In a previous post (Extended data with entecavir & annotated HBV management …) good news on the long term use of entecavir was reported. Another large study indicates that entecavir (ETV) monotherapy generally produces equivalent results to combination therapy with tenofovir (TDF) (Gastroenterol 2012; 143: 619-28).
The authors report their experience with a randomized open-label multi center study with 379 nucleos(t)ide-naive patients; 264 were HBeAg-positive and 115 were HBeAg-negative. At week 96, among all patients, virology response defined as HBV DNA <50 IU/mL was 76.4% in the ETV group and 83.2% in the ETV-TDF group.
In multiple comparisons, the combination group tended to have better virological response except in the HBeAg-negative group (91.1% ETV vs. 89.8% in ETV-TDF). The other comparisons included the HBeAg-positive group (69.8% ETV vs. 80.4% ETV-TDF), low baseline HBV DNA (<10 to the 8th IU/mL) (83% in both groups), and the high baseline HBV DNA (62.0% ETV vs. 78.8% ETV-TDF). Yet, the only group where this was statistically significant was those with high baseline HBV DNA, n= 164 (>10 to the 8th IU/mL).
Biological response was greater in the ETV monotherapy, 81.9% compared with 69% in the combination group. Among HBeAg+ patients, loss of e antigen was comparable: 38.9% in ETV compared with 29.7% in ETV-TDF. In this group, seroconversion to HBeAb+ occurred in 32.5% of ETV compared with 21.7% of combination patients.
Safety: five patients in combination group and two patients in ETV monotherapy group discontinued treatment due to adverse events. Three deaths occurred in the combination group (either on treatment or during followup), with the following causes: cardiac arrest, bile duct tumor, and liver failure. In the patient with liver failure, she had responded to therapy but experienced a breakthrough at week 48. At week 100, she was switched to commercial treatment. Five days later she was hospitalized and died within 1 week. No resistance to either drug was identified. Thus, the authors speculate that nonadherence was an important factor. Also, during the course of the study, five malignancies were diagnosed, including 3 with HCC.
Hepatitis C virus (HCV) now kills more people in the United States than HIV (Ann Intern Med 2012; 156: 271-78). Data from the CDC followed the mortality burden of Hepatitis B (HBV), HCV, and HIV from 1999 to 2007. The data were derived from death certificates & a limitation was that these are often completed by individuals other than the primary physician. Sometimes the exact cause is difficult to discern. However, this is more likely to result in underreports of deaths from viral hepatitis compared with those from HIV.
In total, 21.8 million death certificates were analyzed.
HBV death rate stayed relatively constant –in 2007: 1815 deaths*
HCV death rate increased steadily –in 2007: 15106 deaths*
HIV death rate improved –in 2007: 12734 deaths*
*When infection was cause or underlying contributor of death
One in 33 baby boomers are infected with HCV; most do not know they are infected. Three-fourths of the deaths for HCV are in this age group as well. In addition, it is expected that mortality from HCV will grow over the next 10-15 years without a major intervention. http://www.ajc.com/health/hepatitis-c-deaths-up-1356460.html
Given the increasing HCV disease burden, this strengthens the rationale for more aggressive case finding and the use of more effective & more expensive therapies (see previous blog: The cost of progress in treating Hepatitis C. Among patients with HCV with advanced disease/cirrhosis, monitoring for HCC is important (Looking for trouble).
-Hepatology 2011; 54: 1547. Excess mortality (6x gen population) in those who achieve SVR
-Gastroenterology 2010; 138: 513. Predicts peak cirrhosis due to HCV in year 2020; peak HCV prevalence was year 2000.
-Clin Gastro Hep 2010; 8: 924. Epidemiology 2010.
-Hepatology 2010; 52: 1543. Visceral adiposity is associated with increased histological findings and higher viral loads.
-Gastroenterology 2010; 138: 136. Predicting clinical outcomes: plt<99, Alb <3.5, AST/ALT ratio >1.2, & TB>2 all assoc with 40-50% risk of developing ‘clinical outcome’ in next 3.5yrs. Outcomes: ascites, variceal hemorrhage, decompensation according to CTP (66%), peritonitis, death (2%), encephalopathy
-Hepatology 2009; 49: 729. 5-yr f/u after successful HCV RX, n=150. 2 developed HCC.
-Gastroenterology 2009; 136: 138, 39(ed). HCC occurring c HCV ~1%/yr in HALT-C study. prolonged Rx -not helpful. n=1005
-Hepatology 2008; 47: 1128. Increasing mortality of HCV between 1995-2004. Due to aging of infected individuals.
-Hepatology 2008; 47: 1371. Genotype 4 review.
-Hepatology 2008; 47: 836. 2/121 bx of children had cirrhosis.
-J Pediatr 2007; 150: 168. n=60. Looked at two populations: look back after transfusion and referrals. mean age at infection 7 months, mean time with infection 13yrs. 12% developed significant fibrosis.
-Hepatology 2007; 45: 1076. Large study: Lancet 2006; 368: 938. 39,109 c HBV, 75,834 c HCV, 2,604 c both. death rate: 3.2%, 5.3%, 7.1% respecively. Increased rate of dying c HCV due to drug use rather than liver dz.
-Clin Gastro & Hep 2006; 4: 1190-1191, 1271-78, 1278-1282. slow progression of HCV in 184 untreated women infected in 1977 (mean 27 years) — 2.1% developed cirrhosis. genotype 1B ALT values correlated with change in histology.
-JPGN 2006; 43: 209. Review of 91 cases; 7 c cirrhosis at presentation (mean 11.7yrs)
-Clin Gastro & Hep 2005; 3: 910. cirrhosis in 71% after 60 years in Asian patients; 25% in Caucasian pts 61-80 who presumably had disease for shorter interval.
-Gastroenterology 2003; 125: 1695. obesity/insulin resistance worsens fibrosis in HCV