Liver fibrosis is an important pathological stage for the progression of chronic liver diseases to liver cirrhosis.Timely and accurate assessment of fibrosis degree plays an important role in guiding the treatment of chronic liver diseases.With the development of molecular biology techniques and wide application of molecular diagnostic techniques,the measurement of novel serum molecular diagnostic markers may contribute to the early diagnosis and precise treatment of liver fibrosis.A number of novel serum molecular markers with a diagnostic value have been identified,including fibroblast factor,matrix metalloproteinases and their inhibitors,extracellular matrix-related markers,and non-coding RNAs.In addition,genomics,proteomics,and metabolomics also have certain diagnostic values.

The treatment responses to pegylated interferon alpha (PEG-IFNα)in patients with chronic hepatitis B (CHB)are associated with the genetic polymorphisms,immune status,hepatitis B virus genotype,and viral load of the host.This article reviews the recent studies on influential factors for the responses to PEG-IFNαin CHB patients.The important predictors of the clearance and seroconversion of HB-sAg and HBeAg and sustained virological response include interleukin-28B (IL-28B)gene polymorphism,baseline level of interferon-inducible protein-10,IL-17A,IL-10,tumor necrosis factor-α,viral load and genotype,and changes in serum HBsAg and HBeAg levels at weeks 12 and 24 of treatment.

Objective To measure hepatic ultrasonic integrated backscatter (IBS) in healthy rabbits as a non-invasive quantitative diagnostic means for hepatic steatosis, hepatic fibrosis, and liver cirrhosis; to determine the factors that may influence the IBS measurement. Methods Thirty-five healthy New Zealand white rabbits with normal liver function tests and normal liver biopsies were used in this study. HP Sonos 5500 image system with quantitative analysis function was used for IBS measurement. With the machine setting fixed, and optimal image obtained, left and right liver were divided into near, medial and far areas according to the depth. Further the measurements of IBS in different depth were performed respectively. Meanwhile, in the same liver the IBS image was collected and the change of IBS intensity was measured in various setting of machine index (MI), time gain compensation (TGC) and lateral gain compensation (LGC). Results Average image intensity (AII) of left liver (from near to far areas) was ( 25.38? 2.36)dB, ( 26.32? 2.38)dB, and ( 26.45? 2.28)dB, respectively. The AII of the right liver (from near to far areas) was ( 24.99? 2.23)dB, ( 24.92? 2.59)dB, and ( 25.38? 2.36)dB, respectively. The average standardized AII of image in left livers was significantly higher than that of the right (P

Objective To investigate the effect of lamivudine (LAM) on serum interferon (IFN)-γ and interleukin (IL)-4 levels in patients with chronic hepatitis B(CHB). Methods Serum IFN-γ and IL-4 levels were measured with enzyme-linked immunosorbent assay (ELISA) in 66 CHB patients at baseline and 3, 6, 9 and 12 months after LAM treatment respectively. And 20 healthy volunteers served as healthy control. The comparision of pretreatment and post-treatment was done using t test and numberation data were analyzed by non parametric rank sum test. Results In HBeAg positive patients, the serum level of IFN-γ was (21.03±4.44) ng/L in complete response group, which was higher than partial response group [(13.85±3.92) ng/L] and non-response group [(10.63± 3.11) ng/L] (t=7.56,t=11.87, both P<0.01). Take that IFN-γ is 15.66 ng/L as boundry patients with high baseline IFN-γ level showed much higher complete response rate (31.0% vs 8.7%, x2 =8.391, P<0.01) and lower non-response rate (13.8% vs 52.2%,x2=4. 256, P<0.01) than those with low baseline IFN-γ levels. After LAM treatment, the IFN-γ/IL-4 ratios in complete response patients were approximate or even higher than those in healthy group, whereas the IFN-γ/ IL-4 ratios of patients with partial response and non response were lower than those in healthy group. In HBeAg negative patients, the IFN-γ/IL-4 ratios increased slowly but didn't reach the same levels of healthy group. Conclusions It is suggested that LAM treatment can increase IFN-γ release and reduce IL-4 release in CHB patients. The response type to LAM therapy is associated with the recovery of T helper cell (Th) 1/Th2 balance post-treatment and pretreatment IFN-γ levels.

Liver cirrhosis is the severe period of chronic liver diseases, especially decompensated liver cirrhosis and its complications, such as ascites, esophagogastric variceal bleeding, hepatic encephalopathy, acute kidney injury, and hepatocellular carcinoma, which greatly affect patients’ quality of life and even threaten their lives. Early prevention and treatment of the causes of development and progression and pathogenic mechanism may slow down or reverse liver cirrhosis and its severe complications. Once the disease progresses to portal hypertension and related complications, it is very important to select preventive measures for acute exacerbation of different complications, as well as the methods and timing for treatment in acute stage, which may help to save patients’ lives and improve their prognosis.

OBJECTIVETo investigate the relationship between level of Th17/CD4+T cell ratio in peripheral blood and postoperative complications in patients with hepatitis B virus (HBV)-related cirrhosis after orthotopic liver transplantation (OLT).

METHODSFifty-one patients with HBV-related cirrhosis who received OLT were enrolled in this study. Flow cytometry analysis was performed to measure the proportion of Th17 cells to CD4+T cells at the following time points:pre-OLT, and post-OLT days 7, 14 and 21. The relevant hepatic biochemistry indexes, serum concentration of FK506 and level of procalcitonin (PCT) were detected for all patients after OLT.

RESULTSThe transplant recipients were divided into four groups according to the postoperative complication, which included acute rejection (AR, n=12), postoperative infection (POI, n=10), transient intrahepatic cholestasis (TIHC, n=12) and no complications (n=17). The Th17/CD4+T cell frequencies were notably higher in the AR patients after OLT (vs. before OLT, P less than 0.01) and this increase was positively correlated with rejection activity index (RAI; r=0.759, P=0.004). Up to post-OLT day 14, the frequencies of Th1 7/CD4+T cells in the POI group were similar to those of the AR group but they decreased to near-baseline level at post-OLT day 21.Furthermore, the percentage of Th17/CD4+T cells in the POI group was positively correlated with PCT (r=0.768, P=0.010). The frequencies of Th17/CD4+T cells in the TIHC and no complications groups showed a slowly decreasing trend after OLT and became markedly lower than the before OLT levels (P<0.01). The concentration of FK506 in the AR group was significantly lower than that in the other groups at post-OLT day 14 (P=0.000).

CONCLUSIONSTh17/CD4+T cell level in peripheral blood might be a useful marker for risk assessment and monitoring of OLT postoperative complications, such as acute rejection and postoperative infection, in the early stage, and might help to improve patient prognosis by allowing for timely application of anti-rejection and antibacterial agents.

Calcitonin ; Calcitonin Gene-Related Peptide ; Hepatitis B ; Hepatitis B virus ; Humans ; Liver Cirrhosis ; Liver Transplantation ; Postoperative Complications ; Protein Precursors ; Th17 Cells

Liver cirrhosis is a chronic progressive liver disease. A non-invasive diagnostic technique for hepatic fibrosis combined with liver biochemistry, molecular biology, and immunology, imaging study, liver histopathological assessment, and traditional Chinese medicine (TCM) syndrome differentiation can accurately diagnose the cause, severity of disease, and determine the prognosis. In clinical practice of Western medicine, there are five-stages of cirrhosis classification, with periods 1 and 2 being compensated stage, and periods 3 to 5 being decompensated stage. Etiological treatment and anti-hepatic fibrosis treatment are the basic measures for different disease severity and complications. Comprehensive application of modern medical technology and traditional Chinese medicine differentiation therapy can improve the treatment effect and survival rate.

ObjectiveTo investigate the association of single nucleotide polymorphisms (SNPs) of programmed cell death-1 (PD-1) gene with chronic hepatitis C virus (HCV) infection and the effect of antiviral therapy with interferon combined with ribavirin. MethodsA total of 228 patients with chronic hepatitis C (CHC) who were hospitalized in seven hospitals in Hebei Province, China from October 2010 to October 2012 were enrolled and treated with interferon combined with ribavirin as the individualized antiviral therapy. Eighty-one persons who underwent physical examination were enrolled as control group. The TaqMan probe method was used to detect PD-1 gene polymorphisms. The distribution of alleles and genotypes at PD-1.1 and PD-1.3 were compared between the two groups, and the association between the SNPs of PD-1.1 and PD-1.3 and anti-HCV effect was analyzed. The chi-square test was used for the comparison of categorical data between groups. ResultsThe CHC group showed significantly higher frequencies of T allele and TT genotype at PD-1.1 than the control group (52.41% vs 43.21%, χ2=4.059, P=0.044; 28.51% vs 14.81%, χ2=6.469, P=0.039). The SNPs of PD-1.1 gene were not significantly associated with complete early virologic response or sustained virologic response (both P＞0.05). Both groups had CC genotype at PD-1.3. ConclusionPD-1.1 T allele might be associated with chronic HCV infection, and patients carrying TT genotype have a high risk of chronic HCV infection. PD-1.1 polymorphism is not associated with virologic response to anti-HCV therapy.

OBJECTIVETo explore the clinical application and related factors of FibroTouch in the diagnosis of liver fibrosis in patients with chronic liver disease through comparison of the specificity and sensitivity of FibroTouch and multi-parameter models, and to identify whether FibroTouch is a more accurate and safe method in diagnosis of liver fibrosis and evaluation of the therapeutic effect.

METHODSA total of 190 patients with chronic liver disease were performed liver biopsy and underwent liver stiffness measurement (LSM) using FibroTouch in department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University from January 2014 to February 2015. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) were tested by enzymic method with automatic biochemistry analyzer. Blood platelet counts were detected by automatic blood cell analyzer. AST-to-PLT ratio index (APRI) and fibrosis index based on the 4 factor (FIB-4) were calculated. The diagnostic values of FibroTouch, APRI and FIB-4 for liver fibrosis degree were calculated and compared by receiver operating characteristic (ROC) curves. The related factors of LSM were analyzed by Spearman analysis.

RESULTSThere was significant correlation between LSM and histological fibrosis (r=0.804, P=0.000). The area under ROC curve of LSM for S(≥2, S≥3 and S=4 was 0.894, 0.938 and 0.961, respectively, which was significantly higher than APRI (0.678, 0.698 and 0.658) and FIB-4 (0.765, 0.785 and 0.775). On Spearman analysis, LSM was positively correlated with age, ALT, AST, TBIL ((≥2×ULN) and the grade of liver inflammation (r=0.309, 0.558, 0.504, 0.492 and 0.532, respectively) but negatively with PLT (r=-0.444), (all P<0.05).

CONCLUSIONSLSM is a convenient and reliable approach for diagnosis of liver fibrosis in patients with chronic liver disease. The sensitivity and specificity of Fibrotouch in diagnosis of hepatic fibrosis is superior to APRI and FIB-4, and age, high level ofALT, AST and TBIL (≥2×ULN) were independent predictors of LSM inaccuracy.

Alanine Transaminase ; Aspartate Aminotransferases ; Bilirubin ; Biomarkers ; Biopsy ; Chronic Disease ; Humans ; Liver Cirrhosis ; Platelet Count ; ROC Curve

Chronic hepatitis C in children has an insidious onset and has few available treatment options.Pegylated interferon alpha (Peg-IFNα) combined with ribavirin (RBV),known as the PR regimen for short,used to be the standard regimen;however,treatment response is often affected by various factors including hepatitis C virus genotype,viral load,and host gene polymorphisms,and some children cannot tolerate the adverse reactions of PR regimen.HCV Guidance:Recommendations for Testing,Managing,and Treating Hepatitis C developed by the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America (AASLD/IDSA) in September,2017 recommended that direct-acting antiviral agents (DAAs) can be used for children with hepatitis C who are aged above 12 years or have a body weight of ≥35 kg.Sofosbuvir combined with ledipasvir is the recommended regimen for children with genotype 1,4,5,or 6 infection,and sofosbuvir combined with RBV is recommended for children with genotype 2 or 3 infection.The course of disease is 12 weeks for previously untreated children with genotype 1 infection,children with genotype 1 infection who were treated by IFNα and do not have liver cirrhosis,or children with genotype 2,4,5,or 6 infection,and 24 weeks for children with genotype 1 infection who were treated by IFNα and have liver cirrhosis or children with genotype 3 infection.Further studies are needed to investigate the type of DAAs used in children with chronic hepatitis C aged ＜ 12 years,related regimens,and their safety.As for special populations including children with chronic hepatitis C complicated by HIV infection and those treated by liver transplantation,individualized treatment regimens should be developed with reference to the status of HIV infection and complications of liver transplantation.