• blood donors
• hepatitis C virus
• occult HCV-infection
• patients with hematological diseases

• autoimmune hepatitis
• azathioprine
• budesonide
• immunosuppressive therapy
• liver biopsy
• prednisolone
• pregnancy of pa- tients

• Acute liver failure
• C5a/C5aR
• Sphingosine kinase 1
• p38-MAPK

• Animals
• Blotting, Western
• Complement C5a/metabolism
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Galactosamine/toxicity
• HMGB1 Protein/metabolism
• Interleukin-1beta/metabolism
• Interleukin-6/metabolism
• Kaplan-Meier Estimate
• Leukocytes, Mononuclear/metabolism
• Lipopolysaccharides/toxicity
• Liver/metabolism
• Liver/pathology
• Liver Failure, Acute/chemically induced
• Liver Failure, Acute/metabolism
• Liver Failure, Acute/pathology
• Lysophospholipids/metabolism
• Macrophages, Peritoneal/metabolism
• Mice
• Mice, Inbred BALB C
• Phosphotransferases (Alcohol Group Acceptor)/metabolism
• RNA, Messenger/metabolism
• Random Allocation
• Real-Time Polymerase Chain Reaction
• Receptor, Anaphylatoxin C5a/genetics
• Receptor, Anaphylatoxin C5a/metabolism
• Signal Transduction
• Sphingosine/analogs & derivatives
• Sphingosine/metabolism
• Tumor Necrosis Factor-alpha/metabolism
• p38 Mitogen-Activated Protein Kinases/metabolism

AIM: To evaluate the efficacy of transcatheter arterial chemoembolisation (TACE) compared with surgical intervention and sorafenib for treatment of hepatocellular carcinoma (HCC) in patients with tumor thrombus extending to the main portal vein.

METHODS: From 2009 to 2013, a total of 418 HCC patients with tumor thrombus extending to the main portal vein were enrolled in this study and divided into four groups. These groups underwent different treatments as follows: TACE (n = 307), surgical intervention (n = 54), sorafenib (n = 15) and palliative treatment (n = 42). Overall survival rates were determined by Kaplan-Meier method, and differences between the groups were identified through log-rank analysis. Cox’s proportional hazard model was used to identify the risk factors for survival.

RESULTS: The mean survival periods for patients in the TACE, surgical intervention, sorafenib and palliative treatment groups were 10.39, 4.13, 5.54 and 2.82 mo, respectively. For the TACE group, the 3-, 6-, 12- and 24-mo survival rates were 94.1%, 85.9%, 51.5% and 0.0%, respectively. The corresponding rates were 60.3%, 22.2%, 0.0% and 0.0% for the surgical intervention group and 50.9%, 29.5%, 0.0% and 0.0% for the sorafenib group. Evidently, the results in the TACE group were significantly higher than those in the other groups (P < 0.0001). Furthermore, no significant difference among survival rates was observed between TACE with/without sorafenib (10.22 mo vs 10.52 mo, P = 0.615). No significant difference in survival rates was also found among the surgical intervention, sorafenib and palliative treatment groups (P > 0.05). These values significantly increased after TACE with/without sorafenib compared with other treatments (P < 0.05).

CONCLUSION: For HCC patients with tumor thrombus extending to the main portal vein, TACE can yield a higher survival rate than surgical intervention or sorafenib treatment.

• Hepatocellular carcinoma
• Portal vein
• Tumor thrombus
• Sorafenib
• Transcatheter arterial chemoembolisation
• Surgery

• Adult
• Antineoplastic Agents/adverse effects
• Antineoplastic Agents/therapeutic use
• Carcinoma, Hepatocellular/complications
• Carcinoma, Hepatocellular/mortality
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/therapy
• Chemoembolization, Therapeutic/adverse effects
• Chemoembolization, Therapeutic/mortality
• Chemotherapy, Adjuvant
• Chi-Square Distribution
• Female
• Hepatectomy/adverse effects
• Hepatectomy/mortality
• Humans
• Kaplan-Meier Estimate
• Liver Neoplasms/complications
• Liver Neoplasms/mortality
• Liver Neoplasms/pathology
• Liver Neoplasms/therapy
• Male
• Middle Aged
• Multivariate Analysis
• Neoplastic Cells, Circulating/pathology
• Niacinamide/adverse effects
• Niacinamide/analogs & derivatives
• Niacinamide/therapeutic use
• Odds Ratio
• Phenylurea Compounds/adverse effects
• Phenylurea Compounds/therapeutic use
• Portal Vein/pathology
• Proportional Hazards Models
• Retrospective Studies
• Risk Factors
• Sorafenib
• Time Factors
• Treatment Outcome
• Venous Thrombosis/etiology
• Venous Thrombosis/mortality
• Venous Thrombosis/pathology
• Venous Thrombosis/therapy

AIM: To determine hepatitis C virus (HCV) seroprevalence among the Libyan population using blood donors and applying the autoregressive integrated moving average (ARIMA) model to predict future trends and formulate plans to minimize the burden of HCV infection.

METHODS: HCV positive cases were collected from 1008214 healthy blood donors over a 6-year period from 2008 to 2013. Data were used to construct the ARIMA model to forecast HCV seroprevalence among blood donors. The validity of the model was assessed using the mean absolute percentage error between the observed and fitted seroprevalence. The fitted ARIMA model was used to forecast the incidence of HCV beyond the observed period for the year 2014 and further to 2055.

RESULTS: The overall prevalence of HCV among blood donors was 1.8%, varying over the study period from 1.7% to 2.5%, though no significant variation was found within each calendar year. The ARIMA model showed a non-significant auto-correlation of the residuals, and the prevalence was steady within the last 3 years as expressed by the goodness-of-fit test. The forecast incidence showed an increase in HCV seropositivity in 2014, ranging from 500 to 700 per 10000 population, with an overall prevalence of 2.3%-2.7%. This may be extended to 2055 with minimal periodical variation within each 6-year period.

CONCLUSION: The applied model was found to be valuable in evaluating the seroprevalence of HCV among blood donors, and highlighted the growing burden of such infection on the Libyan health care system. The model may help in formulating national policies to prevent increases in HCV infection and plan future strategies that target the consequences of the infection.

• Autoregressive integrated moving average model
• Libya
• Hepatitis C virus
• Blood donors

Acute kidney injury (AKI) is a common complication in patients with end-stage liver disease and advanced cirrhosis regardless of the underlying cause. Hepatorenal syndrome (HRS), a functional form of kidney failure, is one of the many possible causes of AKI. HRS is potentially reversible but involves highly complex pathogenetic mechanisms and equally complex clinical and therapeutic management. Once HRS has developed, it has a very poor prognosis. This review focuses on the diagnostic approach to HRS and discusses the therapeutic protocols currently adopted in clinical practice.

• Hepatorenal syndrome
• Cirrhosis
• Acute kidney injury
• Diagnosis
• Treatment
• Terlipressin
• Liver support system

AIM: To investigate the etiology and management of a poorly understood complication of transjugular intrahepatic portosystemic shunt; “endotipsitis”.

METHODS: A MEDLINE database search was carried out, reviewing all papers with specific words in the title or abstract, and excluding appropriately. Of 283 papers that were reviewed, 22 papers reporting 53 cases in total were included in the analyses.

RESULTS: No predominant etiology for endotipsitis was identified, but gram-positive organisms were more common among early-onset infections (P < 0.01). A higher mortality rate was associated with Staphylococcus aureus and Candida spp infections (P < 0.01). There was no trend in choice of antibiotic based on the microorganisms isolated and treatment varied from the guidelines of other vegetative prosthetic infections. In endotipsitis “high risk” organisms have been identified, emphasizing the importance of ensuring optimal antimicrobial therapy and adjunctive management strategies.

CONCLUSION: Higher mortality rate was associated with Staphylococcus aureus and Candida spp infections. A prospective multicenter trial is needed before specific treatment can be recommended.

• Transjugular intrahepatic portosystemic shunts
• Transjugular intrahepatic portosystemic shunt infection
• Persistent bacteremia
• Tipsitis
• Antimicrobial therapy

Liver biopsy is still the golden standard in the diagnosis of chronic liver diseases, but it is invasive, which limits its application. Therefore, the search for a reliable noninvasive diagnostic method has attracted more and more attention. Since Fibroscan (FS) was launched in 2003, scholars have paid more attention to this modality, because it is non-invasive, painless, rapid and objective. In this paper, we will review the value of FS in the diagnosis and treatment of chronic liver disease.

• Fibroscan
• Transient elastography
• Chronic liver disease
• Noninvasive diagnosis

Spontaneous bacterial peritonitis (SBP) is a common complication in liver cirrhotic patients with ascites. Polymorphonuclear cells > 250/mL and bacterial cultures of ascitic fluid are main means for diagnosis of SBP. Leukocyte esterase isozyme, pH value, procalcitonin, lactoferrin, granulocyte elastase and phagocytized bacterial DNA in leukocytes from ascitic fluid also play a role in the diagnosis of SBP. Third-generation cephalosporins (especially cefotaxime) are the most appropriate antibiotics for the treatment of SBP. Albumin infusion can prevent renal impairment and reduce mortality among patients with SBP.

• Spontaneous bacterial peritonitis
• Cirrhosis
• Ascites
• Diagnosis
• Treatment

Patatin-like phospholipase domain-containing 3 (PNPLA3 or adiponutrin) displays anabolic and catabolic activities in lipid metabolism, and has been reported to be significantly associated with liver fat content. Various studies have established a strong link between the 148 isoleucine to methionine protein variant (I148M) of PNPLA3 and liver diseases, including nonalcoholic fatty liver disease (NAFLD). However, detailed demographic and ethnic characteristics of the I148M variant and its role in the development of nonalcoholic fatty liver fibrosis have not been fully elucidated. The present review summarizes the current knowledge on the association between the PNPLA3 I148M variant and NAFLD, and especially its role in the development of nonalcoholic fatty liver fibrosis. First, we analyze the impact of demographic and ethnic characteristics of the PNPLA3 I148M variant and the presence of metabolic syndrome on the association between PNPLA3 I148M and NAFLD. Then, we explore the role of the PNPLA3 I148M in the development of nonalcoholic fatty liver fibrosis, and hypothesize the underlying mechanisms by speculating a pro-fibrogenic network. Finally, we briefly highlight future research that may elucidate the specific mechanisms of the PNPLA3 I148M variant in fibrogenesis, which, in turn, provides a theoretical foundation and valuable experimental data for the clinical management of nonalcoholic fatty liver fibrosis.

• PNPLA3 I148M variant
• Polymorphism
• Nonalcoholic fatty liver disease
• Nonalcoholic fatty liver fibrosis

• Ethnicity/genetics
• Female
• Genetic Association Studies
• Genetic Predisposition to Disease
• Humans
• Lipase/genetics
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/enzymology
• Liver Cirrhosis/ethnology
• Liver Cirrhosis/genetics
• Male
• Membrane Proteins/genetics
• Non-alcoholic Fatty Liver Disease/diagnosis
• Non-alcoholic Fatty Liver Disease/enzymology
• Non-alcoholic Fatty Liver Disease/ethnology
• Non-alcoholic Fatty Liver Disease/genetics
• Phenotype
• Polymorphism, Genetic
• Risk Factors
• Sex Factors

• Antiviral drugs
• Health care worker
• Health care-associated infection
• Hemodialysis
• Hepatitis C virus
• Occupational exposure
• Standard precautions
• Unsafe injections

• Antiviral Agents/therapeutic use
• Attitude of Health Personnel
• Cross Infection/diagnosis
• Cross Infection/epidemiology
• Cross Infection/prevention & control
• Cross Infection/transmission
• Cross Infection/virology
• Early Diagnosis
• Health Knowledge, Attitudes, Practice
• Hepatitis C/diagnosis
• Hepatitis C/epidemiology
• Hepatitis C/prevention & control
• Hepatitis C/transmission
• Hepatitis C/virology
• Humans
• Infection Control/methods
• Infectious Disease Transmission, Patient-to-Professional
• Infectious Disease Transmission, Professional-to-Patient
• Occupational Exposure/adverse effects
• Occupational Health
• Predictive Value of Tests
• Risk Assessment
• Risk Factors
• Serologic Tests
• Treatment Outcome

AIM: To investigate the effects of Glytan on splanchnic hemodynamics and its reduction of portal pressure in portal hypertensive rats.

METHODS: Glytan (Ganluotong in Chinese), is composed of salvianolic acid B and diammonium glycyrrhizinate. Portal hypertension (PHT) was induced in the rats by common bile duct ligation (BDL). Hemodynamic studies were performed using the colored microsphere method. Radioimmunoassay (RIA) was used to determine endothelin (ET)-1 levels in the mesenteric circulation. Western blotting methods were used to investigate the effect of Glytan on ET A receptor (ETAR), ET B receptor (ETBR), endothelial NO synthase (eNOS), G-protein-coupled receptor kinase (GRK)2, and β-arrestin 2 expression in the mesentery. The mRNA of ETAR and ETBR was determined using real-time polymerase chain reaction.

RESULTS: Treatment with Glytan reduced portal pressure (PP) and portal territory blood flow (PTBF) and increased both mean arterial pressure (MAP) and splanchnic vascular resistance (SVR). Especially at 4 wk, PP decreased by about 40%, while MAP increased by 13%, SVR increased by 12%, and PTBF decreased by about 21%. The effect of blood flow reduction was greatest in the mesentery (about 33%) at 4 wk. The mesenteric circulation ET-1 levels of BDL rats were lower and negatively correlated with PP at 4 wk. Glytan can increase mesenteric ET-1 content and inhibit ETBR, eNOS, GRK2, and β-arrestin 2 expression in the mesentery. Moreover, Glytan showed no effect on the expression of ETAR protein and mRNA.

CONCLUSION: The decreased PP and PTBF observed after Glytan treatment were related to increased mesenteric vasoconstriction and increased receptor sensitivity to vasoconstrictor.

• Glytan
• Portal hypertension
• Hemodynamics
• Mesentery
• Endothelin-1
• Receptor
• Sensitivity

• Animals
• Benzofurans/pharmacology
• Blood Flow Velocity
• Disease Models, Animal
• Drugs, Chinese Herbal/pharmacology
• Endothelin B Receptor Antagonists/pharmacology
• Endothelin-1/blood
• G-Protein-Coupled Receptor Kinase 2/antagonists & inhibitors
• G-Protein-Coupled Receptor Kinase 2/metabolism
• Glycyrrhetinic Acid/analogs & derivatives
• Glycyrrhetinic Acid/pharmacology
• Hypertension, Portal/blood
• Hypertension, Portal/drug therapy
• Hypertension, Portal/enzymology
• Hypertension, Portal/physiopathology
• Male
• Mesentery/blood supply
• Mesentery/drug effects
• Mesentery/enzymology
• Nitric Oxide Synthase Type III/antagonists & inhibitors
• Nitric Oxide Synthase Type III/metabolism
• Portal Pressure/drug effects
• Protein Kinase Inhibitors/pharmacology
• Rats, Sprague-Dawley
• Receptor, Endothelin B/drug effects
• Receptor, Endothelin B/metabolism
• Signal Transduction/drug effects
• Splanchnic Circulation/drug effects
• Time Factors
• Vasoconstriction/drug effects
• Vasoconstrictor Agents/pharmacology

AIM: To explore the clinical and epidemiological characteristics of hepatitis virus-associated intrahepatic cholangiocarcinoma (ICC).

METHODS: A retrospective analysis of clinical and epidemiological data for 92 patients with pathologically confirmed ICC was conducted. The data between patients with virus-associated ICC and those with non-virus-associated ICC were compared.

RESULTS: The mean age of the 92 patients was 54.29±12.09 years, and there were more male patients. Sixty-five cases were in the hepatitis group and 27 cases in the non-hepatitis group. Male patients in the hepatitis group had significantly earlier age of onset than those in the non-hepatitis group. About 47.69% of patients in the hepatitis group and 18.51% of patients in the non-hepatitis group were diagnosed on physical examination and there was a significant difference in the percentage between the two groups. Alpha-fetoprotein (AFP) positive rate in the hepatitis group (49.23%) was significantly higher than that in the non-hepatitis group (14.81%), while CA199 positive rate in the hepatitis group (33.85%) was significantly lower than that in the non-hepatitis patients (74.07%). HBV infection accounted for 92.31% of the patients with hepatitis, who were mainly HBeAg-negative patients. There was only 1/4 of patients with prior anti-hepatitis B virus therapy. The proportion of patients with liver cirrhosis was about 60% among all ICC patients.

CONCLUSION: Chronic hepatitis virus infection is an important risk factor for the onset of ICC. The exploration of effect of hepatitis virus infection on the occurrence and prognosis of ICC will further provide clues for effective intervention.

• Intrahepatic cholangiocarcinoma
• Hepatitis virus
• Epidemiological characteristics

AIM: To investigate differential expression profile of microRNAs (miRNAs) in plasma of pretreated patients with/without anti-tuberculosis drug-induced hepatotoxicity (ATDH).

METHODS: Plasma samples were collected from patients with/without ATDH before anti-tuberculosis treatment and subjected to miRNA microarray analysis. Twenty-five miRNAs were tested using high-flux real-time quantitative PCR. The target genes of miRNAs were predicted using the Internet software, and the GO functional classification of target proteins was analyzed using the PANTHER tool.

RESULTS: Compared with patients without ATDH, there were 7 miRNAs differentially expressed in patients with ATDH before anti-tuberculosis drug therapy, 4 of which were up-regulated, including miR-4284, miR-3620, miR-652-5p and miR-4800-5p, and 3 down-regulated, including miR-338-3p, miR-424-5p and miR-194-5p.

CONCLUSION: There are differentially expressed miRNAs in the circulation of patients with ATDH before anti-tuberculosis drug therapy, and the up-regulated miRNAs (esp. miR-4284) may be new biological markers for screening ATDH susceptible population.

• Anti-tuberculosis drug
• Hepatotoxicity
• MicroRNA
• Plasma
• Differentially expressed

AIM: To investigate if there is an association between hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and the risk of pancreatic cancer.

METHODS: All relevant studies published before 11 October, 2012 were identified by a systematic search of MEDLINE, EMBASE, BIOSIS Previews and the Cochrane Library databases and with cross-referencing. The observational studies that reported RR or OR estimates with 95%CIs for the association between HBV or HCV and pancreatic cancer were included. A random-effects model was used to summarize meta-analytic estimates. The Newcastle-Ottawa quality assessment scale was applied to assess the quality of the methodology in the included studies.

RESULTS: A total of 8 eligible studies were selected for meta-analysis. Overall, chronic hepatitis B and inactive hepatitis B surface antigen (HBsAg) carrier state (HBsAg positive) had a significantly increased risk of pancreatic cancer with OR of 1.20 (95%CI: 1.01-1.39), especially in the Chinese population (OR = 1.30, 95%CI: 1.05-1.56). Past exposure to HBV (possible occult HBV infection) had an increased OR of pancreatic cancer risk (OR = 1.24, 95%CI: 1.05-1.42), especially among those patients without natural immunity [anti hepatitis B core (HBc) positive/hepatitis B surface antibody (anti HBs) negative], with OR of 1.67 (95%CI: 1.13-2.22). However, past exposure to HBV with natural immunity (anti-HBc positive/anti-HBs positive) had no association with pancreatic cancer development, with OR 0.98 (95%CI: 0.80-1.16), nor did the HBV active replication (hepatitis B e antigen positive status), with OR 0.98 (95%CI: 0.27-1.68). The risk of pancreatic cancer among anti-HBs positive patients was significantly lower than among anti-HBs negative patients (OR = 0.54, 95%CI: 0.46-0.62). Past exposure to HCV also resulted in an increased risk of pancreatic cancer (OR = 1.26, 95%CI: 1.03-1.50). Significant between-study heterogeneity was observed. Evidence of publication bias for HBV/HCV infection-pancreatic cancer association was not found.

CONCLUSION: Chronic HBV and HCV infection increases pancreatic cancer risk. Our findings underscore the need for more studies to confirm this potential relationship.

• Hepatitis B
• Hepatitis C
• Pancreatic cancer
• Observational studies
• Meta-analysis

• Chi-Square Distribution
• Evidence-Based Medicine
• Hepatitis B, Chronic/diagnosis
• Hepatitis B, Chronic/epidemiology
• Hepatitis C, Chronic/diagnosis
• Hepatitis C, Chronic/epidemiology
• Humans
• Observational Studies as Topic
• Odds Ratio
• Pancreatic Neoplasms/diagnosis
• Pancreatic Neoplasms/epidemiology
• Risk Assessment
• Risk Factors

AIM: To analyze the distribution of different hepatitis C virus (HCV) subgenotypes in Heilongjiang province, China.

METHODS: Serum samples from 1 313 patients with HCV infection, including 627 (47.75%) males and 686 (52.25%) females, were subgenotyped using multiplex nested PCR assay. The associations of HCV subgenotypes with gender, age, viral load, and ALT level were analyzed.

RESULTS: Of 1 313 patients, 927 (70.60%) were successfully subgenotyped. Among typable subgenotypes, 1b⁺/2a^- was found in 388 (41.86%) cases, 2a⁺/1b^- in 318 (34.30%) cases, 1b+2a in 197 (21.25%) cases, and 1a+/2b in 24 (2.59%) cases. The percentage of patients with 2a⁺/1b^- subgenotype was significantly higher in females (37.50%) and patients with HCVRNA of (1.000-9.999) × 10⁴ (54.55%), ALT level >200 (60.87%) or ≤ 40 (41.02%) (all P < 0.05). The percentage of patients with 1b⁺/2a^- subgenotype was significantly lower in patients with HCVRNA of (1.000-9.999) × 10⁴ (24.24%) or ALT level >200 (13.04%) (both P < 0.05).

CONCLUSION: Genotypes 1b and 2a are the most prevalent genotypes in Heilongjiang province. The distribution of different HCV subgenotypes is associated with gender, viral load, and ALT level.

• Hepatitis C virus
• PCR
• Subgenotype

Liver transplantation is indicated in patients with acute liver failure, decompensated cirrhosis, hepatocellular carcinoma and rare liver-based genetic defects that trigger damage of other organs. Early referral to a transplant center is crucial in acute liver failure due to the high mortality with medical therapy and its unpredictable evolution. Referral to a transplant center should be considered when at least one complication of cirrhosis occurs during its natural history. However, because of the shortage of organ donors and the short-term mortality after liver transplantation on one hand and the possibility of managing the complications of cirrhosis with other treatments on the other, patients are carefully selected by the transplant center to ensure that transplantation is indicated and that there are no medical, surgical and psychological contraindications. Patients approved for transplantation are placed on the transplant waiting list and prioritized according to disease severity. Thus, the appropriate timing of transplantation depends on recipient disease severity and, although this is still a matter of debate, also on donor quality. These two variables are known to determine the “transplant benefit” (i.e., when the expected patient survival is better with, than without, transplantation) and should guide donor allocation.

• Liver transplantation
• Referral
• Waiting list
• Prioritization
• Allocation
• Timing
• Cirrhosis
• Hepatocellular carcinoma
• Indications
• Contraindications