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Background and aim. In patients with chronic hepatitis C receiving Peg interferon/ribavirin (PEG-IFN/RBV) who do not achieve ≥ 2log-reduction in HCV-RNA at week 12 (null responders, NR) and in those with ≥ 2log-decrease but detectable at week 24 (partial responders, PR) the probability to achieve the sustained virological response (SVR) is almost null. The aim of this study was to investigate the efficacy of individuali- zed schedule of progressively increased RBV doses in the setting of PEG-IFN/RBV treatment. Material and methods. PR or NR to PEG-IFN/RBV instead of discontinuing treatment were enrolled to receive increasing doses of RBV until a target theoretical concentration ([tRBV]) of ≥ 15 μ mol/L (by pharmacokinetic formula based on glomerular filtration rate). HCV-RNA was assessed every 4 weeks and, if detectable, RBV dose was gradually increased until negativization. Twelve weeks later, patients with detectable HCV-RNA disconti- nued therapy while those with undetectable HCV-RNA continued for further 48 weeks. Results. Twenty genotype-1 patients (8 NR and 12 PR) were enrolled. After 12 weeks 9 (45%) were still HCV-RNA positive and were discontinued, while remaining 11 had undetectable HCV-RNA. One stopped treatment for side effects. Ten completed treatment. Five (all PR) achieved SVR. Side effects incidence was similar to that observed during PEG-IFN/RBV. Conclusions. In conclusion, RBV high doses, according to individualized sche- dule, increase SVR in PR on a similar extent to that of triple therapy but without increase of side effects. Such treatment should be considered in PR with no access or intolerant to protease inhibitors (PI). [ABSTRACT FROM AUTHOR]

The benefit of lamivudine (LAM) in hepatitis B virus (HBV) infection is compromised by the progressively increasing emergence of drug-resistant mutant strains. Although the addition of adefovir dipivoxil (ADV) usually induces complete suppression of viral replication, primary non-response to ADV in LAM resistant patients has been reported in a variable percentage of cases. Here we report a case of a patient with HBV infection and hepatocellular carcinoma who started LAM therapy and subsequently developed virological breakthrough. The patient was given ADV, but HBV-DNA negativisation was not reached. However, HBV clearance was obtained when the patient was switched from ADV to tenofovir. Virological evaluations showed two well-known LAM-related mutations (rtL180M and rtM204I) in addition to reverse-transcriptase rtQ215H. This is the first case suggesting that this mutation may have an impact on viral replication. Finally, we also report that rtQ215H is responsive to tenofovir.

With the widespread use of ultrasonography (US) and computerized tomography (CT), the usefulness of alpha-fetoprotein assay in the diagnosis of hepatocellular carcinoma (HCC) has decreased. The aim of our study was to evaluate the best cut-off value for serum alpha-fetoprotein to discriminate between liver cirrhosis (LC) and HCC and the factors influencing levels in a Sicilian population. Three hundred and seventy-two patients with LC and 197 with HCC-associated LC were studied. The etiology was: HCV in 288 cases (77.4%) of LC and 147 cases (75%) of HCC; HBV in 31 cases (8.3%) of LC and 15 cases (7.6%) of HCC; HCV/HBV in 21 cases (5.6%) of LC and 6 cases (3.0%) of HCC; non-viral in 32 cases (8.6%) of LC and 29 cases (15%) of HCC. Hepatic function was estimated by the Child-Pugh's score; the TNM classification was used in HCC. The area under the ROC curve was 0.81 +/- 0.02; the best discriminant cut-off value, calculated as the value of the maximized likelihood ratio, was 30 ng/ml. At this level sensitivity (SE) was 65%, specificity (SP) 89%, positive predictive value (PPV) 74% and negative predictive value (NPV) 79%. When the patients were divided at this cut-off point into two groups according to viral or non-viral etiology, PPV was 70% versus 94%, respectively (p < 0.05). In the non-viral diseases PPV reached 100% for AFP serum levels of 100 ng/ml, while in the viral diseases PPV was 100% when AFP was greater than 400 ng/ml. There were no significant differences in SE, SP or NPV between viral and non-viral liver diseases. Child's classes B and C were more frequent in HCC (chi 2 of MH 7.7, p < 0.0001). There was a correlation between AFP serum values and TNM classification (p < 0.02) and on multiple logistic regression AFP levels > 30 ng/ml correlated positively only with the TNM stage (p < 0.0001). In conclusion, the best cut-off value for serum AFP in our study population was 30 ng/ml, but at this level sensitivity was low. This cut-off value was more useful in detecting non-viral HCC, because PPV was significantly higher than in viral HCC; therefore, our data confirm that the usefulness of AFP in the diagnosis of HCC of viral etiology is limited, being more useful in HCC of non-viral etiology.

Focal nodular hyperplasia (FNH) is a rare benign liver lesion which is difficult to differentiate from other benign liver pathologies and hepatocellular carcinoma. However, with appropriate new imaging techniques it is, at present, possible to diagnose this lesion with certainty thus avoiding invasive tests. Patient follow-up is also facilitated. It is often incidentally discovered during an abdominal ultrasound for other pathologies. Color power Doppler allows, in most cases, one to distinguish it from other focal liver lesions. However, in doubtful cases contrast-enhanced computed tomography and magnetic resonance imaging can help us to define the exact nature of the lesion. It is only occasionally necessary to perform an ultrasound-guided liver biopsy of the nodule and anyhow, once a correct diagnosis has been made, in most cases there is no indication for surgery. In spite of the contradictory results in the literature on the effects of oral contraceptives and pregnancy on the evolution of FNH, it now seems that they do not condition the appearance or the size of FNH and that in a woman with FNH pregnancy should not only be discouraged, but rather favored and closely monitored.