Alcoholic liver disease ( ALD) will likely become one of major etiologies of chronic liver diseases in the future. The diagnosis and management of ALD were recently updated bythe EASL, AASLD, APASL, and Chinese clinical practical guidelines in 2010- 2012. However, the pathogenesis of ALD still remains obscure. In this editorial, we briefly summarize the recently discovered molecular mechanisms, chronic- binge ethanol feeding model ( Gao- binge model) , and therapeutic targets for ALD. We also discuss the different characteristics of ALD between China and Western countries due to differences in ALDH2 genotypes and other genetic factors, drinking patterns, and co- factors. The number of ALD patients is alarmingly rising in China, so it is critical to conduct nationwide large- scale epidemiological ALD surveys, to promote basic and clinical ALD research, and explore novel therapies for ALD in China.

Alcoholic liver disease ( ALD) is a leading cause of chronic liver disease worldwide; however, the pathogenesis of ALD is not fully understood and there are no targeted therapies for ALD. In this review article, we summarize the findings from recent studies that have characterized the pathogenesis and diagnosis of ALD. Several novel therapeutic targets for alcoholic hepatitis are also discussed. There is an urgent need to translate these targets into therapies for patients with ALD.

Alcoholic liver disease ( ALD) is a major and serious health threat. The pathophysiology of ALD is very complex and still largely elusive but we do know now that the oxidative stress- induced liver injury plays a critical and definitive role in the pathogenesis of ALD according to the currently accumulated research data. Therefore a comprehensive review of how the cellular oxidation and antioxidant system impacts the process of occurrence and progression of ALD might shed new as well as significant light on our strategy to prevent and treat ALD.

Alcoholic liver disease ( ALD) has become a major cause of end- stage liver disease after viral liver cirrhosis. However, the impairments due to excessive alcohol intake have not drawn much attention, especially some clinical syndromes that occur in the advanced stage of ALD, such as Madelung syndrome, pseudo Budd- Chiari syndrome, hepatic osteodystrophy, and alcohol withdrawal syndrome ( AWS) . There is no accurate recognition and timely treatment of these syndromes, thus leading to irreversible damage. The clinical manifestation, possible mechanism, and therapeutic principle of the four syndromes are reviewed, aiming to increase the clinicians' awareness of these signals of excessive drinking and to prevent the development and progression of ALD. Early diagnosis of AWS, as well as timely, effective treatment, can not only reduce misdiagnosis and mistreatment, but also reduce the mortality of patients under intensive care.

Severe alcoholic hepatitis ( SAH) is a severe manifestation of alcoholic liver disease, which is associated with high mortality and presence of liver failure or complications, so optimized treatment strategies are needed to improve the survival of SAH patients. For SAH, the management is based on alcohol abstinence, and nutritional support is also necessary; glucocorticoid therapy is still the key of treatment. The patient's condition and treatment outcome can be evaluated according to the Maddrey discriminant function and Lille and MELD scores. Attention should also be paid to the prevention and treatment of complications such as infection and hepatorenal syndrome. Early liver transplantation can be considered for severe patients.

Objective To investigate the relationship between estrogen receptor alpha ( ERα) gene polymorphisms at position 29 and the outcome of hepatitis B virus ( HBV) infection among the population in Gansu, China, and to explore the pathogenesis of chronic hepatitis B ( CHB) at the genetic level. Methods A total of 102 patients with CHB and 106 patients who recovered from HBV infection were included in the study. The ERα gene polymorphisms at position 29 were analyzed by polymerase chain reaction- restriction fragment length polymorphism. The allele frequency was calculated by the gene counting method, and the Hardy- Weinberg equilibrium test was performed. Confounding factors were subjected to unconditional logistic regression analysis. Comparisons of genotype frequency and allele frequency were made by chi- square test ( R × C) . Results The frequencies of TT genotype and T allele of ERα gene polymorphisms at position 29 were significantly higher in the CHB patients than in the patients in the recovery period of HBV infection ( 62. 7% vs 48. 1%, χ2= 4. 502, P < 0. 05; 82. 4% vs 69. 8%, χ2= 4. 478, P < 0. 05) , while the frequencies of CC genotype and C allele were significantly lower in the former than in the latter ( 12. 8% vs 19. 8%, χ2= 27. 219, P < 0. 05; 17. 6% vs 30. 2%, χ2= 4. 478, P < 0. 05) . The risk of chronic HBV infection in patients with T allele was 2. 018 times that in patients with C allele ( OR = 2. 018, CI = 1. 047- 3. 891) . Conclusion The ERα gene with TT genotype at position 29 might be the susceptibility gene for chronic HBV infection.

Objective To investigate the relationship between the expression of phosphatidylinositol 4- kinase III alpha ( PI4KA) in serum and HBV DNA load in patients with chronic hepatitis B ( CHB) . Methods Serum samples were collected from 180 patients with CHB, whose HBV DNA loads were determined by fluorescence quantitative PCR. According to the serum HBV DNA loads, the 180 patients were divided into three groups: high viral load group ( HBV DNA load > 107copies / ml) , medium viral load group ( 105copies / ml≤HBV DNA load≤107copies / ml) , and low viral load group ( HBV DNA load < 105copies / ml) , while the serum samples of 60 healthy people were selected as control group. Enzyme- linked immunosorbent assay was used to determine the concentration of PI4KA in peripheral serum. Results The concentrations of serum PI4KA were ( 2. 29 ± 0. 75) ng /ml in the control group, ( 2. 73 ± 0. 71) ng /ml in the low viral load group, ( 3. 52 ± 0. 78) ng / ml in the medium viral load group, and ( 4. 72 ± 0. 77) ng / ml in the high viral load group. There were significant differences in serum PI4KA concentration between the patient groups with different viral loads and control group ( F = 119. 958, P < 0. 01) , and the PI4KA levels in the three viral load groups were all significantly higher than those in the control group. The HBV DNA load and PI4KA concentration presented a positive correlation with each other ( r = 0. 758, P < 0. 01) - serum PI4KA level would be elevated with the increase in HBV DNA load. Conclusion The concentration of serum PI4KA is closely correlated with the HBV DNA load in patients with CHB, which suggests that PI4KA may play a crucial role in the HBV DNA replication.

Objective To investigate the effect of nonstructural protein 5A ( NS5A) encoded by the human hepatitis C virus ( HCV) RNA genome on human immunodeficiency virus ( HIV) long terminal repeat ( LTR) and to provide an experimental basis for the study on the effect of HCV on HIV. Methods Hepatocellular carcinoma Huh7 cells were divided into blank group, control group, and experimental group to be transfected with plasmid pGL3- LTR- Luc ( containing luciferase reporter gene driven by the LTR promoter) , plasmid pRc / CMV plus plasmid pGL3- LTR- Luc, and plasmid pCNS5A ( containing HCV NS5A gene) plus plasmid pGL3- LTR- Luc, respectively; Huh7 cells were collected 48 h later. The protein and mRNA expression levels of HCV NS5A were measured by immunocytochemistry, Western blot, and RT- PCR. The relative luciferase activity was measured to evaluate the HIV LTR activity and the effect of HCV NS5A on HIV LTR. The activity values were expressed as mean ± SD, and Levene' s test of homogeneity of variance was used; comparison between all groups was made by one- way analysis of variance ( ANOVA) , and comparison between two groups was made by least significant difference ( LSD) test. Results The mRNA and protein expression of HCV NS5A was detected in the cytoplasm of Huh7 cells in experimental group. The one- way ANOVA showed that there were significant differences in LTR luciferase activity between the three groups ( F = 7. 876, P = 0. 002) . The LSD test showed that the experimental group had a significantly higher relative luciferase activity than the blank group and control group ( 22476 ± 4471 vs 15887 ± 3039, P = 0. 002; 22476 ± 4471 vs 16321 ± 4162, P = 0. 008) . Conclusion Huh7 cells can be transfected with the HCV NS5A expression plasmid ( pCNS5A) . HCV NS5A can activate HIV LTR, which suggests that HCV NS5A may be one of the molecular mechanisms of HCV promoting HIV replication.

Objective To investigate the clinical values of indocyanine green ( ICG) retention rate at 15 min ( ICGR15) and effective hepatic blood flow ( EHBF) in evaluating the liver reserve function among patients with chronic hepatitis. Methods Eighty- two patients with chronic hepatitis were included in the study. ICGR15and EHBF were measured by pulse dye densitometry before treatment, and alanine aminotransferase ( ALT) , total bilirubin ( TBil) , albumin, prothrombin activity, and cholinesterase were also measured. ICGR15and EHBF were monitored among mild, moderate, and severe patients, patients with normal ALT and abnormal ALT, and patients with normal TBil and abnormal TBil. The predictive values of ICGR15and EHBF for patients' conditions were analyzed by the receiver operating characteristic ( ROC) curve. The continuous data were expressed as median ± interquartile range. Comparison between more than two groups was made by Kruskal- Wallis H test; comparison between two groups was made by Mann- Whitney U test. Results ICGR15and EHBF showed significant differences between mild and severe patients and between moderate and severe patients ( H = 5. 0 and 12. 0, P < 0. 05 for both; H = 25. 0 and 29. 0, P < 0. 05 for both) . There were no significant differences in ICGR15and EHBF between the patients with normal ALT and those with abnormal ALT ( U = 135. 5, P = 0. 089; U = 146. 0, P = 0. 155) . ICGR15and EHBF also showed significant differences between the patients with normal TBil and those with abnormal TBil ( U = 68. 0, P < 0. 05; U = 84. 0, P < 0. 05) . The areas under the ROC curve of ICGR15, EHBF, ALT, and TBil were 0. 434, 0. 497, 0. 622, and 0. 521, respectively, in mild patients, 0. 969, 0. 075, 0. 900, and 1. 000, respectively, in moderate patients, and 0. 861, 0. 161, 0. 759, and 0. 950, respectively, in severe patients. Conclusions ICG clearance test is an accurate method for quantitatively assessing the liver reserve function and is helpful for taking timely, effective intervention. This test is of great clinical significance.

Objective To evaluate the clinical effect and safety of transjugular intrahepatic portosystemic shunt ( TIPS) in the treatment of portal hypertension due to alcoholic cirrhosis. Methods A retrospective analysis was performed on the clinical data of 30 patients with portal hypertension due to alcoholic cirrhosis who received TIPS in our hospital; the clinical indices before and after TIPS were recorded to evaluate portal venous pressure, ascites, hypersplenism, and liver function. Postoperative follow- up was performed for 2 years to detect the complications including recurrent variceal bleeding, in- stent restenosis, ascites, and hepatic encephalopathy, and the relationship between the incidence of hepatic encephalopathy and clinical indices was analyzed. The change in portal venous pressure after puncture was evaluated by paired t test; the Kaplan- Meier method was used to analyze the correlation between clinical indices and the incidence of hepatic encephalopathy after TIPS. Results The success rate of TIPS was 100% ( 30 /30) . The portal venous pressure was significantly decreased from 37. 27 ± 2. 52 cm H2O before operation to 24. 6 ± 2. 58 cm H2O after operation ( P < 0. 05) . Within 2 years after TIPS, the recurrence rate of variceal bleeding was 3. 3% ( 1 /30) ; the response rate in ascites treatment was 88. 9% ( 16 /18) ; the incidence of in- stent restenosis was 6. 7% ( 2 /30) ; the incidence of hepatic encephalopathy was 40% ( 12 /30) . The Kaplan- Meier analysis indicated that the Child-Pugh classification before TIPS was significantly correlated with the postoperative incidence of hepatic encephalopathy ( P = 0. 04) . Conclusion TIPS is an effective and safe minimally invasive therapy for portal hypertension- related complications in patients with alcoholic cirrhosis. Preoperative Child- Pugh classification is an important influential factor for the postoperative incidence of hepatic encephalopathy.

Objective To analyze the clinical high- risk factors for hepatitis B cirrhosis confirmed by liver biopsy. Methods A case- control study was conducted on the clinical data collected from 237 patients with chronic hepatitis B who were hospitalized and underwent biopsy from April 2009 to October 2012. These patients included 79 cases confirmed by liver biopsy as having liver cirrhosis ( case group) and 158 cases confirmed by biopsy as not having liver cirrhosis ( control group) . Univariate analysis and multivariate logistic regression analysis were used to investigate the clinical risk factors for liver cirrhosis. In the univariate analysis, comparison of categorical data was made by chi- square test, and comparison of continuous data was made by t test. The indices of statistical significance were subjected to multivariate logistic regression analysis. Results The univariate analysis showed that the case group had significantly increased numbers of male cases and HBeAg- negative cases, age, and aspartate aminotransferase ( AST) , gamma- glutamyl transpeptidase ( GGT) , immunoglobulin G ( IgG) , and hyaluronic acid levels ( P < 0. 05) and significantly decreased albumin ( Alb) , hepatitis B virus DNA, and laminin levels and platelet ( PLT) count ( P < 0. 05) , as compared with the control group. The unconditional multivariate logistic regression analysis showed that increasing age [β = 0. 046, odds ratio ( OR) = 0. 955], elevated GGT level ( β = 0. 04, OR = 0. 96) , and increased IgG level ( β = 0. 179, OR = 0. 836) were high- risk factors for liver cirrhosis, while increased Alb level ( β =- 0. 114, OR = 1. 120) and PLT count ( β =- 0. 024, OR = 1. 024) were protective factors for liver cirrhosis. Conclusion Increasing age, decreased Alb level, elevated GGT level, decreased PLT count, and increased IgG level are high- risk factors for liver cirrhosis in patients with chronic hepatitis B whose ALT levels range within 0- 80 U / L. Active monitoring of the above indices, especially PLT, IgG, and GGT, and liver biopsy should be performed if necessary to avoid misdiagnosis of liver cirrhosis in patients with chronic hepatitis B.

Objective To evaluate the value of FibroScan in assessing liver fibrosis in chronic hepatitis B ( CHB) patients with hepatocyte steatosis. Methods Four hundred and eighteen CHB patients who had undergone liver biopsy in Shanghai Ruijin Hospital from January 2009 to December 2011 were enrolled in this study. These patients were divided into hepatocyte steatosis group ( n = 211) and non- hepatocyte steatosis group ( n =207) . FibroScan was performed in both groups on the same day. Comparisons of liver stiffness measurement ( LSM) and liver fibrosis stage determined by FibroScan and Ishak scoring system were made. Comparisons between groups were made by independent- samples t test, Kruskal- Wallis H test, and Nemenyi test. Comparison of categorical data was made by chi- square analysis. Bivariate correlation analysis was performed using the Spearman Rank Correlation coefficient. The influential factors for LSM were determined by stepwise regression analysis. Results There was no significant difference in LSM between the patients of the same liver fibrosis stage in the two groups ( P > 0. 05) , and LSM had a significant positive correlation with liver fibrosis stage in the non- hepatocyte steatosis group ( rs= 0. 650 35, P < 0. 000 1) and hepatocyte steatosis group ( rs= 0. 637 93, P < 0. 000 1) . The stepwise regression analysis showed that aspartate aminotransferase ( AST) , alanine aminotransferase, albumin ( Alb) , total bilirubin, and platelet ( PLT) were significant influential factors for LSM in the non- hepatocyte steatosis group and that PLT, AST, age, Alb, and body mass index were significant influential factors for LSM in the hepatocyte steatosis group. Conclusion FibroScan can be used as a useful tool for assessing liver fibrosis in CHB patients with hepatocyte steatosis.

Objective To investigate the role of integrin- linked kinase ( ILK) in the phenotypic transformation of rat's primary hepatic stellate cells ( HSCs) induced by recombinant connective tissue growth factor ( rCTGF) . Methods Primary HSCs were isolated from normal Sprague Dawley rats by in situ perfusion of collagenase and density gradient centrifugation. After 24 h of adherent cell culture, HSCs were treated with rCTGF for another 24 h before they were transfected with ILK small interfering RNA ( siRNA) or control siRNA. An rCTGF control group ( HSCs treated with only rCTGF) and a blank control group ( HSCs treated with no rCTGF) were also set up. The gene expression levels of α- smooth muscle actin ( αSMA) , ILK, and type I collagen in HSCs were measured by RT- PCR and Western blot at 24 h, 48 h, and 72 h after transfection with siRNA. The t- test was used for comparisons of measurement data. Results rCTGF significantly upregulated αSMA protein, ILK protein, and type I collagen mRNA in rat HSCs compared with the blank control group. Transfection of rat HSCs with ILK siRNA specifically inhibited the rCTGF- induced ILK upregulation. Compared with those in the rCTGF control group, the expression level of ILK protein in the ILK siRNA- transfected HSCs decreased by 72% ± 6% ( t = 21. 39, P < 0. 01) at 24 h, 87% ± 9% ( t = 68. 25, P < 0. 01) at 48 h, and 47% ± 3% ( t = 18. 25, P = 0. 003) at 72 h; the expression levels of αSMA protein and type I collagen mRNA decreased by 5% ± 1% ( t =2.52, P >0.05) and 6% ±3% ( t =1.63, P >0.05) at 24 h, 31% ±7% ( t =34.77, P <0.01) and 20% ±5% ( t =6.71, P <0.05) at 48 h, and 67% ± 8% ( t = 58. 82, P < 0. 01) and 43% ± 6% ( t = 15. 21, P < 0. 01) at 72 h. No changes were observed in the expression levels of ILK protein, αSMA protein, and type I collagen mRNA in HSCs transfected with control siRNA at the same time points. Conclusion ILK may partly mediate the phenotypic transformation of rat HSCs induced by rCTGF.

Alcoholic liver disease ( ALD) has become one of the major public health problems in the world, and its pathogenesis has not yet been completely clarified. Proteomics and metabonomics provide a new way for the studies on ALD, and some progress has been made in this regard. Here, the applications of proteomics and metabonomics in studies on ALD in recent 10 years, as well as existing problems, are comprehensively reviewed, and it is proposed that joint use of proteomics and metabonomics in studies on ALD is a good strategy, which helps to reveal the pathogenesis of ALD in a panoramic view and provide important information for the early detection, clinical diagnosis, treatment, and prognostic evaluation of ALD.

A variety of immunocytes and their cytokines participate actively in the immune responses to hepatitis B virus ( HBV) in the host body. As a class of important cytokines, interleukins play regulatory effects in all aspects of immune responses. Several interleukins which play a significant role in the development, progression, and outcome of hepatitis B and their relationship with HBV infection are reviewed. Analysis showed that in- depth research on the immunoregulatory mechanisms of interleukins can offer new basis and method for the diagnosis and treatment of various types of hepatitis B.