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Hepatite B

Serum hepatitis B surface antigen and hepatitis B e antigen titers: Disease phase influences correlation with viral load and intrahepatic hepatitis B virus markers.
Although threshold levels for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) titers have recently been proposed to guide therapy for chronic hepatitis B (CHB), their relationship to circulating hepatitis B virus (HBV) DNA and intrahepatic HBV replicative intermediates, and the significance of emerging viral variants, remains unclear. We therefore tested the hypothesis that HBsAg and HBeAg titers may vary independently of viral replication in vivo. In all, 149 treatment-naïve CHB patients were recruited (HBeAg-positive, n = 71; HBeAg-negative, n = 78). Quantification of HBeAg and HBsAg was performed by enzyme immunoassay. Virological characterization included serum HBV DNA load, HBV genotype, basal core promoter (BCP)/precore (PC) sequence, and, in a subset (n = 44), measurement of intrahepatic covalently closed circular DNA (cccDNA) and total HBV DNA, as well as quantitative immunohistochemical (IHC) staining for HBsAg. In HBeAg-positive CHB, HBsAg was positively correlated with serum HBV DNA and intrahepatic cccDNA and total HBV DNA (r = 0.69, 0.71, 0.76, P < 0.01). HBeAg correlated with serum HBV DNA (r = 0.60, P < 0.0001), although emerging BCP/PC variants reduced HBeAg titer independent of viral replication. In HBeAg-negative CHB, HBsAg correlated poorly with serum HBV DNA (r = 0.28, P = 0.01) and did not correlate with intrahepatic cccDNA nor total HBV DNA. Quantitative IHC for hepatocyte HBsAg confirmed a relationship with viral replication only in HBeAg-positive patients. Conclusion: The correlation between quantitative HBsAg titer and serum and intrahepatic markers of HBV replication differs between patients with HBeAg-positive and HBeAg-negative CHB. HBeAg titers may fall independent of viral replication as HBeAg-defective variants emerge prior to HBeAg seroconversion. These findings provide new insights into viral pathogenesis and have practical implications for the use of quantitative serology as a clinical biomarker (HEPATOLOGY 2010).


Hepatite C

Identifying hepatitis C virus genotype 2/3 patients who can receive a 16-week abbreviated course of peginterferon alfa-2a (40KD) plus ribavirin.
The objective of this analysis was to compare sustained virological response (SVR) and relapse rates in patients with a rapid virological response (RVR, HCV RNA <50 IU/mL at week 4) randomized to 24 or 16 weeks of treatment with peginterferon alfa-2a (40KD) 180 g/week plus ribavirin 800 mg/day in the multinational ACCELERATE study. The analysis was restricted to patients who received treatment for 80% or more of the planned duration. Of 1309 eligible patients, 863 individuals (65.9%) achieved an RVR and were included in this analysis (458 assigned to 16 weeks and 405 assigned to 24 weeks). The overall SVR rate was significantly higher in patients randomized to 24 weeks of treatment (91% versus 82%; P = 0.0006) and among patients infected with genotype 2 (92% versus 81%; P = 0.0010) but not genotype 3 (90% versus 84%; P = 0.1308). Relapse rates were significantly lower among all patients randomized to 24 weeks of treatment: overall (6% versus 15%, P < 0.0001); in those infected with genotype 2 (5% versus 17%, P = 0.0001), and genotype 3 (7% versus 14%, P = 0.0489). SVR rates in patients with a viral load of 400,000 IU/mL or less randomized to 24 and 16 weeks of treatment were similar, 95% and 91% (P = 0.2012). Significant pretreatment predictors of SVR included assignment to 24 weeks of treatment (P = 0.0006), absence of advanced fibrosis on liver biopsy (P = 0.0032), lower HCV RNA level (P = 0.0017), and lower body weight (P < 0.0001). Conclusion: The standard 24-week regimen of peginterferon alfa-2a (40KD) plus ribavirin is significantly more effective than an abbreviated 16-week regimen in genotype 2/3 patients who achieve an RVR. Abbreviated regimens may be considered in patients with a low baseline viral load who achieve an RVR (Hepatology 2010).


Cirrose Hepática

Sustained virologic response prevents the development of esophageal varices in compensated, Child-Pugh class A hepatitis C virus-induced cirrhosis. A 12-year prospective follow-up study.
The incidence of de novo development of esophageal varices (EV) in patients with compensated liver cirrhosis has been determined by few studies in the short term and never in the long term. The aims of the present study were to determine the incidence and the risk factors associated with the development of EV and to assess whether antiviral treatment and achievement of sustained virologic response (SVR) may prevent de novo EV development in patients with HCV-induced cirrhosis. We studied 218 patients with compensated EV-free, HCV-induced cirrhosis consecutively enrolled between 1989 and 1992 at three referral centers in Milan, Italy. Endoscopic surveillance was performed at 3-year intervals according to international guidelines. SVR was defined as undetectable serum HCV-RNA 24 weeks after treatment discontinuation. During a median follow-up of 11.4 years, 149/218 (68%) patients received antiviral treatment and 34 (22.8%) achieved SVR. None of the SVR patients developed EV compared with 22 (31.8%) of the 69 untreated subjects (P < 0.0001) and 45 (39.1%) of the 115 non-SVR patients (P < 0.0001). On multivariate analysis, HCV genotype 1b (hazard ratio [HR] 2.40; 95% confidence interval [CI] 1.17-4.90) and baseline model for end-stage liver disease (MELD) score (HR 1.20; 95% CI 1.07-1.35 for 1 point increase) were independent predictors of EV. Conclusion: In the long term, the achievement of SVR prevents the development of EV in patients with compensated HCV-induced cirrhosis. Therefore, in these patients, endoscopic surveillance can be safely delayed or avoided. Genotype 1b infection and MELD score identify the subset of patients at higher risk of EV development who need tailored endoscopic surveillance. (Hepatology 2010).


Carcinoma Hepatocelular

The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis.
Nonalcoholic steatohepatitis (NASH) is a well-recognized cause of cirrhosis and has been increasingly associated with the development of hepatocellular carcinoma (HCC). The aims of this study were to (1) estimate the incidence of HCC in patients with NASH-related cirrhosis, (2) compare incidence in NASH-related cirrhosis with hepatitis C virus (HCV)-related cirrhosis, and (3) identify risk factors of HCC in patients with NASH-related cirrhosis compared with HCV-related cirrhosis. Adult patients with cirrhosis secondary to chronic HCV (n = 315) or NASH (n = 195) were evaluated at our hepatobiliary clinic between 2003 and 2007. To assess for HCC development, all patients were monitored using serial abdominal computed tomography and serum alpha-fetoprotein every 6 months. Kaplan-Meier analysis was performed to estimate the cumulative incidence of HCC. Descriptive statistics were computed for all factors. Univariate and multivariate Cox regression analysis were used to assess associations between HCC and factors of interest. The median follow-up was 3.2 years (25th percentile [P25], 75th percentile [P75]: 1.7, 5.7) during which 25/195 (12.8%) of NASH-cirrhotic and 64/315 (20.3 %) of HCV-cirrhotic patients developed HCC (P = 0.03). Yearly cumulative incidence of HCC was found to be 2.6% in patients with NASH-cirrhosis, compared with 4.0% in patients with HCV cirrhosis (P = 0.09). Multivariate regression analysis revealed that older age (P = 0.006) and alcohol consumption (P = 0.002) were independent variables associated with development of HCC in patients with NASH-cirrhosis. Compared with nondrinkers, patients who reported any regular alcohol consumption were at greater risk for HCC development (hazard ratio: 3.6; P25, P75: 1.5, 8.3). Conclusion: Patients with NASH cirrhosis have a greatly increased risk of liver cancer. Alcohol consumption, a modifiable risk factor, appears to be the most significant factor associated with risk of HCC development in our study population (Hepatology 2010).


Esteatose Hepática

Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver disease.
The rising incidence of obesity and diabetes coincides with a marked increase in fructose consumption. Fructose consumption is higher in individuals with nonalcoholic fatty liver disease (NAFLD) than in age-matched and body mass index (BMI)-matched controls. Because fructose elicits metabolic perturbations that may be hepatotoxic, we investigated the relationship between fructose consumption and disease severity in NAFLD. We studied 427 adults enrolled in the NASH Clinical Research Network for whom Block food questionnaire data were collected within 3 months of a liver biopsy. Fructose consumption was estimated based on reporting (frequency × amount) of Kool-aid, fruit juices, and nondietary soda intake, expressed as servings per week, and classified into none, minimum to moderate (<7 servings/week), and daily (7 servings/week). The association of fructose intake with metabolic and histological features of NAFLD was analyzed using multiple linear and ordinal logistic regression analyses with and without controlling for other confounding factors. Increased fructose consumption was univariately associated with decreased age (P < 0.0001), male sex (P < 0.0001), hypertriglyceridemia (P < 0.04), low high-density lipoprotein (HDL) cholesterol (<0.0001), decreased serum glucose (P < 0.001), increased calorie intake (P < 0.0001), and hyperuricemia (P < 0.0001). After controlling for age, sex, BMI, and total calorie intake, daily fructose consumption was associated with lower steatosis grade and higher fibrosis stage (P < 0.05 for each). In older adults (age 48 years), daily fructose consumption was associated with increased hepatic inflammation (P < 0.05) and hepatocyte ballooning (P = 0.05). Conclusion: In patients with NAFLD, daily fructose ingestion is associated with reduced hepatic steatosis but increased fibrosis. These results identify a readily modifiable environmental risk factor that may ameliorate disease progression in patients with NAFLD (HEPATOLOGY 2010).

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