Association between NTCP hepatic expression and inflammation/fibrosis as well as gender-specific differences in chronic HBV-infected patients.

To investigate the relationship between the expression of hepatitis B virus (HBV) functional receptor sodium taurocholate cotransporting polypeptide (NTCP) with disease progression and gender-specific differences in chronic HBV-infected patients. Liver samples were collected from chronic HBV-infected patients who underwent percutaneous liver biopsy or liver surgery. HBV DNA levels and the mRNA and protein expression levels of NTCP in liver tissues were determined. The relationship between NTCP expression and HBV DNA levels, inflammatory activity, fibrosis, and gender-specific differences were analyzed. A total of 94 chronic HBV-infected patients were included. Compared with patients with a METAVIR score of A0-1 or F0-1, patients with score of A2 or F2/F3 had a relatively higher level of NTCP expression. NTCP levels were positively correlated with HBV DNA levels. The inflammatory activity scores and fibrosis scores of women <50 years were significantly lower than those of women ≥50 years and age-matched males. In patients with score A0-2 or F0-3, women <50 years have lower NTCP expression level compared to women ≥50 years and age-matched males. NTCP can promote the disease progression by affecting the viral load of HBV. The NTCP expression difference may be why male and postmenopausal women are more prone to disease progression than reproductive women.

Enhanced anticancer activity of piperine: Structural optimization and chitosan-based microgels with boosted drug delivery.

As a plant-derived drug, piperine possesses therapeutic efficacy for many diseases, but its inherent low solubility and bioavailability have greatly limited its clinical use. Herein, we extracted piperine from black pepper, optimized the structure of piperine to prepare various derivatives, and then explored the anticancer activity of these derivatives. Piperine and its derivatives have high anticancer selectivity against 4T1 cells, exhibiting obvious anticancer properties even at a low concentration of 100 µg/mL. Furthermore, the physicochemical properties of piperine and its derivatives were investigated using density functional theory, demonstrating their considerable biological activity. Moreover, the chitosan-based microgels were prepared to encapsulate the hydrophobic piperine derivative with a high loading efficiency of 81.7 % to overcome the low water solubility of the piperine derivative. It is worth noting that excessive glutathione in tumor cells triggers the degradation of microgels and realizes controllable drug release of up to 72.3 %. Due to its excellent properties, chitosan-based microgels loaded with the piperine derivative can obtain good anticancer behavior of approximately 13.14 % cell viability against 4T1 cells. Therefore, the chitosan-based microgels overcome the low water solubility of the piperine derivative through encapsulation and thus further augment their delivery efficiency and cell internalization capability to realize excellent anticancer activity. This work demonstrates the enhanced anticancer efficacy of the hydrophobic plant-derived drug by means of structural optimization of piperine and chitosan-based microgels with boosted drug delivery.

Comparison of the efficacy and safety of an oral sulfate solution and 3-L polyethylene glycol on bowel preparation before colonoscopy: a phase III multicenter randomized controlled trial.

BACKGROUND AND AIMS: Adequate bowel preparation is crucial for clear mucosal visualization during colonoscopy. We aimed to comprehensively compare oral sulfate solution (OSS) and 3-L split-dose polyethylene glycol (PEG) for bowel preparation before colonoscopy. METHODS: This randomized, active-controlled, noninferiority study was performed in 10 medical centers. Eligible subjects were enrolled to receive OSS or 3-L PEG in a split-dose regimen. The quality of bowel preparation, adverse reactions, and acceptability were evaluated. The quality of bowel preparation was evaluated using the Boston Bowel Preparation Scale. Safety was evaluated by adverse reactions. The study population was divided into the full analysis set (FAS), the safety set, the modified FAS (mFAS), and the per-protocol set (PPS). RESULTS: Three hundred forty-eight potentially eligible subjects were enrolled. Three hundred forty-four subjects were included in the FAS and safety set, 340 subjects were included in the mFAS, and 328 subjects were included in the PPS. Adequate bowel preparation of the OSS was not inferior to 3-L PEG in the mFAS (98.22% vs 97.66%) and the PPS (98.17% vs 98.78%). There was no significant difference in acceptability between the 2 groups (94.74% vs 94.80%, P = .9798). Overall adverse reactions were similar (50.88% vs 44.51%, P = .2370) between the 2 groups. CONCLUSIONS: The split-dose OSS regimen was not inferior to the split-dose 3-L PEG regimen for the quality of bowel preparation in a Chinese adult population. The safety and acceptability of the 2 groups were similar. (Clinical trial registration number: NCT05465889.).

Signal transducer and activator of transcription 3 cooperates with androgen receptor/cell cycle-related kinase signalling pathway in the progression of hepatitis B virus infection and gender differences.

The study aimed to investigate the role of androgen receptor (AR)/cell cycle-related kinase (CCRK) signalling pathway in chronic hepatitis B virus (HBV) infection and gender differences, and the contribution of AR regulatory factor signal transducer and activator of transcription 3 (STAT3) in it. AR, CCRK, and phosphorylated STAT3 expressions in liver tissues of chronic HBV-infected patients and non-HBV controls were determined by western blot and compared between genders. The relationships of expression levels with serum HBV DNA levels, liver inflammation activity, and fibrosis score were analysed in chronic HBV-infected patients. The relationships between expression levels of three proteins were also analysed. HBV-infected patients had significantly higher expression levels of AR, CCRK, and p-STAT3Tyr705 compared with controls (p < .01). The expression levels of AR, CCRK, and p-STAT3Tyr705 in chronic HBV-infected patients with severe inflammation were significantly higher than those with mild inflammation (p < .05). Expression levels in patients with heavier fibrosis (stage F4) were higher than in those with less fibrosis (stages F0-3) (p < .01). No gender differences were observed in AR, CCRK, and p-STAT3Tyr705 levels in non-HBV controls; higher levels were observed in HBV-infected males than in HBV-infected females (p < .05). AR, CCRK, and p-STAT3Tyr705 levels in liver tissues positively correlated with each other (p < .0001) and with serum HBV DNA levels (p < .0001). In conclusion, in this study, we first found concordant over-expression of AR, CCRK, and STAT3 in liver tissues of chronic HBV-infected patients who have not yet developed HCC, significantly correlated with the severity of the disease and showed gender differences. STAT3 may be a potential therapeutic co-target for chronic HBV infection.

Vonoprazan non-inferior to lansoprazole in treating duodenal ulcer and eradicating Helicobacter pylori in Asian patients.

BACKGROUND AND AIM: Duodenal ulcers, especially caused by increasingly drug-resistant Helicobacter pylori, are a concern in Asia. We compared oral vonoprazan versus lansoprazole for efficacy (healing duodenal ulcers) and safety in non-Japanese Asian patients. METHODS: In this phase 3, randomized (1:1), double-blind, double-dummy, parallel-group, non-inferiority study (April 5, 2017, to July 19, 2019), patients with ≥ 1 endoscopically confirmed duodenal ulcer, at 52 hospitals (China, South Korea, and Taiwan), received vonoprazan 20 mg once daily (QD) or lansoprazole 30 mg QD for 6 weeks maximum. Patients with H. pylori received bismuth-containing quadruple therapy including vonoprazan 20 mg twice daily (BID) or lansoprazole 30 mg BID, for 2 weeks, followed by vonoprazan or lansoprazole monotherapy QD (4 weeks maximum). Endpoints were endoscopically confirmed duodenal ulcer healing (Week 4/6; primary) and H. pylori eradication (4 weeks post-treatment; secondary); non-inferiority margins were -6% and -10%, using a two-sided 95% confidence interval (CI). RESULTS: Of 533 enrolled patients, one was lost to follow-up and one withdrew (full analysis set: 531 patients [vonoprazan, n = 263; lansoprazole, n = 268]; 85.4% = H. pylori positive). Vonoprazan was non-inferior to lansoprazole for duodenal ulcer healing (96.9% vs 96.5%; difference 0.4% [95% CI -3.00, 3.79]). H. pylori eradication rates were 91.5% (vonoprazan) and 86.8% (lansoprazole; difference 4.7% [95% CI -1.28, 10.69]). Vonoprazan and lansoprazole were well tolerated, with similar safety profiles, no new safety signals; no deaths occurred. CONCLUSIONS: Vonoprazan was well tolerated and non-inferior to lansoprazole for duodenal ulcer healing and achieved H. pylori eradication above the clinically meaningful threshold (90%), in non-Japanese Asian patients.

Chinese Consensus Report on Family-Based Helicobacter pylori Infection Control and Management (2021 Edition).

OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.

Regular arrangement of collecting venules (RAC) as an endoscopic marker for exclusion of Helicobacter pylori (H. pylori) infection: A systematic review and meta-analysis.

BACKGROUND: Helicobacter pylori (H. pylori) is the most common cause of gastric cancer. Growing evidence suggests that the regular arrangement of collecting venules (RAC) can be used as an endoscopic marker to diagnose H. pylori infection. However, data on the diagnostic accuracy of RAC for H. pylori infection are conflicting. We performed a systematic review and meta-analysis of relevant studies to determine the diagnostic accuracy and clinical utility of RAC for the diagnosis of H. pylori infection. METHODS: We systematically searched PubMed, Embase, Web of Science and the Cochrane Library between inception and Oct 29, 2020, for studies that assessed the diagnostic accuracy of RAC for H. pylori infection. RESULTS: The literature search yielded 2921 non-duplicated screened titles, of which 58 underwent full-text review. Fifteen studies, representing a total of 6621 patients, met the inclusion criteria. The area under the summary receiver operating characteristic curve was 0.98 (95% CI 0.96-0.99). The pooled estimates for RAC were 0.98 (95% CI 0.95-0.99) for sensitivity and 0.75 (95% CI 0.54-0.88) for specificity. The pooled positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 3.8 (95% CI 1.9-7.7) and 0.03 (95% CI 0.02-0.07), respectively. CONCLUSIONS: RAC can be used as an endoscopic marker for exclusion of H. pylori infection. However, it cannot be recommended as a single indicator for the confirmation of H. pylori infection. The conclusion of this study should be treated with caution because significant heterogeneity exists between the evaluated studies.

Atypical adult-onset Still's disease with an initial and sole manifestation of liver injury: A case report and review of literature.

BACKGROUND: Adult-onset Still's disease (AOSD) typically presents with a high spiking fever, polyarthritis, transient maculopapular rash, neutrophilic leukocytosis, and hepatosplenomegaly. It has a wide spectrum of clinical symptoms ranging from mild to severe, with extensive involvement of almost every organ. Although liver involvement in the form of increased hepatic enzymes and bilirubin is common, no AOSD case with liver involvement as the initial manifestation of AOSD has been reported. CASE SUMMARY: A 35-year-old woman presented to the hepatology department with progressively worsening jaundice for one week. Liver chemistry tests revealed a significantly increased liver enzymes and bilirubin level. Given that the clinical examination was unremarkable, liver biopsy was considered because the patient had a history of AOSD 6 years ago. Liver histopathology revealed that most hepatic lobules were still recognizable. Fusional necrosis was observed around most central veins. A few bridging necrotic zones were also found. Infiltration of multiple plasma cells were observed in the necrotic zone, and the reticular scaffold was still expanded. Additionally, no obvious fibrosis was observed in the portal area. Mild mixed inflammatory cell infiltration was noted in the interstitium of the portal area. Further examination was unremarkable except for a remarkably high level of ferritin. Collectively, a presumptive diagnosis of liver injury secondary to AOSD was made. The hepatic involvement responded well to glucocorticoid treatment. CONCLUSION: This case highlights that hepatic involvement as an initial and sole manifestation could be a pattern of relapsed AOSD. The diagnosis of AOSD should be considered in the case of nonresolving liver injury after the exclusion of common etiologies for liver diseases. A liver biopsy can be useful for the differential diagnosis of liver injury associated with AOSD.

Long-term clinical benefit of Peg-IFNα and NAs sequential anti-viral therapy on HBV related HCC.

Analysis of the value of long-term antiviral therapy using sequential Peg-IFN therapy and nucleos(t)ide analogues (NAs) improves the prognosis of HBV-related HCC. HBV-related HCC patients were classified into sequential therapy with Peg-IFNα-2a and NAs, and NAs therapy alone. All patients were followed up for 5 years. The survival rate, HCC recurrence rate, Child-Pugh score, and side effects of drugs were evaluated. Firstly, the early and late cumulative survival rate was higher in patients receiving antiviral therapy compared with the control patients (p<0.05). Patients receiving sequential therapy with Peg-IFNα-2a and NAs showed a higher late cumulative survival rate and significantly reduced early and late recurrence rate, compared to those in the NA-alone group (p<0.05). Single NAs therapy only reduced the late recurrence rate in HCC-patients. Secondly, NAs therapy significantly increased the Child-Pugh score after five years of therapy (five-year therapy 7.03±1.50 vs. initial score 6.63±0.85; p<0.05), whereas the sequential therapy with Peg-IFNα-2a and NAs did not greatly alter the Child-Pugh score (6.88±1.26; p>0.05). Compared to the control patients, patients receiving antiviral therapy (NAs alone or sequential therapy with Peg-IFNα-2a and NAs) exhibited a significantly decreased Child-Pugh score (p<0.05). Compared to NAs alone, sequential therapy with Peg-IFNα-2a and NAs provided a more efficient strategy for improving both the five-year survival rate and the two-year or five-year recurrence rate in patients.

Long-term follow-up of Helicobacter pylori reinfection and its risk factors after initial eradication: a large-scale multicentre, prospective open cohort, observational study.

Helicobacter pylori (H. pylori) recurrence remains a significant public health concern. The study aimed to assess H. pylori reinfection rate and identify its risk factors in China. This prospective open cohort, observational study was performed at 18 hospitals across 15 provinces in China. Consecutive patients who received the successful initial eradication during 1 January 2012 and 31 December 2018 were eligible for enrolment. H. pylori recurrence was defined as reinfection that occurred at more than the 12-month interval after successful initial eradication. Surveyed risk factors that might be associated with reinfection were preliminarily estimated by log-rank test and further determined by Cox regression model to calculate the hazard ratio (HR) and 95% confidence interval (CI). A total of 5193 subjects enrolled in the study. The follow-up intervals varied from 6 to 84 months with a general follow-up rate of 67.9%. Annual reinfection rate was 1.5% (95% CI: 1.2-1.8) per person-year. H. pylori reinfection was independently associated with the following five risk factors: minority groups (HR = 4.7, 95% CI: 1.6-13.9), the education at lower levels (HR = 1.7, 95% CI: 1.1-2.6), a family history of gastric cancer (HR = 9.9, 95% CI: 6.6-14.7), and the residence located in Western China (HR = 5.5, 95% CI: 2.6-11.5) following by in Central China (HR = 4.9, 95% CI: 3-8.1) (all P < 0.05). Reinfection rate of H. pylori in China is relatively low. Patients with specific properties of ethnic groups, education level, family history, or residence location appear to be at higher risk for reinfection.

CXCL8 is a potential biomarker for predicting disease progression in gastric carcinoma.

BACKGROUND: To find potential biomarkers for predicting disease progression in gastric cancer (GC). METHODS: An extensive bioinformatics study of the Cancer Genome Atlas (TCGA) and Oncomine datasets was conducted to define potential mRNA biomarkers for GC. The mRNA expression profiles of 375 GC and 32 neighboring noncancerous adrenal tissues were analyzed. The Oncomine database was used to validate the hub genes. The correlation between candidate hub gene expression and survival of GC patients was analyzed using the Kaplan-Meier method. RESULTS: Ten differentially expressed genes were identified as hub genes, and CXCL8 was the only gene validated as being up-regulated in GC tissues compared to control tissues using both the TCGA and Oncomine databases. Immunofluorescence staining showed that CXCL8 was expressed in GC tissues, and its higher expression predicted worse relapse-free survival in GC patients. CONCLUSIONS: CXCL8 is a potential biomarker for predicting disease progression in GC.

Peg-interferon and nucleos(t)ide analogue combination at inception of antiviral therapy improves both anti-HBV efficacy and long-term survival among HBV DNA-positive hepatocellular carcinoma patients after hepatectomy/ablation.

Antiviral therapy has been shown to improve the prognosis of hepatitis B virus (HBV) DNA-positive hepatocellular carcinoma (HCC) after radical treatment, but antiviral treatments require further optimization. This study aimed to evaluate the efficacies of different antiviral strategies with HCC patients after hepatectomy/ablation. This prospective, randomized, controlled and multi-centre trial enrolled HBV DNA-positive primary HCC patients after hepatectomy/ablation between January 2007 and January 2009. Patients were divided into four groups: early combination (entecavir plus Peg-interferon [IFN]α-2a co-administration during year 1); late combination (addition of Peg-IFNα-2a for 48 weeks after 1 year of entecavir); nucleos(t)ide analogue[NA] monotherapy; and non-antiviral treatment. Primary endpoints included recurrence-free survival and overall survival. A total of 447 patients were enrolled. The 2-year and 8-year recurrence-free survival and 8-year overall survival rates were significantly higher in the early combination group than in the other two antiviral groups (P < .05). After 48-week treatment, more patients achieved an HBsAg reduction >1500 IU/mL and the mean HBsAg level was significantly lower in the early combination group compared with the late combination and NA monotherapy groups (P < .05). Multivariate analysis showed that early combination therapy and a reduction in HBsAg by >1500 IU/mL after 48 weeks of therapy correlated with reduced mortality and disease recurrence. Early introduction of combination antiviral treatment may represent a more effective therapeutic strategy for patients with HBV DNA-positive HCC after hepatectomy/ablation. A reduction in HBsAg by >1500 IU/mL after 48-week treatment is associated with reduced mortality and disease recurrence of HBV DNA-positive HCC patients after hepatectomy/ablation.

The influence of interleukin 28B polymorphisms on the risk of hepatocellular carcinoma among patients with HBV or HCV infection: An updated meta-analysis.

Single nucleotide polymorphisms (SNPs) of the interleukin 28B (IL28B) gene has proven to be associated with the clinical outcome of patients with chronic hepatitis virus B or C (HBV or HCV) infections. However, whether IL28B SNPs have an influence on the risk of hepatocellular carcinoma (HCC) among patients with HBV or HCV infection remains controversial. Therefore, this study aims to determine the association between IL28B polymorphisms and the risk of HCC in individuals with HBV or HCV infection.PubMed, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) databases were used to identify studies meeting the selection requirements using the terms "interleukin 28B", "IFN-lambda-3", "IFNL3", "single nucleotide polymorphisms", "SNPs", "hepatocellular carcinoma", "HCC", "liver cancer".A total of 24 eligible original studies (1 cohort study and 23 case-control studies) involved 20238 individuals (HCC group = 8725 vs control group = 11,513) were included. Both IL28B rs12979860 CC and rs8099917 TT genotypes were significantly associated with a decreased risk of HCC among patients with HBV or HCV infection (OR = 0.71, 95% CI = 0.57-0.88; OR = 0.82, 95% CI = 0.72-0.94, respectively). Egger test and Begg test revealed no' publication bias (P > .05). Sensitivity analyses suggested the robustness of the results in this meta-analysis.Both IL28B rs12979860 CC and rs8099917 TT genotypes are protective factors for the development of HCC among patients with HBV or HCV infection. Future prospective studies examining the impact of IL28B polymorphisms on the risk of HCC and investigating the underlying mechanism for the protective role of IL28B polymorphisms in HCC development are warranted.

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.

Prognostic Significance of Elevated Cholestatic Enzymes for Fibrosis and Hepatocellular Carcinoma in Hospital Discharged Chronic Viral Hepatitis Patients.

Chronic viral hepatitis (CVH) is the root cause of liver fibrosis and subsequent hepatocellular carcinoma (HCC). We conducted a cross-sectional, observational study based on medical records and primary data collection from patients with CVH who were admitted in five hospitals across China between February and September 2013 to determine the prevalence of elevated cholestatic enzymes (ALP and/or GGT above ULN) in discharged Chinese patients with CVH as a primary outcome and secondarily evaluated the relationship of these enzymes with fibrosis and disease severity. Majority of the patients (56%) had cholestatic enzyme elevation at discharge, with high prevalence of liver fibrosis (37.6% vs. 20.1%, p < 0.001) and cirrhosis (Child-Pugh B: 56.9% vs. 48.7%; Child-Pugh C: 17.4% vs. 12.5%; p < 0.001) in addition to significantly higher odds of liver fibrosis (OR 1.54; p = 0.024) and a trend towards higher odds of moderate-to-severe cirrhosis (OR 1.24; p = 0.317) compared to those who had normal enzyme levels. Elevated cholestatic enzyme levels serve as important prognosticators of liver fibrosis in CVH patients. Therefore, pre-discharge testing of cholestatic enzymes is recommended to identify CVH patients and provide prophylactic care.

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.

Sex hormone affects the severity of non-alcoholic steatohepatitis through the MyD88-dependent IL-6 signaling pathway.

Recent research has shown that the occurrence of gender disparity in liver cancer associated with sex differences in MyD88-dependent IL-6 production, but the role of this signaling pathway in sex differences of non-alcoholic steatohepatitis (NASH) remains unknown. To investigate the effects of sex hormone-specific intervention on pathology and progression of NASH, and on the inflammatory TLR-MyD88-IL-6 signaling pathway NASH was modeled in C57/BL6 mice by feeding a methionine and choline-deficient (MCD) diet for 4 weeks. Male mice were subjected to sex hormone-related interventions such as orchidectomy, and orchidectomy combined with administration of either testosterone propionate or estradiol benzoate. Next, the degree of non-alcoholic fatty liver disease activity score (NAS), serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and the expression level of MyD88 and IL-6, were compared between these groups. Males developed more serious inflammatory problems and had a higher NAS than the females. Sex-specific intervention in male mice by orchidectomy reduced NAS, ALT, and AST, and the expression level of MyD88 and IL-6. But administration of exogenous androgen had no influence on either NAS or the expression of ALT, AST, MyD88, and IL-6. On the other hand, exogenous estrogen could alleviate the pathological damage caused by NASH, as well as reduce NAS, ALT and AST, and the expression of MyD88 and IL-6. The result show different sex hormone-related interventions affected the severity of NASH, possibly by modulating the level of sex hormones and regulating the TLR-MyD88-IL-6 signaling pathway.

Helicobacter hepaticus infection in primary hepatocellular carcinoma tissue.

INTRODUCTION: Helicobacter (H.) hepaticus infection causes chronic active hepatitis and induces hepatocellular tumours in A/JCr mice, but evidence of this in humans is scarce. This study aimed to demonstrate the correlation between H. hepaticus and human primary hepatocellular carcinoma (HCC). METHODS: The sera of 50 patients with primary HCC were tested for the presence of anti-H. pylori and anti-H. hepaticus immunoglobulin G (IgG) antibodies. The liver tissues of patients who tested positive for serum antibody were analysed for H. hepaticus-specific 16S rRNA, H. hepaticus cdtB, H. pylori cagA, H. pylori vacA and H. pylori ureC genes using polymerase chain reaction. RESULTS: After the anti-H. pylori antibodies in the serum samples were absorbed by H. pylori antigen, the anti-H. hepaticus IgG serum antibody detection rate was 50.0% in patients with primary HCC. This was significantly higher (p < 0.001) than the detection rate in the benign liver tumour (7.7%) and normal liver tissue (6.3%) groups. Of the 25 primary HCC samples that tested positive for anti-H. hepaticus IgG serum antibody, the H. hepaticus-specific 16S rRNA gene was detected in nine (36.0%) samples. Sequencing showed that the polymerase chain reaction-amplified product exhibited 95.5%-100% homology to the H. hepaticus-specific 16S rRNA gene. Among these nine primary HCC tissue samples, the H. hepaticus cdtB gene was detected in four (44.4%) samples, while no such expression was observed in the benign liver tumour or normal liver tissue groups. CONCLUSION: The present study identified the presence of H. hepaticus infection in patients with primary HCC using serological and molecular biological detection, suggesting that H. hepaticus infection may be involved in the progression of HCC.

Effects of HCV proteins in current HCV transgenic models.

Hepatits C virus (HCV) is an enveloped virus with positive-sense single-stranded RNA genome that causes both acute and persistent infections associated with chronic hepatitis, cirrhosis and hepatocellular carcinoma, which needs fully functional human hepatocytes for its development. Due to the strict human tropism of HCV, only human and higher primates such as chimpanzees have been receptive to HCV infection and development, cognition about pathophysiololgy and host immune responses of HCV infection is limited by lacking of simple laboratory models of infection for a long time. During the past decade, gene transfer approaches have been helpful to the understanding of the molecular basis of human disease. Transgenic cell lines, chimeric and transgenic animal models were developed and had been demonstrated their invaluable benefits. This review focuses on the existing HCV transgenic models and summarize the relative results about probable pathophysical changes induced by HCV proteins.