Severe viral hepatitis has a various etiology,which varies greatly among different regions. Hepatitis B and hepatitis C are commonly seen in China. It has been proved that antiviral therapy has great significance in HBV- related severe liver disease,and they often need long- term or lifetime medication. The selection of drugs should consider potency,low resistance,and safety. Patients with renal insufficiency should use nucleoside analogues with a note of caution. As for patients with HBV infection who plan to use or have already used immunosuppressants,antiviral therapy is of vital importance. Current studies support the therapeutic regimen with direct- acting antiviral agents in patients with severe hepatitis complicated by chronic renal disease. This therapy has achieved a satisfactory effect,but such patients tend to have a higher recurrence rate than general patients. Therefore,more large- scale clinical studies which last for a longer time are needed for validation. In conclusion,effective antiviral therapy should be given with reference to detailed condition,so as to improve the survival rates in patients with severe viral liver disease.

Liver failure is severe liver injury caused by various factors. This article summarizes currently used therapeutic methods for liver failure,and the universally acknowledged therapeutic methods include intensive care and supportive care,etiological treatment,regulation of immune function,prevention and treatment of various complications,supportive treatment with artificial liver,and liver transplantation. It is pointed out that the treatment of liver failure should focus on the multimodality therapy of internal medicine- artificial liver- liver transplantation,and that early diagnosis and treatment should be emphasized in clinical practice. The multimodality therapy should be developed according to the etiology,and complications should be actively prevented and treated. A multidisciplinary team should be established to develop individualized diagnosis and treatment regiments,so as to reduce the mortality rate and improve patients' clinical outcome.

Invasive fungal diseases( IFDs) are an important factor affecting the prognosis of patients with severe liver diseases,and their early diagnosis remains a challenge for clinicians. The four most commonly seen IFDs are candidiasis,aspergillosis,cryptococcosis,and pneumocystis pneumonia. We should pay attention to the risk of developing IFDs in patients with severe liver diseases during clinical management. Particularly,early diagnosis and proper treatment of IFDs are important in high- risk patients. These are vital to improving the prognosis of patients with severe liver diseases.

Objective To investigate the short- term efficacy,long- term efficacy,and adverse effects of elemene combined with transcatheter arterial chemoembolization( TACE) in the treatment of primary liver cancer( PLC). Methods Pub Med,EMBASE,Cochrane Library,Chinese Scientific Journal Full- Text Database,Wanfang Data,CBM,and VIP were searched by two reviewers using the same search strategy for clinical studies on elemene combined with TACE in the treatment of PLC. The Jadad quality scoring system was used to assess the quality of the studies included,and Review Manager 5. 2 software was used for the meta- analysis. Results A total of 9 articles involving487 patients were included. The results of the meta- analysis showed that compared with the TACE group,the elemene- TACE group showed significant increases in the response rate,disease control rate,and 12- and 24- month survival rates( response rate: RR = 1. 43,95% CI: 1. 23- 1. 67,P < 0. 001; disease control rate: RR = 1. 22,95% CI: 1. 11- 1. 32,P < 0. 001; 12- month survival rate: RR = 1. 68,95% CI: 1. 22- 2. 31,P = 0. 001; 24- month survival rate: RR = 2. 91,95% CI: 1. 44- 5. 87,P = 0. 003). As for the incidence of adverse events,the elemene- TACE group showed a significant reduction in the incidence rate of abdominal pain( RR = 0. 59,95% CI: 0. 36-0. 98,P = 0. 04). Conclusion Compared with TACE alone,elemene combined with TACE might improve response rate,disease control rate,and survival rates and reduce adverse events in patients with liver cancer.

Objective To investigate the value of endoscopic ultrasound( EUS) versus magnetic resonance cholangiopancreatography( MRCP) in the diagnosis of obstructive jaundice. Methods A total of 31 patients with obstructive jaundice who visited Beijing Tiantan Hospital,Capital Medical University,from January 2015 to March 2016 were enrolled,and all the patients underwent EUS and MRCP. The sensitivity,specificity,accuracy,and Youden index of EUS and MRCP in the diagnosis of obstructive jaundice were compared. Results Of all patients,16( 51. 61%) were diagnosed with common bile duct stones,1( 3. 23%) was diagnosed with ampullary tumor,6( 19. 35%)were diagnosed with duodenal papillary tumor,3( 9. 68%) were diagnosed with tumor of the head of the pancreas,2( 6. 45%) were diagnosed with bile duct tumor,2( 6. 45%) were diagnosed with bile duct inflammation,and 1 had no stones or space- occupying lesions observed by endoscopic retrograde cholangiopancreatography,EUS,or MRCP. The coincidence rate of EUS in the diagnosis of ampullary tumor,duodenal papillary tumor,and tumor of the head of the pancreas was 100%,and MRCP had a lower coincidence rate in the diagnosis of common bile duct stones and a lower overall coincidence rate of diagnosis than EUS( 81. 25%/76. 67% vs 93. 75%/90. 00%). In the diagnosis of obstructive jaundice,EUS and MRCP had sensitivities of 90. 00% and 76. 70%,specificities of 100%,accuracy rates of 90. 30% and77. 40%,and Youden indices of 0. 90 and 0. 77. Conclusion EUS has a higher value in the diagnosis of obstructive jaundice than MRCP.

Objective To investigate the clinical effect of regular hepatectomy in patients with complex intrahepatic bile duct stones. Methods A retrospective analysis was performed for the clinical data of 98 patients with complex intrahepatic bile duct stones who were treated in our hospital from January to December,2013. The distribution characteristics of intrahepatic bile duct stones,clinical manifestations,extent of operation,time of operation,complications,and surgical outcome were analyzed. Results All the 98 patients completed regular hepatectomy. Of all patients,37 underwent choledocholithotomy with T- tube drainage and segmental hepatectomy,6 underwent resection of the left lateral lobe of the liver,1 underwent left hemihepatectomy,7 underwent resection of a single hepatic segment in the right lobe of the liver combined with segmental hepatectomy,45 underwent combined segmental hepatectomy of the left and right lobes of the liver,and 2 underwent biliary- enteric basin anastomosis after hilar bile duct reconstruction. No patients died during the perioperative period. The mean time of operation was 65. 0 ± 5. 0 min,and the mean intraoperative blood loss was 83. 0 ± 6. 2 ml. No patients experienced residual stones after surgery. Of all patients,5( 5. 1%) experienced complications,among whom 3 experienced bile leakage and 2 experienced blood exudation on the surface of the wound in the liver; 3 patients were diagnosed with intrahepatic cholangiocarcinoma by postoperative pathological examination. All the patients for followed up for 5 years,and 11( 11. 2%) experienced recurrence of stones after surgery. Conclusion Regular hepatectomy is safe and effective in the treatment of complex intrahepatic bile duct stones,with few complications and a low recurrence rate of stones. Therefore,it holds promise for wide clinical application.

Objective To investigate the clinical features of patients with HBV- associated acute- on- chronic liver failure( HBV-ACLF) induced by the discontinuation of necleos( t) ide analogues. Methods A retrospective analysis was performed for 698 patients with a definite diagnosis of HBV- ACLF in The 302 Hospital of PLA from January 2014 to April 2016,and among these patients,150( discontinuation group) had acute- on- chronic liver failure( ACLF) induced by discontinuation,396( previously untreated group) had not received antiviral therapy when they developed this disease for the first time,and the other 152 patients with ACLF caused by other reasons were enrolled as controls. The causative factors,underlying diseases,family history,serum hepatitis B markers,prognosis,and initial onset were summarized,and the drugs used and discontinuation time were recorded for patients who stopped taking necleos( t) ide analogues. The chi-square test was used for the comparison of categorical data between groups. Results Among the 698 patients,355( 50. 86%) had a family history of chronic hepatitis B( CHB),and 93 patients( 62. 00%) in the discontinuation group had a family history of CHB. Among the 150 patients in the discontinuation group,27( 18. 00%) had an underlying disease of chronic hepatitis,among whom 12( 44. 44%) had a family history of CHB,which was significantly lower than the overall level( χ2= 2. 57,P = 0. 07); 123( 82. 00%) had an underlying disease of liver cirrhosis( compensated),among whom 81( 65. 85%) had a family history of CHB,which was significantly higher than the overall level( χ2= 48. 77,P < 0. 001). Of all the patients in the discontinuation group,77. 33%( 116/150) developed the disease within 1 year after discontinuation,and 21. 33%( 32/150) developed the disease during the second year after discontinuation. The HBe Ag- negative patients accounted for 47. 33%( 71/150). In the discontinuation group and previously untreated group,the patients with an underlying disease of chronic hepatitis showed a significantly higher cure and improvement rate than those with an underlying disease of liver cirrhosis( the discontinuation group: 88. 89% vs 53. 66%,χ2= 11. 450,P = 0. 001; the previously untreated group: 71. 79% vs 59. 50%,χ2= 5. 355,P =0. 021). Conclusion Discontinuation of necleos( t) ide analogues results in an increased proportion of patients with liver failure. Long-term antiviral therapy is very important,especially for patients with liver cirrhosis.

Objective To investigate the clinical features of patients with decompensated liver disease complicated by acute stroke. Methods A retrospective analysis was performed for the clinical data of 15 patients who were hospitalized in Beijing You'an Hospital,Capital Medical University and diagnosed with decompensated liver disease complicated by acute stroke from January 2011 to December 2015,including medical history,neurological manifestations,treatment,and prognostic features. Results Among the 15 patients,11 had acute hemorrhagic stroke( AHS),and 4 had acute ischemic stroke( AIS); among the 11 patients with AHS,4( 36. 36%) had hemorrhage caused by brain metastatic tumor of liver cancer( tumor- associated stroke),and 3( 27. 27%) were complicated by liver failure. Among the 15 patients,12( 80%) had disturbance of consciousness as the early neurological manifestation,and the confirmed diagnosis was made based on head CT findings; the treatment mainly included symptomatic support and rehabilitation training. The patients with AHS had poor prognosis.Four( 26. 67%) of the 15 AHS patients died,among these patients,2 had liver failure complicated by AHS,1 had liver cirrhosis complicated by AHS,and 1 had brain metastases complicated by AHS. Conclusion Patients with decompensated liver disease complicated by acute stroke tend to develop the manifestations of AHS,which may be related to a poor clotting mechanism and brain metastasis of liver cancer,and have poor prognosis. Head CT scan should be performed for patients with decompensated liver disease accompanied by neuropsychiatric abnormalities as early as possible to help with early diagnosis and timely treatment.

Objective To investigate the change in serum preptin level and its association with insulin resistance( IR) in patients with nonalcoholic fatty liver disease( NAFLD). Methods A total of 72 patients with NAFLD who visited the outpatient service or were hospitalized in Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine and Dongfang Hospital Affiliated to Tongji University from April to August,2014 were enrolled,and 53 normal controls( NCs) matched by age and sex were also enrolled. All the subjects underwent ultrasound examination,and according to the results of ultrasound examination,the patients were divided into mild,moderate,and severe NAFLD groups. The following parameters were measured: body height,body weight,systolic blood pressure,diastolic blood pressure,waist circumference,hip circumference,liver function parameters,blood lipids,high- sensitivity C- reactive protein,fasting blood glucose,fasting insulin( FINS),glycosylated hemoglobin,and serum preptin level. Body mass index( BMI),waist- hip ratio,and homeostasis model assessment of insulin resistance( HOMA- IR) were calculated. The two- independent- samples t test was used to compare means of continuous data between groups,comparison between group was made by analysis of variance,and multiple comparisons were made by SNK- q test; and the Pearson correlation coefficient method was used for correlation analysis; a multivariate linear regression analysis was used to identify the the correlations between preptin and variables,and a logistic regression analysis was used to identify the associations between variables and NAFLD. Results The NAFLD patients had a significant increase in the preptin level compared with the control group( 385. 54 ± 72. 78 pg/ml vs 303. 85 ± 57. 54 pg/ml,t =- 6. 76,P < 0. 001); the mild,moderate,and severe NAFLD groups showed gradual increases and significant differences in the preptin level( 328. 58 ± 53. 51 pg/ml,376. 71 ± 57. 77 pg/ml,and 449. 35 ± 56. 95 pg/ml,respectively,P < 0. 001).The Pearson correlation analysis showed that serum preptin level was positively correlated with BMI( r = 0. 475,P < 0. 001),HOMA- IR( r =0. 671,P < 0. 001),and FINS( r = 0. 763,P < 0. 001). The multivariate linear regression analysis showed that FINS and HOMA- IR were independent influencing factors for serum preptin level. The logistic regression analysis showed that preptin was closely associated with NAFLD. Conclusion Preptin is closely associated with the development of NAFLD and may be involved in the development and progression of NAFLD by affecting insulin resistance.

Objective To investigate the expression of patatin- like phospholipase domain- containing protein 3( PNPLA3) and sterol regulatory element- binding protein- 1c( SREBP- 1c) in the rat model of nonalcoholic fatty liver disease( NAFLD) treated by blueberry combined with probiotics,as well as its mechanism of action in NAFLD. Methods A total of 36 clean Sprague- Dawley rats were divided into normal group( NG),model group( MG),spontaneous recovery group( SRG),blueberry group( BG),probiotics group( PG),and blueberry- probiotics group( BPG). Tissue sections were prepared after the experiment ended to observe serological and histological changes and measure the mRNA and protein expression of PNPLA3 and SREBP- 1c. A one- way analysis of variance was used for comparison between multiple groups; the SNK- q test was used for data with homogeneity of variance,and the Tamhane's- T2 test was used for data with heterogeneity of variance. Results The six groups showed significant differences in liver index,serum alanine aminotransferase,total cholesterol,triglyceride,low- density lipoprotein,and high- density lipoprotein( F = 384. 908,188. 554,75. 523,94. 667,95. 235,and132. 586,all P < 0. 01). The NAFLD activity score also showed a significant difference between the six groups( F = 71. 896,P < 0. 01),and BPG showed a significantly greater reduction in the NAFLD activity score than MG,SRG,BG,and PG( all P < 0. 01). The six groups showed significant differences in the positive rates of PNPLA3 and SREBP- 1c in liver tissue( F = 175. 527 and 110. 504,both P < 0. 01),and BPG showed a significantly greater reduction in the positive rates of PNPLA3 and SREBP- 1C than MG,SRG,BG,and PG( all P <0. 01). The mRNA and protein expression of PNPLA3 and SREBP- 1c showed a significantly difference between the six groups.( F =375. 822,410. 379,288. 940,116. 054,all P < 0. 01). BPG showed significant reductions in the mRNA expression of PNPLA3 and SREBP- 1c compared with MG,SRG,BG,and PG( all P < 0. 01). Conclusion Blueberry combined with probiotics can effectively improve the structure of pathological tissues in NAFLD and reduce hepatocyte fatty degeneration. Its mechanism may be that the combination of blueberry and probiotics can reduce inflammation induced by inflammatory factors and downregulate the expression of SREBP- 1c,and thus weaken PNPLA3 gene transcription,enhance cholesterol metabolism,and reduce lipid deposition. Therefore,it can be applied as adjuvant therapy for NAFLD.

More than 20% of chronic hepatitis C( CHC) patients receiving the antiviral therapy with interferonα( IFNα) experience depression,and fluoxetine is often used to alleviate this symptom. Fluoxetine has anti- inflammatory properties and can change the synthesis of liver lipids,but its influence on antiviral therapy for CHC and related mechanism remain unknown. Recent studies show that fluoxetine can inhibit hepatitis C virus( HCV) infection and reduce the production of reactive oxygen species( ROS) and lipid accumulation in Huh7. 5cells; in addition,it can promote the antiviral effect mediated by IFNα through activating STAT1 and JNK signaling pathways and thus reduce HCV viral load and the level of alanine aminotransferase in CHC patients. Fluoxetine elevates PPAR response element activity in CHC patients,and its inhibitory effect on HCV infection and lipid accumulation were partly reversed by antagonists including PPARβ/γ,suggesting that fluoxetine inhibits HCV infection,ROS production,and lipid accumulation through regulating PPARβ/γ and JNK/STAT pathways.

Minimal hepatic encephalopathy( MHE) is a common complication in the progression of liver cirrhosis,and cando great harm to patients and the society. This disease has hidden clinical symptoms,and fine intelligence tests and nerve electrophysiological examination can find abnormalities in intelligence and mental status. If no treatment is given in time,MHE can easily progress to hepatic encephalopathy. Therefore,it is important to clarify the pathogenesis of MHE and give a definite diagnosis. MHE has a complex pathogenesis,and scholars at home and abroad have put forward various hypotheses based on in- depth studies. In recent years,great achievements have been made in traditional Chinese and Western medicine for the treatment of MHE. This article reviews resarch advances in the pathogenesis of MHE worldwide and achievements in the diagnosis and treatment of MHE based on traditional Chinese and Western medicine.

Liver fibrosis is the intermediate process in the progression of various chronic liver diseases to liver cirrhosis,and its serious complications affect the prognosis of patients with chronic liver diseases. However,so far,there remain no effective drugs for the treatment of liver fibrosis. This article investigates the development and progression of liver fibrosis from the aspects of signaling pathways and molecular mechanisms and briefly introduces the latest research advances in the roles of signaling pathways,including transforming growth factor- β/Smad pathway,platelet- derived growth factor pathway,leptin signaling pathway,and connective tissue growth factor pathway,chemokines,neuroendocrine factors,and angiogenesis in the development of liver fibrosis,so as to enhance the knowledge of the development of liver fibrosis and provide a theoretical basis for the research on molecular- targeted drugs based on the pathogenesis of liver fibrosis.

Abnormal activation of the mitogen- activated protein kinase( MAPK) signaling pathway is closely associated with the development,progression,and metastasis of liver cancer. This article introduces the expression of MAPK proteins in liver cancer and its role in the proliferation,differentiation,and metastasis of liver cancer,and elaborates on the value of the MAPK signaling pathway in the treatment and prognostic evaluation of liver cancer. It is pointed out that the MAPK signaling pathway plays an important role in the development/progression and treatment of liver cancer and is a potential molecular target for the treatment and prognostic evaluation of liver cancer.

Drug- induced liver injury( DILI) is a major reason for the recall of marketed drugs and the failure of clinical trials. Detection of potential liver injury remains a challenge for clinical management and preclinical drug safety studies. Currently,serum levels of alanine aminotransferase and aspartate aminotransferase are the gold standards for evaluating liver injury. However,these biomarkers are nonspecific and insensitive,and often result in false- positive results. Therefore,researchers have never stopped searching for the biomarkers of DILI with high sensitivity and specificity. This review summarizes recent research progress in the biomarkers of DILI to better predict and diagnose DILI.

Autophagy is a pathway of intracellular degradation,in which autophagic vacuoles are formed to transport intracellular biomacromolecules and damaged organelles to lysosomes. Autophagy plays an important role in the maintenance of the dynamic balance of liver function. Abnormal liver cells can be eliminated by autophagy. This article reviews the close relationship of autophagy with the proliferation of liver cells,non- parenchymal liver cells,and hepatic stem cells. Analysis has shown that autophagy may restore the volume and function of the liver by promoting the proliferation of liver cells and hepatic stem cells,which can be stopped in time to prevent tumor development. Autophagy may promote the activation of non- parenchymal liver cells during liver dysfunction,which can inhibit the regeneration of liver cells,and,in the meantime,lead to the development and progression of liver fibrosis. When the tumor is being formed,autophagy plays an important role in the transformation of normal cells into cancer cells; malignant regeneration of liver cells is activated but not terminated in time.