Association of serum albumin and aspartate transaminase with 5-year all-cause mortality in HIV/hepatitis C virus coinfection and HIV monoinfection

Abstract

Objective Liver disease markers have been associated with mortality in HIV-infected individuals, in the modern era of effective antiretroviral therapy. Our objective was to determine which markers are most predictive of mortality in HIV-monoinfected and HIV/HCV-coinfected persons. Research Design and Methods We measured serum albumin, total protein, calculated globulin, aspartate transaminase (AST), and alanine transaminase (ALT) in 193 HIV/HCV-coinfected and 720 HIV-monoinfected persons in the study of Fat Redistribution and Metabolic Change in HIV Infection. We evaluated associations of each marker with five-year, all-cause mortality, adjusting for cardiovascular, HIV-related factors, inflammation, renal disease, muscle, and adiposity. Results After 5 years of follow-up, overall mortality was 21% in HIV/HCV-coinfected and 12% in HIV-monoinfected participants. After multivariable adjustment, lower albumin and higher AST were independently associated with increased mortality. Lower albumin was associated with 49% increased odds of mortality overall (per 0.5g/dL decrease, 95%CI:1.2–1.9); the association was stronger in HIV/HCV-coinfected (OR=2.1, 95%CI:1.4–3.2) versus HIV-monoinfected (OR=1.3, 95%CI:1.0–1.7; HCV-by-albumin interaction: p=0.038). Higher AST was associated with 41% increased odds of mortality (per AST doubling; 95%CI:1.1–1.8); associations were much stronger among HIV/HCV-coinfected (OR=2.5, 95%CI:1.5–4.1) than HIV-monoinfected (OR=1.1, 95%CI:0.8–1.5; HCV-by-AST interaction: p=0.0042). Conclusions Lower serum albumin and higher AST appear to be important mortality risk factors in HIV/HCV-coinfection, but much less so in HIV-monoinfected individuals. The association of low albumin with mortality may reflect its role as a negative acute phase response protein. AST levels do not appear to be useful in predicting mortality in HIV-monoinfection, and should be considered primarily in the context of HCV-coinfection.

Gamma gap thresholds and HIV, hepatitis C, and monoclonal gammopathy

“…Our study found that an elevated gamma gap demonstrated a high specificity for HIV, which is consistent with HIV's effect on humoral immunity resulting in hypergammaglobulinemia [23][24][25]. However, the gamma gap generated by hypergammaglobulinemia is affected by severity of HIV per CD4 count and viral load [26] and its treatment status [25,27,28], which may explain the higher prevalence ratios at lower gamma gap thresholds as well as the poor sensitivity of elevated gamma gap for HIV. Prior studies have shown that regardless of treatment status and viremic level, those with HIV exhibit more intense staining at the gamma region of the serum electrophoresis, represented by antibodies such as IgG and IgA, than those without HIV [27,29], resulting in hypergammaglobulinemia.…”

“…Similar to HIV, the gamma gap demonstrated a high specificity for HCV infection. The mechanism for this specificity could also be related to B cell activation [30,31] in addition to reduced albumin synthesis secondary to liver disease and poor nutrition [26]. Like HIV, disease severity and treatment status affect gamma gap levels and may contribute to its poor sensitivity.…”

Transplant advocacy in the era of the human immunodeficiency virus organ policy equity act

“…Liver and renal diseases are the leading causes of death in HIV‐positive individuals . At the beginning of the HIV epidemic, patients with HIV infections were not considered eligible for transplantation for fear that the immunosuppressive medication would advance the HIV infection.…”

“…Liver and renal diseases are the leading causes of death in HIVpositive individuals. 4,5 At the beginning of the HIV epidemic, patients with HIV infections were not considered eligible for transplantation for fear that the immunosuppressive medication would advance the HIV infection. With advancements in immunosuppression drugs, some transplant hospitals performed kidney and liver transplants in HIV-positive individuals with uninfected deceased donor organs.…”

Consenting to HIV-positive organ donation in the USA: legal and ethical considerations in comparison with a South African context

“…28 As waiting lists remain very long and many USA patients can wait up to 10 years for a deceased donor kidney transplant, many patients will accept an HIV-positive organ instead of waiting on an HIVnegative organ.…”