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Hepatitis C at Retrovirus Conference
Reported by Jules Levin
  Here are links to two additional hepatitis reports from the Retrovirus Conference:
Retrovirus Hep C & B Report, by Nancy Shulman, MD
Retrovirus Report: HCV, GBV-C, and Hepatic Complications in HIV infected Persons; Liver transplantation successful in HCV/HIV coinfected
Hospitalizations Increase for Liver Related Complications in HIV
Using comprehensive hospital discharge data from 12 states (including California, Florida, NY, New Jersey), these researchers from Johns Hopkins and the NIH Agency for Healthcare Research and Quality evaluated trends in HIV-related in-patient admission rates and lengths of stay in 1996, 1998, and 2000 as a function of selected discharge diagnoses.
They evaluated 327,306 HIV hospitalizayions between 1996-2000. Hospitalizations for opportunistic infections decreased significantly from 41% to 29%. But hospitalizations for liver related complications increased significantly from 13% to 18% (P<0.001). Mean length of stay was significantly longer for liver related complications than for non-liver related complications. The proportion of all HIV admissions covered by Medicare increased from 17% to 25%. By contrast, the proportion of liver related Medicare admissions significantly rose from 17% to 25% (P<0.0001). The authors concluded that if this trend continues, liver related complications may become one of the principal co-morbiditiesin HIV-infected patients. (I think it is the leading cause of morbidity and death). This trend could have a dramatic impact on the burden of disease, the costs of care, and publicly funded insurance.
HCV/HIV Coinfected Have More Advanced Liver Disease
A French-Spanish research group offered this for background. In HCV mono-infected patients with elevated ALT levels 51% and 24% have no (F0) or just portal fibrosis (F1), respectively; whereas portal fibrosis with septa (F2), many septa (F3), or cirrhosis (F4) is recognized in 9.9%, 9.7% and 5.3%, respectively, but this information is not well known for HIV-positives.
The researchers 500 examined HCV/HIV coinfected patients. 86% of the patients were IDUs. Liver fibrosis stage was F0 (13.2%), F1 (35%), F2 (18.7%), F3 (21.5%), and F4 (12%). In the multivariate logistic regression analysis, 3 factors were the best predictors of severe liver fibrosis (F3-F4): duration of HCV infection > 15 yrs (Odds Ratio 3.6; age > 20 yrs at the time of HCV infection (OR 3.3); and history of high alcohol intake (OR 2.5). Patients estimated to be infected for more than 15 years had severe liver fibrosis in 46% of cases. Severe liver fibrosis was not associated with the CD4 count, HCV genotype, HCV viremia, gender, or use of HAART. This means that a patientŐs CD4 count, HCV genotype & viral load, gender or use of HAART had nothing to do with the more progressed HCV disease in patients, according to these study results. . The authors concluded that more advanced stages of liver fibrosis are seen in HIV-HCV co-infected patiets than in HCV-mono-infected paients. Overall, up to 1/3 of those with elevated ALT levels show severe liver fibrosis (F3-F4), but increases significantly with duration of HCV infection mounting up to 50% after 15 years of carrying HCV. Thus, treatment of HCV infection should be not delayed unnecessarily given that lower response rates are seen in cirrhotics. Abst. 830. Martin-Carbonero et al.
Extreme ALT Elevations Associated With Liver Disease Progression
A French research group conducted a study to analyze the impact of HAART and immune restoration on liver histological status in HIV-HCV co-infected patients. Eligible patients had a HCV RNA load above the limit of detection, no cirrhosis or liver failure, no HCV treatment within the 12 last months (mos). They were enrolled at initiation of HAART (mo 0), and followed at mo 1, 3, 6, 9, and 12, in a prospective multi-centre cohort (TRIVIR-ANRS HC EP1). A liver biopsy was performed at month 0 and month 12. Histological progression (HP) was defined as an increase of 3 2 units in the Knodell score and 3 1 unit in the Metavir score between month 0 and month 12. Potential factors associated with HP were studied: sex, age, body mass index, HIV and HCV transmission category, AIDS, CD4 cell count, HIV and HCV viral load, HCV genotype, alcohol use and type of antiretroviral treatment of HAART at baseline, immunologic response (IR; a double CD4 cell count or a 100/mm3 increase between M0 and M12), onset of transaminases elevation (TE; alanine aminotransferase level 3 5-fold the upper limit of normal value). At baseline, median CD4 cell count was 278/mm3, median levels of HIV and HCV RNA were 4.4 log10 copies/mL and 6.2 IU/mL, respectively.
No relationship was found between IR and HP (23% of HP in pts with IR, 17% in pts without IR, p = 1.00) or other baseline characteristics and HP. ALT elevation (TE) was defined as >5 times above the upper limit of normal value. TE occurred in 5 patients (20%) and 1 case was considered drug-related, 2 were alcohol-related and 2 were HCV-related. TE was significantly associated with HP (80% of HP in pts with TE, 5% in patients without TE, p =0.002). The researchers concluded that these data suggest that IR following the initiation of HAART is not associated with a progression of liver lesions. However, careful monitoring of liver enzymes and alcohol suppression are highly recommended in HIV-HCV co-infected patients. Abst. 831. Zylberberg et al.
HCV/HIV Coinfected Patients at Increased Risk for Diabetes
Patients with an ICD-9 diagnosis of HIV were identified from the VA administrative database from 1991 onwards. Data on age, gender, race, history of and first date of HIV, HCV and DM diagnoses, and history of alcohol use was extracted from the VA administrative database. The disease data was based on ICD-9 codes. The ICD-9 codes for HIV and HCV have been validated in the Veterans Aging Cohort Study (VACS).
These researchers performed an analysis on 41,262 male veterans in care with HIV infection between October 1991 and September 2001. Among these patients, 17.9% were co-infected with HCV. Of the 41,262 HIV infected patients, 14.8% had a diagnosis of DM. The prevalence of DM in HCV infected patients was 19.7% compared with 13.7% (chi square = 167; p < 0.001) in the HCV negative patients. In a logistic regression model, the unadjusted odds ratio of having a DM diagnosis in HCV infected patients was 1.53 (95% CI 1.43 - 1.63). After controlling for age, race, history of drug and alcohol use, the adjusted odds ratio was 1.71 (95% CI 1.59 - 1.84). Age, Black or Hispanic race and a history of an alcohol related diagnosis were significantly associated with a diagnosis of DM in the multivariate model. Adjustment was not made for two important predictors of DM in general population, body mass index and family history, because of lack of this information in the administrative database.
These researchers report their study shows that veterans in care with HIV are at a higher risk of DM than the US population in general. Almost 14% of HIV infected veterans in care were diagnosed to have DM. This compares with a prevalence of 11.83% in veterans in care overall, and 6.2% in the general population in the United States. (http://www.niddk.nih.gov/health/diabetes/pubs/dmstats/dmstats.htm#7; accessed Jan 08, 2003)
Co-infection with HCV increased this risk to 19.7%, a relative increase of 44% in this study. The risk increased with increasing age and was higher in African American and Hispanic as compared with White veterans. Traditional risk factors for DM include body mass index, family history of DM, increasing age, and Black or Hispanic race. While these researchers could not adjust for the body mass index or family history, (because this information was not available in the VA Administrative database) age, Black and Hispanic race, and a diagnosis of an alcohol related illness were significantly associated with a diagnosis of DM.
The researchers also reported this background information. A link between HCV and DM has been established by several investigators. It is not surprising since HCV is a major cause of liver cirrhosis, which in turn predisposes patients to DM though insulin resistance. While some of the HCV related DM is due to the liver damage it induces, it does not completely explain the association. In patients with comparable liver damage due to hepatitis B virus (HBV) or other causes of liver disease, the risk of DM is lower than in patients with HCV related liver disease. In a large retrospective study, 21% of the HCV infected patients but only 12% of the HBV infected patients were found to have DM. Among patients with cirrhosis, HCV was associated with a higher prevalence of DM than HBV.
The authors concluded that these findings are significant for patient care as well as policy issues. A higher risk of DM in HCV-HIV co-infected veterans suggests that this group should be targeted for screening and early intervention to reduce the long-term complications of DM. Abst. 836. Butt et al.