Acute myocardial injury is common in patients with COVID-19 and impairs their prognosis.

OBJECTIVE: We sought to explore the prevalence and immediate clinical implications of acute myocardial injury in a cohort of patients with COVID-19 in a region of China where medical resources are less stressed than in Wuhan (the epicentre of the pandemic). METHODS: We prospectively assessed the medical records, laboratory results, chest CT images and use of medication in a cohort of patients presenting to two designated covid-19 treatment centres in Sichuan, China. Outcomes of interest included death, admission to an intensive care unit (ICU), need for mechanical ventilation, treatment with vasoactive agents and classification of disease severity. Acute myocardial injury was defined by a value of high-sensitivity troponin T (hs-TnT) greater than the normal upper limit. RESULTS: A total of 101 cases were enrolled from January to 10 March 2020 (average age 49 years, IQR 34-62 years). Acute myocardial injury was present in 15.8% of patients, nearly half of whom had a hs-TnT value fivefold greater than the normal upper limit. Patients with acute myocardial injury were older, with a higher prevalence of pre-existing cardiovascular disease and more likely to require ICU admission (62.5% vs 24.7%, p=0.003), mechanical ventilation (43.5% vs 4.7%, p<0.001) and treatment with vasoactive agents (31.2% vs 0%, p<0.001). Log hs-TnT was associated with disease severity (OR 6.63, 95% CI 2.24 to 19.65), and all of the three deaths occurred in patients with acute myocardial injury. CONCLUSION: Acute myocardial injury is common in patients with COVID-19 and is associated with adverse prognosis.

[Association of Vitamin D Receptor Polymorphisms with Response to Antiviral Therapy in Patients with Chronic Hepatitis C].

OBJECTIVE: To assess the influence of vitamin D receptor (VDR) gene Bsm I, Fok I, Taq I and Apa I polymorphisms on the response to antiviral therapy in patients with chronic hepatitis C (CHC). METHODS: There were total 124 patients with CHC treated with pegylated interferon plus ribavirin. VDR gene Bsm I, Fok I Taq I and Apa I polymorphisms were analyzed in 71 patients with sustained virological response (SVR) and 53 patients without SVR (non-SVR) by polymerase chain reaction-MassARRAY (PCR-MassARRAY). RESULTS: The distributions of VDR genotype met Hardy-Weinberg equilibrium (all P > 0.05). There were no significant differences in VDR Fok I, Taq I, Apa I allele and genotype frequencies between SVR and non-SVR patients (all P > 0.05). The Bsm I (GA) genotype was significant higher in the patients with SVR compared to those with non-SVR (Χ2 = 3.967, P = 0.046). Three SNPs at VDR gene (Bsm I, Taq I and Apa I) were in strong linkage disequilibrium. Linkage disequilibrium coefficient (D') between Bsm I and Taq I was 1.000 and the correlation coefficient (r2) was 0.741. D' between Bsm I and Apa I was 1.000 and r2 was 0.082. D' between Taq I and Apa I was 0.829 and r2 was 0.076. No relation existed between haplotypes and response to therapy (P > 0.05). CONCLUSION: Vitamin D receptor gene Bsm I polymorphism may be associated with the therapeutic response to antiviral therapy with pegylated interferon plus ribavirin in chronic hepatitis C patients.

Predictors of Pegylated Interferon Alpha and Ribavirin Efficacy and Long-Term Assessment of Relapse in Patients With Chronic Hepatitis C: A One-Center Experience From China.

BACKGROUND: Sustained virological response (SVR) and virological relapse maintain pivotal roles in the management of chronic hepatitis C (CHC); however, there is little data regarding the long-term outcomes of patients with CHC in China. OBJECTIVES: We aimed to investigate the predictive factors of therapeutic effect and viral relapse in patients who achieved end-of-treatment response (ETR). PATIENTS AND METHODS: We retrospectively analyzed clinical, biochemical and virological data of 169 adult patients with CHC from China who were not treated with pegylated interferon-alpha (PEG IFN-α) and ribavirin, of which 142 achieved ETR and with a follow-up period ranging from six months to six years. Statistical analysis was performed by SPSS 20.0. RESULTS: Of the 169 patients, 124 (73.4%) achieved SVR and 23 (16.2%) experienced relapses post-therapy in cases of ETR patients. We considered sex, age, alanine aminotransferase, aspartate transaminase, baseline hepatitis C virus RNA level, HCV genotypes, IL28B rs12979860 genotype, rapid virological response (RVR), and early virological response (EVR). For antiviral effect in patients with CHC, HCV genotypes (2, 3) (χ(2) = 11.285, P = 0.001), IL28B genotype (rs12979860 CC) (χ(2) = 16.552, P < 0.001), RVR (χ(2) = 37.339, P < 0.001), and EVR (χ(2) = 70.265, P < 0.001) were significantly correlated with achieving SVR. For ETR patients with long-term follow-up, the relapse rate within six months was significantly higher than within other periods during six-year follow-up (χ(2) = 7.792, P = 0.005). Relapse was virtually not observed after therapy ceased for 48 weeks. The IL28B genotype (rs12979860 CT/TT) (OR = 0.102; 95% CI, 0.031-0.339; P < 0.001), lower RVR (OR = 0.239; 95% CI, 0.078-0.738; P = 0.013), and EVR (OR = 0.102; 95% CI, 0.016-0.661; P = 0.017) were independent risk factors for relapse. CONCLUSIONS: Our study comprehensively explored the predictive factors of therapeutic effect of administered drugs and analyzed viral relapse during a six-months to six-year follow-up period from China. The SVR may not be the perfect endpoint of HCV therapy in Chinese people; we recommend 48 weeks after treatment withdrawal as the suitable time point.

Interferon Lambda 4 Polymorphism Predicts Sustained Viral Response in Hepatitis C Virus Patients Irrespective of Hepatitis C Virus Genotypes, Ethnicity or Treatment Regimen: Results From a Meta-Analysis.

CONTEXT: There is growing evidence that interferon lambda 4 (IFNL4) polymorphism is related to sustained virological response (SVR) in hepatitis C virus (HCV) infection. We analyzed the relationship between IFNL4 (rs368234815) polymorphism and SVR in dual- and triple- therapy in HCV genotype 1, 2, 3 and 4 infected Asian, Caucasian and African patients. EVIDENCE ACQUISITION: We performed a systematic search of PubMed, Medline, Embase, EBSCO and Web of Science databases up to July 2015. Data of qualified studies were analyzed using the meta-analysis method in Stata 12.0 software. RESULTS: Ten studies involving 4765 patients were included in the analysis. Of overall studies, SVR was more frequent in TT/TT genotype compared to TT /ΔG+ΔG /ΔG (OR = 4.439, 95% CI: 3.410 - 5.778). Genotype stratification analyses revealed rs368234815 TT/ TT was associated with higher SVR in G1, G2/3 and G4 HCV patients (ORG1 = 4.661, 95% CI: 3.937 - 5.518; ORG2/3 = 1.896, 95% CI: 1.265 - 2.841; ORG4 = 6.074; 95% CI: 3.129 - 11.788). Ethnicity stratification analyses of G1 patients showed that SVR was more frequent with TT/ TT genotype in Asians (OR= 8.245, 95% CI: 5.475 - 12.416), Caucasians (OR = 4.166, 95% CI: 3.441 - 5.042) and Africans (SVR: 37.5% vs 17.0%, P = 0.017). Moreover, similar results presented in therapy stratification analyses both in patients with dual-therapy (OR = 3.857; 95% CI: 3.288 - 4.524) or triple-therapy (OR = 8.119; 95% CI: 4.942 - 13.340). CONCLUSIONS: Favorable IFNL4 rs368234815 genotype is a strong predictor of SVR in HCV patients, irrespective of HCV genotypes, ethnicity or treatment regimen. Thus, detection for IFNL4 rs368234815 polymorphism may be beneficial to guide the clinician in the individualization of therapy and design.

[Efficacy of combination therapy with pegylated-interferon alfa-2a plus ribavirin in autoantibody-positive chronic hepatitis C patients].

To evaluate the therapeutic efficacy of antiviral combination therapy with pegylated-interferon alpha-2a plus ribavirin (RBV) in patients with autoantibody-positive chronic hepatitis C (CHC) and to investigate the impact of the presence of autoantibodies on the treatment outcome. Eighty-six consecutive CHC patients who underwent a 48-week treatment regimen composed of Peg-IFNa-2a (135 or 180 mug/wk) plus weight-based RBV ( less than or equal to 65 kg, 800 mg/d; 65 to 75 kg, 1000 mg/d; more than or equal to75 kg, 1200 mg/d ). Prior to treatment (baseline) and at end of treatment (EOT; week 48), levels of antinuclear antibody (ANA), anti-smooth muscle antibody (SMA), anti liver/kidney microsomal antibody type 1 (LKM1), anti-La (SSB), and anti liver cytosolic-1 (LC-1) were detected by indirect immunofluorescence. At baseline, during treatment (weeks 4, 12, 24, and 36), EOT, and 24 weeks after EOT, levels of HCV RNA were assessed by real-time quantitative PCR. Rapid virological response (RVR) was defined as HCV RNA less than 10(3) copy/ml at week 4. Sustained virologic response (SVR) was defined as HCV RNA load below the lower limit of detection at 24 weeks after EOT. Correlation between autoantibodies and treatment-induced reduced HCV RNA load was assessed by univariate analysis of variance or chi-squared tests. Autoantibodies were detected in 24 patients, which included 14 ANA-positive patients, five SMA-positive patients, three LKM1-positive patients, one patient with double-positivity for ANA and SSB, and one patient with double-positivity for ANA and LC-1. The autoantibody-positive patients and autoantibody-negative patients showed similar rates of RVR (70.8% vs. 72.5%, P more than 0.05) and SVR (81.4% vs. 82.2%, P more than 0.05). Antiviral therapy with Peg-IFNa-2a RBV can effectively reduce the HCV RNA load in autoantibody-positive CHC patients; however, the presence of autoantibodies may not be an independent predictor of therapy outcome.

Study of the expression levels of Hepatocyte nuclear factor 4 alpha and 3 beta in patients with different outcome of HBV infection.

Hepatocyte nuclear factors 4 alpha (HNF4α) and 3 beta (HNF3ß) are members of a group of liver-enriched transcription factors (LETFs) that play important roles in regulating the replication of hepatitis B virus (HBV) and liver inflammation. However, the relationship of the level of HNF4α and HNF3ß with the severity of HBV-infected liver diseases is unclear. In this study, liver tissue samples from different types of HBV patients were collected, and HNF4α and HNF3ß expression were detected by immunohistochemistry. The expression of HNF4α was significant higher in patients with severe hepatitis B(SHB) than those with chronic hepatitis B(CHB) and liver cirrhosis(LC) (both P < 0.05), but similar between patients with CHB and LC (P > 0.05). And the expression of HNF3ß was similar among patients with CHB, LC and SHB (P > 0.05 for all pairwise comparison). This suggests that the expression level of HNF4α was different in patients with different outcome of HBV infection, high expression level of HNF4α may correlate with occurrence of SHB.

[Association of interleukin 28B polymorphisms with response to pegylatedinterferon plus ribavirin therapy for chronic hepatitis C].

OBJECTIVE: To investigate the characteristics of gene polymorphisms at rs12979860 of interleukin 28B (IL28B) and explore the relationships between the genetic polymorphisms and the antiviral therapy efficiency for chronic hepatitis C patients in the Sichuan region of China. METHODS: Data from 56 patients treated for 48 weeks with PEG-IFN alpha-2a plus weight-based Ribavirin (RBV), which were followed for 24 weeks after the end of treatment, were analyzed. And the IL28B rs12979860 genotype was detected by polymerase chain reaction-restriction techniques (PCR) and sequencing analysis. RESULTS: Two genotypes, CC (76.8%) and CT (23.2%), were identified in the study. There are no significant correlation in sex, age, body weight, routes of infection, baseline ALT value, baseline viral load and hepatitis C viral (HCV) genotype between the patients with CC genotype and CT genotype (P>0.05). PEG-IFN alpha-2a plus RBV showed a conspicuous therapeutic effect in patients of the Sichuan region of China, and the rate of sustained virological response (SVR) was 82.1% (46/56). The higher rates of SVR were observed in patients with IL28B genotype CC than genotype CT (90.7% versus 53.8%, P=0.009). Statistically higher proportion of SVR wasn't observed in patients with lower baseline viral load (< or =6 x 10(5) IU/mL) [88.2% versus 79.5% in patients with higher baseline viral load (> or = 6 x 10(5) IU/mL), P=0.684] and statistically lower proportion of SVR wasn't observed in patients infected with HCV genotype 1 (76.9% versus 92.9% in patients infected with HCV genotype non-1, P = 0.363). The higher rates of SVR were observed in patients with IL28B genotype CC than patients with genotype CT in the group of higher baseline viral load (> or = 6 x 10(5) IU/mL) (87.5% versus 42.9%, P=0.033) and in HCV genotype 1 infected patients (89.7% versus 50.0%, P=0.025). CONCLUSION: CC genotype was accounted for the majority at rs12979860 in patients of the Sichuan region of China. The higher rates of SVR were observed in IL28B genotype CC than genotype CT. Compared to HCV viral genotype and baseline viral load, IL28B genotype may predict the treatment effect of greater value.

Factors predicting the efficacy of adefovir dipivoxil on treatment-naïve chronic hepatitis B patients at 48 weeks.

BACKGROUND/AIMS: To reveal possible factors predicting the effect of adefovir dipivoxil (ADV) treatment on chronic hepatitis B (CHB) and optimize the utilization of ADV. METHODS: In total, 168 treatment-naïve CHB patients were enrolled, including 117 hepatitis B e antigen (HBeAg)-positive patients and 51 HBeAg-negative patients who met the inclusion criteria. All patients were treated with ADV 10 mg per day for 48 weeks. Multiple logistic regression analyses were used to investigate baseline factors, and responses at weeks 12 and 24 were analyzed as predictive values. RESULTS: Multiple regression analyses showed that baseline HBeAg status and HBV DNA levels significantly affected the virological response (VR) (p<0.05), baseline ALT levels were an independent predictor of serological response (SR) (p<0.05) and the body mass index (BMI) may affect the biochemical response (BR) (p<0.05). There was a statistically significant difference in the VR and SR between patients with a primary nonresponse (PNR) at week 12 and those with a VR at week 12 (p<0.01). Additionally, the VR was significantly different between patients with HBV DNA lower than 10(3) copies/mL at week 24 and those with greater than 10(3) copies/mL (p<0.01). CONCLUSIONS: Patients with negative HBeAg, lower HBV DNA levels and higher ALT values at baseline are more suitable for ADV treatment, whereas patients with lower BMIs may be more amenable to ALT normalization. Adjustments for treatment strategy should be considered if PNR at week 12 or HBV DNA ≥10(3) copies/mL at week 24 is observed.

[Lamivudine-resistant analysis and management for chronic hepatitis B patients with initial lamivudine therapy].

OBJECTIVE: To study the factors influencing the long-term usage of lamivudine (LAM) in chronic hepatitis B (CHB) patients and the management after drug-resistance. METHODS: 383 cases of naive CHB patients in our outpatient clinic were treated with lamivudine (100 mg/d) and followed up for at least over 1 year from 2001 to 2010. 129 cases encountered lamivudine-resistance and were then divided into two groups: patients in group A were switched to adefovir dipivoxil (ADV) alternative treatment and those patients in group B were added with ADV for continuous treatment. Efficacy assessment factors included serum HBV markers, HBV DNA, ALT, AFP and other biochemical indicators. RESULTS: Among the 383 cases, patients with HBV DNA negative conversion (PCR below test line) at 3 months, 6 months, 1 year, 2 years, 3 years and > 3 years after initial treatment were respectively 156 cases (40.7%), 213 cases (55.6%), 228 cases (59.5% ), 217cases (56.7%), 214 cases (55.9%) and 213 cases (55.6%). HBeAg/HBeAb seroconversion occurred in 62 cases (22.6%). 12 cases were found with primary LAM resistance, 129 cases with HBV breakthrough and rebound, the cumulative resistance rate was 36.8% and the cumulative rebound rate was 34.8%. High baseline viral load, baseline ALT levels < 2 ULN, Lower virologic response rate at week 24 were associated with a higher rebound rate (chi2 is 35.716, 8.728, 43.534, respectively, all with P < 0.01).Viral breakthrough and rebound occurred in 112 patients (86.8%) within 1 year and a half, 123 patients (95.3%) occurred at the end of 2 years and no patient with viral breakthrough and rebound after 5 years. For the patients with viral rebound in group A and group B, the rates of HBV DNA loss were 22.7% (15/66) and 58.7% (37/63) respectively, and the viral response rates were 59.1% (39/66) and 87.3% (52/63) respectively, with chi2 values equaled 17.364 and 12.975 respectively (P < 0.01). CONCLUSION: For the chronic hepatitis B patients on initial treatment with lamivudine, the viral rebound occurred mainly within 2 years. LAM combined with ADV is more effective than ADV alone for lamivudine-resistant patients.

De novo combination of lamivudine and adefovir versus entecavir monotherapy for the treatment of naïve HBeAg-negative chronic hepatitis B patients.

PURPOSE: Either combination treatment or monotherapy using agents with a high genetic barrier are recommended for hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). The aim of this study was to compare effect of naïve HBeAg-negative CHB patients with either de novo combination of lamivudine (LAM) and adefovir dipivoxil (ADV) or entecavir (ETV) monotherapy. METHODS: HBeAg-negative CHB patients (n = 71) with ALT levels between 2 and 10 times the upper normal limit and HBV DNA levels >10(4) copies/mL were enrolled. Patients were treated with either LAM 100 mg plus ADV 10 mg per day (n = 31) or ETV 0.5 mg per day (n = 40) for 48 weeks. RESULTS: The average reduction in HBV DNA level compared with baseline were 5.16 ± 1.69 log in the LAM + ADV group and 5.36 ± 1.70 log in the ETV group by week 48 (P = 0.624). The virological response (VR) rates were 80.65 and 77.5%, the biochemical response (BR) rates were 93.55 and 90.00% at week 48 in the LAM + ADV and ETV groups, respectively. There was no significant difference in the VR and BR between the two groups. During the 48-week treatment period, virological breakthrough and serious side effects were not noted in any patient. CONCLUSIONS: Both LAM + ADV combination therapy and ETV monotherapy are effective in naïve HBeAg-negative CHB patients, but further studies are needed to obtain long-term results.

Prospective evaluation of FibroScan for the diagnosis of hepatic fibrosis compared with liver biopsy/AST platelet ratio index and FIB-4 in patients with chronic HBV infection.

BACKGROUND: The FibroScan (FS), the aspartate aminotransferase-to-platelet ratio index (APRI), and the FIB-4 index are simple and inexpensive methods to detect liver fibrosis. AIMS: The primary objective was to evaluate the performance of FS for the noninvasive diagnosis of hepatic fibrosis in Western Chinese patients with chronic hepatitis B virus (HBV) infection compared with APRI and FIB-4; the secondary objective was to determine liver stiffness measurement (LSM) cutoff values for the noninvasive diagnosis of significant fibrosis and liver cirrhosis. METHODS: Overall, 175 consecutive patients with chronic HBV infection, successful liver biopsy, and alanine aminotransferase levels ≤2× ULN were prospectively studied. Liver fibrosis was graded by an independent pathologist using the METAVIR (F0-F4) classification. APRI and FIB-4 were calculated from laboratory data. RESULTS: The area under receiver operating characteristics curves (AUROC) for LSM for significant fibrosis (METAVIR F2-3) and cirrhosis (F4) was 0.95 (95% confidence interval, 0.91-0.98) and 0.98 (0.96-0.99), respectively. For the detection of significant fibrosis and cirrhosis, the AUROC of APRI were 0.81 (0.74-0.87) and 0.83 (0.77-0.90); the AUROC of FIB-4 were 0.86 (0.80-0.91) and 0.77 (0.68-0.85). FS optimal cutoff values for the identification of significant fibrosis and cirrhosis were 7.9 and 13.8 kPa, respectively. CONCLUSIONS: FS is a reliable predictor of significant fibrosis and cirrhosis in Western Chinese patients with chronic HBV infection, and is superior to APRI and FIB-4. FS cutoff values could be considered as clinical reference for detecting significant fibrosis and cirrhosis.

[Association between the influential factors and the effectiveness of pegylated interferon alpha-2a plus ribavirin as a combination treatment for chronic hepatitis C patients].

To evaluate the efficacy and to investigate the association between the length of the treatment period and the cumulative dose of pegylated interferon alpha-2a (PegIFN alpha-2a) plus ribavirin (RBV) and the effectiveness of antiviral therapy. We analyzed data from 117 patients treated for 48 weeks with PEG-IFN alpha-2a (135mug or 180mug/week) plus weight-based RBV (800 mg/d for patients is less than or equal to 65 kg, 1000 mg/d for patients 65-75 kg and 1200 mg/d for patients is more than or equal to 75 kg) under care at West China Hospital. HCV RNA was assessed at baseline, Week 4, 12 and 24, the end of treatment (EOT) and after 24 weeks follow-up (sustained virological response; SVR) with a test range of 1.0*10(3) to 5.0*10(7) IU/ml. Patients were stratified by age, gender, weight, route of transmission, duration of infection, baseline HCV RNA level and PegIFN alpha-2a or RBV dosage. HCV genotype was assessed in 29 patients (genotype 1b, 21; genotype 2a, 7; genotype 1b/2a, 1). Rapid virological response (RVR; HCV RNA negative at week 4), complete early virological response (cEVR; HCV RNA negative at week 12), EOT response, and SVR were achieved in 88 (75.2%), 110 (94%), 114 (97.4%) and 96 (82.1%) patients, respectively. Younger age, lower weight and shorter speculated infection years were associated with higher SVR rates (91.4% vs 72.9%, x2=6.796, P value is less than 0.05; 85% vs 50%, x2=5.433, P value is less than 0.05; 96.7% vs 77%, x2=5.852, P value is less than 0.05). SVR significantly increased with treatment length (38.5%, 66.7%, and 88.8% for is less than or equal to 29 weeks, 29-38 weeks, and is more than or equal to 38 weeks, respectively). SVR significantly increased with total cumulative treatment doses (38.5%, 66.7% and 88.8% for is less than or equal to 60%, 60%-80% and is more than or equal to 80% of PegIFN dose respectively; 33.3%, 85.3% and 96.8% for is less than or equal to 60%, 60%-80% and is more than or equal to 80% in RBV dose respectively) in all patients. Less than 80% of standard dose of RBV was not sufficient even if given enough PegIFN (is more than or equal to 80% cumulative treatment dose) in patients who achieved RVR. Chinese patients treated with peginterferon alpha-2a plus ribavirin have high rates of SVR. It is important to complete the target length of treatment and to continue the target dosage to achieve SVR.

Nucleoside analogue can improve the long-term prognosis of patients with hepatitis B virus infection-associated acute on chronic liver failure.

BACKGROUND: The prognosis of patients with hepatitis B virus (HBV)-associated acute on chronic liver failure (ACLF) is extremely poor. AIM: This study was designed to evaluate the efficacy and safety of nucleoside analogue treatment of patients with HBV-associated ACLF. METHODS: We used a retrospective review of eligible patients from April 2006 to December 2008. Eligible subjects received 0.5 mg entecavir daily until October 2009 (group A), 100 mg lamivudine daily until October 2009 (group B), or no nucleoside analogue (group C). The primary endpoints were three-month survival and the rate of recurrence of HBV-associated ACLF. The secondary endpoints were HBV DNA levels, liver function, the model of end-stage liver disease (MELD) score, and adverse events. RESULTS: A total of 104 consecutive patients were recruited, and 33, 34, and 37 patients were randomly allocated to groups A, B, and C, respectively. Although no significant difference in three-month survival was observed, levels of HBV DNA and rates of recurrence of HBV-associated ACLF were lower. Liver function and MELD score were not significantly improved despite significantly reduced HBV DNA levels. CONCLUSIONS: These data indicated that nucleoside analogue treatment did not improve the short-term prognosis of patients with HBV-associated ACLF although it was efficacious and safe in the management of HBV DNA levels. Intriguingly and importantly, continuous nucleoside analogue treatment can significantly reduce the rate of recurrence, which might be indicative of the further benefit of long-term survival.

Histological changes in chinese chronic hepatitis B patients with ALT lower than two times upper limits of normal.

The role of ALT as a predictor of liver injury has been questioned. The aim of this study is to use liver biopsy to assess the degree of liver injury in patients with chronic hepatitis B(CHB) whose ALT < 2 x upper limit of normal (ULN). A total of 49.2% of patients in this study had significant inflammation (grade >or=2) and 36.4% had significant fibrosis (stage >or=2). The frequency of serious inflammation and fibrosis was similar in patients with different ALT levels. The level of serum HBV DNA was not significantly associated with the extent of inflammation and fibrosis. Advanced age was a significant independent predictor of histological damage and the presence of more significant inflammation and fibrosis. We conclude that many CHB patients with ALT < 2 x ULN have significant liver inflammation or fibrosis and that liver biopsy is necessary to assess liver damage and should be used to assess the need for anti-viral therapy.

[Assessment of disease activity and liver fibrosis in chronic viral hepatitis by magnetic resonance diffusion-weighted imaging].

OBJECTIVE: To investigate the diagnostic value of magnetic resonance diffusion-weighted imaging (DWI) technique in assessing the disease activity and liver fibrosis of chronic viral hepatitis. METHODS: A total of 49 patients with chronic viral hepatitis who received liver biopsy and 10 healthy volunteers were included in this study. All of them underwent DWI on a 3.0 T magnetic resonance imaging system. When the gradient factor b value was set at 100, 200, 400, 600, and 800 s/mm2, the apparent diffusion coefficient (ADC) of the liver was measured respectively. Biopsy specimens were scored for necroinflammation and liver fibrosis according to the Knodell histological activity index. RESULTS: The ADC values of the right lobe in both controls and patients were lower than those of the left lobe. When the b value was set at 400, 600, and 800 s/mm2, the differences of the ADC values between the fibrosis group (n = 36) and the non-fibrosis group (n = 23, including 10 cases of normal subjects) were statistically significant (P < 0.01). When the b value was set at 800 s/mm2, the ADC values among the different degrees of necroinflammation and grades of liver fibrosis were also significantly different (P < 0.05, P < 0.01). CONCLUSION: DWI is a valuable method for in vivo and noninvasive assessment of the disease activity and liver fibrosis of chronic viral hepatitis.

Recombinant human hepatocyte growth factor for liver failure.

The purpose of this paper is to evaluate the efficacy and safety of recombinant human hepatocyte growth factor (rh-HGF) for liver failure (LF) using meta-analysis of data from the literature involving available randomized controlled trials of rh-HGF plus comprehensive therapy (CT) compared with that of CT alone (Therapy I versus II) in treating LF. We searched the Cochrane Library, MEDLINE, EMBASE, CBMdisc, and CNKI as well as employing manual searches. Based on our search criteria, we found 21 trials, involving 5902 patients. Our results showed that Therapy I, compared with therapy II, significantly reduced the overall mortality (RR=0.62; 95% CI, 0.59-0.66; p=0.0001). Compared to two clinical types of LF (acute and acute-on-chronic), therapy I perhaps had significant effect on mortality due to sub-acute LF, RR and 95% CI were 0.76 [0.65, 0.89], 0.66 [0.60, 0.74], and 0.58 [0.53, 0.64], respectively. Additionally, there was a reduction in mortality of patients that had evidence for an early stage of LF compared to the two other clinical stages of LF (Middle and Advanced); RR and 95% CI were 0.34 [0.24, 0.49], 0.49 [0.44, 0.55], and 0.87 [0.82, 0.93], respectively. No serious adverse events were reported. We conclude that Therapy I may reduce mortality in LF, especially in sub-acute LF and the early stage of LF. However, considering the strength of the evidence, additional randomized controlled trials are needed before Therapy I can be recommended routinely.

[The relationship between 31P magnetic resonance spectroscopy and the histopathology of livers of chronic viral hepatitis patients].

OBJECTIVE: To investigate the correlations between 31P-magnetic resonance spectroscopy (MRS) findings and histopathological grading and staging of the livers of chronic viral hepatitis patients. METHODS: Thirty-one patients with chronic viral hepatitis and 18 healthy volunteers were enrolled for this study. All of them underwent routine MRI plain scan and 31P-MRS of their livers. Peak areas of PME, PDE, PCr, Pi, gamma-ATP, beta-ATP and alpha-ATP were calculated. The concentrations of the phosphorus compounds of their livers, including PME, PDE, PCr, Pi, gamma-ATP, beta-ATP and alpha-ATP were measured. Percutaneous liver biopsies were performed on all 31 patients 0 to 7 days after their 31P-MRS examinations. Biopsy specimens were scored for fibrosis and necroinflammation according to the Knodell histological activity index. According to their necroinflammation scores, the 31 patients were divided into groups: slight hepatitis (7 patients), mild hepatitis (11), moderate hepatitis (8) and severe hepatitis (5). According to their fibrosis scores, the patients were divided into groups: no fibrosis (7 patients), portal fibrosis (11), bridging fibrosis (5) and cirrhosis (8). RESULTS: The PME%, PDE% and PME/PDE of the hepatitis patients and of the control volunteers had significant statistical differences. The differences of PME%, PDE% and PME/PDE among different grades and stages also had statistical significance. When PME/PDE=0.78, 0.95 and 1.11 were set as the cut-off points for different grades of necroinflammation, and PME/PDE=0.79, 0.95 and 1.10 were set as the cut-off points for different stages of fibrosis, a sensitivity of 80.0%-87.5% and a specificity of 42.9%-72.7% were achieved. CONCLUSION: PME/PDE is a sensitive marker for diagnosing the severity of chronic viral hepatitis. A rise of PME/PDE in hepatitis patients represents an increase of synthesis and a decrease in the breakdown of hepatocytes.

Tissue microarray for high-throughput analysis of gene expression profiles in hepatocellular carcinoma.

AIM: To study the expression profiles of HBsAg, HBcAg, p21WAF1/CIP1 (p21), Rb genes in hepatocellular carcinoma (HCC) and to investigate their roles in the hepatocar-cinogenesis. METHODS: HCC tissue microarray containing 120-min tissues of 40 HCC cases was constructed. HBsAg, HBcAg, p21 and Rb proteins were immunohistochemically stained by streptavidin-peroxidase conjugated method (S-P). The expression loss of these genes in cancerous, para-cancerous tissues and adjacent normal liver tissues of 40 HCCs were comparatively examined. RESULTS: The positive rate of HBsAg expression in cancerous tissues of 40 HCCs was 7.5%, which was lower than that in para-cancerous and adjacent normal liver tissues (chi2 =12.774, P < 0.01; chi2 = 18.442, P < 0.01). The positive rate of HBcAg expression in cancerous tissues of 40 HCCs was 20.0%, which was also lower than that in para-cancerous and adjacent normal liver tissues (chi2 = 9.482, P < 0.01; chi2 = 14.645, P < 0.01). p21 protein deletion rate in cancerous tissues of 40 HCCs was 27.5%, which was higher than that in para-cancerous and adjacent normal liver tissues (chi2 = 7.439, P < 0.01; chi2 = 11.174, P < 0.01). p21 protein deletion correlated remarkably with the pathological grade of HCC (chi2 = 0.072, P < 0.05). Rb protein deletion rate in cancerous tissues of 40 HCCs was 42.5%, which was also higher than that in para-cancerous and adjacent normal liver tissues (chi2 = 10.551, P < 0.01; chi2 = 18.353, P < 0.01). Rb protein deletion rate did not correlate remarkably with tumor size or pathological grade of HCC (chi2 = 0.014, P > 0.05; chi2 = 0.017, P > 0.05). CONCLUSION: Expression deletion of HBsAg, HBcAg, p21 and Rb proteins in HCCs may play important roles in the carcinogenesis of HCC. Tissue microarray is an effective high-throughput technique platform for cancer research.