Acute HIV Infection Results in Subclinical Inflammatory Cardiomyopathy.

The impact of excess viral RNA on myocardial function and morphology in the setting of acute human immunodeficiency virus (HIV) infection remains unknown. In this study, 49 patients with acute HIV infection showed increased levels of N-terminal prohormone of brain natriuretic peptide, a surrogate of myocardial function, which decreased with viral suppression and normalization of systemic inflammation (79 pg/mL vs 28 pg/mL; P < .001). A comparable change was seen with levels of troponin T, a marker of morphologic myocardial damage (4.9 ng/L vs 1.5 ng/L; P < .001). In conclusion, we observed significant functional and morphological myocardial impairment during acute HIV infection, fueled by inflammatory activation and extensive viral replication, resulting in a reversible subclinical inflammatory cardiomyopathy.

Non-invasive liver fibrosis assessment and HCV treatment initiation within a systematic screening program in HIV/HCV coinfected patients.

BACKGROUND AND AIM: Hepatitis C virus (HCV) therapy should be considered without delay in all patients with significant (SIGFIB) or advanced liver fibrosis (ADVFIB). We aimed to investigate the rates of treatment initiation with interferon-free regimens within a screening program for SIGFIB/ADVFIB in human immunodeficiency virus/HCV coinfected patients (HIV/HCV). METHODS: The FIB-4 was calculated in all HIV/HCV from 2014-2016. HIV/HCV were counselled by the HIV clinic and referred to the Division of Gastroenterology and Hepatology for transient elastography (TE) and evaluation for HCV therapy. Patients were stratified by FIB-4 of 7.1 kPa/>9.5 kPa, respectively. RESULTS: Among 1348 HIV+ patients, 16% (210/1348) had detectable HCV-RNA. One hundred HIV/HCV had a FIB-4 ≥1.45. Among these, 57% (57/100) underwent TE. The majority of these patients had SIGFIB (75%; 43/57) or ADVFIB (37%; 21/57), however, interferon-free treatment was initiated in only 56% (24/43). In addition, fifty-two percent (57/110) of HIV/HCV with FIB-4 <1.45 underwent TE. Interestingly, 40% (23/57) and 18% (10/57) of these patients showed SIGFIB or even ADVFIB, respectively, and 78% (18/23) finally received interferon-free treatment. Overall, only 20% (42/210) of HIV/HCV received interferon-free treatment. CONCLUSION: FIB-4 was not useful for ruling out SIGFIB/ADVFIB in our cohort of HIV/HCV. Treatment was initiated only in a small proportion (20%) of HIV/HCV during the first 2 years of interferon-free treatment availability, although the observed proportion of patients with SIGFIB (assessed by TE) was considerably higher (58%). Thus, it requires the ongoing combined efforts of both HIV and HCV specialists to increase treatment uptake rates in this special population.

The Impact of PNPLA3 rs738409 SNP on Liver Fibrosis Progression, Portal Hypertension and Hepatic Steatosis in HIV/HCV Coinfection.

BACKGROUND: Faster fibrosis progression and hepatic steatosis are hallmarks of HIV/HCV coinfection. A single nucleotide polymorphism (SNP) of the PNPLA3-gene is associated with development of non-alcoholic steatohepatitis and a worse outcome in alcoholic liver disease. However, the role of PNPLA3 rs738409 SNP on liver fibrosis and steatosis, portal hypertension, and virological response in HIV/HCV coinfection remains unclear. METHODS: In this cross-sectional study PNPLA3 (rs738409) and IL28B (rs12979860) SNPs were determined in 177 HIV/HCV coinfected patients. Liver fibrosis and steatosis-staged by liver biopsy and transient elastography using the Controlled Attenuation Parameter (CAP)-and portal hypertension (hepatic venous pressure gradient, HVPG) were compared across PNPLA3 genotypes. RESULTS: 75 (42.4%) patients tested positive for a PNPLA3 minor/major risk allele (G/C:66; G/G:9) showed comparable fibrosis stages (median F2 vs. F2; p = 0.292) and similar amounts of hepatic steatosis (CAP: 203.5 ± 41.9 vs. 215.5 ± 59.7 dB/m; p = 0.563) as compared to patients without a PNPLA3 risk allele. Advanced liver fibrosis was neither associated with PNPLA3 (p = 0.253) nor IL28B-genotype (p = 0.628), but with HCV-GT3 (p = 0.003), higher BMI (p = 0.008) and higher age (p = 0.007). Fibrosis progression rate (0.27 ± 0.41 vs. 0.20 ± 0.26 units/year; p = 0.984) and HVPG (3.9 ± 2.6 vs. 4.4 ± 3.0 mmHg; p = 0.472) were similar in patients with and without PNPLA3 risk alleles. SVR rates to PEGIFN/RBV therapy were similar across PNPLA3 genotypes. CONCLUSIONS: The presence of a PNPLA3 risk allele had no independent impact on liver disease or virological response rates to PEGIFN/RBV therapy in our cohort of HIV/HCV coinfected patients.

Revisiting liver disease progression in HIV/HCV-coinfected patients: the influence of vitamin D, insulin resistance, immune status, IL28B and PNPLA3.

BACKGROUND & AIMS: To perform a comprehensive study on independent modulators of liver fibrosis progression and determinants of portal pressure considering immune status, insulin resistance (IR), serum 25-hydroxyvitamin D (25(OH)D) levels, genetic variants of patatin-like phospholipase domain-containing protein 3 (PNPLA3) and interleukin 28B (IL28B) in a thoroughly documented cohort of HIV/hepatitis C-coinfected (HIV/HCV) patients. PATIENTS & METHODS: 25(OH)D deficiency (25(OH)DDEF), IR and low CD4(+) T-lymphocyte nadir (lowCD4NAD) were defined as 25(OH)D <20 ng × ml(-1) , HOMA-IR >2 and CD4nadir <200 cells × µl(-1) respectively. Liver fibrosis progression rate (FPR) was calculated as METAVIR F units divided by the number of years since HCV infection. Patients with a FPR > median FPR were assigned to the highFPR group. RESULTS: Among 86 HIV/HCV, the median FPR was 0.167 units × years(-1) . While the prevalence of prior alcohol abuse, lowCD4NAD and 25(OH)DDEF was higher among highFPR patients, the prevalence of IR was comparable. The association between 25(OH)DDEF and FPR was confirmed in a subgroup of patients with METAVIR stage F0/F1/F2 in which 25(OH)D levels are not affected by the severity of liver disease. The distribution of IL28B C/C and PNPLA3 non-C/C was similar, while PNPLA3 G/G was exclusively observed in highFPR patients. LowCD4NAD (OR: 2.95; 95% CI: 1.05-8.24; P = 0.039) and 25(OH)DDEF (OR: 5.62; 95% CI: 2.05-15.38; P = 0.001) were independently associated with highFPR and showed an additive effect. Portal pressure correlated with prior alcohol abuse, HCV-genotype 3, CD4(+) nadir and 25(OH)D levels. CONCLUSIONS: Two potentially modifiable factors, CD4(+) nadir and 25(OH)D levels, were both independent modulators of liver fibrosis progression and determinants of portal pressure. Further studies are warranted to assess the relevance of PNPLA3 for FPR in HIV/HCV.

Low vitamin D levels are associated with impaired virologic response to PEGIFN + RBV therapy in HIV-hepatitis C virus coinfected patients.

BACKGROUND: Low 25-hydroxyvitamin D [25(OH)D] levels are commonly found in HIV-hepatitis C virus (HCV) coinfected patients and are associated with liver fibrosis. No association between 25(OH)D levels and response to pegylated interferon α-2a/2b plus ribavirin (PEGIFN + RBV) has yet been reported for HIV-HCV coinfected patients. DESIGN: Epidemiological characteristics, HIV and HCV infection parameters, liver biopsies, as well as data on virologic response was available in 65 patients who received chronic hepatitis C (CHC) therapy with PEGIFN + RBV within a prospective trial. 25(OH)D levels were retrospectively assessed using stored screening serum samples obtained within 35 days prior to CHC treatment. METHODS: According to their 25(OH)D levels, patients were assigned to the normal (>30 ng/ml; D-NORM), the insufficiency (10-30 ng/ml; D-INSUFF), or the deficiency (<10 ng/ml; D-DEF) group. HCV-GT 1/4, high HCV-RNA load (>6 × 10 IU/ml), advanced liver fibrosis (METAVIR F3/F4), and IL28B rs12979860non-C/C were considered as established risk factors for treatment failure in HIV-HCV coinfected patients. RESULTS: Thirty-seven (57%) and 15 (23%) patients presented with D-INSUFF and D-DEF, respectively, whereas only 13 (20%) patients had normal 25(OH)D levels. Substantial differences in cEVR (D-NORM 92% vs. D-INSUFF 68% vs. D-DEF 47%; P = 0.008) and SVR (D-NORM 85% vs. D-INSUFF 60% vs. D-DEF 40%; P = 0.029) rates were observed between 25(OH)D subgroups. Especially in difficult-to-treat patients with multiple (three to four) established risk factors, low 25(OH)D levels were clearly associated with lower rates of SVR [patients without 25(OH)D deficiency 52% vs. D-DEF 0%; P = 0.012]. CONCLUSION: Low 25(OH)D levels may impair virologic response to PEGIFN + RBV therapy, especially in difficult-to-treat patients. Vitamin D supplementation should be considered and evaluated prospectively in HIV-HCV coinfected patients receiving CHC treatment.

A prospective evaluation of pulmonary, systemic and hepatic haemodynamics in HIV-HCV-coinfected patients before and after antiviral therapy with pegylated interferon and ribavirin.

BACKGROUND: Patients coinfected with HIV and HCV are at risk for developing portal hypertension (PHT), hyperdynamic circulation and pulmonary arterial hypertension (PAH). Data on the influence of antiviral therapy with pegylated interferon-α (PEG-IFN-α) and ribavirin (RBV) are limited. METHODS: Haemodynamic parameters, including hepatic venous pressure gradient (HVPG), pulmonary arterial pressure (PAP(mean)), cardiac output (CO) and systemic vascular resistance (SysVR), were prospectively evaluated before and after PEG-IFN-α+RBV therapy in 80 HIV-HCV-coinfected patients. RESULTS: Baseline evaluation showed a mean HVPG of 4.7 mmHg, CO of 6.15 l/min and PAP(mean) of 14.8 mmHg. PHT was present in 26% of patients, hyperdynamic circulation in 5% and PAH in 4%. Patients with advanced fibrosis (METAVIR stage F3/F4; n=32) had significantly higher CO (P=0.008), lower SysVR (P=0.035), higher PAP(mean) (P=0.018) and higher pulmonary vascular resistance (P=0.022) than patients with stage F0-F2 fibrosis (n=48). Both hyperdynamic circulation and PAH were significantly associated with liver stiffness, fibrosis stage and portal pressure; a non-significant trend was found for CD4(+) T-cell counts and HIV RNA levels. No significant changes in PAP(mean), CO and SysVR were observed after PEG-IFN-α+RBV treatment, although a significant decrease in HVPG was noted in patients with HCV eradication (P=0.013). CONCLUSIONS: The overall prevalence of hyperdynamic circulation and PAH in HIV-HCV coinfection is low. Advanced fibrosis, increased liver stiffness, elevated portal pressure and probably CD4(+) T-cell count and HIV viraemia represent risk factors for hyperdynamic circulation and PAH. PHT is present in 26% of HIV-HCV-coinfected patients evaluated for antiviral therapy. Successful HCV eradication significantly decreases HVPG.