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Biomedical subjects

F Bonino

Publications and source records attributed to F Bonino.

At least 55 records · Page 3Linked to original sources
PubMed1997

Liver targeting of antiviral nucleoside analogues through the asialoglycoprotein receptor.

In order to reduce the extrahepatic side-effects of antiviral nucleoside analogues in the treatment of chronic viral hepatitis, these drugs are conjugated with galactosyl-terminating macromolecules. The conjugates selectively enter hepatocytes after interaction of the carrier galactose residues with the asialoglycoprotein receptor present in large amounts and high affinity only on these cells. Within hepatocytes the conjugates are delivered to lysosomes where enzymes split the bond between the carrier and the drug, allowing the latter to become concentrated in the liver. The validity of this chemotherapeutic strategy has been endorsed by a clinical study. Adenine arabinoside monophosphate (ara-AMP), conjugated with lactosaminated human serum albumin (L-HSA) and administered to hepatitis B virus (HBV)-infected patients for 28 days, exerted an antiviral activity to the same extent as the free drug without producing any clinical side-effects, including the severe neurotoxicity caused by the free drug. Preclinical studies are now underway with conjugates obtained using lactosaminated poly-L-lysine (Lac-poly(Lys)) as the hepatotropic carrier. These new conjugates have some advantages over those prepared with L-HSA: they can be administered by the intramuscular route; they are obtained entirely by chemical synthesis, thus eliminating the problems involved in the use of haemoderivatives; they have a heavy drug load, which permits administration of smaller quantities of conjugate that are more easily digested in lysosomes; and they enable higher quantities of drug to be introduced into hepatocytes. The results of the experiments with two Lac-poly(Lys) conjugates, one with ara-AMP and one with ribavirin, are reported in this review.

Animals↗
PubMed1997

IgM antibody against measles virus in patients with inflammatory bowel disease: a marker of virus-related disease?

OBJECTIVE: Viral infections of the mesenteric microvascular endothelium have been hypothesized as pathogenetic factors in inflammatory bowel diseases. The aim of this study was to determine whether immunoglobulin M (IgM) antibody against measles virus is associated with disease. PATIENTS AND METHODS: The IgM antibody was detected by indirect antibody test in 36 patients with evidence of Crohn's disease (23 males and 13 females, median age 40 years, range 20-66), 22 patients with ulcerative colitis (14 males and 8 females, median age 42 years; range 19-65), 59 patients with a chronic active hepatitis (35 males and 24 females, median age 56 years, range 38-77) and 30 blood donors (20 males and 10 females, median age 45 years, range 29-62). RESULTS: Twenty-eight of 36 patients (78%) with Crohn's disease and 13 of 22 patients (59%) with ulcerative colitis tested positive as compared to only 3 of 89 (3.3%) controls (P < or = 0.001). CONCLUSION: The detection of IgM anti-measles virus in the majority of patients with Crohn's disease and in about half of ulcerative colitis patients as compared to a very low prevalence in patients with other chronic inflammatory disease is consistent with the hypothesis that the measles virus has pathogenetic implications in inflammatory bowel diseases.

Adult↗
PubMed1997

A new hepatitis C virus-like flavivirus in patients with cryptogenic liver disease associated with elevated GGT and alkaline phosphatase serum levels.

The intriguing co-infection of two flaviviruses (GBV-A and GBV-B) in tamarins and the recent discovery of another flavivirus (GBV-C/HGV) in humans raises the question of the relations between hepatitis C virus (HCV) and GBV-C/HGV. To address this issue the sera of 285 patients with liver disease (102 patients with cryptogenic and 183 with known forms of chronic liver disease) and 19 patients without liver disease were tested for HGV-RNA. GBV-C/HGV-RNA was detected by RT-PCR using primers encompassing 5'NC and NS5 regions and hybridization with specific biotinilated and radiolabelled probes. GBV-C/HGV RNA was found in 11 of 20 (55%) acute hepatitis C patients, in 13 of 117 (11.1%) patients with chronic hepatitis C, in 11 of 27 patients with a liver transplant (40.7%), one of 19 (5.3%) patients with chronic HBV infection, 15 out of 102 (14.7%) patients with cryptogenic liver disease and two out of 19 patients with inflammatory bowel disease. In cryptogenic patients, elevated serum gammaglutamyl transpeptidase (GGT, higher than twice the normal values) and alkaline phosphatase (ALP, above normal values) levels were significantly associated with GBV-C/HGV-RNA infection (P < 0.001). In conclusion GBV-C/HGV appears to be transmitted in humans by blood exposure and to be associated with liver disease in HCV co-infected patients and in a minority of patients with cryptogenic disease. The virus is only occasionally pathogenic for the liver and when liver damage is present; the association with the combined elevation of GGT and APH serum levels might represent a specific feature of the liver tropism of the agent.

Adolescent↗
PubMed1997

Impact of interferon-alpha therapy on the development of hepatocellular carcinoma in patients with liver cirrhosis: results of an international survey.

Clinico-epidemiological data show that the most severe forms of hepatitis C virus (HCV) associated liver disease occur in patients with multifactorial liver damage. We found that the prevalence of hepatitis B virus (HBV) markers in anti-HCV positive patients with cirrhosis complicated by hepatocellular carcinoma (HCC) is higher than in cirrhotics with comparable age and disease history, but without HCC. HBV can persist in integrated forms in HBsAg negative, anti-HBc positive individuals and we may speculate that in such patients concurrent liver pathogens, as HCV, could cause HCC more easily than in patients without previous exposure to HBV. Analysing the relations between age at HCC diagnosis and the different risk factors in consecutive HCC patients we found that patients with single hepatitis virus infections (HBsAg and/or anti-HCV positive) were of an older median age than patients with multiple hepatitis virus infections. We also studied patients with compensated cirrhosis and hepatitis virus infections. untreated or treated with interferon-alpha. The independent effect of treatment was analysed by matching groups with regard to all the other significant HCC risk factors. The overall relative HCC risk was three times higher (risk ratio 3.1) in untreated vs treated anti-HCV positive patients and more than six times higher (risk ratio 6.2) in untreated vs treated anti-HCV positive/anti-HBc negative patients. The difference between treated and untreated patients was not statistically significant in hepatitis B surface antigen carriers and in anti-HCV positive/anti-HBc positive patients. The evidence that HBV coinfection may worsen the course of liver cirrhosis in patients with chronic hepatitis C is intriguing, but it has important practical consequences. It warrants the identification of high risk patients with chronic hepatitis C who need to be treated as early as possible and patients who can still benefit from interferon-alpha therapy once cirrhosis has already been diagnosed.

Carcinoma, Hepatocellular↗
PubMed1997

Human CD4+ T-cell response to hepatitis delta virus: identification of multiple epitopes and characterization of T-helper cytokine profiles.

The T-cell-mediated immune response plays a crucial role in defense against hepatotropic viruses as well as in the pathogenesis of viral chronic hepatitides. However, very little is known about the role of specific T cells during hepatitis delta virus (HDV) infection in humans. In this study, the T-cell response to HDV in chronic hepatitis B virus (HBV) carriers with HDV superinfection was investigated at different levels. Analysis of peripheral blood mononuclear cell (PBMC) proliferation in response to a recombinant form of large hepatitis delta antigen (HDAg) revealed that 8 of 30 patients studied (27%) specifically responded to HDAg. By employing synthetic peptides spanning the entire HDAg sequence, we found that T-cell recognition was directed against different antigenic determinants, with patient-to-patient variation in the pattern of response to peptides. Interestingly, all responders had signs of inactive HDV-induced disease, while none of the patients with active disease and none of the control subjects showed any significant proliferation. More accurate information about the specific T-cell response was obtained at the clonal level. A panel of HDAg-specific CD4+ T-cell clones from three HDV-infected individuals and fine-specificity analysis revealed that the clones tested individually recognized four epitopes corresponding to amino acids (aa) 26 to 41, 50 to 65, 66 to 81, or 106 to 121 of HDAg sequence. The study of human leukocyte antigen (HLA) restriction revealed that peptides 50 to 65 and 106 to 121 were presented to specific T cells in association with multiple class II molecules. In addition, peptide 26 to 41 was efficiently generated after processing of HDAg through the endogenous processing pathway. Cytokine secretion analysis showed that all the CD4+ T-cell clones assayed were able to produce high levels of gamma interferon (IFN-gamma), belonging either to T helper-1 (Th1) or Th0 subsets and that some of them were cytotoxic in a specific assay. This study provides the first evidence that detection of a specific T-cell response to HDAg in the peripheral blood of individuals with hepatitis delta is related to the decrease of HDV-induced disease activity. The HDAg epitopes identified here and particularly those recognized by CD4+ T cells in association with multiple major histocompatibility complex class II molecules may be potentially exploited for the preparation of a vaccine for prophylaxis and therapy of HDV infection.

CD4-Positive T-Lymphocytes↗
PubMed1997

Relevance of inapparent coinfection by hepatitis B virus in alpha interferon-treated patients with hepatitis C virus chronic hepatitis.

The aim of the study was to investigate whether an "inapparent" coinfection by hepatitis B virus (HBV) in anti-HCV-positive chronic liver disease patients may influence interferon (IFN) response. Fourteen anti-HCV-positive, hepatitis B surface antigen (HBsAg)-negative but serum HBV-DNA-positive patients and 111 anti-HCV-positive, HBsAg-negative, and HBV-DNA-negative patients with chronic hepatitis were treated with 3 MU of recombinant alpha-2a IFN 3/week for 1.2 months. Serum HBV-DNA and HCV-RNA were determined before treatment, after 6-12 months, and at the time of alanine aminotransferase (ALT) flare-up by HBV polymerase chain reaction (PCR) and HCV PCR, respectively. IgM anti-HBc were tested using the IMx Core-M assay (Abbott Laboratories, North Chicago, IL). By the end of treatment, ALT values had become normal in 4/14 HBV-DNA-positive patients (28%), but all "responders" (4/4) relapsed. IgM anti-HBc was detected both before treatment and during ALT elevation in three patients and only during ALT relapse in another three. In the remaining 111 patients, a biochemical response to IFN treatment was observed in 54% and relapse of ALT values in 47%. "Inapparent" HBV/HCV coinfection may be implicated in cases of resistance to IFN. HBV replication and HBV-related liver damage may persist in patients in whom HCV replication was inhibited by current doses of IFN, as suggested also by the presence of IgM anti-HBc in some cases. Further studies will show the effect of different treatment schedules. HBV-DNA and/or IgM anti-HBc detection with very sensitive methods may be important both as a prognostic factor and as a tool for better understanding of intervirus relationships and mechanisms involved in multiple hepatitis virus infections.

Adult↗
PubMed1997

Clinical relevance of anti-interferon antibodies in the serum of chronic hepatitis C patients treated with interferon-alpha.

The development of anti-interferon (anti-IFN) antibodies in the serum of patients undergoing antiviral therapy has been postulated as one possible cause of interpatient variability in response to therapy. We analyzed the relationship between the appearance of anti-IFN antibodies and the loss of response to interferon-alpha (IFN-alpha), as characterized by a breakthrough of serum aminotransferase after a period of complete biochemical remission. The analysis involved clinical trials where neutralizing anti-IFN antibodies were detected by standardized and comparable methods. The results show that a time relationship between breakthrough and anti-IFN antibodies is observed in only a few cases and is independent of the type of IFN-alpha preparation used. Thus, causes of IFN resistance other than anti-IFN antibodies must also be implicated in most breakthrough cases. Another potential is the selection of drug-resistant viral strains. Current ration behavior following the appearance of breakthrough (from whatever cause) in clinical practice advocates changing treatment to a different type of IFN-alpha. The detection of anti-IFN enzyme-linked immunosorbent assay (ELISA) antibodies or IFN neutralizing antibodies does not appear to provide any additional information for decision making.

Alanine Transaminase↗
PubMed1997

Platelet and white blood cell counts during therapy with different types of alpha interferon in patients with chronic viral hepatitis. Investigators of the Alpha Interferon Study Group of Piemonte, Italy.

BACKGROUND: Platelet and white blood cell counts decrease in chronic viral hepatitis patients treated with alpha interferon. AIM: To analyse whether delta negative variations in platelets and white blood cells are influenced by type, dose and duration of alpha interferon treatment, we studied 340 consecutive patients (mean treatment 8 months, range 4-18 months). PATIENTS AND METHODS: A total of 204 (60%) patients were treated with recombinant alpha interferons (30% alpha-2a and 30% alpha-2b), 64 (19%) with N3.leukocytic and 72 (21%) N1.lymphoblastoid natural interferons. Median age and male/female ratios were comparable in the 3 groups (41, 41 and 43 years and 2.3, 2.6 and 2.5, respectively). The lowest platelets and white blood cells counts were observed between the 2nd and the 4th month of therapy in all patients. Age, sex, aetiology and duration of interferon therapy did nor influence the platelets and white blood cells reduction rates. The decrease was lower for patients treated with N3.leukocytic interferon than for the other interferons. A significant difference was observed between interferon doses when the groups treated with 3 or 9-10 MIU were compared. However, dose or cirrhosis-related bias are ruled out by similar proportions of cirrhosis and patients treated with 3 MIU in the 3 groups of patients treated with different types of interferon. CONCLUSIONS: The type of interferon appears to represent a major cause of the different haemopoietic toxicity. The lowest toxicity of N3.leukocytic interferon may have clinical implications for the choice of interferon in patients with low baseline platelets and white blood cells counts. These findings prompt prospective studies on larger series of patients.

Adult↗
PubMed1997

Intrahepatic expression of c-fos, c-myb and c-myc oncogenes: correlation with virus-induced chronic liver disease and response to interferon.

BACKGROUND & AIMS: Oncogenes were activated in experimental models of hepatocyte regeneration. We studied the intrahepatic expression of c-fos, c-myb and c-myc protooncogenes in 117 patients with chronic liver disease: 12 with hepatitis B, 15 HBsAg carriers, 73 with hepatitis C and 17 with non-viral liver damage. METHODS: Oncoproteins were detected by indirect immunofluorescence using high affinity and monoclonal antibodies. Grade and stage of liver damage were measured by numerical score. RESULTS: Nuclear c-fos and/or c-myb were found in 7 (58.3%) hepatitis B patients, in 38 (52%) hepatitis C patients, in 1 (6.6%) HBsAg carrier (p < 0.004) and in none of the non-viral disease patients (p < 0.0001). In no case was c-myc detected. Oncoproteins were correlated with the histological activity index (p < 0.0001) and its components: lobular degeneration and periportal necrosis (p < 0.0001), fibrosis (p < 0.005) and portal inflammation (p < 0.03). Thirty-one chronic hepatitis C patients were treated with alpha-IFN: 9 out of 14 oncoprotein-positive patients (64%) were non-responders, 5 (36%) relapsed and none was a sustained responder. Conversely 9 out of 17 (53%) oncoprotein-negative patients, including 3 patients with histologically active cirrhosis, showed long-term response (p < 0.005). CONCLUSIONS: Intrahepatic c-fos and c-myb were detected in chronic viral hepatitis patients, but not in non-viral liver diseases. Their expression correlated with the grade and stage of liver disease and with poor response to alpha-IFN.

Adult↗
PubMed1996

Adenine arabinoside monophosphate coupled to lactosaminated human albumin administered for 4 weeks in patients with chronic type B hepatitis decreased viremia without producing significant side effects.

A conjugate of adenine arabinoside monophosphate (ara-AMP) with the liver-targeting molecule lactosaminated human serum albumin (L-HSA) was administered by intravenous infusion for 28 days to eight patients with chronic type B hepatitis. The daily dose varied among the patients, ranging from 34 mg/kg to 53 mg/kg (equal to 1.5 and 2.3 mg/kg ara-AMP, respectively). Pharmacokinetic analysis indicated that, at every dose tested, the conjugate was disposed of without accumulation. Viral DNA serum levels fell markedly during treatment; values rose again when treatment was ceased. The L-HSA-ara-AMP conjugate did not cause either the neurotoxic side effects of free ara-AMP or other adverse clinical reactions. It produced a significant increase both in serum alkaline phosphatase activity and platelet number, and a small but significant decrease in erythrocyte number. These laboratory parameters returned to normal levels within 2 months after treatment. The conjugate induced the production of small amounts of antibodies (approximately 20 pmol of conjugate bound by 1 mL of serum) in one patient only. In conclusion, the present results indicate that the L-HSA-ara-AMP conjugate can exert the antiviral activity of ara-AMP in chronic type B hepatitis patients without producing the neurotoxic side effects which hamper a 4-week period of treatment with the free drug.

Adult↗
PubMed1996

Demonstration of specific detection of anti-HCV IgM core antibodies.

The specificity of IgM isotype response directed against the putative core of hepatitis C virus (HCV core IgM) was demonstrated in HCV IgM EIA reactive samples. No interference was noted when samples with increasing levels of rheumatoid factor (RF) alone, or in combination with graded concentrations of anti-HCV IgG (HCV IgG), were tested. No deterioration in assay specificity was seen in 30 sera from patients wih monoclonal gammapathies (all isotypes). With Protein G affinity chromatography, RF/HCV IgG immune complexes and HCV core IgM antibodies displayed different binding characteristics, HCV core IgM appeared in the buffer eluate while HCV IgG/RF remained bound. With sucrose density gradient centrifugation HCV core IgM sedimented at 17-19S.

Antigens, Viral↗
PubMed1996

Quantitative analysis of IgM anti-HBc in chronic hepatitis B patients using a new "gray-zone" for the evaluation of "borderline" values.

BACKGROUND/METHODS: In order to define the clinical significance of borderline levels of IgM anti-HBc in chronic hepatitis B patients, we followed up 89 untreated hepatitis B patients (19 HBeAg pos and 70 anti-HBe pos) for 1 year, with monthly monitoring of IgM anti-HBc using a highly sensitive quantitative microparticle enzyme immunoassay (IMx CORE-M, Abbott). As a control group we used 304 healthy subjects: 150 HBsAg negative and anti-HBc/anti-HBs positive, and 154 without markers of HBV infection. The statistical analysis performed by Receiver Operating Characteristic curve indicated the 100% sensitivity cut-off at 0.081 IMx index and 100% specificity cut-off at 0.358 IMx index. RESULTS: We could define the range of a chronic hepatitis B "gray-zone" between 0.100 [80.6% specificity (95% CI, 76.2%-85%), 96.6% sensitivity (95% CI, 92.8%-100%)] and 0.200 [95.7% specificity (95% CI, 93.4%-98%) and 78.7% sensitivity (95% CI, 70.2%-87.2%)] of the IgM anti-HBc-IMx index. In fact, none of the chronic hepatitis B patients had IgM anti-HBc-IMx values persistently below 0.100 during the follow-up, whereas 57.3% had values persistently higher than 0.200. In 38.2%, IgM anti-HBc values occasionally fell within the "gray-zone" limits. In the remaining four patients (4.4%), the results overlapped the "gray-zone" values. CONCLUSIONS: These results suggest that the use of a chronic hepatitis B "gray-zone" for values of quantitative IgM anti-HBc assays helps to distinguish "true healthy carriers" from asymptomatic chronic anti-HBe positive hepatitis B patients who have been shown to have temporary remissions of liver disease and frequently undetectable serum HBV-DNA.

Adolescent↗
PubMed1996

High prevalence of autoimmune phenomena in hepatitis C virus antibody positive patients with lymphoproliferative and connective tissue disorders.

The aim of this study was to investigate whether hepatitis C virus (HCV) may perturb the immune system towards autoreactivity. We studied the relationship between the prevalence of anti-HCV and the presence of laboratory and/or clinical autoimmune features in 300 patients: lymphoid malignancies (167) and autoimmune disorders (connective tissue diseases 100; idiopathic thrombocytopenic purpura (ITP) 33). As a control, hepatitis B surface antigen (HBV) and anti-hepatitis B core antigen (anti-HBc) were related to the same parameters. Anti-HCV and anti-HBV were detected in 68/300 (22.6%) and 70/300 (24.6%) patients, respectively. HCV prevalence was 18% in lymphoproliferative disorders (anti-HBc 28.1%) and 26% in connective tissue disease (anti-HBc 16.3%). Among ITP cases, 12/33 (36.4%) were anti-HCV+ and 10/33 (30.3%) anti-HBc+. In 24/30 (80%) anti-HCV+ patients with lymphoproliferative disorders at least one serologic or clinical autoimmune abnormality was detected. To the contrary, only 10/45 (22.2%) anti-HBc+ patients with lymphoproliferative disorders had at least one serologic or clinical abnormality (P < 0.0001). A statistically significant correlation was observed between HCV prevalence and the number of autoimmune alterations in both lymphoproliferative and connective tissue disorders, which was not found for anti-HBc. These data suggest that HCV may skew the immune system toward the production of autoantibodies and also support the possibility that some cases of ITP may be linked to both HCV and HBV infection.

Adolescent↗
PubMed1996

Hepatitis G virus RNA in the serum of patients with elevated gamma glutamyl transpeptidase and alkaline phosphatase: a specific liver disease? [corrected].

We tested the sera of 67 consecutive patients for hepatitis G virus (HGV) RNA by reverse transcriptase-polymerase chain reaction (RT-PCR). These patients (42 males and 25 females, median age 35 years, range 13-64 years) had liver disease of unknown aetiology and were without markers of hepatitis (A-E) viruses or signs of genetically determined, autoimmune, alcoholic or drug-induced liver disease. The controls in this study were 110 patients (50 females and 60 males, median age 45 years, range 9-65 years) with chronic hepatitis B virus (HBV) infection (19 patients) or hepatitis C virus (HCV) infection (91 patients). Ten of 67 (14.9%) patients with cryptogenic disease were positive for HGV RNA by at least three separate tests; HGV RNA was also detected in one of 19 (5.3%) hepatitis B surface antigen (HBsAg) carriers and in nine of 91 (16.6%) patients with antibody to HCV. These data suggest that HGV occurs as frequently in HCV-infected patients as in those with cryptogenic disease. Elevated serum gamma glutamyl transpeptidase (gamma-GT) (higher than twice the normal value) and alkaline phosphatase levels were found in eight of 10 (80%) HGV RNA positive patients and in six of 57 (10.5%) HGV RNA negative patients (P < 0.0001). Five (50%) HGV RNA positive patients had non-specific inflammatory bile duct lesions. A statistically significant difference was observed between HGV RNA positive and negative patients with chronic HBV or HCV infections (P < 0.029). Therefore, the spectrum of liver disease associated with HGV is wide, but a characteristic lesion of the bile duct leading to elevation of cholestatic enzymes might be specific for this virus.

Adolescent↗
PubMed1996

Treatment of woodchuck hepatitis virus infection in vivo with 2', -3'-dideoxycytidine (ddC) and 2',-3'-dideoxycytidine monophosphate coupled to lactosaminated human serum albumin (L-HSA ddCMP).

Dideoxycytidine (ddC) is a nucleoside analogue active against human immunodeficiency virus and with in vitro activity against human hepatitis B virus. We investigated the ability of ddC to inhibit one of the Hepadnaviridae, the woodchuck hepatitis virus and compared the results with the effect obtained by a conjugate of lactosaminated human serum albumin 2',-3'-dideoxycytidine monophosphate (L-HSA ddCMP). This compound specifically enters the hepatocyte via the asialoglycoprotein receptor. We treated five chronic woodchuck hepatitis virus carriers with intravenous injections of 0.5 mg/kg body weight of ddC for 5 consecutive days, and under the same protocol five woodchucks with 10.4 mg/ kg L-HSA ddCMP, a dose equivalent to 0.25 mg/kg of free ddC. A reduction of serum woodchuck hepatitis virus DNA (5-125 fold) was observed during therapy in three out of five animals receiving ddC and in two of the five animals treated with L-HSA ddCMP. In responding woodchucks, virus DNA levels rebounded immediately after stopping therapy. No signs of toxicity were observed during or after the course of therapy. These preliminary results of short-term treatment indicate that ddC has anti-viral activity against woodchuck hepatitis virus. When the dose was reduced by 50%, L-HSA ddCMP showed anti-viral activity to an even lesser degree.

Animals↗
PubMed1996

Risk of HBV reinfection after liver transplantation in HBsAg-positive cirrhosis. Primary hepatocellular carcinoma is not a predictor for HBV recurrence. The European Cooperative Study Group on Liver Cancer and Transplantation.

Two hundred and twenty-eight patients who underwent orthotopic liver transplantation for hepatitis B-related cirrhosis in 11 European Liver Transplant Centers were collected. The male/female ratio was 184/44, with a median age of 41 years (13-66). In 55 patients (24%) hepatocellular carcinoma was associated with liver disease. All cases were stratified for pre-orthotopic liver transplantation viral characteristics: HBV-DNA neg/HBeAg neg: 106 patients (47%), HBV-DNA neg/Delta pos: 80 (35.5%), HBV-DNA pos/HBeAg pos: 28 (12.5%), other 14 (5%). In 49 patients (21.4%) post-orthotopic liver transplantation passive prophylaxis with anti-HBs immunoglobulins was not followed, while in 179 patients the anti-HBs serum titer was kept above 100-200 mU/ml. Overall 5-year actuarial survival of the series was 54%. One hundred and eighty-five patients were evaluable for HBsAg reappearance in the serum at various intervals after orthotopic liver transplantation. Overall 3-year HBV-free survival of these patients was 55%. There was a significant difference in 3-year HBV-free survival between HBV-DNA neg (52%), HBV-DNA pos (13%) and Delta pos (73%) patients (p: 0.03). Sixty-three percent of patients in the prophylaxis group were HBV-free, compared to only 25% of untreated patients (p < 0.001). Three-year HBV-free survival in patients with or without HCC was 44% and 59%, respectively. Cox-multivariate analysis revealed that only post-transplantation prophylaxis (p: 0.003) and pre-transplantation viral activity (p: 0.004) can be considered as independent factors affecting HBV recurrence. Candidates with hepatocellular carcinoma in HBV-cirrhosis should not be excluded from orthotopic liver transplantation, supporting the idea of a higher risk of post-transplantation viral reactivation.

Adolescent↗
PubMed1996

[Is HCV RNA detectable in the ultrafiltrate?].

We investigated by molecular biology the possibility that the HC virus passes by the dialysis membranes into the ultrafiltrate, making the HD monitor a way of HCV transmission. HCV-RNA was tested in blood and in UF samples during 2 HD sessions at T-0, 30, 60, 120 min and at HD end. HCV-RNA was measured by RT-PCR. Viraemia in patients was > 10(-4) gen Eq/ml and remained unchanged along HD, HCV-RNA was not found in whole UF and its x100 concentrates during the HD. We failed to prove the passage of the HCV into the UF, at least in standard conditions.

Hemofiltration↗