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N Smania,
M Gandolfi,
V Marconi,
A Calanca,
C Geroin,
S Piazza, P Bonetti,
P Fiorini,
A Cosentino,
C Capelli,
D Conte,
M Bendinelli,
D Munari,
P Ianes,
A Fiaschi,
A Picelli
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ABSTRACT: Gait training with the help of assistive technological devices is an innovative field of research in neurological rehabilitation. Most of the available gait training devices do not allow free movement in the environment, which would be the most suitable natural and motivating condition for training children with neurological gait impairment.
To evaluate the potential applicability of a new robotic walking aid as a tool for gait training in non-ambulatory children with Cerebral Palsy.
Single case study
Outpatient regimen
A 11-years-old child unable to stand and walk independently as a result of spastic tetraplegic cerebral palsy (CP).
The experimental device was a newly actuated version of a dynamic combined walking and standing aid (NF-Walker®) available in the market which was modified by means of two pneumatic artificial muscles driven by a foot-switch inserted in the shoes. The child was tested at baseline (while maintaining the standing position aided by the non-actuated NF-Walker®) and in the experimental condition (while using the actuated robotic aid). The outcome measures were: 2-minute walking test, 10-metre walking test, respiratory and heart parameters, energy cost of locomotion.
At baseline, the child was unable to perform any autonomous form of locomotion. When assisted by the actuated aid (i.e. during the experimental condition), the child was successful in moving around in his environment. His performance was 19.63 m in the 2-minute walking test and 64 s in the 10-metre walking test. Respiratory and heart parameters were higher than healthy age-matched children both at baseline and in the experimental condition. The energy cost of gait, which was not valuable in the baseline condition, was significantly higher than normality during the experimental condition.
The new robotic walking aid may help children suffering from CP with severe impairment of gait to move around in their environment.
This new robotic walking device may have a potential impact in stimulating the development and in training of gait in children with neurological gait impairment. Future studies are warranted in order to test this hypothesis.
European journal of physical and rehabilitation medicine 03/2012; 48(1):147-53. · 1.40 Impact Factor
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ABSTRACT: Approximately 75%-85% of patients with chronic hepatitis C virus (HCV) infection do not have a sustained response when treated with interferon (IFN). Limited information exists on the efficacy of retreatment with IFN alone in these patients. The aim of this study was to define the efficacy of IFN retreatment in chronic hepatitis C.
Ninety-two patients with chronic hepatitis C who had shown transient or no response to recombinant IFN-alpha were randomly retreated with different schedules of lymphoblastoid IFN-alpha and followed up for 12 months after therapy to define biochemical and virological response.
None of 26 initial nonresponders obtained a sustained response with retreatment, independent of the schedule used. Thirteen of 66 patients (20%; 95% confidence interval [CI], 10.9-31.3) with transient response during the primary cycle developed a sustained biochemical and virological response when retreated, including 3 of 41 (7%; 95% CI, 1.5-9.9) of those receiving the same schedule and 10 of 25 (40%; 95% CI, 21.1-61.3; P < 0.004) of those retreated with a higher dosage and for a longer period. Shorter disease duration (P = 0.02), higher alanine aminotransferase (P = 0.002) and lower gamma-glutamyltransferase levels (P = 0.004), HCV genotype other than HCV-1 (P = 0.03), and a negative serum HCV-RNA test at the end of the primary cycle (P = 0.000) were associated with sustained response.
Patients with chronic hepatitis C who have a relapse after a complete response to a 6-month IFN-alpha treatment should be retreated for 12 months. Nonresponders should not be retreated with IFN alone.
Gastroenterology 11/1997; 113(5):1654-9. · 11.68 Impact Factor
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P Bonetti,
L Chemello,
C Antona,
A Breda,
P Brosolo,
P Casarin,
C Crivellàro,
G Donà,
S Martinelli,
R Rinaldi,
V Zennaro,
M Santonastaso,
F Urban,
P Pontisso,
A Alberti
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ABSTRACT: In chronic hepatitis C (HCV) infection, treatment with interferon is associated with a rather low rate of sustained response and many treated patients do not achieve significant benefit. Efforts have therefore been made to identify non-responders as early as possible to avoid unjustified costs and side-effects. We treated 106 cases of HCV with an algorithm based on the results of sequential alanine aminotransferase (ALT) and HCV RNA determinations, using an initial dose of 6 MU thrice weekly for 4 months, and modified the subsequent treatment according to the biochemical and virological profile. Thirty-three out of 48 patients (68.7%) who were HCV RNA negative with normal ALT at 4 months after initiation of treatment were sustained responders when treated for an additional 4-month period with a reduced 3 MU dose, while sustained response was achieved in 12.5% of HCV RNA positive patients treated with a higher dosage and for a more prolonged period of time. Our findings indicate that HCV RNA monitoring during interferon therapy may be useful in modifying of the treatment schedule for the individual patient.
Journal of Viral Hepatitis 04/1997; 4(2):107-12. · 4.09 Impact Factor
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G Fattovich,
G Giustina,
F Degos,
F Tremolada,
G Diodati,
P Almasio,
F Nevens,
A Solinas,
D Mura,
J T Brouwer, [......],
C Casarin, P Bonetti,
P Fuschi,
J Basho,
A Tocco,
A Bhalla,
R Galassini,
F Noventa,
S W Schalm,
G Realdi
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ABSTRACT: Few data are available concerning the long-term prognosis of chronic liver disease associated with hepatitis C virus infection. This study examined the morbidity and survival of patients with compensated cirrhosis type C.
A cohort of 384 European cirrhotic patients was enrolled at seven tertiary referral hospitals and followed up for a mean period of 5 years. Inclusion criteria were biopsy-proven cirrhosis, abnormal serum aminotransferase levels, absence of complications of cirrhosis, and exclusion of hepatitis A and B viruses and of metabolic, toxic, or autoimmune liver diseases.
Antibodies against hepatitis C virus were positive in 98% of 361 patients tested. The 5-year risk of hepatocellular carcinoma was 7% and that of decompensation was 18%. Death occurred in 51 patients (13%), with 70% dying of liver disease. Survival probability was 91% and 79% at 5 and 10 years, respectively. Two hundred five patients (53%) were treated with interferon alfa. After adjustment for clinical and serological differences at baseline between patients treated or not treated with interferon, the 5-year estimated survival probability was 96% and 95% for treated and untreated patients, respectively.
In this cohort of patients, life expectancy is relatively long, in agreement with the morbidity data showing a slowly progressive disease.
Gastroenterology 03/1997; 112(2):463-72. · 11.68 Impact Factor
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ABSTRACT: To define long-term outcome in patients with chronic hepatitis C who remain viremic after sustained biochemical response to interferon-alpha therapy.
Prospective evaluation of an outpatient cohort.
University hospital.
107 patients with chronic hepatitis C who maintained normal aminotransferase levels as long as 12 months after interferon-alpha therapy. Patients were followed prospectively for an additional 6 to 36 months.
Aminotransferase levels were monitored at 3-month intervals. Serum hepatitis C virus (HCV) RNA was tested by polymerase chain reaction before therapy, at the end of therapy, and 12 months after therapy. The HCV genotype was defined by spot hybridization using serum specimens obtained before treatment.
Hepatitis C virus RNA was detected in 27 (25%) patients with sustained biochemical response; 80 (75%) patients were negative for HCV RNA. Patients positive for HCV RNA were older (P < 0.001), had received a smaller interferon-alpha dose (P = 0.02), and were more frequently infected with HCV genotype 2 (P < 0.01). Liver histologic findings were active in 57% of patients positive for HCV RNA, despite normal alanine aminotransferase levels, compared with only 12% of patients who were negative for HCV RNA (P = 0.01). The estimated probability of hepatitis relapse by 4 years after therapy was 53% in viremic patients and 0% in patients negative for HCV RNA (P < 0.001).
Patients with chronic hepatitis C should be tested for serum HCV RNA 1 year after a sustained biochemical response to interferon-alpha therapy to determine whether the response is complete and permanent.
Annals of internal medicine 07/1996; 124(12):1058-60. · 16.73 Impact Factor
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ABSTRACT: Alpha-interferon (IFN-alpha) is an effective treatment for chronic hepatitis C, but only 20% to 30% of patients are apparently cured with the current recommended schedule of 3 MU given three times a week for 6 months. To evaluate the efficacy of more aggressive treatment regimens, we have conducted a randomized trial in 174 patients with chronic hepatitis C using three different schedules: (1) 12-month treatment starting with 6 MU/ three times a week and decreasing the dose on the basis of serum alanine transaminase (ALT) activities (group A: 59 cases); (2) fixed dose of 3 MU three times a week for 12 months (Group B: 61 cases), (3) fixed dose of 6 MU three times of week for 6 months (Group C: 54 cases). Patients were evaluated during therapy for biochemical and virological response and followed for at least 12 months after therapy to assess long-term efficacy and liver histological outcome. The genotype of infecting HCV was also analyzed in all patients, and predictors of response were determined by multivariate analysis. Serum ALT became normal during therapy in 76% of patients (95% confidence interval [CI]: 63 to 86), 65% (CI: 52 to 77), and 74% (CI: 60 to 85) in groups A, B, and C, respectively (P = NS). The corresponding figures for sustained response 12 months after therapy were 49% (CI: 36 to 62), 31% (CI: 20 to 44), and 28% (CI: 16 to 42)(A vs. B, P = .06; A vs. C, P = 0.03). Eighty-six percent of patients with sustained response cleared HCV-RNA from serum, and 72% improved histologically.(ABSTRACT TRUNCATED AT 250 WORDS)
Hepatology 10/1995; 22(3):700-6. · 11.66 Impact Factor
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ABSTRACT: Three main patterns of response are seen when interferon-alpha (IFN-alpha) is used for the treatment of chronic hepatitis C: 1 sustained response with alanine-aminotransferase (ALT) normalization that is maintained after cessation of therapy, with or without clearance of serum hepatitis C virus (HCV) RNA; 2 transient response with ALT normalization during therapy followed by relapse after its withdrawal, and 3 no response with no or only partial reduction in ALT levels. In order to define variables that could predict each of these three types of response we studied 321 cases of chronic hepatitis C treated with IFN-alpha in two consecutive trials conducted in our Unit. By univariate analysis, age < 45 years (P < 0.01), known disease duration < 60 months (P < 0.01), normal gamma-glutamyl-transpeptidase (gamma GT) levels (P < 0.01) and infection by HCV genotype 2 or HCV genotype 3 (P < 0.01) were found to be statistically associated with sustained response while age > 45 years (P < 0.01), body weight (P = 0.05), cirrhosis (P < 0.01) and elevated gamma GT levels (P < 0.01) were associated with no response. By multivariate analysis sustained response was predicted by HCV genotype 2 (P < 0.01) and HCV genotype 3 (P < 0.01), known disease duration (P < 0.01), patient's age (P < 0.05) and associated with the use of a more aggressive treatment schedule (P < 0.05). Transient response with relapse was predicted by known duration of disease (P < 0.05), HCV genotype 1 (P < 0.05) and female sex (P < 0.05). No response was statistically associated with elevated gamma GT levels (P < 0.01), higher body weight (P < 0.05) and with the less aggressive regimen of 3 MU of natural IFN-alpha given three times weekly for 6 months (P < 0.05). These results indicate that the HCV genotype as well as the schedule of treatment greatly affect the pattern of response to IFN in chronic hepatitis C and allow us to define criteria to predict which type of response is more likely in individual patients.
Journal of Viral Hepatitis 01/1995; 2(2):91-6. · 4.09 Impact Factor
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ABSTRACT: Hepatitis C virus is the most frequent cause of chronic non-A, non-B hepatitis, and the antibodies to structural and nonstructural proteins encoded by viral genome have been suggested to be markers of ongoing HCV infection. We studied the behavior of these antibodies during interferon therapy in 18 patients with chronic hepatitis C and also during a follow-up period of at least four years. A significant decrease of anti-HCV titer was found only in patients who had shown positive response to therapy and all of them were anti-HCV negative at the end of follow-up. Analysis by recombinant immunoblotting assay showed that only anti-c100 were affected by interferon therapy, whereas anti-c22 and anti-c33 were not modified. Using polymerase chain reaction to detect small amounts of HCV genome in serum, we could confirm that the behavior of HCV-RNA during and after interferon therapy is similar to that of anti-HCV and the loss of anti-c100 seems to be closely related to HCV-RNA disappearance from serum. Our patients with chronic hepatitis C were found to be of type 1b and 2, according to the recent score of Simmonds, and the clearance of serum HCV-RNA during treatment and its sustained negative status are closely related to genotype 2 and to long-term positive response to interferon.
Digestive Diseases and Sciences 12/1994; 39(11):2497-502. · 2.12 Impact Factor
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Journal of Hepatology 08/1994; 21(1):135. · 9.26 Impact Factor
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ABSTRACT: Patients treated with alpha-2a interferon for chronic hepatitis C may produce anti-interferon antibodies whose effect, if any, on the individual response to therapy has not been fully clarified. The prevalence and kinetics of anti-interferon, including those of neutralizing type, have been studied in 60 patients with chronic hepatitis C enrolled in a randomized controlled trial of recombinant alpha-2a interferon. Thirty patients received interferon while 30 were untreated controls. Two different methods, an enzyme immunoassay and an antiviral neutralization bioassay, were used and serial serum samples from each patient were analyzed. Enzyme immunoassay-positive anti-interferon appeared in 60.7% of treated patients within 6 months of therapy; antiviral neutralization bioassay-positive anti-interferon appeared in 52.9% of these enzyme immunoassay-positive patients, and was associated with high enzyme immunoassay reactivity and long-term persistence. Anti-interferon was detected in 75% of patients showing no response to interferon. Antibodies were also detected in three out of six patients who showed alanine aminotransferase normalization persisting up to the end of treatment and in 8 out of 14 patients who showed an initial marked reduction or even normalization of alanine aminotransferase, followed by reactivation of liver damage during treatment. Interestingly, patients who became anti-interferon positive before complete alanine aminotransferase normalization later showed reactivation of liver damage independently of interferon dose reduction, while patients who became positive for anti-interferon after complete alanine aminotransferase normalization either did not reactivate or did so only after interferon dose reduction.(ABSTRACT TRUNCATED AT 250 WORDS)
Journal of Hepatology 04/1994; 20(3):416-20. · 9.26 Impact Factor
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ABSTRACT: Sixty consecutive patients with chronic hepatitis C were included in a randomized controlled trial of recombinant human interferon-alpha 2a vs. no treatment. Treated patients received tapering doses of interferon thrice weekly for 1 yr. Twenty treated cases (66.7%) normalized serum aminotransferase levels within the first 4 mo of treatment, but reactivation or breakthrough frequently occurred afterward (20% in both cases). Only one of the untreated patients showed spontaneous normalization of serum aminotransferase levels. Liver histology did not improve in patients without a biochemical response or with breakthrough during therapy, whereas it did not worsen in long-term responders and reactivating patients. Lack of response does not appear to be related to serum interferon antibodies, although their early appearance is more frequent in patients who showed reactivation later on. No biochemical parameter was found to be predictive for positive response to treatment. Antibody to c100 became negative in 62.5% of long-term responders, whereas no change was recorded in other treated patients or controls. Reactivation and breakthrough often occur during treatment, and further studies are needed to determine the most effective schedule (dose and time) of interferon treatment. Loss of c100 antibody during therapy may be a marker of long-term maintenance of response to interferon therapy.
Hepatology 02/1994; 19(1):1-5. · 11.66 Impact Factor
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ABSTRACT: 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.
Journal of Hepatology 02/1993; 17 Suppl 3:S123-6. · 9.26 Impact Factor
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ABSTRACT: Serum alanine aminotransferase (ALT) activity and antibody to hepatitis B core antigen (anti-HBc) were proposed as surrogate markers of non-A, non-B (NANB) infection. In this study we analyzed 649 consecutive repeat blood donors to define the possible exclusion rate if both surrogate markers were implemented in our Blood Service, and to assess risk factors associated with elevated ALT levels. One hundred and seven blood donors (16.5%) had slightly elevated ALT levels (higher than the upper reference value, but less than twice this level), but only 15 (2.3%) had a level higher than mean log + 2.25 SD. Seventy-seven (11.8%) resulted anti-HBc positive. Blood donors with elevated ALT levels and those who were anti-HBc positive belonged to different populations, being only 6 (0.9%) positive for both surrogate markers. Only two known donors (0.3%) resulted anti-HCV positive, and each of them was implicated in one of the four post-transfusion hepatitis (PTH) cases observed in 200 recipients of blood from these 649 donors. Both were negative for anti-HBc but one had elevated ALT levels. Male sex, age, alcohol use and obesity resulted all independently and significantly associated with elevated ALT levels. For both alcohol use and body weight we observed a significant linear relationship with serum ALT levels. These findings suggest that in our Region the exclusion of blood donors with ALT levels above the reference value, or those anti-HBc positive, would exclude an unacceptably high rate of blood donors without proven evidence of post-transfusion hepatitis prevention.(ABSTRACT TRUNCATED AT 250 WORDS)
The Italian journal of gastroenterology 07/1992; 24(5):237-41.
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ABSTRACT: 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.
Archives of virology. Supplementum 02/1992; 4:299-303.
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ABSTRACT: The prevalence of antibody to hepatitis C virus (HCV) was studied in 207 patients with chronic liver disease of unknown etiology, in relation to clinical, epidemiological and histological features. Serum antibody to C-100 epitope of HCV was detected by ELISA in 82.6% of patients, with a significant difference compared with a group of patients with primary biliary cirrhosis (10%). The presence of anti-HCV antibody in serum did not correlate with age, sex, histological diagnosis, and activity and duration of the disease, nor with serum anti-HBc, used as a marker of exposure to hepatitis B virus infection. These results strongly support the view that most cases that were previously defined as cryptogenic forms of chronic liver disease are in fact related to HCV infection. There was a correlation between serum anti-HCV antibody and history of risk for parenteral exposure or of acute hepatitis. This correlation was particularly evident for transmission by parenteral route, suggesting that HCV infection may be transmitted often by this route (36.8% among anti-HCV antibody-positive patients and 11.1% among anti-HCV-negative patients). Liver disease in patients without risk factors for parenteral transmission and with lower prevalence of anti-HCV antibody may be caused by other as yet unidentified non-A, non-B (non-C) agents or may be of nonviral origin.
Journal of Medical Virology 12/1991; 35(3):151-4. · 2.82 Impact Factor
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ABSTRACT: The prevalence of antibody to hepatitis C virus (HCV) was studied in 207 patients with chronic liver disease of unknown etiology, in relation to clinical, epidemiological and histological features. Serum antibody to C-100 epitope of HCV was detected by ELISA in 82.6% of patients, with a significant difference compared with a group of patients with primary biliary cirrhosis (10%). The presence of anti-HCV antibody in serum did not correlate with age, sex, histological diagnosis, and activity and duration of the disease, nor with serum anti-HBc, used as a marker of exposure to hepatitis B virus infection. These results strongly support the view that most cases that were previously defined as cryptogenic forms of chronic liver disease are in fact related to HCV infection. There was a correlation between serum anti-HCV antibody and history of risk for parenteral exposure or of acute hepatitis. This correlation was particularly evident for transmission by parenteral route, suggesting that HCV infection may be transmitted often by this route (36.8% among anti-HCV antibody-positive patients and 11.1% among anti-HCV-negative patients). Liver disease in patients without risk factors for parenteral transmission and with lower prevalence of anti-HCV antibody may be caused by other as yet unidentified non-A, non-B (non-C) agents or may be of nonviral origin.
Journal of Medical Virology 10/1991; 35(3):151 - 154. · 2.82 Impact Factor
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ABSTRACT: A randomized, controlled trial was undertaken to evaluate the response to recombinant interferon alfa-2a in patients with hepatitis B surface antigen negative chronic active hepatitis of unknown aetiology (community-acquired non-A, non-B hepatitis). Thirty patients were treated with thrice weekly interferon in a dose of 6 million units for 1 month, followed by 3 million units for 3 months and 1 million units maintenance therapy for 8 months. Patients who relapsed were returned to the previously effective dose. A control group of 30 patients received no treatment and were followed up for 12 months. Overall, 21/30 (70%) of treated patients had a complete response, with normalization of serum aminotransferase levels, and a further three (10%) had a partial response (a decrease to less than 50% of baseline levels). No significant changes were observed in the control patients. Five (24%) of the 21 complete responders relapsed during months 2-4 and 8/21 (38%) relapsed during maintenance therapy. Three (23%) of these 13 patients had a return to normal serum aminotransferase levels when the dose was increased and 7/13 (54%) demonstrated a significant decrease. In a retrospective analysis of patients' sera for antibody to hepatitis C virus, 23/26 patients testing positive were treatment responders compared to 1/4 antibody negative patients. Our results suggest that interferon alfa-2a is an effective treatment for community-acquired non-A, non-B hepatitis, but reactivation during treatment occurred in 62% of patients. We recommend use of a higher dose of interferon for at least 1 year with long-term follow up in order to exclude early or late reactivation after treatment withdrawal.
Journal of Hepatology 02/1990; 11 Suppl 1:S68-71. · 9.26 Impact Factor
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ABSTRACT: In an attempt to evaluate a possible correlation between cryptogenic chronic liver disease and a present or past hepatitis B virus (HBV) infection, we studied 17 patients with hepatitis B surface antigen (HBsAg)-negative, nonalcoholic chronic liver disease; 9 of them were positive for serum HBsAg detected by a solid-phase enzyme immunoassay with monoclonal antibody (M-EIA) and 8 were negative for the same marker. Liver hepatitis B core antigen (HBcAg), studied by an indirect immunofluorescence technique, was present in 55.5% of the patients positive for serum HBsAg by M-EIA. In the same group of patients, liver HBV-DNA was found in 66.6% of the patients. On the other hand, only 1 patient without serum positivity for HBsAg by M-EIA was positive for liver HBcAg and HBV-DNA. None of our patients showed serum positivity for HBV-DNA sequences. We conclude that HBV infection may be a possible cause of cryptogenic chronic liver disease; this HBV-related, HBsAg-negative chronic liver disease seems to have no viral replication or undetectable levels of HBV-DNA in serum. HBsAg, detected by a monoclonal assay, seems to be a suitable marker to identify this subgroup of patients with HBsAg-negative chronic liver disease.
Digestion 02/1988; 39(4):251-6. · 2.05 Impact Factor
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ABSTRACT: In an attempt to evaluate a possible correlation between cryptogenic chronic liver disease and a present or past hepatitis B virus (HBV) infection, we studied 17 patients with hepatitis B surface antigen (HBsAg)-negative, nonalcoholic chronic liver disease; 9 of them were positive for serum HBsAg detected by a solid-phase enzyme immunoassay with monoclonal antibody (M-EIA) and 8 were negative for the same marker. Liver hepatitis B core antigen (HBcAg), studied by an indirect immunofluorescence technique, was present in 55.5% of the patients positive for serum HBsAg by M-EIA. In the same group of patients, liver HBV-DNA was found in 66.6% of the patients. On the other hand, only 1 patient without serum positivity for HBsAg by M-EIA was positive for liver HBcAg and HBV-DNA. None of our patients showed serum positivity for HBV-DNA sequences. We conclude that HBV infection may be a possible cause of cryptogenic chronic liver disease; this HBV-related, HBsAg-negative chronic liver disease seems to have no viral replication or undetectable levels of HBV-DNA in serum. HBsAg, detected by a monoclonal assay, seems to be a suitable marker to identify this subgroup of patients with HBsAg-negative chronic liver disease.
Digestion 08/1970; 39(4):251-256. · 2.05 Impact Factor
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Annali italiani di medicina interna: organo ufficiale della Societa italiana di medicina interna 2(3):195-200.
