Lack of correlation between serum anti-HBcore detectability and hepatocellular carcinoma in patients with HCV-related cirrhosis

BACKGROUND: While the likelihood of developing hepatocellular carcinoma (HCC) in patients coinfected with both HBV and HCV is increased, the role of previous exposure to HBV as a risk factor associated with tumor occurrence in subjects with HCV-related cirrhosis has not been fully investigated.
AIM: To assess whether serum anti-HBc positivity, as a marker of previous HBV exposure, is associated with HCC development in HCV-related positive, hepatitis B surface antigen (HBsAg) negative patients with cirrhosis treated with alfa-interferon (IFN) monotherapy.
PATIENTS AND: A database including 883 consecutive patients (557 men, mean age 54.7 yr) with histologically
METHODS: proven cirrhosis treated with IFN between 1992 and 1997 was analyzed. All subjects have been surveilled every 6 months by ultrasound. Independent predictors of HCC were assessed by Cox multiple regression analysis.
RESULTS: Mean follow-up was 96.1 months. Anti-HBc testing was available in 693 cases and, among them, 303 patients (43.7%) were anti-HBc seropositive. Anti-HBc positive patients were more often men (67.0% vs 58.7%, P = 0.03), had lower transaminase levels (3.3 ± 2.0 vs 3.8 ± 2.5 u.l.n., P = 0.004), and had higher rate of alcohol intake (38.3% vs 22.5%, P < 0.001) than anti-HBc negative patients. Overall, the incidence rates of HCC per 100 person-years were 1.84 (95% CI 1.34–2.47) in the anti-HBc positive patients and 1.86 (95% CI 1.41–2.42) in anti-HBc negative ones. By Cox multiple regression, there was no association of serum anti-HBc with HCC development (HR 1.03, 95% CI 0.69–1.52) or liver-related deaths incidence (HR 1.21; 95% CI 0.76–1.95).
CONCLUSIONS: In comparison with anti-HBc negative subjects, serum anti-HBc positive patients with HCV-related/HBsAg negative cirrhosis treated with IFN monotherapy did not show a greater risk of HCC.     

Cigarette smoking and the risk of supraventricular and ventricular tachyarrhythmias in high-risk cardiac patients with implantable cardioverter defibrillators

Introduction: Nicotine elevates serum catecholamine concentration and is therefore potentially arrhythmogenic. However, the effect of cigarette smoking on arrhythmic risk in coronary heart disease patients is not well established.
Methods and Results: The risk of appropriate and inappropriate defibrillator therapy by smoking status was analyzed in 717 patients who received an implantable cardioverter defibrillator (ICD) in the Multicenter Automatic Defibrillator Implantation Trial-II. Compared with patients who had quit smoking before study entry (past smokers) and patients who had never smoked (never smokers), patients who continued smoking (current smokers) were significantly younger and generally had more favorable baseline clinical characteristics. Despite this, the adjusted hazard ratio (HR) for appropriate ICD therapy for fast ventricular tachycardia (at heart rates ≥180 b.p.m) or ventricular fibrillation was highest among current smokers  (HR = 2.11 [95% CI 1.11–3.99])  and intermediate among past smokers  (HR = 1.57 [95% CI 0.95–2.58])  , as compared with never smokers (P for trend = 0.02). Current smokers also exhibited a higher risk of inappropriate ICD shocks  (HR = 2.93 [95% CI 1.30–6.63])  than past  (HR = 1.91 [95% CI 0.97–3.77])  and never smokers (P for trend = 0.008).
Conclusions: In patients with ischemic left ventricular dysfunction, continued cigarette smoking is associated with a significant increase in the risk of life-threatening ventricular tachyarrhythmias and inappropriate ICD shocks induced by rapid supraventricular arrhythmias. Our findings stress the importance of complete smoking cessation in this high-risk population.     

Hepatitis C virus related cirrhosis: time to occurrence of hepatocellular carcinoma and death

BACKGROUND: In patients with hepatitis C virus (HCV) infection and cirrhosis, long term outcome and the incidence of hepatocellular carcinoma (HCC) are still debated. DESIGN: From January 1987 to January 1997, 416 patients (240 male, median age 57 years) with uncomplicated Child-Pugh A HCV related cirrhosis were followed in two Paris area centres from diagnosis of cirrhosis until death or reference date (1 June 1998). The analysis used a three state disability model generalising the Cox model. RESULTS: Of the 416 patients, 60 developed HCC with a five year rate of 13.4% (95% confidence interval (CI) 9.0-17.8%) and 83 died (including 34 with HCC), with a five year death rate of 15.3% (95% CI 12.6-18.0%). By multivariable analysis, time to HCC relied on age (hazard ratio (HR) 1.05 per year; p=0.0005), male sex (HR 2.13; p=0.01), oesophageal varices (HR 2.36; p= 0.008), decreased platelet count (HR 0.99; p=0. 03), and bilirubin level (HR 1.01; p=0.003), while death after HCC was mainly related to tobacco consumption (HR 1.04; p=0.0006). In contrast, death free of HCC was dependent on age (HR 1.04; p=0.01), oesophageal varices (HR 2.75; p=0.001), low platelet count (HR 0.99; p=0.006), and albumin level (HR 0.90; p=0.0001). CONCLUSION: The incidence of HCC and mortality should be higher in these patients than previously stated, and prognostic factors of HCC and death are closely related age and symptoms of portal hypertension.     

Clinical features and outcomes of cirrhosis due to non-alcoholic steatohepatitis compared with cirrhosis caused by chronic hepatitis C

Background and Aim:  Ethnic differences in non-alcoholic steatohepatitis (NASH) are well-documented, but there has been no study on the prognosis of Japanese NASH patients with cirrhosis. Accordingly, we compared cirrhotic NASH with liver cirrhosis caused by chronic hepatitis C (LC-C) to clarify its clinical features and define the risk factors for death.
Methods:  A prospective evaluation of the outcomes of NASH patients with severe fibrosis was started in 1990. Data on age- and sex-matched patients with biopsy-proven LC-C were collected retrospectively and used as the control.
Results:  There were 68 patients with cirrhotic NASH and 69 with LC-C. The Child–Turcotte–Pugh (CTP) class was similar in these two groups. Although the outcome of the NASH group was better than that of the LC-C group, cirrhotic NASH followed a similar course to that of LC-C; that is, complications of cirrhosis developed, including hepatocellular carcinoma (HCC; the 5-year HCC rate was 11.3% for NASH and 30.5% for HCV) and death (the 5-year survival rates were 75.2% and 73.8%, respectively). HCC was the leading cause of death in both groups (NASH, 47%; HCV, 68%). The occurrence of HCC and the CTP class were significant risk factors for mortality in NASH patients according to a multivariate analysis (HCC: hazard ratio [HR] 7.96, 95% confidence interval [CI] 2.45–25.88, CTP class A: HR 0.17, 95% CI 0.06–0.50).
Conclusion:  In conclusion, the present study confirmed that cirrhotic NASH has a similar course to LC-C. The occurrence of HCC was the strongest predictor of mortality in the NASH groups. These findings may be helpful when deciding on therapeutic interventions for NASH and also for the daily management of these patients.     

Reduced Peak Atrial Systolic Mitral Annular Velocity Predicts the Development of Nonvalvular Atrial Fibrillation

We investigated whether the echocardiographic parameters of the left atrium (LA) can predict the development of nonvalvular atrial fibrillation (AF). Among 14,062 patients ( > 20 years old) who underwent an echocardiographic examination were evaluated, 2,606 patients who underwent follow-up ECG with an interval of > 6 months were investigated. Newly developed AF was noted in 42 (1.6%) patients with follow-up duration of 31.8 ± 8.9 months. Cox regression analysis revealed that a higher left atrial volume index (hazard ratio [HR ]= 1.06; 95% confidence interval [CI] 1.03–1.09, P < 0.001), relative wall thickness (RWT) of ≥ 0.407 (HR = 2.74, 95% CI 1.39–5.41, P = 0.004), a reduced peak atrial systolic mitral annular velocity (HR = 0.845, 95% CI 0.72–0.99, P = 0.037), and an advanced age (HR = 1.04, 95% CI 1.01–1.07, P = 0.009) were independently related to the development of nonvalvular AF. Therefore, reduced A ' , which is parameter of LA contractile function, might be an important predictor for the development of nonvalvular AF.     

Expression of the HCRP1 mRNA in HCC as an independent predictor of disease-free survival after surgical resection

Aim:  Hepatocellular carcinoma (HCC)-related protein-1 ( HCRP1 ) gene was located at chromosome 8p22, a frequently deleted region in HCC. The gene product was a subunit of mammalian Endosomal Sorting Complex Required for Transport (ESCRT)-I, essential for degradation of epidermal growth factor receptors. In this study, we examined the prognostic role of HCRP1 mRNA expression in HCC.
Methods:  The expression of HCRP1 mRNA in HCC was assessed in 125 patients receiving surgical resection of HCC. Using the adjacent non-cancerous tissues as a reference, 55 and 70 patients expressing high and low levels of HCRP1 mRNA, respectively, were identified. The predictive value of HCRP1 mRNA expression in postoperative survival was evaluated.
Results:  Expression of HCRP1 mRNA was not associated with any of the baseline clinicopathological parameters. However, univariate analysis showed that it was associated with a better disease-free survival ( P  < 0.001) and overall survival ( P  = 0.032). Stepwise Cox multivariate proportional hazards regression analysis showed that the expression of HCRP1 mRNA (hazard ratio [HR], 0.396; 95% confidence interval (CI), 0.233–0.674; P  = 0.001), tumor number (HR, 1.596; 95% CI, 1.221–2.087; P  = 0.001), serum aspartate aminotransferase (HR, 1.002; 95% CI, 1.000–1.003; P  = 0.031) and the presence of microvascular invasion (HR, 1.852; 95% CI, 1.131–3.032; P  = 0.014) were included as independent predictors for disease-free survival.
Conclusion:  Expression of HCRP1 mRNA served as an independent predictor for postoperative disease-free survival in HCC patients.     

Racial differences in liver transplantation outcomes in the MELD era

OBJECTIVES:  Beginning February 28, 2002, the Model for End-Stage Liver Disease (MELD) score was introduced to better allocate donor livers. Racial differences in orthotopic liver transplantation (OLT) outcomes prior to this time have been attributed to late listing of some racial groups. Racial differences in post-transplant survival in the MELD era have not been previously examined.
METHODS:  We performed a retrospective observational cohort study using the United Network for Organ Sharing database for adult liver transplants performed between 2002 and 2006. We examined patient and graft survival at 2 yr and compared disease-specific survival rates among the different races.
RESULTS:  A total of 10,409 whites, 1,133 blacks, 1,548 Hispanics, and 765 transplant recipients belonging to other races were included in the study. On multivariate analysis, blacks had lower overall (hazard ratio for death [HR] 1.29, 95% confidence interval [95% CI] 1.10–1.52) and graft (HR 1.38, 95% CI 1.20–1.58) survival at 2 yr compared to whites, while Hispanics had better overall (HR 0.78) and graft (HR 0.82) survival. Compared to whites, blacks transplanted for hepatitis C or HCC had lower survival at 2 yr.
CONCLUSION: In the MELD era, black patients have significantly lower overall and graft survival at 2 yr compared to whites.     

High Levels of Serum C-Reactive Protein Are Associated with Greater Risk of All-Cause Mortality, but Not Dementia, in the Oldest-Old: Results from The 90+ Study

OBJECTIVES: To evaluate whether high levels of C-reactive protein (CRP) in serum are associated with greater risk of all-cause dementia or mortality in the oldest-old.
DESIGN: Prospective.
SETTING: Research clinic and in-home visits.
PARTICIPANTS: Population-based sample of adults (N=227; aged 93.9±2.8) from The 90+ Study, a longitudinal cohort study of people aged 90 and older.
MEASUREMENTS: CRP levels were divided into three groups according to the assay detection limit: undetectable (<0.5 mg/dL), detectable (0.5–0.7 mg/dL), and elevated (≥0.8 mg/dL). Neurological examination was used to determine dementia diagnosis ( Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition , criteria). Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using Cox regression, and results were stratified according to and apolipoprotein E4 (APOE4) genotype.
RESULTS: Subjects with detectable CRP levels had significantly greater risk of mortality (HR=1.7, 95% CI=1.0–2.9), but not dementia (HR=1.2, 95% CI=0.6–2.1), 0.4 to 4.5 years later than subjects with undetectable CRP. The highest relative risk for dementia and mortality was in APOE4 carriers with detectable CRP (dementia HR=4.5, 95% CI=0.9–23.3; mortality HR=5.6, 95% CI=1.0–30.7).
CONCLUSION: High levels of CRP are associated with greater risk of mortality in people aged 90 and older, particularly in APOE4 carriers. There was a trend toward greater risk of dementia in APOE4 carriers with high CRP levels, although this relationship did not reach significance. High levels of CRP in the oldest-old represent a risk factor for negative outcomes.     

Hepatitis C virus genotype 1b as a major risk factor associated with hepatocellular carcinoma in patients with cirrhosis: a seventeen-year prospective cohort study

Hepatocellular carcinoma (HCC) is the most frequent cause of death in patients with hepatitis C virus (HCV)-induced cirrhosis. Despite a number of studies in different populations worldwide suggesting an association between HCV genotype 1 and the risk of HCC, no consensus has emerged yet on this matter, which is still controversial. In an attempt to clarify this issue, a prospective study of 163 consecutive HCV-positive patients with cirrhosis, who were enrolled between January 1989 and December 1990, was carried out. HCC occurrence was detected by ultrasound surveillance every 6 months. Independent predictors of HCC were assessed with a Cox regression analysis. After a median follow-up of 10.7 years, 44 [4.26/100/year, confidence interval (CI) = 3.11-5.68/100/year] of 104 patients infected with genotype 1b developed HCC versus 10 (1.69/100/year, CI = 0.82-3.09/100/year) of 52 patients infected with genotype 2a/c (P = 0.0001). Multivariate analysis showed that HCV genotype 1b was independently associated with HCC development [hazard ratio (HR) = 3.02, 95% CI = 1.40-6.53]. Other predictors of HCC were esophageal varices (HR = 2.15, 95% CI = 1.03-4.47), male gender (HR = 2.12, 95% CI = 1.10-4.11), and age over 60 years (HR = 5.96, 95% CI = 1.23-28.8). Conclusion: HCV genotype 1b is associated with a statistically significant higher risk of developing HCC. Patients with cirrhosis that are infected with this genotype require more intensive surveillance for the early detection and aggressive management of neoplasia.     

Risk factors for hepatocellular carcinoma in patients with alcoholic or viral C cirrhosis.

BACKGROUND & AIMS: Influence of being overweight and diabetes mellitus on the occurrence of hepatocellular carcinoma (HCC) in patients with cirrhosis has not been evaluated prospectively. The aim of this study was to show the predictive value of these factors in a cohort of 771 patients with well-compensated alcohol- or hepatitis C (HCV)-related cirrhosis who were screened prospectively for HCC. METHODS: The predictive value for HCC occurrence was assessed by using the log-rank test and the Cox proportional hazards model. At enrollment, the mean age was 61.4 +/- 10 years and 431 patients were men. Cirrhosis was caused by alcohol (n = 478), HCV (n = 220), or the association of both factors (n = 73). The mean body mass index (BMI) was 25.4 kg/m(2) and 231 patients were diabetic. RESULTS: During a mean follow-up period of 4.2 +/- 3 years, 220 patients developed HCC. In univariate analysis, a BMI of 25 kg/m(2) or more, diabetes, male sex, age older than 60 years, and HCV infection were risk factors for HCC. In multivariate analysis, predictive factors were a BMI between 25-30 kg/m(2) (hazard ratio [HR], 2.0; 95% confidence interval [CI], 1.4-2.7), BMI of 30 kg/m(2) or more (HR, 2.8; 95% CI, 2.0-4.0), diabetes (HR, 1.6; 95% CI, 1.2-2.1), age 60-70 years (HR, 2.4; 95% CI, 1.3-4.3), age older than 70 years (HR, 3.0; 95% CI, 1.7-5.5), male sex (HR, 2.0; 95% CI, 1.4-2.7), HCV (HR, 1.6; 95% CI, 1.1-2.2), and mixed (HR, 2.6; 95% CI, 1.7-4.0) etiology. We found a positive linear relationship between BMI level and HCC incidence during follow-up evaluation. CONCLUSIONS: Overweight and diabetes mellitus are associated with an increased risk of HCC occurrence in patients with HCV- or alcohol-related cirrhosis.     

On-treatment monitoring of adefovir therapy in chronic hepatitis B: virologic response can be assessed at 24 weeks

Summary.  Patients with chronic hepatitis B (CHB) who will and those who will not respond to adefovir (ADV) monotherapy need to be identified at an early stage in order to adjust treatment and prevent future development of antiviral resistance. In a single-centre cohort study, we investigated 76 CHB patients [50% hepatitis B e antigen (HBeAg)-positive] treated with long-term ADV monotherapy. During a median follow-up of 122 (24–185) weeks, 42 (55%) patients achieved virologic response (VR), defined as HBV-DNA levels <10³ copies/mL, and 10 patients (13%) developed genotypic ADV resistance. Independent baseline predictors of VR were HBeAg negativity [hazard ratio (HR) 2.98; 95% confidence interval (CI) 1.24–7.19; P  =   0.02], high alanine aminotransferase (ALT) levels (HR 1.11; 95% CI 1.05–1.18; P  =   0.001), and low HBV-DNA levels (HR 0.56; 95% CI 0.41–0.75; P  <   0.001). HBV-DNA at week 24 demonstrated a higher predictive value for VR than HBV-DNA at week 48. Important predictors of genotypic resistance were presence of cirrhosis (HR 6.54; 95% CI 1.39–30.9; P  =   0.018), and not achieving VR during treatment (HR 6.60; 95% CI 1.35–32.4; P  =   0.008). Patients without VR at week 24 already demonstrated a trend towards the emergence of ADV resistance ( P  =   0.07). HBV-DNA at week 24 was a better on-treatment predictor of VR than HBV-DNA at week 48, and ADV-resistant mutations developed more frequently in patients without VR at week 24. Therefore, our study suggests that virologic response to ADV therapy can be assessed at 24 weeks, instead of the generally recommended 48 weeks.     

Effect of hepatitis B and C virus infections on the natural history of compensated cirrhosis: a cohort study of 297 patients

OBJECTIVES: The aim of this study was to compare the prognosis of patients with hepatitis B surface antigen (HBsAg) positive and those with antibody to hepatitis C (anti-HCV) positive cirrhosis. METHODS: This was a retrospective cohort study of 297 untreated Western European patients with compensated viral cirrhosis (Child class A; 161 patients with hepatitis type B and 136 with type C) who were followed for a median period of 6.6 yr. RESULTS: At diagnosis, median age was lower (48 vs 58 yr, respectively) in HBsAg-positive cirrhotic patients. The Kaplan-Meier 5-yr probability of hepatocellular carcinoma (HCC) was 9% and 10% in HBsAg and anti-HCV-positive cirrhotic patients, respectively; the corresponding figures for decompensation unrelated to HCC were 16% and 28% and for survival were 86% and 84%, respectively. After adjustment for clinical and serological differences at baseline, the relative risk (95% CI) for HCC, decompensation and mortality was 1.53 (CI = 0.81-2.89), 0.59 (CI = 0.37-0.94), and 1.44 (CI = 0.85-2.46) respectively, in HBsAg-positive patients compared with anti-HCV-positive cirrhotic patients. Among HBsAg-positive cirrhotic patients, the relative risk for HCC, decompensation, and mortality was 0.89 (CI = 0.30-2.63), 4.05 (CI = 1.09-15.1), and 5.9 (CI = 1.64-21.3), respectively, in HBV-DNA positive (HBeAg positive or negative) compared with HBV-DNA negative (HBeAg negative) patients at entry. CONCLUSIONS: Patients with HBV infection may present with cirrhosis about 10 yr earlier than those with HCV infection. HCV infection tends to be associated with a higher risk of decompensation, but these data should take into consideration the heterogeneity of HBV-related cirrhosis in terms of viremia levels and risk of hepatic failure. Survival shows no significant differences according to HBV or HCV etiology in Western European cirrhotic patients.     

Mannose-binding lectin 2 rs11003123 polymor-phism is associated with the development of hepatocellular carcinoma in patients with hepa-titis B-related cirrhosis in the Chinese population

BACKGROUND: Mannose-binding lectin 2 (MBL2) plays a key role in the host immune response, but whether it is associ-ated with hepatocellular carcinoma (HCC) is not clear. The present study aimed to identify the association between MBL2 gene polymorphisms and HCC in patients with hepatitis B virus (HBV)-related cirrhosis in the Chinese population.
METHODS: A single-nucleotide polymorphism of MBL2, rs11003123, was genotyped and analyzed in a case-control study of HBV-related cirrhotic patients with HCC (n=77) and without HCC (n=40).
RESULTS: We found that Child-Pugh proifles, model for end-stage liver disease score, and the incidence of encephalopathy were all higher in the non-HCC group (P<0.05). A signiifcant association between allele mutants and HCC occurrence was demonstrated by allele comparison (A vs G) (OR=0.34; 95%CI: 0.15-0.76;P=0.006). Heterozygous comparison (GA vs GG) revealed that the individuals with GA mutants had a reduced risk of HCC occurrence compared with those with GG wild type (adjusted OR=0.28; 95% CI: 0.10-0.80;P=0.004). In a dominant model (GA+AA vs GG), a decreased risk of HCC occurrence was observed in individuals with variant geno-types (GA and AA) compared with those with the wild type (adjusted OR=0.30; 95% CI: 0.11-0.85;P=0.004). However, no statistically signiifcant associations were observed between rs11003123 and prognosis of patients with HCC after liver transplantation in both recurrence-free survival and overall survival (P=0.449 andP=0.384, respectively).
CONCLUSION: MBL2 rs11003123 polymorphism may be a marker for the risk of HCC occurrence in patients with HBV-related cirrhosis in the Chinese population.     

New scoring system for predicting relapse after lamivudine-induced hepatitis B e-antigen loss in chronic hepatitis B patients

Aim:  In endemic areas of hepatitis B virus (HBV) infection, lamivudine-induced hepatitis B e-antigen (HBeAg) loss is not durable. We developed a scoring system to predict the relapse after lamivudine-induced HBeAg loss.
Methods:  Of 93 HBeAg-positive chronic hepatitis B patients receiving lamivudine therapy, we studied the 30 patients who achieved HBeAg loss. Qualitative polymerase chain reaction assays for HBV DNA were performed after HBeAg loss; if results were negative on two consecutive occasions, lamivudine treatment was stopped. Serum HBV DNA levels at the time of HBeAg loss were determined using stored serum by the Cobas Amplicor HBV Monitor Kit.
Results:  Cumulative relapse rates were 44%, 55.8% and 59.8%, after 1, 2 and 5 years, respectively. Univariate analysis showed that the risk factors for relapse were age (≥ 30 years), HBV DNA level (≥ 60 IU/mL) at the time of HBeAg loss and liver cirrhosis. Independent risk factors for relapse were age (odds ratio [OR], 4.3; 95% confidence interval [CI], 1.2–17.6) and serum HBV DNA level at the time of HBeAg loss (OR, 5.1; 95% CI, 1.3–21.6). We developed a scoring system based on these independent risk factors. No relapse was observed for patients with a risk score of 0. For patients with a risk score of 1, the relapse rates were 41%, 49% and 56% at 1, 2 and 5 years, respectively. All patients with a risk score of 2 relapsed ( P  = 0.01).
Conclusion:  Our new scoring system may be useful for predicting relapses in patients with lamivudine-induced HBeAg loss. Treatment strategies should be individualized according to risk score.     

Combination therapy with transarterial chemoembolization and interferon-α compared with transarterial chemoembolization alone for hepatitis B virus related unresectable hepatocellular carcinoma

Background and Aims:  The present study was carried out to test the hypothesis that interferon-α (IFN-α) treatment would reduce or postpone the recurrence rate and improve the overall survival rate in patients after transarterial chemoembolization (TACE) treatment of hepatitis B virus (HBV) related unresectable hepatocellular carcinoma (HCC).
Methods:  216 patients with unresectable HBV-related HCC were randomized into a TACE group and a TACE-IFN group, each group had 108 patients. In the TACE-IFN group, patients received IFN-α1b at a dose of 3 million units (mu) three times a week by intramuscular injection one week after/before TACE treatment, for 48 weeks.
Results:  The median disease-free survival in the TACE-IFN treatment group was 23.6 months (95% CI: 21.4–25.8) and 20.3 months (95% CI: 15.8–24.8) in the TACE group ( P  = 0.027). The disease free rate at 24 months in the TACE group was lower than in the TACE-IFN group (39.8% vs 59.3%, P  = 0.004). The median overall survival was 29 months (95% CI: 27.5–32.1) in the TACE-IFN group and 26 months (95% CI: 20.1–31.9) in the TACE group ( P  = 0.003). The 2-year overall survival in the TACE-IFN group was higher than in the TACE group (72.2% vs 52.8%, P  = 0.003).
Conclusions:  IFN-α treatment reduced recurrence and improved the survival of patients after TACE treatment of HBV-related HCC, with acceptable toxicities.     

Serum levels of fibrosis biomarkers measured early after liver transplantation are associated with severe hepatitis C virus recurrence

Abstract: This prospective study analyzed the relationship between several biological markers related to liver fibrosis at 3 months and 1 year post liver transplantation in 37 patients (19 with hepatitis C virus [HCV], 18 with alcoholic liver disease). Severe HCV recurrence (HCV-SR) was defined as fibrosis stage ≥F1 (METAVIR score) at 1 year and/or a value of hepatic venous pressure gradient ≥6 mmHg. We found HCV-SR patients had higher values of monocyte chemotactic protein-1 (MCP-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and hyaluronic acid (HA) than non-severe HCV recurrence patients ( P <0.05). Moreover, receiver operating characteristic curve analysis showed that interferon-inducible protein 10 (IP-10) (area under the curve [AUC]: 0.74; confidence interval [CI] 95%: 0.49–0.91; P =0.043), MCP-1 (AUC: 0.78; CI 95%: 0.54–0.94; P =0.007), sVCAM-1 (AUC: 0.89; CI 95%: 0.67–0.98; P =0.005), and HA (AUC: 0.80; CI 95%: 0.55–0.94; P =0.035) have good predictive capacity for identifying severe HCV infection. The evaluation of these biomarkers may be useful in the early identification of patients in whom a more aggressive therapeutic approach could be necessary.     

Effect of alcohol, cigarette smoking, and diabetes on occurrence of hepatocellular carcinoma in patients with transfusion-acquired hepatitis C virus infection who develop cirrhosis

AIM: Alcohol drinking, cigarette smoking, and diabetes have been claimed as risk factors for hepatocellular carcinoma in case-control studies. The aim of this study was to define the impact of these risk factors on the development of hepatocellular carcinoma in hepatitis C virus-related liver cirrhosis. METHODS: A historical cohort of 138 patients with posttransfusion hepatitis C virus-related cirrhosis was selected by reviewing all files of patients referred to our liver unit. Sixty-three of them (46%) developed hepatocellular carcinoma. RESULTS: At univariate analysis, risk factors for hepatocellular carcinoma were observed in patients aged above 59 years [P=0.004; relative risk (RR): 2.08, 95% confidence interval (CI): 1.19-3.68], male sex (P<0.001; RR: 2.48, 95% CI: 1.59-3.87), habit of alcohol drinking (P=0.001; RR: 1.89, 95% CI: 1.24-2.88), and duration of alcohol consumption of more than 30 years (P=0.02; RR: 2.08, 95% CI: 0.98-4.40). At Cox regression analysis, only male sex was an independent predictive factor (beta=0.86; P=0.002; hazard ratio=2.4, 95% CI: 1.3-4.1). CONCLUSION: Diabetes, smoking, and alcohol drinking were not independently related to the risk of developing hepatocellular carcinoma in hepatitis C virus-related cirrhosis.     

Liver stiffness predicts clinical outcome in human immunodeficiency virus/hepatitis C virus-coinfected patients with compensated liver cirrhosis

Our aim was to assess the predictive value of liver stiffness (LS), measured by transient elastography (TE), for clinical outcome in human immunodeficiency virus / hepatitis C virus (HIV/HCV)-coinfected patients with compensated liver cirrhosis. This was a prospective cohort study of 239 consecutive HIV/HCV-coinfected patients with a new diagnosis of cirrhosis, done by TE, and no previous decompensation of liver disease. The time from diagnosis to the first liver decompensation and death from liver disease, as well as the predictors of these outcomes, were evaluated. After a median (Q1-Q3) follow-up of 20 (9-34) months, 31 (13%, 95% confidence interval [CI]: 9%-17%) patients developed a decompensation. The incidence of decompensation was 6.7 cases per 100 person-years (95% CI, 4.7-9-6). Fourteen (8%) out of 181 patients with a baseline LS < 40 kPa developed a decompensation versus 17 (29%) out of 58 with LS ≥ 40 kPa (P = 0.001). Factors independently associated with decompensation were Child-Turcotte-Pugh (CTP) class B versus A (hazard ratio [HR] 7.7; 95% CI 3.3-18.5; P < 0.0001), log-plasma HCV RNA load (HR 2.1; 95% CI 1.2-3.6; P = 0.01), hepatitis B virus coinfection (HR, 10.3; 95% CI, 2.1-50.4; P = 0.004) and baseline LS (HR 1.03; 95% CI 1.01-1.05; P = 0.02). Fifteen (6%, 95% CI: 3.5%-9.9%) patients died, 10 of them due to liver disease, and one underwent liver transplantation. CTP class B (HR 16.5; 95% CI 3.4-68.2; P < 0.0001) and previous exposure to HCV therapy (HR 7.4; 95% CI 1.7-32.4, P = 0.007) were independently associated with liver-related death; baseline LS (HR 1.03; 95% CI 0.98-1.07; P = 0.08) was of borderline significance. CONCLUSION: LS predicts the development of hepatic decompensations and liver-related mortality in HIV/HCV-coinfection with compensated cirrhosis and provides additional prognostic information to that provided by the CTP score.     

Hepatocellular carcinoma progression in hepatitis B virus-related cirrhosis patients receiving nucleoside (acid) analogs therapy: A retrospective cross-sectional study

BACKGROUNDAntiviral therapy cannot completely block the progression of hepatitis B to hepatocellular carcinoma (HCC). Furthermore, there are few predictors of early HCC progression and limited strategies to prevent progression in patients with HBV-related cirrhosis who receive nucleos(t)ide analog (NA) therapy.AIMThe study aim was to clarify risk factors and the diagnostic value of alpha-fetoprotein (AFP) for HCC progression in NA-treated hepatitis B virus (HBV)-related cirrhosis patients.METHODSIn this retrospective cross-sectional study, we analyzed the clinical data of 266 patients with HBV-related cirrhosis who received NA treatment between February 2014 and April 2020 at Zhejiang Provincial People’s Hospital. The patients were divided into two groups, 145 who did not progress to HCC (No-HCC group), and 121 who progressed to HCC during NA treatment (HCC group). The logistic regression analysis was used to analyze the risk factors of HCC progression. The diagnostic value of AFP for HCC was evaluated by receiver operating characteristic (ROC) curve analysis.RESULTSUnivariate analysis showed that age ≥ 60 years (P = 0.001), hepatitis B and alcoholic etiology (P = 0.007), smoking history (P < 0.001), family history of HBV-related HCC (P = 0.002), lamivudine resistance (P = 0.011), HBV DNA negative (P = 0.023), aspartate aminotransferase > 80 U/L (P = 0.002), gamma-glutamyl transpeptidase > 120 U/L (P = 0.001), alkaline phosphatase > 250 U/L (P = 0.001), fasting blood glucose (FBG) ≥ 6.16 (mmol/L) (P = 0.001) and Child-Pugh class C (P = 0.005) were correlated with HCC progression. In multivariate analysis, age ≥ 60 years [hazard ratio (HR) = 3.089, 95% confidence interval (CI): 1.437-6.631, P = 0.004], smoking history (HR = 4.001, 95%CI: 1.836-8.716, P < 0.01), family history of HBV-related HCC (HR = 6.763, 95%CI: 1.253-36.499, P < 0.05), lamivudine resistance (HR = 2.949, 95%CI: 1.207-7.208, P = 0.018), HBV DNA negative (HR = 0.026, 95%CI: 0.007-0.139, P < 0.01), FBG ≥ 6.16 mmol/L (HR = 7.219, 95%CI: 3.716-14.024, P < 0.01) were independent risk factors of HCC progression. ROC of AFP for diagnosis of HCC was 0.746 (95%CI: 0.674-0.818). A cutoff value of AFP of 9.00 ug/L had a sensitivity of 0.609, and specificity of 0.818 for diagnosing HCC.CONCLUSIONAge ≥ 60 years, smoking history, family history of HCC, lamivudine resistance, HBV DNA negative, FBG ≥ 6.16 mmol/L were risk factors of HCC progression. Serum AFP had limited diagnostic value for HCC.     

The Prognostic Significance of Bundle Branch Block in High-Risk Chronic Stable Vascular Disease Patients: A Report from the HOPE Trial

Objective: The prognostic significance of left and right bundle branch block (LBBB and RRBB) in patients with chronic stable cardiovascular (CV) disease is not well characterized and was evaluated in the Heart Outcomes Prevention Evaluation (HOPE) study cohort.
Design: Observational analysis of data prospectively collected in the HOPE trial.
Setting and Patients: HOPE was a multicenter, international trial, which evaluated ramipril and vitamin E in 9,541 patients aged ≥55 years with CV disease or diabetes with ≥1 CV risk factor(s) but without heart failure (HF) or known left ventricular systolic dysfunction. Follow-up extended for a median of 4.5 years. Electrocardiograms were obtained at baseline in all study participants and were read centrally.
Main Outcome Measures: Major CV events (defined as CV death, myocardial infarction, or stroke), heart failure, CV death, all-cause death, and sudden death.
Results: Baseline LBBB was present in 246 (2.6%) patients and was associated with increased risk for major CV events (HR = 1.54; 95% CI, 1.18–2.02), CV death (HR 2.29; 95% CI, 1.63–3.20), heart failure (HR 2.99; 95% CI, 2.31–3.87), sudden death (HR 3.17; 95% CI, 2.13–4.73), and all-cause death (HR = 2.10; 95% CI, 1.59–2.77). In multivariate models, LBBB remained an independent predictor of heart failure, sudden death, CV death, and all-cause death (P ≤ 0.002 for all). Baseline RBBB was present in 428 (4.5%) of patients and was not associated with increased CV risk.
Conclusions: In patients with stable chronic CV disease, LBBB but not RBBB is an independent predictor of heart failure, sudden death, CV death, and all-cause death.