patients in the group of inflammatory necrosis classification ≥G2 were mainly male, and were associated with a family history of hepatitis B. Patients in the group of fibrosis stage ≥S2 was older than < S2 group, and the ALT level of fibrosis stage ≥S2 group was higher. And those patients were often associated with a family history of hepatitis B, but there was no significant difference among the HBV-DNA level and gender constitution. HBV-DNA and family history were the independent risk fac-tors of liver inflammation necrosis≥G2, and family history was the only independent risk factor of fibrosis stage≥S2. Conclusion The patients of HBeAg-negative chronic HBV-infected with PNAL, regardless of the ALT and HBV-DNA, must have a liver biopsy. The pa-tients with high level of HBV-DNA and with a family history of hepatitis B should be performed liver puncturing accordingly.

Objective To explore the effect of combination of telbivudine( LdT)and adefovir dipivoxil(ADV)on renal function in patients with chronic hepatitis B( CHB). Methods The CHB patients with renal injury due to lamivudine(LAM)resistance and combination with ADV,who visited in First Affiliated Hospital of Zhejiang Chinese Medical University were enrolled into this study. The randomized controlled trial was performed in this study. The patients were divided into two groups by table of random number:the LAM + ADV group( original treatment was continued)and the LdT + ADV group (LAM was replaced with LdT). The levels of HBV DNA,alanine aminotransferase( ALT),serum creatinine(Scr),estimated glomerular filtration rate(eGFR),urinary beta 2-microspheres(Uβ2-MG), and serum creatine kinase(sCK)were compared between the 2 groups at baseline,24 and 48 weeks of treatments. Results A total of 79 patients were enrolled into the study. There were 41 patients in the LAM + ADV group and 38 in the LdT + ADV group. The differences of sex distribution,age,body weight and the basal level between the 2 groups were not statistically significant(all P > 0. 05). There were no HBV DNA breakthrough in patients during 48 weeks of treatment in both groups. The differences of ALT levels at different time points in patients in the 2 groups were not statistically significant(all P > 0. 05). In the LAM + ADV group,the Scr levels at 24 and 48 weeks of treatment were higher than those at baseline [(117 ± 11),(122 ± 12)μmol/ L vs.(113 ± 12)μmol/ L]. The difference between the baseline and 48 weeks of treatment was statistically significant(P < 0. 05). The levels of Scr in the LdT + ADV group at 24 and 48 weeks of treatment were lower than those at baseline[(104 ± 10),(99 ± 9)μmol/ L vs. (109 ± 10)μmol/ L]( all P < 0. 05). The levels of eGFR in the LAM + ADV group at 24 and 48 weeks of treatment were lower than those at baseline[(68. 9 ±12. 2),(66. 1 ±7. 6)ml·min-1 ·1. 73 m-2 vs.(70. 9 ± 8. 1)ml · min-1 · 1. 73 m-2 ]. The difference between the baseline and 48 weeks of treatment was statistically significant(P < 0. 05). The levels of eGFR in the LdT + ADV group at 24 and 48 weeks of treatment were higher than those at baseline[(75. 1 ± 11. 4),(79. 6 ± 31. 1)ml·min-1 ·1. 73 m-2 vs. (71. 4 ± 10. 6)ml·min-1 ·1. 73 m-2 ](all P < 0. 05). The levels of Uβ2-MG in the group of LAM + ADV at 24 and 48 weeks of treatment were higher than those at baseline[4 611(23 920,740),4 719(24 109, 967)μg/ L vs. 4 601(23 807,611)μg/ L]. The difference between the baseline and 48 weeks of treatment was statistically significant(P < 0. 05). The levels of Uβ2- MG in the LdT + ADV group at 24 and 48 weeks of treatment were lower than those at baseline[3 251(12 890,220),1 950(10 119,73)μg/ L vs. 4 109 (24 703,633)μg/ L]. The difference between the baseline and 48 weeks of treatment was statistically significant(P < 0. 05). The difference of sCK levels between the baseline and 24 and 48 weeks of treatments [(99 ± 31),(99 ± 36),(96 ± 37)]were not statistically significant(all P > 0. 05). The sCK levels in the LdT + ADV group at 24 and 48 weeks of treatments were higher than those at baseline[(107 ± 38),(130 ± 56)U/ L vs. (97 ± 31)U/ L]. The difference between the baseline and 48 weeks of treatment was statistically significant(P < 0. 05). The differences of Scr,eGFR,Uβ2-MG,and sCK levels at baseline and 48 weeks of treatment in the 2 groups were statistically significant(all P < 0. 05). Conclusions The therapeutic regimen of telbivudine combination with adefovir dipivoxil can improve the renal function in patients with CHB. The change of sCK level should be monitor closely during the treatment.

Objective To explore the effect of combination of telbivudine( LdT)and adefovir dipivoxil(ADV)on renal function in patients with chronic hepatitis B( CHB). Methods The CHB patients with renal injury due to lamivudine(LAM)resistance and combination with ADV,who visited in First Affiliated Hospital of Zhejiang Chinese Medical University were enrolled into this study. The randomized controlled trial was performed in this study. The patients were divided into two groups by table of random number:the LAM + ADV group( original treatment was continued)and the LdT + ADV group (LAM was replaced with LdT). The levels of HBV DNA,alanine aminotransferase( ALT),serum creatinine(Scr),estimated glomerular filtration rate(eGFR),urinary beta 2-microspheres(Uβ2-MG), and serum creatine kinase(sCK)were compared between the 2 groups at baseline,24 and 48 weeks of treatments. Results A total of 79 patients were enrolled into the study. There were 41 patients in the LAM + ADV group and 38 in the LdT + ADV group. The differences of sex distribution,age,body weight and the basal level between the 2 groups were not statistically significant(all P > 0. 05). There were no HBV DNA breakthrough in patients during 48 weeks of treatment in both groups. The differences of ALT levels at different time points in patients in the 2 groups were not statistically significant(all P > 0. 05). In the LAM + ADV group,the Scr levels at 24 and 48 weeks of treatment were higher than those at baseline [(117 ± 11),(122 ± 12)μmol/ L vs.(113 ± 12)μmol/ L]. The difference between the baseline and 48 weeks of treatment was statistically significant(P < 0. 05). The levels of Scr in the LdT + ADV group at 24 and 48 weeks of treatment were lower than those at baseline[(104 ± 10),(99 ± 9)μmol/ L vs. (109 ± 10)μmol/ L]( all P < 0. 05). The levels of eGFR in the LAM + ADV group at 24 and 48 weeks of treatment were lower than those at baseline[(68. 9 ±12. 2),(66. 1 ±7. 6)ml·min-1 ·1. 73 m-2 vs.(70. 9 ± 8. 1)ml · min-1 · 1. 73 m-2 ]. The difference between the baseline and 48 weeks of treatment was statistically significant(P < 0. 05). The levels of eGFR in the LdT + ADV group at 24 and 48 weeks of treatment were higher than those at baseline[(75. 1 ± 11. 4),(79. 6 ± 31. 1)ml·min-1 ·1. 73 m-2 vs. (71. 4 ± 10. 6)ml·min-1 ·1. 73 m-2 ](all P < 0. 05). The levels of Uβ2-MG in the group of LAM + ADV at 24 and 48 weeks of treatment were higher than those at baseline[4 611(23 920,740),4 719(24 109, 967)μg/ L vs. 4 601(23 807,611)μg/ L]. The difference between the baseline and 48 weeks of treatment was statistically significant(P < 0. 05). The levels of Uβ2- MG in the LdT + ADV group at 24 and 48 weeks of treatment were lower than those at baseline[3 251(12 890,220),1 950(10 119,73)μg/ L vs. 4 109 (24 703,633)μg/ L]. The difference between the baseline and 48 weeks of treatment was statistically significant(P < 0. 05). The difference of sCK levels between the baseline and 24 and 48 weeks of treatments [(99 ± 31),(99 ± 36),(96 ± 37)]were not statistically significant(all P > 0. 05). The sCK levels in the LdT + ADV group at 24 and 48 weeks of treatments were higher than those at baseline[(107 ± 38),(130 ± 56)U/ L vs. (97 ± 31)U/ L]. The difference between the baseline and 48 weeks of treatment was statistically significant(P < 0. 05). The differences of Scr,eGFR,Uβ2-MG,and sCK levels at baseline and 48 weeks of treatment in the 2 groups were statistically significant(all P < 0. 05). Conclusions The therapeutic regimen of telbivudine combination with adefovir dipivoxil can improve the renal function in patients with CHB. The change of sCK level should be monitor closely during the treatment.

Objective To assess the prognostic significance of pre-treatment hypercoagulable state in cervical cancer patients. Methods With retrospective analysis, pre-treatment coagulation indicators and platelets from 321 cervical cancer patients from stages I to IV were collected. The pre-treatment coagulation parameters were investigated along with tumor stage and survival data. Result Advanced tumor stage was associated with elevated fibrinogen (Fbg) and platelet (PLT) levels (P < 0.05). Patients with higher levels of Fgb, PTA and PLT suffered from higher risk of recurrence (P<0.05). Multivariate survival analyses showed that tumor stage, Fgb and PTA were independent prognostic factors for disease free survival. Conclusion Coagulation parameters can be served as useful tool for predicting recurrence of cervical cancer.

OBJECTIVE To investigate the epidemiology of bacterial infections isolated from liver disease patients with septic shock and analyze the antimicrobial susceptibility of major pathogens to provide reference for clinical therapy. METHODS A retrospective survey was conducted in 83 liver disease patients with septic shock of our hospital from Jan 2005 to Aug 2006. Identification and susceptibility of pathogens were assayed by MicroScan Auto-4 System. RESULTS The infection was frequently identified in intra-abdominal cavity (73.5%),blood stream (24.1%) or respiratory tract (13.3%). The top 3 pathogens were Escherichia coli (36.6%),Klebsiella pneumoniae (15.9%) and Staphylococcus aureus (6.1%). Gram-negative bacilli were usually resistant to multiple antimicrobial agents,but less resistant to imipenem,levofloxacin or piperacillin-tazobactam. Extended-spectrum ?-lactamases (ESBLs) positive rates of E. coli and K. pneumoniae were 53.3% and 7.7%. Asprergillus and Candida glabrata were the predominant pathogens from fungal infections,and they were mostly resistant to fluconazole. CONCLUSIONS Pathogens of liver disease patients with septic shock are mostly multi-drug resistant. The microbiological surveillance is important for guiding clinical therapy.

Objective To investigate the safe model to prevent and treat complications caused by various artificial liver support system(ALSS).Methods The complications in 191 patients with severe hepatitis during the ALSS(Including plasma exchange、plasma exchange associated with continuous venovenous hemofiltration、plasma exchange associated with hemodiafiltration、plasma exchange associated with plasma absorption、molecular absorbents recycling system) treatment were observed and analyzed. Results During the treatment 287 episodes occurred and the rate of complications was 50.44%(287/569).The clinical manifestation included rash,numbness/tetany,hypotension,blood clotting in the channel,chest distress, disequilibrium syndrome,errhysis on dwell catheter,effusion on dwell catheter.75.61% of these complications was caused by plasma exchange.The rate of complications was the lowest during the treatment of plasma exchange associated with hemodiafiltration.All of these complications got better after prompt sypotomatic therapies were taken.Conclusions Although the rate of complications was high during the treatment of ALSS,all of the complications got better after prompt sypotomatic therapies were taken.This therapeusis must be performed by intensive care.It is more safe than others during the treatment of plasma exchange associated with hemodiafiltration.

OBJECTIVE To analyze clinical and etiologic characteristics of indwelling venous catheter-related infection(CRI) in artificial liver support system(ALSS)-treated patients and explore the measures of prevention and treatment.METHODS Bacterial culture and drug sensitivity test were performed in cusp of catheters after being pulled out and the peripheral blood in liver failure patients.RESULTS Sixty four strains were isolated including 56 Gram-positive strains,2 Gram-negative strains and 6 fungi ones,respectively.The most frequent organism was Staphylococcus epidermidis which had high sensitivity to vancomycin.CONCLUSIONS The most effective measure is removing catheters in time,and vancomycin is the most optimal agent for CRI.

OBJECTIVE To investigate the epidemiology of bacterial infections in patients with severe liver disease in intensive care unit(ICU) and analyze the antimicrobial susceptibility of major pathogens to provide reference for clinical therapy.METHODS A retrospective survey was conducted in 206 patients with severe liver disease in ICU of our hospital from Oct 2005 to Dec 2006.Identification and susceptibility of pathogens were assayed by MicroScan Auto-4 System.RESULTS Infection was identified in 70.87% of the 206 patients with severe liver disease.Most infections were caused by single pathogen.The infection was frequently identified in respiratory tract,blood stream or intra-abdominal cavity.The top 5 pathogens were Escherichia coli(12.8%),Klebsiella pneumoniae(9.9%),Staphylococcus haemolyticus(8.5%),Pseudomonas aeruginosa(7.8%) and Stenotrophomonas maltophilia(6.4%).Gram-negative bacilli were usually resistant to multiple antimicrobial agents,but less resistant to piperacillin-tazobactam or imipenem.Most of S.haemolyticus isolates were meticillin-resistant(MRSH)(25%),which were susceptible to penicillin,ampicillin and vancomycin.CONCLUSIONS Pathogens of patients with severe liver disease in ICU are mostly multi-drug resistant.The microbiological surveillance is important for guiding clinical therapy.