Search

Background and Objective: The extended treatment with lamivudine in patients with chronic hepatitis B is associated with the emergence of resistances. Patients with resistance to lamivudine show a loss of biochemical and virological responses and a higher progression of their liver disease. Adefovir dipivoxil, an analogue of the nucleotides, is effective for the treatment of patients with resistance to lamivudine. The aim of this study was to evaluate the efficacy, safety and resistance of adefovir dipivoxil in patients with chronic hepatitis B refractory to treatment with lamivudine., Patients and Method: One hundred and twenty hepatits B virus patients refractory to lamivudine were treated with adefovir dipivoxil. Seventy-four patients were followed up during two years. In all cases, the hepatitis B virus-DNA was determined by polymerase chain reaction, and in those cases without response to treatment, the presence of resistances to adefovir and lavimudine were studied., Results: At the second year of treatment, we observed a biological response of 54.1%, a biochemical response of 62.2%, while an elimination of hepatitis B e antigen was seen in 21% cases. 20% patients developed resistance to adefovir dipivoxil, and the most frequent detected mutations were: A181V, A181T and N236T. Drug safety was excellent; in fact, only one adverse effect related to the drug was detected., Conclusions: Treatment with adefovir dipivoxil for 2 years in mono-therapy in patient who are previously non-responders to lavimudine is associated with a high biochemical and virologycal response with an excellent safety. At the second year of treatment, the adefovir dipivoxil resistance rate is 20%.

Background & Aims: Patients with chronic hepatitis C who do not respond rapidly to therapy have a low chance of developing a sustained virologic response (SVR) when treated for 48 weeks. This study investigated whether treatment for 72 weeks increases the rate of SVR in patients with detectable hepatitis C virus (HCV)-RNA levels at week 4 of treatment., Methods: A total of 510 treatment-naive patients were treated with peginterferon-alfa2a (180 microg/wk) plus ribavirin (800 mg/day). Patients with detectable HCV-RNA levels at week 4 (n = 326) were randomized to complete 48 (group A, n = 165) or 72 weeks (group B, n = 161) of treatment. Patients with undetectable HCV-RNA levels at week 4 (n = 184) were allocated into group C (n = 148) or group D (n = 36), according to HCV genotype and baseline viremia, and treated for 24 or 48 weeks, respectively. All patients were followed-up for 24 weeks after the end of treatment., Results: The end-of-treatment response rate (61%) was similar in groups A and B, but the SVR rate was higher in group B (45% vs 32% in A; P = .01). In genotype 1-infected patients randomized to group A (n = 149) or B (n = 142), SVR rates were 28% and 44%, respectively (P = .003). The incidence of adverse events was similar in all groups. Treatment discontinuation was more frequent in group B (36%) than in group A (18%) (P = .0004). SVR rates in groups C and D were 79% and 64%, respectively., Conclusions: Extension of treatment with peginterferon-alfa2a plus ribavirin from 48 to 72 weeks significantly increases the rate of SVR in patients with detectable viremia at week 4 of treatment.

Purpose: To evaluate the accuracy of magnetic resonance (MR) imaging in the quantification of hepatic iron concentration., Materials and Methods: Between April 1999 and June 2001, 112 patients were recruited prospectively. All had undergone liver biopsy and hepatic iron concentration quantification with spectrophotometry, followed by MR imaging. MR imaging involved use of four gradient-echo sequences and one spin-echo sequence. Signal intensity (SI) was measured on images obtained with each sequence by means of regions of interest placed in the liver and paraspinal muscle to obtain the liver-to-muscle SI ratio. The relationship between hepatic iron concentration and SI ratio for each sequence was analyzed with multiple linear regression. Receiver operating characteristic analysis was performed to find the diagnostic thresholds., Results: Sixty-eight patients had normal hepatic iron levels (<36 micromol/g), 23 had hemosiderosis (36-80 micromol/g), and 21 had hemochromatosis (>80 micromol/g). With all sequences, an inverse linear relationship between iron concentration and SI ratio was apparent. The authors generated a mathematic model to estimate the iron concentrations from MR imaging data (r = 0.937). For estimated concentrations of more than 85 micromol/g, the positive predictive value for hemochromatosis was 100%; for those less than 40 micromol/g, the negative predictive value for hemochromatosis was 100%. For estimated concentrations of more than 58 micromol/g, the positive predictive value for iron overload was 100%; for those less than 20 micromol/g, the negative predictive value for iron overload was 100%., Conclusion: MR imaging is a useful and noninvasive diagnostic tool for quantification of hepatic iron concentration., (Copyright RSNA, 2003)

In order to analyse the prevalence and significance of cryoglobulinaemia in patients with chronic hepatitis C virus (HCV) infection and the possible relationship of cryoglobulinaemia with the genotypes of HCV, we studied 89 patients with chronic HCV infection, 42 healthy controls and 22 patients with alcoholic cirrhosis. The patients with HCV were divided into three different groups according to the presence of cirrhosis and alanine aminotransferase levels. Moreover, in 20 patients with HCV and cryoglobulinaemia, HCV RNA sequences were quantified in serum and in cryoprecipitate. Cryoglobulins were detected more frequently in patients with chronic HCV infection than in healthy controls (42.6% vs. 4.7%; P<0.0001). Cryoglobulins were present in 68.4% of patients with HCV-related cirrhosis, which was nearly twice the figure in noncirrhotic HCV-infected patients and alcoholic cirrhotic patients. There were no differences in age, sex, aminotransferase levels or HCV genotype distribution in HCV-infected patients with or without cryoglobulinaemia. Only 13% of patients with chronic HCV infection and cryoglobulins showed symptoms of cryoglobulinaemia. There was a linear association between HCV RNA concentration in sera and in cryoprecipitates (P<0.0005). Patients with chronic HCV infection had a high prevalence of cryoglobulinaemia, especially in advanced forms of the disease, but clinical findings are few. There was no relationship with the genotype of HCV. The presence of HCV RNA in cryoprecipitates supported the hypothesis on the aetiological role of HCV in mixed cryoglobulinaemia.

Objective: We aimed to investigate the modifications of HCV RNA (genomic and antigenomic strands) in peripheral blood mononuclear cells (PBMCs) of long-term responder patients to alpha-interferon therapy, and their usefulness as criteria of definitive HCV eradication., Methods: We studied 10 patients with chronic hepatitis C with > 1 yr of sustained response after alpha-interferon therapy (normal alanine aminotransferase [ALT] and negative serum HCV RNA). Serum HCV RNA and genotyping were determined. Approximately 2 and 4 yr after completion of treatment we investigated the presence of HCV RNA (genomic and antigenomic strands) in PBMCs. Eight of 10 patients were rebiopsed 2 yr after discontinuation of treatment., Results: The mean follow-up was 46.6 +/- 4.6 months (range, 39-51 months). In this period, all patients remained in sustained response. In the first determination, all patients had HCV RNA genomic strands and two patients had antigenomic strands detectable in PBMCs. Two years later only two patients had genomic and none had antigenomic strands detectable. After 4 yr of sustained response, eight of 10 patients lost HCV RNA from PBMCs., Conclusions: In the long-term follow-up, the majority of patients with chronic hepatitis C with sustained response after alpha-interferon therapy progressively lost HCV RNA from PBMCs. This determination in PBMCs is not a predictor of response.

We report two cases of acute hepatotoxicity after treatment with amoxicillin-clavulanic. Viral hepatitis serology and autoantibodies were negative. Biliary tree obstruction and other etiologies were excluded. After discontinuation of the drug the evolution was favorable with clinical improvement and normalization of liver tests. Liver biopsy made in one patient showed cholestasic hepatitis with hepatocellular necrosis and other patient was treated with ursodeoxycholic. Also, we analyse potential utility of ursodeoxycholic acid administration in toxic cholestasis.

Background/aims: To investigate the possible role of HIV infection in the natural history of chronic parenterally-acquired hepatitis C., Methods: A multicenter cross-sectional study was performed in 547 patients with chronic parenterally-acquired hepatitis C with or without HIV infection (116 HIV-positive and 431 HIV-negative). Approximate duration of HCV infection was estimated in all patients included, and histologic diagnoses made at different time intervals following HCV infection were analyzed in both groups. Factors related to serum HCV-RNA levels were also investigated., Results: Histologic findings were similar in liver biopsies from both HIV-infected and noninfected patients. However, in the first 10 years, 13 out of 87 (14.9%) HIV-positive subjects developed cirrhosis, in comparison with 7 out of 272 (2.6%) in the HIV-negative group (p < 0.01). Similar results were found in the first 5 and 15 years, respectively, and most of the HIV-negative patients with cirrhosis (42 out of 56) developed cirrhosis in a time interval longer than 15 years. Consequently, mean interval from estimated time of HCV infection to cirrhosis was significantly longer in HIV-negative than HIV-positive patients (23.2 vs. 6.9 years; p < 0.001). Chronic active hepatitis (with and without cirrhosis) and long duration of HCV infection were significantly associated with higher HCV load (p < 0.05). Finally, HIV-positive patients with CD4+ cell counts > 500 cells/ml showed a lower HCV load than those with < 500 cells/ml (p < 0.05)., Conclusions: HIV infection modifies the natural history of chronic parenterally-acquired hepatitis C with an unusually rapid progression to cirrhosis. HIV-related immunodeficiency may be a determinant of higher hepatitis C viremia levels and more severe liver damage.

Aim: To investigate serologic changes and risk of reactivation in hepatitis B chronic carriers., Patients and Methods: Two hundred chronic HBs-Ag positive patients were included (follow-up greater than 18 months). According to the HBeAg/Anti-HBe status at the moment of inclusion they were classified in 3 groups: I: 40 patients HBeAg positive, II: 158 anti-HBe positive and III: 2 HBeAg/Anti-HBe negatives. All patients were screened in the follow-up for biochemical test, hepatitis B, C and D virus serology, DNA.HBV by hybridization, alpha fetoprotein and abdominal ultrasound., Results: Mean age was 35 +/- 12 years (14-61), and mean follow-up 71 +/- 35.1 months (18-252). In the follow-up 28 patients in group I seroconverted HBeAg/Anti-HBe, 18 spontaneously (annual rate 10%). In group II four patients out off 158 were DNA HBV positive. Only 3 chronic HBV carriers lost HBsAg and developed Anti-HBs (annual rate 0,25%). Reactivation of viral activity was detected in 13 patients Anti-HBe positive, DNA.HBV negative. HBeAg appeared during reactivation in six, both HBeAg/Anti-HBe were negative in one, and six were unchanged. Reactivation was significantly more frequent in chronic carriers with high GPT activity (13 out off 75, 17.3%) than in patients with normal GPT (0 out off 107, 0%) (p < 0.0005)., Conclusions: Reactivation of HBV activity is frequent in HBsAg chronic carriers Anti-HBe positive, DNA.HBV negative and who are abnormal GPT levels; these patients should be considered at risk of reactivation. The control in the follow-up of HBV chronic carriers with persistently normal GPT, without advanced liver disease, may not be so frequent. The increased infectiousness during reactivation of HBV activity must be taken account for prophylaxis of HBV infection in chronic carriers contacts.

Pyogenic liver abscess is a relatively rare disease, often concerning elderly patients in bad general condition and with underlying diseases. We report the case of a 77-year-old female with gastric cancer and liver abscesses by Streptococcus anginosus.

Objective: To assess the prevalence of hepatitis C virus (HCV) antibodies in patients attending a trauma unit or admitted to hospital for elective surgery, and to identify risk factors for acquiring HCV infection., Design: A cross-sectional study., Setting: The emergency room of a Department of Orthopaedic Surgery and a hospital for elective (non-digestive) surgery., Patients: A study population of 1824 subjects (mean age 40.1 +/- 18.1 years) and sera from a control group of 4703 blood donors giving their first donation., Interventions: Serum samples were screened for HCV antibodies by second-generation enzyme-linked immunosorbent assays and recombinant immunoblot assays., Main Outcome Measures: HCV serostatus and the relationship between anti-HCV-positivity and age, intravenous drug use, tattoos, blood transfusion, a history of hepatitis and exposure to a contact who had had hepatitis., Results: The overall prevalence of anti-HCV antibodies was 2.85% in the study population and 0.5% among blood donors (chi 2 = 64.5; P < 0.0001). Anti-HCV-positivity was more common in men (3.8 versus 1.9%; P < 0.05) and in subjects with history of hepatitis (13.5 versus 2.0%; P < 0.001), exposure to a contact who had had hepatitis (12.5 versus 1.9%; P < 0.001), blood transfusion (7.8 versus 2.3%; P < 0.001), tattoos (36 versus 2.4%; P < 0.001) and intravenous drug use (85.7 versus 1.9%; P < 0.001). However, one third of subjects had no risk factors for HCV infection. The logistic regression analysis confirmed a statistically significant association (P < 0.05) between anti-HCV-positivity and intravenous drug use, tattoos, blood transfusion, a history of hepatitis and exposure to a contact who had had hepatitis., Conclusions: These results show almost a five-fold higher prevalence of anti-HCV among patients attending a trauma unit or admitted to hospital for elective surgery than among blood donors.

We present the case of a patient with alcoholic chronic pancreatitis who developed pancreatic ascites. The analysis of ascitic fluid was diagnostic; and ERCP showed one fistula in the pancreatic head to the peritoneal cavity. The patient was treated by continuous somatostatin infusion (250 micrograms/h) for 15 days resulting in the disappearance of the ascites and avoiding the risky surgical therapy.

To investigate the response of mentally retarded individuals (MR) with Down's syndrome (Down-MR) to recombinant hepatitis B vaccine, three doses (20 micrograms per dose) were administered on the usual schedule (months 0, 1 and 6) to two groups of MR with mean age of 14.6 years. The first group consisted of 32 MR-Down. The second group consisted of 35 MR other etiologies (non Down-MR). Both had the same sex distribution and similar ages and weight/height index. The post vaccination anti-HBs titers were measured on months 1, 2, 6 and 8. The results could be analysed in 63 MR. Eight months after vaccination, 100% of Down-MR and 91% of non Down-MR developed a response to the vaccine (anti-HBs greater than 10 IU/l). Both groups achieved high antibody titers (geometric mean 4.298 and 6.424, respectively). A significant inverse correlation of anti-HBs with age was found, but not with sex of with the weight-height index. It was concluded that Down-MR in young age have a normal response to recombinant hepatitis B vaccine at the usual dose and schedule. Therefore, the goal to suppress the reservoir of hepatitis B in Down-MR both in institutions for MR and in normal schools should be achieved.