Effect of Helicobacter pylori eradication on TLR2 and TLR4 expression in patients with gastric lesions.

OBJECTIVE: Helicobacter pylori (Hp) is recognized by TLR4 and TLR2 receptors, which trigger the activation of genes involved in the host immune response. Thus, we evaluated the effect of eradication therapy on TLR2 and TLR4 mRNA and protein expression in H. pylori-infected chronic gastritis patients (CG-Hp+) and 3 months after treatment. METHODS: A total of 37 patients CG-Hp+ were evaluated. The relative quantification (RQ) of mRNA was assessed by TaqMan assay and protein expression by immunohistochemistry. RESULTS: Before treatment both TLR2 and TLR4 mRNA in CG-Hp+ patients were slightly increased (TLR2 = 1.32; TLR4 = 1.26) in relation to Hp-negative normal gastric mucosa (P ≤ 0.05). After successful eradication therapy no significant change was observed (TLR2 = 1.47; TLR4 = 1.53; P > 0.05). In addition, the cagA and vacA bacterial genotypes did not influence the gene expression levels, and we observed a positive correlation between the RQ values of TLR2 and TLR4, both before and after treatment. Immunoexpression of the TLR2 and TLR4 proteins confirmed the gene expression results. CONCLUSION: In conclusion, the expression of both TLR2 and TLR4 is increased in CG-Hp+ patients regardless of cagA and vacA status and this expression pattern is not significantly changed after eradication of bacteria, at least for the short period of time evaluated.

Histological evolution of hepatitis C virus infection after renal transplantation.

BACKGROUND: information regarding histological progression of hepatitis C after renal transplant (RTx) is scarce. AIMS: To analyze clinical and laboratory evolution and histological progression of hepatitis C in patients evaluated before and after RTx. METHODS: Twenty-two HCV-infected patients submitted to liver biopsy pre- and post-RTx were included. A semiquantitative analysis of necroinflammatory activity and fibrosis staging was performed and the two biopsies were compared. RESULTS: Patients were mostly men (73%) with mean age of 36±9 yr. Time post-transplant was 4±2 yr and time between biopsies was 5±2 yr. An elevation of alanine aminotransferase (p=0.041) and aspartate aminotransferase (p=0.004) levels was observed in the post-transplant period. Fibrosis progression after renal transplantation was observed in 11 (50%) of the patients, and necroinflammatory activity worsening was observed in 7 (32%) of the patients. The histological progression occurred even among those without significant histological lesions in pre-transplant biopsy. CONCLUSION: The findings of this study suggest that the practice of indicating treatment in the pre-transplant phase based mainly on histological disease should be revised, because a high proportion of patients present disease progression. Because interferon cannot be used safely after RTx, treatment should be indicated for all ESRD patients with hepatitis C.

Long-term efficacy of rituximab in hepatitis C virus-associated cryoglobulinemia.

Mixed cryoglobulinemia is one of the most closely related extrahepatic manifestations of hepatitis C virus and requires a challenging therapeutic approach depending on the severity of the symptoms. Here, we describe the long-term follow-up of a patient with important cutaneous, articular and neural manifestations of cryoglobulinemia associated with chronic hepatitis C treated with rituximab. A 42-year-old woman who did not respond to previous interferon-based treatments (standard and pegylated interferon plus ribavirin) and corticosteroids was subjected to treatment with rituximab at a dose of 375 mg/m(2) per week for 4 consecutive weeks. The drug was well tolerated and complete improvement of arthralgia was immediately evident. There was gradual improvement of lower limbs paresthesia and healing of a leg ulcer that had been active for 5 years. The clinical and immunological responses induced by rituximab are sustained over long-term follow-up, and this case illustrates the drug efficacy for non-responder patients to antiviral therapy.

Is early virological response as predictive of the hepatitis C treatment response in dialysis patients as in non-uremic patients?

OBJECTIVE: The aim of the present study was to determine whether hepatitis C virus (HCV) RNA present at week 12 is a good predictor of the response to interferon (IFN) monotherapy in hemodialysis patients with hepatitis C. METHODS: Hemodialysis patients with hepatitis C who were treated between 1997 and 2008 with IFN monotherapy for 48 weeks without dose reduction were included. The predictive value of HCV RNA at week 12 for achieving a sustained virological response (SVR) was determined. RESULTS: Forty patients (mean age 47±9 years; 75% males and 80% with genotype 1) were included. Septal fibrosis or cirrhosis was observed in 38% of these patients. Twelve (30%) of the 40 patients achieved SVR. HCV RNA was undetectable at week 12 in 68%. The positive predictive value of HCV RNA at week 12 was 45% and the negative predictive value was 100%. CONCLUSIONS: The presence of HCV RNA at week 12 had a high negative predictive value for SVR in hemodialysis patients with chronic hepatitis C treated with IFN for 48 weeks. Therefore, if HCV RNA is detected at week 12, treatment should be discontinued due to the low probability of a sustained response.