 |
|
|
| |
Antiretrovirals May be Double-Edged Sword for Liver Fibrosis: glucose levels associated with advancing fibrosis and increased CD4 count associated with slower fibrosis progression
|
| |
| |
8th International Congress on Drug Therapy in HIV Infection
November 12-16, 2006
Glasgow, Scotland
Mark Mascolini
Note from Jules Levin: it is well known that diabetes is associated with accelerated liver fibrosis, so there is no reason this should not be true in HCV-HIV coinfected patients. I think it works both ways, diabetes and elevated glucose harm the liver and can lead to fibrosis, and impaired liver function and hepatitis can lead to impaired glucose tolerance. As well, several research findings have found that successful HAART may slow HCV disease progression for some individuals and I say some because fibrosis progression is multifactorial, that is many factors are involved in whether or not fibrosis progresses. Here Barreiro's finding that a higher CD4 count is protective makes sense. Perhaps the question is-is this due to increased CD4 count or reduced HIV RNA, or both. Barreiro also finds increased ALT upped the risk of fibrosis; rather I think fibrosis causes increased ALT. In a paper presented at ICAAC Cooper from Canada found having HCV is associated with lower lipids levels, and lipids can increase once HCV is eradicated, which was my personal experience.
Antiretroviral-induced CD4 gains may protect against advanced liver fibrosis in people coinfected with hepatitis C virus (HCV), according to results of a 489-person study at Carlos III Hospital in Madrid [1]. But treatment's impact on liver enzymes and glucose could offset that plus and speed liver damage, reported Pablo Barreiro.
Carlos III investigators scrutinized records of 489 people coinfected with HIV and HCV, 181 (37%) of whom had advanced liver fibrosis, defined as liver stiffness greater than 9.5 Kpa on the noninvasive FibroScan test. People with advanced fibrosis were older (average 44 versus 42 years, P < 0.001), had a lower CD4 count (average 486 versus 553, P = 0.012), and had a higher average HCV load (6.39 versus 6.05 log, P = 0.002), higher alanine aminotransferase (ALT) (88 versus 64 IU/L, P = 0.04), higher glucose (102 versus 98 mg/dL, P = 0.001), and higher triglycerides (176 versus 148 mg/dL, P = 0.03). Patients with advanced fibrosis were more likely to be male (76% versus 67%, P = 0.02), and a bigger proportion of them smoked or once smoked (55% versus 34%).
Analyzing 3291 patient-years of antiretroviral exposure, Barreiro found that only 3.5% of patients had never taken antiretrovirals, while 34.7% had used nevirapine, 48.7% efavirenz, and 74.1% a protease inhibitor (PI). Longer PI use correlated with advanced liver fibrosis (rho = 0.11, P = 0.01), and longer ritonavir-boosted PI use had a stronger correlation with advanced fibrosis (rho 0.81, P < 0.001). But PI use did not raise the fibrosis risk independently of other risk factors. Use of individual nucleosides, nevirapine, or efavirenz did not correlate with fibrosis.
Multivariate analysis linked four factors to advanced fibrosis--a higher CD4 count proved protective, while alcohol abuse, higher ALT, and higher glucose inflated the risk of fibrosis (Table). Every additional 100 CD4 cells lowered the risk of fibrosis 20%, while every 10 IU/L higher ALT upped the risk 20% and every 10 mg/dL higher glucose reading jacked up the risk 50%. Alcohol abuse doubled the risk of advanced fibrosis.
Barreiro and colleagues suggested that antiretroviral therapy may be a "double-edged sword" when considering liver fibrosis in HCV-coinfected people, warding off advanced fibrosis by promoting CD4 gains, but threatening the liver with higher glucose and ALT. Most HIV liver experts agree, though, that the benefits of antiretroviral therapy far outweigh its drawbacks in coinfected people.
Reference
1. Barreiro P, Labarga P, Ruiz-Sancho A, et al. Factors associated with progression of liver fibrosis in HIV/HCV-co-infected patients: influence of antiretrovirals and metabolic disturbances. 8th International Congress on Drug Therapy in HIV Infection, November 12-16, 2006, Glasgow. Abstract P313.
|
| |
|
|
|
|
|
