Hepatic peroxisome proliferator-activated receptor γ and α-mRNA expression in HCV-infected adults is decreased by HIV co-infection and is also affected by ethnicity

OBJECTIVE: To determine peroxisome proliferator activated receptor α and γ mRNA expression in liver tissue of hepatitis C virus-infected patients with and without human immunodeficiency virus and its possible contribution to an acceleration of liver disease progression. METHODS: We measured peroxisome proliferator-activated receptor α and γ mRNA expression by real-time polymerase chain reaction in liver tissues from 40 subjects infected only with hepatitis C virus, 36 subjects co-infected with hepatitis C virus and human immunodeficiency virus and 11 normal adults. RESULTS: Hepatic mRNA expression of both peroxisome proliferator-activated receptors was significantly lower in hepatitis C virus-infected subjects with and without human immunodeficiency virus co-infection compared to the controls. Non-black race was also identified as a predictor of lower peroxisome receptor α and γ mRNA expression. Compared to subjects infected only with hepatitis C virus, liver peroxisome receptor γ mRNA expression was significantly lower in hepatitis C virus/human immunodeficiency virus-co-infected subjects (0.0092 in hepatitis C virus/human immunodeficiency virus-co-infection vs. 0.0120 in hepatitis C virus-only; p=0.004). Hepatic peroxisome receptor α mRNA expression in the hepatitis C virus-infected patients was lower in the presence of human immunodeficiency virus co-infection in non-black subjects (0.0769 vs. 0.1061; p=0.02), whereas the levels did not vary based on human immunodeficiency virus status among black subjects. CONCLUSION: mRNA expression of both peroxisome proliferator-activated receptors is impaired in hepatitis C virus-infected liver and further reduced by human immunodeficiency virus co-infection, although the suppressive effects of the viruses are substantially mitigated in black patients.

Strong correlation by ultrasonography of hepatomegaly and the presence of co-infection in HIV/HCV cirrhotic patients

OBJECTIVES: Progression of hepatic fibrosis is accelerated in patients co-infected with human immunodeficiency virus and hepatitis C virus compared to hepatitis C virus mono-infected patients. This study aimed to compare ultrasound features and selected clinical and biochemical variables between patients with human immunodeficiency virus/hepatitis C virus co-infection (n = 16) versus hepatitis C virus mono-infection (n = 16). METHODS: Each patient underwent abdominal ultrasound, and a specific evaluation was performed in order to detect findings consistent with chronic liver disease. Characterization of spleen size, liver structural pattern, diameter of the portal, spleen, and mesenteric veins was based on classical ultrasound parameters. Propensity score was used for control of selection bias and performed using binary logistic regression to generate a score for each patient. The Fisher and Mann-Whitney tests were used to evaluate categorical variables and continuous variables, respectively. RESULTS: On univariate analysis right hepatic lobe size was larger in human immunodeficiency virus/hepatitis C virus patients (157.06 ± 17.56 mm) compared to hepatitis C virus mono-infected patients (134.94 ± 16.95 mm) (p = 0.0011). The left hepatic lobe was also significantly larger in human immunodeficiency virus/hepatitis C virus patients Cirrhosis (115.88 ±22.69 mm) versus hepatitis C virus mono-infected patients (95.06 ±24.18 mm) (p= 0.0177). Also, there was a strong correlation between hepatomegaly and co-infection (p=0.005). CONCLUSION: Human immunodeficiency virus infection was the primary variable influencing liver enlargement in this population. Hepatomegaly on ultrasound was more common among cirrhotic human immunodeficiency virus/hepatitis C virus co-infected patients than among cirrhotic hepatitis C virus mono-infected patients. This aspect is very important in the management of human immunodeficiency virus/hepatitis C virus co-infected patients, because screening for hepatocellular carcinoma is necessary in this population.

Liver fibrosis progression in HIV/hepatitis C virus coinfected patients with normal aminotransferases levels / Progressão da fibrose hepática em portadores de coinfecção HIV/vírus da hepatite C com níveis de aminotransferases normais

INTRODUCTION: Approximately 30% of hepatitis C virus (HCV) monoinfected patients present persistently normal alanine aminotransferase (ALT) levels. Most of these patients have a slow progression of liver fibrosis. Studies have demonstrated the rate of liver fibrosis progression in hepatitis C virus-human immunodeficiency virus (HCV-HIV) coinfected patients is faster than in patients infected only by HCV. Few studies have evaluated the histological features of chronic hepatitis C in HIV-infected patients with normal ALT levels. METHODS: HCV-HIV coinfected patients (HCV-RNA and anti-HIV positive) with known time of HCV infection (intravenous drugs users) were selected. Patients with hepatitis B surface antigen (HBsAg) positive or hepatitis C treatment before liver biopsy were excluded. Patients were considered to have a normal ALT levels if they had at least 3 normal determinations in the previous 6 months prior to liver biopsy. All patients were submitted to liver biopsy and METAVIR scale was used. RESULTS: Of 50 studied patients 40 (80%) were males. All patients were treated with antiretroviral therapy. The ALT levels were normal in 13 (26%) patients. HCV-HIV co-infected patients with normal ALT levels had presented means of the liver fibrosis stages (0.77±0.44 versus 1.86±1.38; p<0.001) periportal inflammatory activity (0.62±0.77 versus 2.24±1.35; p<0.001) and liver fibrosis progression rate (0.058±0.043 fibrosis unit/year versus 0.118±0.102 fibrosis unit/year) significantly lower as compared to those with elevated ALT. CONCLUSIONS: HCV-HIV coinfected patients with persistently normal ALTs showed slower progression of liver fibrosis. In these patients the development of liver cirrhosis is improbable.

INTRODUÇÃO: Aproximadamente, 30% dos portadores de hepatite crônica C apresentam níveis de aminotransferases persistentemente normais (APNL). A maioria destes pacientes tem lenta progressão da fibrose hepática. Em portadores de coinfecção VHC-HIV, estudos têm demonstrado que a progressão da fibrose hepática é mais rápida que a observada em indivíduos infectados somente pelo VHC. Há poucos estudos que verificaram as características histológicas da hepatite crônica C em pacientes coinfectados pelo HIV APNL. MÉTODOS: Portadores de coinfecção VHC-HIV (HCV-RNA e anti-HIV positivos) com tempo de infecção pelo VHC conhecido (uso de drogas intravenosas) foram selecionados. Aqueles com hepatitis B surface antigen (HbsAg) positivo ou que tenham sido submetidos à terapia antiviral para hepatite C antes da biópsia hepática foram excluídos. Pacientes com pelo menos 3 determinações normais da ALT nos últimos 6 meses antes da biópsia hepática foram considerados como tendo APNL. Todos foram submetidos a biópsia hepática que foi classificada de acordo com a escala METAVIR. RESULTADOS: Foram incluídos 50 pacientes, 40 (80%) homens. Todos receberam terapia antirretroviral. Os níveis de ALT foram persistentemente normais em 13 (26%) pacientes. Pacientes coinfectados com APNL apresentaram menor média dos estágiosde fibrose hepática (0,77±0,44 versus 1,86±1,38; p<0,001), dos índices de atividade inflamatória periportal (0,62±0,77 versus 2,24±1,35; p<0,001) e progressão mais lenta da fibrose hepática (0,058±0,043 unidades de fibrose /ano versus 0,118±0,102 unidades de fibrose/ano) quando comparados àqueles com aminotransferases elevadas. CONCLUSÕES: Portadores de coinfecção VHC-HIV com APNL apresentam progressão mais lenta da fibrose hepática. Nesses pacientes o desenvolvimento de cirrose hepática é improvável.