Serum leptin and ghrelin in chronic hepatitis C patients with steatosis.

AIM: To determine the associations between leptin and ghrelin concentrations and sustained virological response (SVR) in chronic hepatitis C patients with steatosis. METHODS: We retrospectively assessed 56 patients infected with hepatitis C virus (HCV) genotype-1 and 40 with HCV genotype-3. Patients with decompensated cirrhosis, and those with other causes of chronic liver disease, were excluded. Serum HCV-RNA concentrations were measured before the initiation of treatment; at weeks 12 (for genotype 1 patients), 24 and 48 during treatment; and 24 wk after the end of treatment. Genotype was determined using INNO-LIPA HCV assays, and serum leptin and ghrelin concentrations were measured using enzyme-linked immunosorbent assay. Biopsy specimens were scored according to the Ishak system and steatosis was graded as mild, moderate, or severe, according to the Brunt classification. RESULTS: Overall, SVR was positively related to the presence of genotype-3, to biopsy-determined lower histological stage of liver disease, and lower grade of steatosis. Patients ≥ 40 years old tended to be less responsive to therapy. In genotype-1 infected patients, SVR was associated with a lower grade of liver steatosis, milder fibrosis, and an absence of insulin resistance. Genotype-1 infected patients who did not achieve SVR had significantly higher leptin concentrations at baseline, with significant increases as the severity of steatosis worsened, whereas those who achieved SVR had higher ghrelin concentrations. In genotype-3 infected patients, SVR was associated only with fibrosis stage and lower homeostasis model assessment insulin resistance at baseline, but not with the degree of steatosis or leptin concentrations. Genotype-3 infected patients who achieved SVR showed significant decreases in ghrelin concentration at end of treatment. Baseline ghrelin concentrations were elevated in responders of both genotypes who had moderate and severe steatosis. CONCLUSION: Increased serum leptin before treatment may predict non-SVR, especially in HCV genotype-1 infected patients, whereas increased ghrelin may predict SVR in genotype-1.

European vs. Egyptian HCV-4 patients with elevated baseline HCV RNA, treated with PEG-IFN-α2a and ribavirin: the role of rapid and early virologic response.

BACKGROUND AND AIMS: Despite the recent spread of hepatitis C virus genotype 4 (HCV-4) into European countries, very little is known about the influence of ethnicity on treatment outcomes in patients with HCV-4. The aim of this study was to compare the virologic response (VR) rates of: rapid virologic response (RVR), early virologic response (EVR), VR at 24 weeks of treatment, at end of treatment (EoT), and sustained virologic response (SVR) of European and Egyptian HCV-4 patients. METHODS: Sixty (30 Europeans - Group A; and 30 Egyptians - Group B) chronic HCV-4 subtype A adult patients with elevated baseline viral load (>800 000 IU/m L) were treated for a fixed period of 48 weeks with pegylated interferon α2a (PEG-IFN- α2a) and ribavirin. During the study, HCV-RNA levels were measured at weeks 4,12,24,48 and 72. RESULTS: Baseline characteristics, including liver histology, were similar in the two groups. RVR, EVR and HCV-RNA at week 24 in Groups A and B were (RVR 26.7% vs. 30.0%) (EVR 23.3% vs. 16.7%) (in week 24 13.3% vs. 16.7%). Overall SVR rates were 36.7% (11/30) for Group A and 26.7% (8/30) for Group B (P = 0.59). For group B, RVR was the weakest indicator for SVR as compared with RVR of group A, where RVR was the best SVR indicator CONCLUSIONS: The overall response to treatment was similar, but ethnic origin or previous history and treatment of schistosomiasis may influence intermediate response rates of chronic HCV-4a infected patients with elevated baseline HCV-RNA.

Impact of hepatitis B exposure on sustained virological response rates of highly viremic chronic hepatitis C patients.

AIM: To evaluate the impact of hepatitis B core antibody (anti-HBc) seropositivity in sustained virological response (SVR) rates in treatment-naïve, chronic hepatitis C (CHC) patients with high pretreatment viral load (>800000 IU/mL). METHODS: 185 consecutive CHC patients (14.4% cirrhotics, 70.2% prior intravenous drug users) treated with pegylated interferon-a2b plus ribavirin, for 24 or 48 weeks based on viral genotype, were retrospectively analyzed. SVR was confirmed by undetectable serum HCV-RNA six months after the end of treatment schedule. RESULTS: Thirty percent of CHC/HBsAg-negative patients were anti-HBc-positive. Anti-HBc positivity was more prevalent in cirrhotic, compared to noncirrhotic patients (76.9% versus 19.5%, P < .05). Serum HBV-DNA was detected in the minority of anti-HBc-positive patients (1.97%). Overall, 62.1% of patients exhibited SVR, while 28.6% did not; 71.4% of non-SVRs were infected with genotype 1. In the univariate analysis, the anti-HBc positivity was negatively associated with treatment outcome (P = .065). In the multivariate model, only the advanced stage of liver disease (P = .015) and genotype-1 HCV infection (P = .003), but not anti-HBc-status (P = .726), proved to be independent predictors of non-SVR. CONCLUSION: Serum anti-HBc positivity does not affect the SVR rates in treatment-naïve CHC patients with high pretreatment viral load, receiving the currently approved combination treatment.

Patient's age modifies the impact of the proposed predictors of sustained virological response in chronic hepatitis C patients treated with PEG-interferon plus ribavirin.

BACKGROUND: The aim of this study was to investigate the effect of patient's age on the impact of typically proposed predictors of sustained virological response (SVR) in treatment-naïve, high-pretreatment viral load (>700.000 IU/ml), chronic hepatitis C (CHC) patients treated under real-life conditions in Greece. METHODS: We retrospectively analyzed 185 CHC patients (14.4% cirrhotics) who had been treated with weight-adjusted dosing (1.5 microg/kg per week) of pegylated interferon-a2b (PEG) plus genotype-based ribavirin (RIB) for 24 or 48 weeks of treatment, based on viral genotype. SVR was confirmed by undetectable serum HCV-RNA 6 months after the end of treatment. RESULTS: Overall, 68.5% of patients exhibited SVR and 31.5% were non-responders (non-SVRs). Among the non-SVRs, 71.4% were infected with HCV genotype-1. Importantly, 71.4% of genotype 4-infected treated patients exhibited SVR. In the multivariate analyses, only the early histological stage of liver disease (p=0.015) and the presence of genotype non-1 infection (p=0.003) were independent predictors of SVR. For patients younger than 35 years, none of the baseline parameters and neither viral genotype (p=0.284) nor the stage of liver disease (p=0.351) was an independent predictor of non-SVR, whereas for patients between 35 and 55, only the presence of genotype-1 infection independently predicted non-SVR (p=0.008). For older patients (>55 years), only the histological stage of liver disease (p=0.047) and not the viral genotype (p=0.275) independently predicted non-SVR. CONCLUSIONS: The impact of the typical predictors of SVR, such as viral genotype and liver histopathology, is modified according to patient's age in currently approved combination treatment.

Water as a fast acting wax softening agent before ear syringing.

BACKGROUND: Dispute exists over the best treatment for softening occlusive earwax. Some require the patient to go away for days before returning for syringing. Some syringe immediately with no preparation. METHODS: An open, nonblinded, randomised controlled trial was conducted in one rural general practice. Effects of instillation of water into the ear canal for 15 minutes before syringing were compared to effects of syringing immediately. RESULTS: Thirty-nine ears (of 26 patients) were randomised. Ear wax was removed entirely by syringing in all ears. Prior instillation of water required a mean 7.5 (+/- 7.3) attempts at syringing versus a mean 25.4 (+/- 39.4) attempts for ears that were syringed immediately (p=0.043). DISCUSSION: Prior installation of water before syringing seems to be an effective and simple method of reducing the number of attempts required to clear the ear of occlusive wax.

Relationship between intracranial pressure and critical closing pressure in patients with neurotrauma.

BACKGROUND: The driving pressure gradient for cerebral perfusion is the difference between mean arterial pressure (MAP) and critical closing pressure (CCP = zero flow pressure). Therefore, determination of the difference between MAP and CCP should provide an appropriate monitoring of the effective cerebral perfusion pressure (CPP(eff)). Based on this concept, the authors compared conventional measurements of cerebral perfusion pressure by MAP and intracranial pressure (CPP(ICP)) with CPP(eff). METHODS: Simultaneous synchronized recordings of pressure waveforms of the radial artery and blood flow velocities of the middle cerebral artery were performed in 70 head trauma patients. CCP was calculated from pressure-flow velocity plots by linear extrapolation to zero flow. RESULTS: Intracranial pressure measured by intraventricular probes and CCP ranged from 3 to 71 and 4 to 70 mmHg, respectively. Linear correlation between ICP and CCP was r = 0.91. CPP(ICP) was 77 +/- 20 mmHg and did not differ from CPP(eff); linear correlation was r = 0.92. However, limits of agreement were only +/- 16.2 mmHg. Therefore, in 51.4% of the patients, CPP(ICP) overestimated CPP(eff) by 19.8 mmHg at most. CONCLUSION: Assuming that CPP(eff) (MAP - CCP) takes into account more determinants of cerebral downstream pressure, in individual cases, the actual gold standard of CPP determination (MAP - ICP) might overestimate the CPP(eff) of therapeutic significance.