Prevalence and Severity of Liver Disease in HIV Urban Clinic in Baltimore
BRIEF SUMMARY--This is an important study for several reasons. 45% at the Hopkins HIV Clinic were coinfected with HCV, which is a lower rate than some other reports which have been as high as 80-90%. Perhaps most important is that Sulkowski reported despite having undetectable HIV (<400 copies/ml) many people had cirrhosis. Among these study patients, 76% were receiving antiretroviral therapy, the average CD4 was 400, CD4 nadir was 190, 54% had undetectable HIV viral load (<400). Risks for cirrhosis in this group of HCV/HIV coinfected individuals were alcohol (5.2 times), Caucasian race (5.9 times), female sex (6.5 times), duration of HCV, and most surprisingly and notable HIV <400 (2.9 times). As a qualification for this study it should be noted that 49% of the patients were considered alcoholic and this can impact on HCV progression. Additional significant findings included-- heterosexual transmission was reported to be 14%, and among men who have sex with men 9.8%. 97% of African Americans and 80% of caucasians had genotype 1. HIV patients may be less likely to clear HCV than persons with HCV alone; 50% of the patients biopsied had advanced liver fibrosis.
Further research is needed to understand if there is a relationship between undetectable HIV viral suppression and advancing liver disease. Sulkowski concluded that his findings support recommendations from the PHS/IDSA Guidelines that HCV is an opportunistic pathogen. And better treatment strategies need to be implemented.
DEATH RATES: 12% of those who died had HCV alone, but 25% coinfected individuals with cirrhosis (n=14) died of End Stage Liver Disease. And 3 died with coinfection but without cirrhosis.
Mark Sulkowski from Johns Hopkins University reported on the prevalence and severity of liver disease in his urban HIV clinic in Baltimore. About one year ago the 1999 USPH/IDSA Guidelines declared HCV an opportunistic disease in HIV-infected persons, and made the following recommendations for care in HIV clinics:
The purpose of Sulkowski's study was to:
Johns Hopkins has an observational HIV cohort at their clinic with a longitudinal database of over 2300 patients in East Baltimore. They colect data prospectively, and have been screening for HCV since 1996. They established a HCV referral clinic in 1997.
PREVALENCE of ANTIBODY HCV+ by HIV RISK GROUP N=1742
In the HCV Coinfection clinic 1742 patients were screened between 1997 and 2000. 798 were HCV+. 226 were referred for HCV evaluation. 101 received liver biopsies and the results are presented below. 125 patients have not received biopsies, and 23 of these patients had advanced liver disease diagnosed clinically or radiographically at the time of their presentation and were considered cirrhotic. Other patients were not biopsied due to lack of control of HIV disease or other contraindications for further therapy (inadequate insurance, active substance abuse).
BASELINE CHARACTERISTICS n=226
HEPATITIS C VIROLOGY
They performed HCV-RNA on 215 persons and found 6.8% (14/215) were HCV PCR negative. This suggests clearance of the virus. Since this percent is lower than the 15-20% normally found to clear HCV, suggesting that HIV patients may be less likely to clear HCV. PCR should be performed because some patients are aviremic.
101 PATIENTS WHO RECEIVED BIOPSY
Total Ishak modified HAI necroinflammatory score was 4.6± 2.4 (maximum possible 18). Three patients had evidence of drug induced hepatitis (drug-related cholestatic hepatitis). The evidence was such that the remaining patients had hepatitis due to HCV (no other pathology identified).
ISHAK MODIFIED HAI FIBROSIS STAGE
Sulkowski said; "nearly 50% of the patients biopsied had relatively advanced fibrotic disease, whereas 5% had no fibrosis and 20% had minimal disease or a score of 1".
OUTCOMES & RISK FACTORS FOR THOSE WITH HCV-CIRRHOSIS
For this analysis they looked at the 33 persons with biopsy proven cirrhosis as well as the 23 individuals with the clinical diagnosis.
Multivariate Logistic Regression Model
RISK FACTORS FOR HCV-CIRRHOSIS
Not surprisingly, risk factors for HCV-cirrhosis were alcohol consumption (5.2 times), Caucasian ethnicity (5.9 times) and female gender (5.5 times). Surprisingly, HIV viral suppression (<400) at the time of biopsy was also a risk factor for cirrhosis. 60% of patients with cirrhosis on biopsy had undetectable (<400) HIV viral load compared to 30% for those who on biopsy had lesser disease. At the microphone, Doug Dieterich raised the question whether if this finding of an association between viral suppression & the presence of cirrhosis could be related to the effect on the immune system by HIV suppression. I think he's suggesting that an improved immune system may be prone to evoking an immune response that attacks infected liver cells and kills them off, and thus may be harming the liver. I believe this is the same mechanism suggested for why several months after starting HAART and CD4s increase that LFTs may spike up. Alternately, I suggest that perhaps, the viral suppression may be a surrogate for some other reason.
The median duration of HCV disease to cirrhosis was said to be 19 years but I'm not sure how this was arrived at.
Sulkowski recommended research to understand the relationship between HIV suppression (HAART) and its impact on HCV disease. He also said his data support the PHS/IDSA recommendations in that HCV appears to behave as an opportunistic pathogen recommended. And further implementation strategies for treating HCV need to be considered.