Current treatment of chronic hepatitis C in China: Dilemma and potential problems.

Major advances have been made in the treatment of chronic hepatitis C virus (HCV) infection with the advent of direct-acting antiviral agents (DAAs). China has the most cases of HCV infection worldwide, but none of the DAAs has been approved in mainland China so far, and interferon (IFN)-α-based treatment remains the standard of care. HCV patients without response or with contraindications to IFN-based therapy have no alternative options. However, many patients buy DAAs, especially the generic forms of sofosbuvir, from other countries or areas. Under these circumstances, the use of these drugs may cause many predictable and unpredictable problems in ethics, law and medical practice. Given the obstacles of legal accessibility to DAAs and the potential problems of obtaining and using DAAs in China, the early launching of the DAAs in China or the legalization of buying drugs from areas outside China and using these drugs in China is an urgent issue and needs to be dealt with as soon as possible, in the interest of the patients.

Prognostic role of neutrophil-to-lymphocyte ratio in colorectal cancer: a systematic review and meta-analysis.

The prognostic role of inflammation index like neutrophil-to-lymphocyte ratio (NLR) in colorectal cancer (CRC) remains controversial. We conduct a meta-analysis to determine the predictable value of NLR in the clinical outcome of CRC patients. The analysis was carried out based on the data from 16 studies (19 cohorts) to evaluate the association between NLR and overall survival (OS) and progression-free survival (PFS) in patients with CRC. In addition, the relationship between NLR and clinicopathological parameters was assessed. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was used as the effect size estimate. Our analysis results indicated that elevated pretreatment NLR predicted poorer OS (HR: 1.813, 95% CI: 1.499-2.193) and PFS (HR: 2.102, 95% CI: 1.554-2.843) in patients with CRC. Increased NLR is also significantly associated with the poorer differentiation of the tumor (OR: 1.574, 95% CI: 1.226-2.022) and higher carcino-embryonie antigen (CEA) level (OR: 1.493, 95% CI: 1.308-1.705). By these results, we conclude that NLR gains a prognostic value for patients with CRC. NLR should be monitored in CRC patients for rational stratification of the patients and adjusting the treatment strategy.

Risk factors and clinical characteristics of portal vein thrombosis after splenectomy in patients with liver cirrhosis.

BACKGROUND: Portal vein thrombosis (PVT) is a potential lethal complication and may have negative influence on the prognosis after splenectomy in patients with liver cirrhosis. Prevention and timely detection of PVT are quite significant. There is a lack of knowledge about the clinical features and risk factors of PVT. Our study aimed to investigate the risk factors and clinical characteristics of PVT in order to figure out the high-risk individuals. METHODS: We collected the clinical data of 472 consecutive patients with non-neoplastic liver cirrhosis who had undergone splenectomy from January 2008 to December 2010 in our institution. Clinical and surgical characteristics of patients who developed PVT postoperatively and those who did not develop PVT were compared. Univariate and multivariate analyses of risk factors of PVT were performed. The mortality and rebleeding rate of the patients were also evaluated. RESULTS: Of the 472 patients, 52 were excluded from the study. PVT developed in 71 (71/420, 16.9%) patients. Multivariate analysis revealed that wider preoperative portal vein diameter, postoperative thrombocytosis, prolonged prothrombin time and periesophagogastric devascularization were significantly correlated with PVT development [odds ratio (OR): 5.701, 2.807, 1.850 and 2.090, respectively]. The incidence of PVT in patients who took antiplatelet drugs was not lower than that in those who did not. Follow-up showed that patients in the PVT group had a tendency towards reduced overall survival but it was not statistically significant. Gastrointestinal bleeding occurred more often in the PVT group than that in the non-PVT group (P=0.044). CONCLUSIONS: Wider preoperative portal vein diameter, postoperative thrombocytosis, prolonged prothrombin time and periesophagogastric devascularization are independent risk factors of PVT. PVT is related with higher risk of postoperative gastrointestinal hemorrhage but has no significant impact on the overall survival.

Therapeutic liver repopulation for metabolic liver diseases: Advances from bench to bedside.

Metabolic liver diseases are characterized by inherited defects in hepatic enzymes or other proteins with metabolic functions. Therapeutic liver repopulation (TLR), an approach of massive liver replacement by transplanted normal hepatocytes, could be used to provide the missing metabolic function elegantly. However, partial and transient correction of the underlying metabolic defects due to very few integrated donor cell mass remains the major obstacle for the effective and widespread use of this approach. Little engraftment and proliferation insufficiency lead to the poor outcome. This article reviews the advances in the mechanisms of initial engraftment and selective proliferation and suggests some effective treatment strategies, from pharmacological preconditioning to stem cell transplantation, to optimize liver repopulation with liver cell transplantation. Enhancing cell viability and plating efficiency, increasing sinusoidal spaces, regulation of sinusoidal endothelial cell barrier and controlling inflammatory reaction may promote initial cell engraftment. Liver-directed irradiation, reversible portal vein embolization and fetal liver stem/progenitor cell transplantation induce preferential proliferation of donor cells substantially without severe side-effects. Furthermore, it seems better to use combined approaches to achieve a high level of liver repopulation for the management of metabolic liver diseases.

[Effects of sediment resuspension on bacterioplankton community composition].

To determine the response of bacterioplankton community to sediment resuspension we set up two different intensities of the sediment resuspension in experimental microcosms. We employed the terminal restriction fragment length polymorphism (T-RFLP), denaturing gradient gel electrophoresis (DGGE) methods to characterize the bacterial community structure. The result demonstrated that the species richness of the bacterioplankton in the treatment with sediment resuspension was higher than that in the controls without sediment resuspension. The bacterioplankton species richness and community diversity in the treatment with weak sediment resuspension (WR) was higher than that with strong sediment resuspension (SR). The relationship between bacterioplankton and environmental factors were investigated using canonical correspondence analysis (CCA) and redundancy analysis (RDA). The CCA and RDA results showed that there was a high degree of correlation between bacterioplankton community composition with Cladocera and particulate phosphorus (PP). It indicates that the sediment resuspension of shallow lakes has a significant effect on the species richness and diversity of bacterioplankton. We speculate the main reason is the dynamics of zooplankton community structure and the function of nutrient concentration influenced by the sediment resuspension.

[Effects of granulocyte colony-stimulating factor on hepatocyte apoptosis in acute liver failure: experiment with rats].

OBJECTIVE: To explore the effects of granulocyte colony- stimulating factor (G-CSF) on hepatocyte apoptosis in acute liver failure (ALF) and possible mechanism thereof. METHODS: One hundred and sixty SD rats underwent intraperitoneal injection of D-galactosamine (D-GalN) 1.4 g/kg so as to establish AFL models and then were randomly divided into 2 equal groups: G-CSF therapy group, injected hypodermically with recombinant human G-CSF 50 microg x kg(-1) x d(-1) 2 hours after D-GalN injection for 3 consecutive days, and placebo control group, injected hypodermically with normal saline for 3 consecutive days. Liver samples were collected from 6 rats of each group 6 h, 12 h, 1 day, and 3 days after D-GalN injection respectively. Another six normal rats were used as normal control group. Hepatocyte apoptosis rate was measured by flow cytometry. Immunohistochemistry was used to detect the expression of Bcl-2 and caspase-3, a proapoptosis protein, in the liver sections. RESULTS: The survival rate of the G-CSF therapy group was 53.3%, significantly higher than that of the placebo control group (33.3%, P = 0.027). The hepatocyte apoptosis rate and expression rates of Bcl-2 and caspase-3 in the liver sections after D-GalN injection increased along with time. The hepatocyte apoptosis rate peaked 1 day after the D-GalN injection in both groups. The maximum hepatocyte apoptosis rate of the G-CSF group was 29% +/- 7%, significantly lower than that of the placebo control group (44% +/- 12%, P = 0.026). The gray scale of Bcl-2 in liver sections at hour 12 of the G-CSF group was 152 +/- 37, significantly lower than that of the placebo control group (161 +/- 7, P = 0.012). and the gray scale of Bcl-2 on day 1 of the G-CSF group was 150 +/- 12, significantly lower than that of the placebo control group (159 +/- 9, P = 0.018). The gray scales of caspase-3 on days 1 and 3 of the G-CSF group were 189.6 +/- 4.6 and 184.7 +/- 4.8 respectively, both significantly higher than those of the placebo control group (169.6 +/- 15.7 and 160.0 +/- 5.0, both P = 0.000). CONCLUSION: Apoptosis is a key mechanism contributing to ALF. G-CSF prevents ALF induced by D-GalN, thus raising the survival rate. G-GSF shows an inhibitory efficacy on hepatocytes apoptosis by probably up-regulating Bcl-2 and reducing caspase-3 expression.

[Polymorphism of codon25 in signal peptide region of transforming growth factor beta 1 and its association with chronic hepatitis C virus infection].

OBJECTIVE: To investigate the possible relationship between polymorphism of codon25 in signal peptide region of transforming growth factor beta 1 (TGFb1) and hepatitis C virus (HCV) infection susceptibility. METHODS: Genotypes of TGFb1 of 191 subjects (85 HCV infected patients and 106 healthy controls) were studied. Genotypes of TGFb1 codon25 were determined by amplification refractory mutation system (ARMS). RESULTS: Differences of codon25 polymorphism were not found between HCV infected patients and the controls (P more than 0.05), which showed a similar pattern between the chronic hepatitis C group and HCV-associated liver cirrhosis group (P more than 0.05). There were no differences of genotype distribution of codon25 between ALT normal and ALT elevated patients (P more than 0.05), but G allele frequency was higher in ALT elevated group (P=0.040). There were great differences between the distribution of genotypes (P=0.005) and allele frequency (P=0.000) of the HCV RNA positive and the negative groups in that the HCV RNA positive group differed greatly from the negative group. CONCLUSION: Polymorphism of TGFb1 codon25 may influence the grade of liver inflammatory activity. High G allele frequency of codon25 may be associated with viremia in patients with chronic HCV infection. It seems that polymorphism of codon25 in the signal peptide region of TGFb1 may contribute to the outcome of HCV infected patients.

[Effects of leaf damage and sediment type on compensatory growth of submerged macrophyte Vallisneria spiralis].

Through a 2 x 2 factorial outdoor experiment, the effects of leaf damage and sediment type on the compensatory growth of submerged macrophyte Vallisneria spiralis were examined. The results showed that leaf damage and sediment type had significant effects on the cumulative biomass, biomass allocation, and ramet number of V. spiralis. Compared with undamaged plant, the strongly damaged one had a decrease of cumulative biomass and ramet number and an increase of biomass allocation, but no evident difference was observed between weakly damaged and undamaged plants. The cumulative biomass of undamaged and strongly damaged plants was lower in infertile sediments (bank sediment) than in fertile sediments (lake sediment), but that of weakly damaged plant was almost the same in the two sediments. The biomass allocation and ramet number of V. spiralis were higher in bank sediment than in lake sediment. Leaf damage and sediment type also affected the relative growth rate (RGR) of V. spiralis. Leaf damage resulted in an increase of RGR, but the difference of RGR between weak damage and strong damage was not evident. The RGR of undamaged and strongly damaged plants was significantly higher in lake sediment than in bank sediment, but that of weakly damaged plant was almost the same in the two sediments. The mechanisms of the compensatory growth of V. spiralis were discussed.

Correlation of serum leptin levels with anthropometric and metabolic parameters and biochemical liver function in Chinese patients with chronic hepatitis C virus infection.

AIM: To determine serum leptin levels and investigate their correlations with anthropometric and metabolic parameters and biochemical liver function in patients with chronic hepatitis C virus (HCV) infection and their potential clinical implications. METHODS: Forty-two chronic HCV-infected patients without anti-viral treatment were enrolled in this study, 30 patients had chronic hepatitis C, 10 had cirrhosis, and 2 had hepatocellular carcinoma (HCC). Thirty age- and sex-matched healthy individuals served as controls. Serum leptin levels were determined by ELISA. The biochemical liver function and serum lipids were determined at the same time. The height and body weight of patients and controls were measured, and body mass index (BMI) and body fat were calculated simultaneously. The correlations of serum leptin levels with anthropometric and metabolic parameters and biochemical liver function were assessed statistically. RESULTS: The mean of serum leptin levels in patients with chronic hepatitis C, HCV-associated cirrhosis, HCV-associated HCC and control groups was (6.13+/-3.94), (5.25+/-4.21), (4.17+/-0.28), and (3.59+/-3.44) ng/mL, respectively. The serum leptin level in patients with chronic hepatitis C was significantly higher than that in controls. The serum leptin levels between cirrhotic patients and controls and between male and female cirrhotic patients had no significant difference. Serum leptin levels were positively-correlated with body fat, BMI, and apolipoprotein B (Apo B) in patients with chronic HCV infection. The serum alanine aminotransferase (ALT) levels were closely-correlated with BMI in patients with chronic hepatitis C. CONCLUSION: HCV infection interferes with fat and lipid metabolism in patients with chronic HCV infection and leptin may play a role in hepatosteatosis.

Sequential changes of serum ferritin levels and their clinical significance in lamivudine-treated patients with chronic viral hepatitis B.

AIM: To study the sequential changes of serum ferritin levels in lamivudine-treated patients with chronic viral hepatitis B and the clinical implications. METHODS: Thirty-eight patients with chronic viral hepatitis B were prospectively studied during their treatment with lamivudine. Each patient received 100 mg oral lamivudine daily for 12 mo, and was observed and tested for blood biochemistry and hepatitis B virus (HBV) DNA levels and serum ferritin levels at baseline and at 3, 6 and 12 mo during the treatment. Serum HBV DNA levels were quantitatively determined using fluorescent quantitative polymerase chain reaction (FQ-PCR), and serum ferritin levels were measured by radioimmunoassay. The sequential changes of serum ferritin levels and their relationships with virological, serological and biochemical responses in the patients were analyzed. RESULTS: All the patients had a baseline HBV DNA level higher than 1 x 10(7) copies/L as determined by FQ-PCR and positive HBsAg and HBeAg and abnormal ALT levels. At the end of the 12-mo treatment, 19 of the 38(50.00%) patients had undetectable serum HBV DNA levels by FQ-PCR, and 12(31.58%) became negative for serum HBeAg and 10(26.32%) had seroconversion from HBeAg to HBeAb. Nineteen out of the 38(50.00%) patients had biochemically normal ALT levels after 12-mo lamivudine treatment. Sequential determination showed that lamivudine treatment significantly reduced ferritin levels in chronic hepatitis B patients. When the patients were divided into different groups according to their post-treatment virological, serological and biochemical responses for analysis of the sequential changes of ferritin levels, it was found that the decrease of ferritin levels in HBV DNA-negative group was significantly more obvious than that in HBV DNA-positive group at 6 mo during the treatment (P=0.013). Consecutive comparisons showed that ferritin levels at 3 mo of treatment were obviously decreased as compared with the baseline levels (P<0.05) in HBeAg-negative group, and the decrease of serum ferritin levels in patients with normalized ALT was more significant than that in patients with abnormal ALT at the end of the 12-mo treatment (P=0.048). CONCLUSION: Lamivudine treatment can reduce the serum ferritin levels in chronic viral hepatitis B patients and decreases of ferritin levels can be more significant in patients exhibiting virological, serological and biochemical responses, indicating that dynamic observation of serum ferritin levels in patients with chronic viral hepatitis B during lamivudine treatment might be helpful for monitoring and predicting patients' responses to the therapy.