Spontaneous loss of hepatitis C virus RNA from serum is associated with genotype 1 and younger age at exposure.

A variety of factors have been associated with spontaneous loss of hepatitis C virus (HCV)-RNA from serum, including infecting HCV type, although results are conflicting. This study aimed to investigate further whether infecting HCV type was linked to spontaneous loss of HCV-RNA. Serum samples from 321 untreated HCV antibody positive patients presenting at the Hepatology clinic at Addenbrooke's Hospital, Cambridge between 2004 and 2007 were tested. These individuals were classified either as HCV antibody and HCV-RNA positive (viremic, n = 219) or HCV antibody positive and repeatedly HCV-RNA negative (non-viremic, n = 102). Infecting HCV type was identified by genotyping (viremic) or serotyping (non-viremic). Binomial regression analysis investigated the independent effect of HCV type on spontaneous loss of HCV-RNA from serum by comparing the two groups. Ninety-one percent of patients were found to be either genotype 1 or genotype 3. The prevalence of type 1 infection was greater among non-viremic (64.5%) than viremic individuals (45%). After controlling for the effects of potential confounding factors, multivariable analyses showed that individuals with type 1 infections were more likely to be non-viremic than genotype 3 infections (RR = 2.07; 95% CI: 1.25, 3.43; P = 0.005). Individuals infected at an older age were also less likely to become HCV-RNA negative spontaneously (RR = 0.42 comparing those infected at ≥20 years of age against those infected at <20 years of age, 95% CI: 0.25, 0.72; P = 0.002). In conclusion, the results suggest that HCV genotype 1 infections are more likely than genotype 3 infections to become spontaneously non-viremic, as are infections acquired at younger age.

Predicting progressive hepatic fibrosis stage on subsequent liver biopsy in chronic hepatitis C virus infection.

Retrospective cross-sectional studies indicate that 20% with chronic hepatitis C virus (HCV) infection become cirrhotic within 20 years. Known risk factors for advanced hepatic fibrosis include age at time of infection, male sex, excess alcohol consumption and cytokine polymorphisms. Prospective study to assess and identify factors predictive of change in hepatic fibrosis stage in chronic HCV infection by interval protocol liver biopsy was performed. One hundred and five patients with paired liver biopsy specimens separated by a mean 41 months were recruited from a cohort of 823 HCV carriers. Five per cent developed worsening hepatic fibrosis by more than two stages. In 43% there was no change in fibrosis stage. Excessive alcohol intake currently (P = 0.037) or previously (P = 0.07) predicted progression. In contrast, always having a normal alanine transaminase (P = 0.038) and always being negative in serum for HCV RNA (P =0.067) predicted no progression. Three models were developed to predict outcome. Progressive fibrosis was predicted by baseline fibrosis (P = 0.018), steatosis (P = 0.02) and age (P = 0.017). The rate of progressive fibrosis was predicted by baseline fibrosis (P = 0.0002), steatosis (P =0.039) and lobular inflammation (P = 0.09). Fibrosis stage on the second biopsy was predicted by baseline fibrosis alone (P = 0.01). The rate of progression varies widely. Alcohol misuse is an important co-factor. Progressive fibrosis can be predicted at first liver biopsy, where baseline fibrosis is most critical, allowing targeted therapy for those with early disease and a significant risk of progression.

Successful treatment with adefovir dipivoxil in a patient with fibrosing cholestatic hepatitis and lamivudine resistant hepatitis B virus.

Fibrosing cholestatic hepatitis (FCH) is a severe clinical and histological variant of hepatitis B virus (HBV) infection seen most commonly in the HBV infected allograft after liver transplantation. Without treatment, FCH is fatal, rapidly and universally. Remission has been reported with lamivudine but is associated with evolving resistance to lamivudine. Adefovir dipivoxil has recently been reported to be a potent and highly effective inhibitor of HBV replication in both wild-type and lamivudine resistant HBV infection. We report a case of FCH 15 months after liver transplantation for HBV related cirrhosis despite therapy with lamivudine and hepatitis B immunoglobulin (HBIg). Within two weeks of commencing treatment with adefovir dipivoxil 10 mg once daily, the patient had made a remarkable recovery with resolution of jaundice and normalisation of liver biochemistry. HBV DNA and hepatitis B e antigen were lost from serum subsequently and liver histology had improved at four months. This case report suggests firstly, that advanced FCH can be reversed and secondly, that addition of adefovir dipivoxil to lamivudine and HBIg may be an effective antiviral strategy.

Reliability of perceived exertion during graded exercise testing in apparently healthy adults.

PURPOSE: Ratings of perceived exertion (RPE) are widely used for monitoring individuals during graded exercise testing. Studies of the reliability of RPEs across various exercise conditions have produced mixed results. The purpose of this study was to assess the reliability of RPEs during graded exercise testing by comparing the perceptual-physiological relationship between the Bruce and Balke treadmill protocols throughout a broad range of relative exercise intensities. METHODS: Thirty-eight middle-aged men and women completed two maximal treadmill graded exercise testing separated by 48 hours. Test order was randomly assigned. RPEs were compared across protocols and between gender at selected exercise intensities using a series of two-way analysis of variances with repeated measures. RESULTS: A comparison of RPEs (Borg 15-point scale) during the graded exercise testing revealed significant protocol and gender differences at 40%, 60% and 80% of maximal heart rate reserve. RPEs were significantly higher during the Balke protocol compared to the Bruce at each intensity (45% = 9.5 +/- 2.0 vs. 8.3 +/- 1.6; 60% = 12.7 +/- 2.4 vs. 11.1 +/- 2.3; 80% = 15.7 +/- 2.2 vs. 14.1 +/- 2.0). In addition, men rated each intensity significantly higher than the women (P < 0.05). CONCLUSIONS: The results from the present study confirm that the perceptual-physiological relationship observed during graded exercise testing varies as a function of the treadmill protocol employed and that these differences extend throughout the exercise training intensity range (40--80% of maximal heart rate reserve) recommended for healthy adults. The perceptual differences between the protocols could not be accounted for by any of the physiological measures assessed within the study. These results have implications when using RPEs from exercise testing for exercise prescription purposes.