Recurrent HCV hepatitis after liver transplantation.
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Biomedical subjects
Publications and source records attributed to A Alberti.
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Neurological complications of cyclosporin (CyA) therapy are frequent, usually occurring within the 1st month after transplantation. Though leukoencephalopathy is one of them, it is rarely documented. Here we report the case of an anti-HCV-positive patient with cirrhosis who underwent liver transplantation and developed cyclosporin-induced leukoencephalopathy. The presenting symptoms were dysarthria, difficulty walking, and dysphagia. They were first noted 6 months after transplantation in association with an episode of recurrent HCV acute hepatitis. White matter abnormalities were evident on computed tomography (CT) scanning and magnetic resonance (MR) imaging. This condition improved to some degree after cyclosporin withdrawal. To our knowledge this is the second reported case of CyA neurotoxicity occurring late after liver transplantation. Moreover, the association with acute hepatitis suggests the possibility of graft dysfunction as a contributing and triggering factor.
Expression of cytokeratins no. 7 and no. 19, typical of the mature biliary tract and of embryonic and fetal hepatocytes, has been evaluated in primary liver tumors from 12 children. Of 7 children with hepatoblastoma, 6 were strongly reactive for cytokeratin no. 19 and only 4 were weakly positive for cytokeratin no. 7. In contrast, the remaining tumors, including 2 hepatocarcinomas, 1 sarcoma, 1 hamartoma and 1 hemangioma were positive for cytokeratin no. 7, while cytokeratin 19 was present in 1 hepatocarcinoma and in the hamartoma. All these tumors, as well as 1 hepatoblastoma and the sarcoma, were also reactive for cytokeratin no. 8, typical of hepatic cells.
BACKGROUND: The "in vivo" interplay between hepatitis B virus (HBV) and hepatitis C virus (HCV) both in terms of replication activity and cytopathic effect on liver cells is poorly understood. The aim of the study was to investigate their reciprocal influence in patients with HBV and HCV coinfection. METHODS: HBV and HCV genomic sequences in the serum and liver of 55 patients with chronic liver disease who were positive for anti-HCV and for markers of HBV were studied. RESULTS: Twenty-five hepatitis B surface antigen-positive patients, without markers of hepatitis D virus (HDV) infection, showed an inverse relation between seropositivity for HCV RNA and for HBV DNA (P < 0.001). HCV genomic sequences were detected in the liver of all patients positive for HBV DNA but negative for HCV RNA in serum. The biochemical activity and the histological severity of liver disease were lower in HCV RNA-positive/HBV DNA-negative patients, compared with HCV RNA (serum)-negative/HBV DNA-positive cases (P < 0.005). Nine of 10 patients with concurrent HDV infection were negative for serum and liver HCV RNA. None of 20 hepatitis B surface antigen-negative/HCV RNA-positive patients with antibodies to HBV had HBV DNA detectable in serum or liver. CONCLUSIONS: Our findings indicate a reciprocal inverse relation between HBV and HCV replication. Patients positive for antibody to HCV with antibodies to HBV usually have no evidence of HBV DNA persistence in the liver.
A 14-year-old girl with chronic hepatitis B had seroconversion from hepatitis B e antigen to antibody and achieved biochemical remission after 2 years. The disease reactivated 9 years later when a precore mutant had become the prevalent hepatitis B virus strain in serum. These results suggest that selection of a precore mutant might induce reactivation during adult life of chronic hepatitis B acquired in childhood, thus worsening the prognosis.
Two hundred and thirty-four patients with chronic non-A, non-B hepatitis, 86% positive for anti-HCV by ELISA, were treated with recombinant interferon-alpha 2a or with natural (human-leukocytes-derived) interferon-alpha using different dosage and periods of administration. Interim analysis of follow-up data indicate that 65-70% of patients treated initially with 6 MU, thrice weekly, of recombinant interferon-alpha 2a achieved a complete biochemical response (normalization of alanine aminotransferase: ALT) during therapy compared to 56-58% of those treated with 3 MU, thrice weekly, of recombinant or natural interferon-alpha. A 12-month schedule of interferon administration appeared superior to a 6-month schedule in reducing the probability of reactivation of liver disease after therapy withdrawal, although further data are needed to confirm such a conclusion. The probability of response to interferon in terms of maintaining normal ALT after withdrawal did not appear to be influenced by sex, while it was significantly higher in patients aged below 45 years and in those without cirrhosis.
Fifteen patients with B-cell chronic lymphocytic leukemia (B-CLL) have been treated with alpha 2b-interferon (alpha IFN) for one year (3 mega units subcutaneously three times a week). The hematological response and the modulation of immunophenotype, serum levels of soluble interleukin-2 receptor (sIL-2R) and tumour necrosis factor (TNF) have been monitored. Hematologically 67% of cases were classified as responders, although no complete responses were observed; three cases progressed during treatment, and two patients showed stable disease. Both peripheral lymphocytes and CD24+ cell absolute number significantly decreased after twelve months of IFN treatment (40.7 +/- 17 x 10(9)/l versus 15.8 +/- 6 x 10(9)/l, mean values +/- sd, p < 0.01, and 30.4 +/- 5.5 x 10(9)/l versus 8.1 +/- 2.8 x 10(9)/l, p < 0.05, respectively), while CD24+ cell percentage did not change (72.1% +/- 4.6 versus 67.5% +/- 8.8, p not significant). In the majority of cases myelomonocytic markers (CD11c, CD14, CD11b) transitorily decreased during the treatment. Serum sIL-2R levels, elevated in all cases before IFN treatment, increased in responders. Serum TNF levels decreased in patients showing high values before the treatment. The explanation of these findings and their possible implication are discussed.
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We performed continuous echocardiographic examination during the i.v. administration of rtPA in three patients with recent-onset, mobile right atrial thrombosis, in order to assess both the timing and mode of thrombus resolution. In all these cases, right atrial thrombus disappeared before the scheduled dose (100 mg i.v. within three hours) was completed: 60 mg of rtPA were required in the first patient, and 50 mg in the other two. In the first case, the thrombus divided into numerous smaller fragments chaotically moving in the right chambers before disappearing; in the second, the echo reflectivity of the thrombus gradually diminished and the mass showed multiple echo-lucent cavities before disappearing; in last case, the atrial mass migrated from the right atrium to the right ventricle before disappearing. None of the patients experienced any symptoms at the dissolving of the thrombus; bleeding complications occurred in all three (in one, at the site of previous PTCA; in another, at the site of arterial and venous puncture; in the third the haematoma was localized at the site of a previous orthopedic operation) but only two required blood transfusion. In patients with right atrial thrombosis, continuous echocardiographic examination allows us to identify both the timing and mode of thrombus resolution, and the occurrence of new-onset peripheral pulmonary embolization. This information can help in optimizing the dosage of the drug in patients in whom bleeding complications can be suspected to occur after thrombolytic therapy.
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Patients with hepatitis C virus infection may have circulating antibodies to various structural and nonstructural antigens of the virus. To assess whether the antibody profile is related to epidemiological or clinical features of chronic infection or to viral replication, sera from 172 consecutive patients with biopsy-proven chronic non-A, non-B hepatitis were studied for antibodies to nonstructural and structural hepatitis C virus antigens and for serum hepatitis C virus RNA with the polymerase chain reaction using primers derived from the 5' noncoding region. Three subgroups could be identified on the basis of their seroreactivity to hepatitis C virus: 133 cases (77.3% [group A]) were positive on first- and second-generation assays and had antibodies to C100-3 and to C22, C33c or both identified on recombinant immunoblot assay; 23 cases (13.4% [group B]) were positive only on second-generation assay and reacted with C22, C33c or both but not with C100-3; and 26 cases (9.3% [group C]) were negative for all hepatitis C virus antibodies. Mean age and sex distributions were similar among the three groups; a history of transfusion was more frequent among cases in group B (p = 0.06). These patients also had the highest serum aminotransferase values (p = 0.001). Liver histological studies showed active necroinflammatory changes in 69.2% of patients in group A and 52.2% of those in group B but only in 25% of cases in group C. Serum hepatitis C virus RNA was frequently detected in patients of groups A and B, independent of their recombinant immunoblot assay profiles.(ABSTRACT TRUNCATED AT 250 WORDS)
We employed the so-called event-correlated potential (ECP) P300, a neurophysiological test which explores the circuits of attention and memory in the brain and is altered in subjects with a dismetabolic or degenerative encephalopathy, in order to evaluate the cognitive faculty in two groups of uremic patients [18 on continuous ambulatory peritoneal dialysis (CAPD), 15 on hemodialysis (HD)] comparable with respect to age and time on dialysis. The values of latency (msec) of P300 resulted in CAPD patients 356 +/- 26 in CZ (central zero electrodes) and 357.5 +/- 25 in PZ (parietal zero electrodes), not significantly different from the values in normal controls (341 +/- 14.5 in CZ and 340 +/- 15.6 in PZ) and in HD patients postdialysis (354 +/- 24.4 in CZ and 354 +/- 25.6 in PZ). On the contrary, the predialytic values of HD patients (384 +/- 25.6 CZ and 385 +/- 25.5 in PZ) were significantly different from the postdialytic values and from the values of CAPD patients and controls (p < 0.01). These results support the conclusion that HD is able to restore a normal cognitive faculty only transiently in the postdialytic phase, while CAPD maintains this important function steadily close to the normal range, thus being clearly better than HD.
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There is controversy about clinical management of patients who persistently have antibodies to hepatitis C virus (anti-HCV) but who have no symptoms and signs of liver disease. We have taken liver biopsy samples from 23 such patients (16 of whom had normal alanine aminotransferase [ALT] values) to assess prevalence of liver disease and to see whether anti-HCV and HCV-RNA correlated with histological findings. 16 patients had histological evidence of chronic hepatitis, which was not predicted by serum ALT or by the pattern of specificity of anti-HCV. All 16 cases with hepatitis C viraemia (HCV-RNA detected by polymerase chain reaction), including 9 with normal ALT, had chronic hepatitis on biopsy (p less than 0.001), whereas 7 HCV-RNA-negative cases had normal liver histology. These findings indicate that serum HCV-RNA is a sensitive and specific marker of liver disease in anti-HCV-positive subjects, independent of ALT values, and challenge the idea of the existence of "true" healthy carriers of HCV.
The presence of hepatitis B virus (HBV) has been evaluated in liver specimens from 11 children with primary liver tumors and negative results of serologic testing for HBV markers. HBV-DNA sequences were detected by the polymerase chain reaction procedure, using different sets of oligonucleotide primers from highly conserved regions of HBV genome. Two of three children with histologic diagnosis of hepatocellular carcinoma were positive for HBV-DNA in the liver, whereas the remaining children, including six patients with hepatoblastoma, one patient with hemangioma, and one patient with hamartoma, were negative. These findings support the hypothesis of a primary role of HBV in the development of hepatocellular carcinoma in children from nonendemic areas and without overt HBV infection.
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Thirty-two patients with chronic hepatitis B treated with alpha interferon were tested for 12 different antibodies. Only a minority (18%) of cases developed antinuclear antibodies and none developed clinical signs of autoimmune disease. These data suggest that, at the dose regimen used, interferon therapy of chronic hepatitis B is not associated with triggering of autoimmunity.
In a randomized controlled trial of Interferon (IFN) in 60 patients (30 treated and 30 controls) with cryptogenic chronic active liver disease, 70% of treated patients showed complete response, but a high rate of biochemical relapse (62%) was noted. In these cases, a second response to higher doses of IFN has been more difficult and less frequent. A response to IFN was found in 88.5% of anti-HCV positive treated patients and only in 25% of anti-HCV negative. We suggest that serum anti-HCV is a suitable test to predict the response to IFN.