Regulatory polymorphism of CXCL10 rs1439490 in seronegative occult hepatitis C virus infection.

AIM: To examine the relationship between the single nucleotide polymorphism CXCL10 rs1439490 and seronegative occult hepatitis C virus (HCV) infection (OCI). METHODS: One hundred and three cases of seronegative OCI and 155 cases of seropositive chronic HCV infection (CHC) were diagnosed at five Liver Centers in Northeastern China, from 2012 to 2016. CXCL10 rs1439490, rs1440802, and IL-28B rs12979860 were analyzed by sequencing. Serum CXCL10 was measured by ELISA. Intrahepatic CXCL10 was determined by quantitative PCR and immunohistochemical semi-quantitative scoring. Liver necroinflammation and fibrosis were scored according to the METAVIR system. RESULTS: CXCL10 rs1439490 G/G was more prevalent in OCI patients (n = 93/103; 90.3%) than in CHC patients (n = 116/155; 74.8%; P = 0.008). OCI patients had lower serum CXCL10 levels than CHC patients (192.91 ± 46.50 pg/mL vs 354.78 ± 102.91 pg/mL, P < 0.0001). Of IL-28B rs12979860 C/C patients, OCI patients with rs1439490 G/G had lower serum and liver levels of CXCL10 and lower levels of liver necroinflammation and fibrosis than non-G/G patients. OCI patients had higher alanine aminotransferase normalization rates after Peg-interferon treatment than CHC patients (P < 0.05) and serum CXCL10 decreased significantly (P < 0.0001). Liver necroinflammation and fibrosis were alleviated in 8 OCI patients after treatment. Multivariate analysis indicated that rs1439490 G/G significantly influenced the occurrence of OCI in HCV infection (OR = 0.31, 95%CI: 0.15-0.66, P = 0.002). CONCLUSION: CXCL10 rs1439490 G/G is positively associated with OCI in HCV infection and antiviral outcome.

Morphological and Transcriptomic Analysis Reveals the Osmoadaptive Response of Endophytic Fungus Aspergillus montevidensis ZYD4 to High Salt Stress.

Halophilic fungi have evolved unique osmoadaptive strategies, enabling them to thrive in hypersaline habitats. Here, we conduct morphological and transcriptomic response of endophytic fungus (Aspergillus montevidensis ZYD4) in both the presence and absence of salt stress. Under salt stress, the colony morphology of the A. montevidensis ZYD4 changed drastically and exhibited decreased colony pigmentation. Extensive conidiophores development was observed under salt stress; conidiophores rarely developed in the absence of salt stress. Under salt stress, yellow cleistothecium formation was inhibited, while glycerol and compatible sugars continued to accumulate. Among differentially expressed unigenes (DEGs), 733 of them were up-regulated while 1,619 unigenes were down-regulated. We discovered that genes involved in the accumulation of glycerol, the storage of compatible sugars, organic acids, pigment production, and asexual sporulation were differentially regulated under salt stress. These results provide further understanding of the molecular basis of osmoadaptive mechanisms of halophilic endophytic fungi.

China Medical Team: Medical rescue for "4.25" Nepal earthquake.

In recent years, global natural disasters have been frequent and resulted in great casualties and property loss. Since Wenchuan earthquake, the disaster emergency rescue system of China has obtained considerable development in various aspects including team construction, task scheduling, personnel training, facilities and equipments, logistics, etc. On April 25, 2015, an earthquake that measured 8.1 on the Richter scale attacked Nepal. Chinese government firstly organized a medical team, named China Medical Team, and sent it to the attacked region in Nepal to implement medical rescue. The medical team completed the rescue mission successfully and creatively based on their experiences.

Long-term antiviral efficacy of entecavir and liver histology improvement in Chinese patients with hepatitis B virus-related cirrhosis.

AIM: To evaluate the clinical outcomes of 240-wk treatment with entecavir (0.5 mg) in Chinese nucleoside-naive patients with cirrhosis. METHODS: A total of 204 nucleoside-naive patients with compensated (n = 96) or decompensated (n = 108) hepatitis B virus (HBV)-induced cirrhosis at the Department of Gastroenterology of the China-Japan Union Hospital (Jilin University, Changchun, China) who were treated with entecavir (0.5 mg) for 240 wk were enrolled in this study. Liver biopsy samples obtained from 38 patients prior to treatment (baseline) and at week 240 were evaluated by different independent histopathologists. Efficacy assessments included the proportions of patients who achieved an HBV DNA level < 500 copies/mL, the association of interleukin-28B genetic variation with antivirus therapy, clinical outcomes, and histologic improvement. Changes in liver disease severity were analyzed, and liver histologic evaluation was performed in 38 patients with paired biopsies. Student t tests were used to compare the means of continuous variables between the groups, and the proportions of patients who achieved the endpoints were compared using the χ(2) test. RESULTS: At week 240, 87.5% of the patients with compensated cirrhosis and 92.6% of the patients with decompensated cirrhosis achieved a HBV DNA level < 500 copies/mL. Three patients had genotypic entecavir resistance within the 240-wk period. No significant association was observed between virologic response and interleukin-28 genotype (CT, 88.2% vs CC, 90.6%). The proportion of patients with Child-Pugh class A disease was significantly increased at week 240 (68%) from the baseline (47%; P < 0.01). The proportion of patients with Child-Pugh class B disease was significantly decreased at week 240 (25%) from the baseline (39%; P = 0.02). In the patients with paired liver biopsies, the mean reduction in the Knodell necroinflammatory score from the baseline was 3.58 ± 1.03 points (7.11 ± 1.80 vs 3.53 ± 1.35, P < 0.01). The mean reduction in Ishak fibrosis score from the baseline was 1.26 ± 0.64 points (5.58 ± 0.50 vs 4.32 ± 0.81, P < 0.01). CONCLUSION: Entecavir is an effective treatment option for patients with HBV-related compensated or decompensated cirrhosis that can result in sustained virologic suppression and histologic improvement.

3.0T ¹H magnetic resonance spectroscopy for assessment of steatosis in patients with chronic hepatitis C.

AIM: To investigate the utility of (1)H magnetic resonance spectroscopy ((1)H MRS) as a noninvasive test for steatosis in patients infected with hepatitis C virus. METHODS: Ninety patients with chronic hepatitis C and pathology data underwent 3.0T (1)H MRS, and the results of MRS and pathological analysis were compared. RESULTS: This group of patients included 26 people with mild fatty liver (28.89%), 16 people with moderate fatty liver (17.78%), 18 people with severe fatty liver (20.0%), and 30 people without fatty liver (33.33%). The water peak was near 4.7 parts per million (ppm), and the lipid peak was near 1.3 ppm. Analysis of variance revealed that differences in the lipid peak, the area under the lipid peak, ratio of the lipid peak to the water peak, and ratio of the area under the lipid peak to the area under the water peak were statistically significant among the groups. Specifically, as the severity of fatty liver increased, the value of each index increased correspondingly. In the pairwise comparisons, the mean lipid peak, area under the lipid peak, ratio of the lipid peak to the water peak, and ratio of the area under the lipid peak to the area under the water peak were significantly different between the no fatty liver and moderate fatty liver groups, whereas no differences were noted between the severe fatty liver group and the mild or moderate fatty liver group. Area under the ROC curve (AUC) of area ratio in lipid and water and ratio in lipid and water in the no fatty liver group to mild fatty liver group, mild fatty liver group to moderate fatty liver group, and moderate fatty liver disease group to severe fatty liver group, were 0.705, 0.900, and 0.975, respectively. CONCLUSION: (1)H MRS is a noninvasive technique that can be used to provide information on the effect of liver steatosis on hepatic metabolic processes. This study indicates that the (1)H MRS can be used as an indicator of steatosis in patients with chronic hepatitis C.

[Clinical antiviral effects of Peg-IFNa-2a in patients with chronic hepatitis B].

OBJECTIVE: To evaluate antiviral effects of Peg-IFNa-2a in patients with chronic hepatitis B. METHODS: 92 chronic hepatitis B patients were enrolled to receive the treatment with Peg-IFNa-2a 180 µg subcutaneous injection once weekly. The patients who did not get early response were divided into 3 groups: group 1, extend the treatment to 72 weeks; group 2, combined with nucleus(s)ide analogue (entecavir or adefovir) treatment; group 3, continue the treatment until 48 weeks. HBV DNA and quantitative HBsAg were assessed at baseline, week 12, 24, 36 and after 24 weeks follow-up. RESULTS: Patients in group 1 had significantly higher SVR rate (78.3%) than patients in group 3 (38.1%, X2=7.33, P<0.05). The mean reduction of HBsAg in group 1 at 24 weeks of post-treatment follow up was higher than that in group 3 (t=2.11, P<0.05). In group 2 the mean reductions of HBV DNA at 24 weeks of post-treatment follow up were (3.9+/-1.1) log10 copy/ml and (3.7+/-1.3) log10 copy/ml respectively with combination of entecavir or adefovir, both of which were significantly higher than that in group 3(t=8.45 and 6.31, P<0.05); the SVR rates in the entecavir group and the adefovir group (83.3% and 85.7%, respectively) were significantly higher than that in group 3 (X2=8.20 and 7.78, P<0.05); the mean reductions of HBsAg in the entecavir group and the adefovir group [(0.8+/-0.5) log10 IU/ml and (0.9+/-0.3) log10 IU/ml, respectively ] were significantly greater than group 3[(0.4+/-0.3) log10 IU/ml, t=3.05 and 4.58, P<0.05]. The level of HBV DNA and C genotype were the main predictors of response. CONCLUSION: Individualizing therapy by prolonging the duration of Peg-IFNa-2a treatment to 72 weeks or adding nucleoside analogues such as entecavir and adefovir in patients without early response may substantially increase the SVR rate and lead to the decrease of HBsAg.

[Clinical antiviral effects of telbivudine in patients with chronic hepatitis B].

OBJECTIVE: To analyze antiviral effects of telbivudine in patients with chronic hepatitis B. METHOD: 72 chronic hepatitis B patients without prior history of antiviral therapy were treated with telbivudine 600mg once daily. RESULTS: At week 4, 37.5% of the patients achieved undetectable HBV DNA, and 33.3% achieved ALT normalization. At week 108, 87.5% of the patients achieved undetectable HBV DNA, and 91.7% achieved ALT normalization. HBeAg seroconversion occurred in 23.9% of the 46 HBeAg positive patients. The rates of undetectable HBV DNA and HBeAg seroconversion at week 108 in the patients with HBV DNA < 3 log(10) copies/ml at week 12 were significant higher than those in patients with HBV DNA >or= 3 log(10) copies/ml. The rate of undetectable HBV DNA at week 108 in the patients with HBV DNA < 3 log(10) copies/ml at week 24 was significantly higher than that in patients with HBV DNA >or= 3 log(10) copies/ml, and the rate of antiviral resistance rate at week 108 in the patients with HBV DNA < 3 log(10) copies/ml at week 24 was significantly lower than that in patients with HBV DNA >or= 3 log(10) copies/ml. Antiviral therapy could significantly improve Child-Pugh score in patients with liver cirrhosis. CONCLUSION: Telbivudine treatment results in suppression of HBV and high HBeAg seroconversion, and improvement of Child-Pugh score in the patients with liver cirrhosis.

[Antiviral effects of entecavir in patients with hepatitis B virus-related cirrhosis].

OBJECTIVE: To analyze antiviral effects of entecavir in patients with hepatitis B virus-related cirrhosis. METHODS: 104 patients of hepatitis B virus-related cirrhosis with no previous history of antiviral therapy were treated with entecavir 0.5 mg once daily. 37 patients were taken hepatic histologic examination before and after the treatment. RESULTS: Mean reductions of serum HBV DNA was 5.1 log10 96 weeks after the treatment, HBV DNA became undetectable in 98.1% patients, and ALT became normal in 80.7% patients; HBeAg seroconversion occurred in 13.9% of the 72 HBeAg positive patients; 61.5% of these patients were infected with genotype C HBV, and 26.9% were infected with genotype B HBV. The genotype of HBV was not associated with the therapeutical effect. Child-pugh score was associated with the progression of the disease: the proportion of patients with disease progression was highest in Child-Pugh C grade patients and lowest in Child-Pugh A grade patients. The level of the HBV DNA load was positively correlated with Knodell HAI score at the baseline and 96 weeks after the treatment. CONCLUSION: Entecavir treatment results in suppression of HBV replication and delayed progression of fibrosis in patients with hepatitis B virus-related cirrhosis.

Outpatient procedures on the glans and anterior urethra under a new local anaesthesia: intracorpus spongiosum anaesthesia.

OBJECTIVE: To determine the efficacy of intracorpus spongiosum anaesthesia during minor procedures on the glans and anterior urethra in the outpatient clinic. METHODS: Sixty-nine consecutive male patients underwent various procedures on the glans penis or anterior urethra under intracorpus spongiosum anaesthesia, which was performed by injection of 3 mL of 1% lidocaine into the glans penis. The effect of this anaesthetic technique was assessed by questionnaire using a pain scale. RESULTS: Following injection of lidocaine, the anaesthetic effect was immediate and very satisfactory. The minor procedures, varying from 8 to 68 minutes in duration, were successfully completed under the new local anaesthesia. Of the 69 patients, 63 (91.3%) felt no pain and six (8.7%) reported either minor or moderate discomfort that was tolerable and could be ignored. There were no serious complications with this anaesthetic technique except for three patients (4.3%) who had instantaneous trance during lidocaine injection. CONCLUSION: Intracorpus spongiosum anaesthesia is an effective, simple, safe anaesthetic technique for minor procedures on the glans and anterior urethra in an outpatient setting. With this new local anaesthesia, the total cost of many procedures on the glans and anterior urethra can be markedly reduced.