A 70-year-old Woman with Asymptomatic Ferroportin Disease.

A 59-year-old Japanese woman presented with hyperferritinemia. We decided against iron removal treatment because there were no symptoms or signs of iron-induced organ damage. A follow-up study revealed a gradual increase in transferrin saturation. The patient underwent a second examination at 66 years old. A liver biopsy showed substantial iron deposits in hepatocytes and Kupffer cells but no inflammation or fibrosis. Serum hepcidin-25 levels were highly parallel with hyperferritinemia. A genetic analysis revealed a G80S mutation in SLC40A1. These features are compatible with those of ferroportin disease. The patient remained asymptomatic at 70 years old, suggesting that the iron-loading condition may have been benign.

α-fetoprotein levels after interferon therapy predict regression of liver fibrosis in patients with sustained virological response.

BACKGROUND AND AIMS: Eradicating chronic hepatitis C virus (HCV) infection improves liver fibrosis and reduces hepatocellular carcinoma (HCC) incidence in chronic HCV patients. We evaluated the relationship between fibrosis regression, as assessed by sequential biopsies, and clinical factors of patients with sustained virological response (SVR). METHODS: We retrospectively enrolled 130 patients (74 men; 60.1 ± 8.1 years) with chronic HCV treated with interferon and ribavirin therapy who achieved SVR. To evaluate the change in fibrosis stage over time, all patients underwent a pre-therapy initial biopsy and a second biopsy after achieving SVR. RESULTS: The mean time between biopsies was 5.5 ± 1.2 years. Fibrosis stage regressed in 55 patients (42.3%), remained stable in 69 (53.1%), and progressed in 6 (4.6%). The mean fibrosis stage significantly decreased, from 2.01 ± 0.99 units to 1.61 ± 1.24 units (P < 0.001). Aspartate aminotransferase, γ-glutamyltransferase, and α-fetoprotein (AFP) levels at 24 weeks after the end of treatment (EOT) were significantly lower, and the platelet count at 24 weeks after the EOT was significantly higher in patients with fibrosis regression than in those without. Logistic regression analysis confirmed that lower AFP levels (< 5.4 ng/mL) at 24 weeks after the EOT (odds ratio [OR], 4.626; 95% confidence interval [CI], 1.557-13.153; P = 0.006) and HCV genotype 2 (OR, 2.198; 95% CI, 1.010-4.786; P = 0.047) were significant independent predictive factors for regressed fibrosis after SVR. CONCLUSIONS: Lower post-treatment AFP levels and HCV genotype 2 significantly correlated with liver fibrosis regression after SVR.

Progressive fibrosis significantly correlates with hepatocellular carcinoma in patients with a sustained virological response.

AIM: Hepatocellular carcinoma develops even in some patients who achieve a sustained virological response following treatment for hepatitis C virus infection. This study investigated the relationship between changes in fibrosis, as assessed by sequential biopsies, and development of hepatocellular carcinoma in patients who achieved a sustained virological response for hepatitis C virus. METHODS: We enrolled 97 patients with sustained virological response who had undergone initial biopsies before therapy and sequential biopsies at an average of 5.8 ± 1.9 years after the initial biopsy. Factors associated with hepatocellular carcinoma were retrospectively analyzed. RESULTS: The liver fibrotic stage regressed in 44 patients (45%), remained stable in 47 patients (48%) and progressed in six patients (6%). The fibrotic stage significantly decreased, from 1.54 ± 0.86 to 1.16 ± 1.07 units. Hepatocellular carcinoma was identified in 12 patients (12.4%). The cumulative incidence of hepatocellular carcinoma in patients with progressive fibrosis was significantly higher than that in patients with regressed or stable fibrosis (P < 0.001). A Cox proportional hazards regression analysis confirmed that progressive fibrosis in sequential liver biopsies (hazard ratio [HR], 8.30; P = 0.001) and low platelet counts before treatment (HR, 8.69; P = 0.006) were significant independent factors associated with the development of hepatocellular carcinoma in patients with a sustained virological response. CONCLUSION: Progressive fibrosis, assessed by sequential biopsies, was significantly correlated with development of hepatocellular carcinoma in patients who had achieved a sustained virological response for hepatitis C virus.

Pegylated interferon monotherapy in patients with chronic hepatitis C with low viremia and its relationship to mutations in the NS5A region and the single nucleotide polymorphism of interleukin-28B.

AIM: Previous studies have suggested that patients with chronic hepatitis C with a low pretreatment hepatitis C virus (HCV) level have a high sustained virological response (SVR) rate, and that there would be a subpopulation of patients in which HCV can be eradicated with pegylated interferon (PEG IFN) alone without a decrease in SVR. However, the efficacy of PEG IFN monotherapy in patients with low HCV RNA levels is unclear. Several studies have reported that interferon sensitivity-determining region (ISDR) and the single-nucleotide polymorphism (SNP) of interleukin-28B (IL-28B) contribute to IFN response, but these relationships are controversial. The aim of this study was to determine whether the SNP of IL-28B (rs8099917) and amino acid substitutions in the ISDR among patients with low HCV levels affect the response to PEG IFN monotherapy. METHODS: One hundred and four patients with low-level HCV infection were studied. Low HCV level was defined as 100 KIU/mL or less. RESULTS: SVR was achieved in 94 patients (92.2%). HCV levels (≤50 KIU/mL) and ISDR (≥2 mutations) were associated with SVR on univariate analysis. The rates of SVR in the patients with IL-28B genotypes TT, TG and GG were 94.5%, 77.8% and 100%, respectively. The G allele tended to be associated with poor response to IFN therapy (P = 0.0623). On multivariate analysis, the ISDR was the factor predictive of SVR (P = 0.004). CONCLUSION: The ISDR is significantly associated with a good response to PEG IFN monotherapy in patients with low HCV levels.