Kamila Wójcik

Sudden hearing loss in chronic hepatitis C patient suffering from Turner syndrome, treated with pegylated interferon and ribavirin

Sudden hearing loss is a very rare complication of interferon–alpha treatment. At this time, hearing loss in patients treated with pegylated interferon and ribavirin has only been described in two reports. We present a case of a 27-year-old patient who was diagnosed with Turner syndrome, treated for hepatitis C with pegylated interferon and ribavirin, and suffered from hearing loss during the 10th week of treatment. Audiometric examination revealed a bilateral sensorineural hearing loss (SNHL). Auditory brainstem response (ABR) measures confirmed the diagnosis. We decided to comply with the patients request to continue therapy, which only led to slight further deterioration of the patients hearing ability. However, 18 months after the end of therapy a follow-up audiometric examination disclosed a bilateral SNHL.

Insulin resistance, adipokine profile and hepatic expression of SOCS-3 gene in chronic hepatitis C

AIM To analyze adipokine concentrations, insulin resistance and hepatic expression of suppressor of cytokine signaling 3 (SOCS-3) in patients with chronic hepatitis C genotype 1 with normal body weight, glucose and lipid profile. METHODS The study group consisted of 31 patients with chronic hepatitis C and 9 healthy subjects. Total levels of adiponectin, leptin, resistin, visfatin, omentin, osteopontin and insulin were measured using an ELISA kit. The hepatic expression of SOCS-3 was determined by the use of the reverse transcription polymerase chain reaction method. RESULTS Homeostasis model assessment for insulin resistance (HOMA-IR) values were significantly higher in hepatitis C virus (HCV) infected patients without metabolic disorders compared to healthy controls (2.24 vs 0.59, P = 0.0003). Hepatic steatosis was observed in 32.2% of patients with HCV infection and was found in patients with increased HOMA-IR index (2.81 vs 1.99, P = 0.05) and reduced adiponectin level (5.96 vs 8.37, P = 0.04). Inflammatory activity (G ≥ 2) was related to increased osteopontin concentration (34.04 vs 23.35, P = 0.03). Advanced liver fibrosis (S ≥ 2) was associated with increased levels of omentin and osteopontin (436.94 vs 360.09, P = 0.03 and 32.84 vs 20.29, P = 0.03) and reduced resistin concentration (1.40 vs 1.74, P = 0.047). No correlations were reported between adipokine profile, HOMA-IR values and hepatic expression of the SOCS-3 gene. CONCLUSION We speculated that no relationship between adipokines and HOMA-IR values may indicate that HCV can induce insulin resistance itself. Some adipokines appear to be biochemical markers of steatosis, inflammation and fibrosis in patients with chronic HCV infection.

Hepatic HMOX1 expression positively correlates with Bach-1 and miR-122 in patients with HCV mono and HIV/HCV coinfection.

Aim To analyze the expression of HMOX1 and miR-122 in liver biopsy samples obtained from HCV mono-and HIV/HCV co-infected patients in relation to selected clinical parameters, histological examination and IL-28B polymorphism as well as to determine whether HMOX1 expression is dependent on Bach-1. Materials and Methods The study group consisted of 90 patients with CHC: 69 with HCV mono and 21 with HIV/HCV co-infection. RT-PCR was used in the analysis of HMOX1, Bach-1 and miR-122 expression in liver biopsy samples and in the assessment of IL-28B single-nucleotide polymorphism C/T (rs12979860) in the blood. Moreover in liver biopsy samples an analysis of HO-1 and Bach-1 protein level by Western Blot was performed. Results HCV mono-infected patients, with lower grading score (G<2) and higher HCV viral load (>600000 IU/mL) demonstrated higher expression of HMOX1. In patients with HIV/HCV co-infection, the expression of HMOX1 was lower in patients with lower lymphocyte CD4 count and higher HIV viral load. IL28B polymorphism did not affect the expression of either HMOX1 or miR-122. Higher HMOX1 expression correlated with higher expression of Bach-1 (Spearman’s ρ = 0.586, p = 0.000001) and miR-122 (Spearman’s ρ = 0.270, p = 0.014059). Conclusions HMOX1 and miR-122 play an important role in the pathogenesis of CHC in HCV mono-and HIV/HCV co-infected patients. Reduced expression of HMOX1 in patients with HIV/HCV co-infection may indicate a worse prognosis in this group. Our results do not support the importance of Bach-1 in repression of HMOX1 in patients with chronic hepatitis C.

Expression of selected genes in liver biopsy specimens in relation to early virological response in patients with chronic hepatitis C with HCV mono- and HIV/HCV co-infection

The aim of our study was to evaluate the significance of IL-28B single-nucleotide polymorphism and hepatic expression of IFI27, SOCS3 and miR-122 in order to predict early virological response (EVR) in patients infected with HCV genotype 1 or 4. The study group consisted of 65 patients: 46 with HCV mono- and 19 with HIV/HCV co-infection. Analyses of IL-28B single-nucleotide polymorphism C/T (rs12979860) in the blood and expression of SOCS3, IFI27 and miR-122 in liver biopsy samples obtained before PegIFN and ribavirin treatment were performed by the RT-PCR method. EVR was defined as a >2log decline in HCV viremia at week 12. EVR was associated with a lower expression of IFI27 and a more frequent presence of the IL28BCC genotype. IFI27 expression was lower in patients with the CC genotype, irrespective of EVR. In multivariate logistic regression, only IL28B CC genotype and age above 40 years influenced EVR (OR =5.09 and 0.29 respectively). In contrast to IFI27, expression of miR-122 and SOCS3 in patients with different IL28B genotypes was not statistically significantly different. A correlation between miR-122 and SOCS3 was found (Rho =0.495094 p< 0.0001). Analysis of IFI27, SOCS3 and miR-122 hepatic expression does not provide substantial benefits for the prognosis of EVR. The only independent prognostic factors for EVR are age and IL28B genotype. The prognostic significance of IFI27 expression for EVR is dependent on the genetic polymorphism of IL28B.

The Influence of Treatment with Pegylated Interferon-Alfa and Ribavirin on Neutrophil Function and Death in Patients with HIV/HCV Coinfection

In patients with human immunodeficiency virus (HIV) as well as in patients with hepatitis C virus (HCV) infection the impairment of neutrophil activity is observed. We decided to analyze how treatment with pegylated interferon-alfa (Peg-IFN-alfa) and ribavirin affects neutrophil function in HIV/HCV coinfected patients. The study group consisted of 18 patients with HIV/HCV coinfection, on combination antiretroviral treatment (cART), aged between 27 and 42 y (mean 33.1±4.5 y). At the beginning of treatment with Peg-IFN-alfa and ribavirin all patients had an undetectable HIV viral load, and CD4 T-cell counts higher than 350 cells/μL. At two time points, before and after 12 wk of treatment with Peg-IFN-alfa and ribavirin, we examined intracellular levels of reactive oxygen species (ROS), and expression of selected adhesion molecules on whole blood neutrophils, along with apoptosis and necrosis of these cells. These analyses were done with flow cytometry. During anti-HCV therapy undetectable HIV levels were maintained in all patients. Treatment with PEG-IFN-alfa and ribavirin resulted in increases in the expression of CD11b and CD18, and decreases of CD16 and CD62L. However, only the change in CD62L expression was statistically significant (p<0.05). Moreover, the treatment resulted in increased apoptosis of neutrophils, while necrosis remained unchanged. After 12 wk of treatment, an increase in ROS production by neutrophils stimulated with PMA was observed (p<0.01). In HIV/HCV coinfected patients on cART, PEG-IFN-alfa and ribavirin treatment caused an activation of neutrophil function, yet it did not affect the suppression of HIV replication.

“Efficacy and safety of nucleoside‐sparing regimen based on raltegravir and ritonavir‐boosted darunavir in HIV‐1‐infected treatment‐experienced patients”

To assess the efficacy and tolerability of dual therapy containing raltegravir (RAL) and ritonavir boosted darunavir (DRV/r) in HIV‐1‐infected treatment‐experienced patients.

Hepatic expression of miR-122 and antioxidant genes in patients with chronic hepatitis B

INTRODUCTION The pathogenesis of chronic hepatitis B depends on both, the immune response and oxidative stress. AIM OF THE STUDY To assess the hepatic expression of miR-122 and the antioxidant genes: HMOX-1, NQO1 and GFER1, in liver biopsy specimens obtained from patients with chronic hepatitis B, with regard to selected clinical and histological parameters, using RT-PCR. RESULTS The study group comprised 34 HBV-infected patients. Statistically significant associations were found between lower hepatic expression of HMOX-1 and greater severity of liver inflammation (p=0.04). However, significantly higher expression of NQO1 was observed in patients with advanced liver fibrosis (p=0.035). Hepatic expression of miR-122 in HBV patients was not associated with viral load or liver injury. CONCLUSION The hepatic expression of HMOX-1and NQO1 may be associated with liver injuries in chronic hepatitis B. However, hepatic expression of miR-122 does not seem to correspond to progression of the liver disease.

The assessment of renal function in HIV-positive patients before the introduction of antiretroviral therapy

Summary Background A wide clinical spectrum of kidney diseases has been recognized in individuals with HIV (human immunodeficiency virus). The aim of this retrospective study was to assess renal function in HIV patients before the introduction of combined antiretroviral therapy (cART). Material and Methods The study group consisted of 106 HIV-positive patients (72 males, 34 females). The level of serum creatinine and creatinine clearance using the Cockcroft-Gault formula were assessed. Urine analysis for proteinuria was performed. The relationship between HIV infection including CD4 cells count, CD4 nadir and renal function was determined. Results The correlation between the creatinine clearance and CD4 nadir and CD4 cells count before the introduction of cART was found (p = 0.037, p = 0.036). Conclusion: The kidney dysfunction measured with the creatinine clearance before the introduction of cART was associated with the immunodeficiency.

Surveillance for portal hypertension in the course of liver cirrhosis

Non-invasive liver fibrosis assessment techniques are under development for evaluating the severity of liver disease and portal hypertension. The paper presents practical arrangements for the diagnosis and treatment of portal hypertension in patients with chronic liver disease, established in the Baveno VI Consensus Workshop for diagnosis and treatment of portal hypertension. Currently, the diagnostic standard of liver disease severity is transient elastography, which can identify patients with clinically significant portal hypertension (liver stiffness > 20 kPa). The paper presents the eligibility criteria for endoscopy and the principle of repeating the assessment of oesophageal varices. It also describes the primary and secondary prevention of gastroesophageal haemorrhage, the treatment of oesophageal bleeding and the treatment of liver vessel thrombosis.

Efficacy and direct costs of chronic hepatitis C treatment with first generation NS3/4A protease inhibitors in a real life population

Introduction Recent years have brought a significant advance in chronic hepatitis C (CHC) treatment that includes development of direct acting antivirals (DAA). Two of them, boceprevir (BOC) and telaprevir (TVR), were first approved for treatment of patients infected with CHC genotype 1 in combination with pegylated interferon (P) and ribavirin (R). Our aim was to evaluate the efficacy and direct costs of BOC/PR and TVR/PR in a real life population. Material and methods The study included adult patients qualified for the CHC Therapeutic Programme treated with TVR/PR or BOC/PR. Treatment was continued for 24 or 48 weeks. Sustained virological response, treatment discontinuation due to adverse events and lack of virological response rates were compared. Results A total of 243 adult patients with CHC were included. TVR/PR and BOC/PR were administered in respectively 122 and 121 patients. Thirty-two patients (13%) were treatment-naïve, whereas liver cirrhosis/advanced fibrosis was observed in 138 patients (56.7%). Overall, 43.6% of patients achieved a sustained virologic response (SVR). In the BOC/PR group the SVR rate was significantly lower than in the TVR/PR group (33.1% vs. 54.1%; p = 0.00094). Lack of response to therapy was observed in 41.3% and 12.3% of patients receiving BOC and TVR, respectively (p < 0.00001). The direct cost of achieving SVR in one patient was 285 450 PLN with BOC and 185 757 PLN with TVR. Conclusions The very low treatment efficacy may be the result of inclusion criteria that allowed treatment of patients with advanced liver fibrosis/liver cirrhosis or previous treatment failure. Telaprevir seems to be significantly more potent against hepatitis C virus, with similar safety and tolerance.