Hepatitis C virus genotypes HCV-1a and HCV-1b: the clinical point of view.
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Biomedical subjects
Publications and source records attributed to A Alberti.
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Precore/core genes from hepatitis B e antigen (HBeAg)-positive and antibody to HBeAg (anti-HBe) positive individuals with active hepatitis have been analyzed to search for correlations with response to interferon before and after treatment. Pretreatment, no precore stop codon mutants were detected, even at the 3% level, in HBeAg-positive responders or nonresponders. In anti-HBe-positive patients, precore mutants did not influence response. No significant core amino acid variability was observed in HBeAg-positive patients, irrespective of interferon response. However, anti-HBe-positive cases had multiple core protein substitutions, mostly in B- ant T-helper cell epitopes, but responders had fewer (P = .02 for responders versus nonresponders and reactivators). None of four responders, three of seven reactivators, and three of three nonresponders had mutations within the major T-helper epitope from aa50 to aa69 (P = .03). Precore mutants appeared in eight of nine natural seroconverters compared with 3 of 10 interferon-induced anti-HBe seroconverters (P = .01). Those in whom precore wild-type remained after treatment often tested negative in the last available sample using polymerase chain reaction (PCR), whereas emergence of mutants led to ongoing viremia in all cases. In anti-HBe-positive cases, precore sequences remained stable during therapy, except for 2 cases in whom a precore mutant appeared accompanied by reactivation. In the core protein, anti-HBe-positive cases selected a mean of 3.5, 1.6, and 1.7 amino acid substitutions in responders, nonresponders, and reactivators respectively (P = NS). In conclusion, core but not precore sequence before therapy may predict response. Appearance of precore mutants during therapy usually predicts failure to clear virus but substitution in core does not influence outcome.
Infections by the hepatitis B or C virus are extremely common causes of acute and chronic liver disease, and coexistence of the two viruses in the same patient is not rare. Evidence has been found that such interaction may play an important role in fulminant hepatitis and in the development of hepatocellular carcinoma in cirrhotic patients. Liver disease activity and prognosis have been reported to be generally more serious in the presence of double infection, although an inverse relationship in the replicative levels of the two agents has been noted, suggesting viral interference, particularly in cases of chronic hepatitis. Thus, the two viruses seem to inhibit each other at the molecular level, while cytopathic effects appear to be enhanced. Further studies are needed to explain the mechanisms of these apparently contrasting effects.
The authors report the case of a patient with juvenile rheumatoid arthritis (Still's disease) who underwent laparotomic hysterectomy under general anesthesia. Tracheal intubation was performed with the aid of a fibroscope, as recommended in the literature, given that impairment of the cervical spine and the temporo-mandibular joint made it extremely unlikely that direct laryngoscopy could be performed. The authors also report the methods recommended by other authors in order to guarantee a sufficiently deep anesthetic plane together with patency of the airways in patients suffering from Still's disease.
The case of a 23 years old woman, affected by the Cohen syndrome, who underwent general anesthesia for extensive dental surgery, is reported. The Cohen syndrome is an autosomal recessive syndrome that causes mental retardation, obesity, short stature as well as oral, ocular, and limb anomalies. The problems the anesthesiologist could deal with include the capacity of the patient to cooperate; difficult intubation because of maxillary hypoplasia, micrognathia, narrow and high-arched palate, and prominent maxillary central incisors; generalized muscular hypotonia; moderate leukopenia, that could theoretically increase the risk of infection: and, finally, possible associated mitral valve prolapse or hiatus hernia. In the case reported the presence of mitral valve prolapse or hiatus hernia was ruled out echographically. The patient was premedicated with diazepam and atropine i.m.; general anesthesia was carried out by propofol-fentanyl association and myorelaxation was obtained with atracurium. Nasotracheal intubation was performed easily in spite of oral anomalies so that the usefulness of thyromental distance, which was 7 cm long, as a clinical test to evaluate a potentially difficult intubation was confirmed. Noteworthy, the thyromental distance was the only test which was suitable for the uncooperative patient. At the end of surgery muscular tone recovered promptly and the endotracheal tube could be regularly removed. No complication was registered postoperatively.
The role of hepatitis C virus (HCV) infection in severe liver failure (LF) following bone marrow transplantation is still uncertain. We therefore decided to determine the presence of HCV-RNA in 31 patients who died of severe LF after BMT and in 26 matched BMT controls who did not develop LF. HCV-RNA was identified by polymerase chain reaction and anti-HCV by second generation enzyme-linked immunoassay and by 4-band recombinant immunoblotting assay in serum samples obtained before and after BMT. Biochemical and clinical parameters of liver disease were obtained by reviewing clinical records. LF developed at a median interval of 80 days (20-570) from transplantation and was clinically assessed as VOD (n = 7), liver GVHD (n = 5) or hepatitis (n = 19). HCV-RNA was detected, respectively, in 15/31 (48%) and in 12/26 (46%) of LF patients and controls (P = 0.9). Conversely, the risk of dying of LF was 62% and 53% (P = 0.5) respectively, for HCV-RNA positive and negative patients. Anti-HCV profile did not correlate with viremia, nor with type of liver disease. These findings indicate that, despite a 47% prevalence of HCV infection in our series, HCV-RNA positivity was neither a predictor of VOD nor a marker for life-threatening liver disease.
A 66-year-old woman was admitted to our department with an 11-month history of multiple transient ischemic attacks and strokes. A 2-dimensional echocardiographic study revealed an intracardiac tumor attached both to the chordae and to the anterolateral papillary muscle of the mitral valve. The patient underwent excision of the tumor, which necessitated concomitant mitral valve replacement. She remains free of symptoms 1 year postoperatively, with no echocardiographic evidence of recurrence of the tumor. To date, 19 cases of surgically treated papillary fibroelastomas of the mitral valve have been reported in the English-language literature. We add the description of our case to emphasize the importance of this tumor as an identifiable and curable cause of cerebral and coronary embolization. The frequent occurrence of cardiac valve tumors suggests the use of 2-dimensional echocardiography in patients who are experiencing transient ischemic attacks or strokes, as well as in those who sustain a myocardial infarction despite normal coronary arteries at angiography. When papillary fibroelastoma is diagnosed, surgical treatment must be considered because of the high risk of embolization.
BACKGROUND: Chronic hepatitis C may lead to cirrhosis and hepatocellular carcinoma in a subset of patients. Because response rates with interferon alfa therapy are unsatisfactory, new therapies are needed. METHODS: We conducted a three-arm, randomized trial in 45 interferon-naive men (mean age 40.6 +/- 12 years) with chronic hepatitis C to compare treatments: group A, ribavirin alone (15 mg/kg daily for 6 months); group B, interferon alone (3 MU thrice weekly for 6 months); and group C, interferon plus ribavirin at the above doses. Histologic outcomes of therapy were assessed by pretreatment and post-treatment liver biopsies. RESULTS: In group A, alanine aminotransferase levels normalized during therapy in 66% of those with HCV-1b and 34% of those with HCV-2a, but all patients relapsed after treatment ended. In group B, alanine aminotransferase levels normalized during treatment in 66%, 75%, and 100% of patients infected with HCV-1b, HCV-2a, and HCV-3, respectively; however, a sustained response was noted in only 25% of those with HCV-3. In group C, a sustained normalization of alanine aminotransferase with negative serum HCV RNA was seen in 20% of those with HCV-1b, 40% of those with HCV-2a, and 75% of those with HCV-3 12 months after therapy. One year after therapy ended, group C demonstrated a significant sustained response (47%) as well as a significant reduction in piecemeal necrosis and portal inflammation (p < 0.05). CONCLUSIONS: Combination therapy was significantly superior to ribavirin or interferon monotherapy in producing a sustained response in interferon-naive patients with chronic hepatitis C (p < 0.05). The results of our study suggest that ribavirin potentiates the effect of interferon therapy in chronic hepatitis C.
BACKGROUND: Patients with cirrhosis have a high risk of hepatocellular carcinoma (HCC) but it is unclear how the etiology of liver disease influences tumor development. The authors evaluated hepatitis B and C virus (HBV, HCV) infection in cirrhosis in relation to the risk of HCC. METHODS: Two hundred and ninety consecutive cirrhotic patients were followed prospectively with periodic ultrasound examination. At entry, patients were tested for markers of HBV and HCV to assess relation to tumor development during follow-up. RESULTS: Twenty and five-tenths percent of patients were hepatitis B surface antigen (HBsAg) positive and 68.9% were positive for HCV antibodies. Previous alcohol abuse was present in 26.2%. During follow-up (46.3 +/- 21.4 months), HCC developed in 32 patients (11.0%) (annual incidence approximately 3%) including 19.6% of HBsAg-positive patients, 12.2% of HCV antibody positive patients and 14.4% of patients with a history of alcohol abuse. The highest rate of HCC was in patients with dual HBsAg and anti-HCV positivity with or without previous alcohol abuse, whereas the lowest incidence (0%) was in cases without risk factors. By univariate analysis, age older than 59 years (P < 0.005), longer duration of cirrhosis (P < 0.005), serum alpha-fetoprotein levels higher than 20 ng/ml (P < 0.05), and dual HBsAg and HCV positivity (P < 0.02) appeared to be associated with HCC. By multivariate analysis, age (P < 0.01), positivity for HBsAg and HCV antibodies (P < 0.05), male sex (P < 0.05), and previous alcohol abuse (P < 0.08) were independently related to tumor appearance. CONCLUSIONS: These results, although confirming that male sex and previous alcohol abuse are risk factors for hepatocellular carcinoma in cirrhosis, indicate that concurrent hepatitis B and C virus infection determines the highest risk of developing hepatocellular carcinoma.
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A 15-year-old girl was admitted to ICU in a comatose state. She presented with mydriasis, areflexia, hypoxemia and seizures. She was immediately intubated and connected to a ventilator. The seizures were reversed with intravenous diazepam. CT scan was negative. EEG showed a diffuse fast activity and theta waves with spikes in the anterior and temporal regions, bilaterally. The gastric lavage was suggestive of drug ingestion. The patient completely recovered after 6 h of mechanical ventilation and supportive management. Mydriasis was still present after the resolution of neurological symptoms. The girl told us she had ingested 10 tablets (3 g-55 mg/kg) of Loftyl (buflomedil) for suicidal intention. The buflomedil concentrations at 2-3 h from ingestion were 24.8 mg/l in the blood, 324.4 mg/l in the urine and 6.9 mg/l in the gastric content. The p-desmethyl metabolite was also identified in the urine. Buflomedil is a rheological agent largely used as a vasodilator in some European countries. Some recent reports have emphasized the risk of acute intoxication with this drug. Relatively low doses (50-60 mg/kg) have been associated with an important neurological toxicity and a high mortality. We suggest that the clinical picture we observed might be related to a neuroleptic-type action of buflomedil. We bring to attention the risk of a large, uncontrolled diffusion of a drug capable to cause serious consequences at relatively low doses.
Two distinct serologic types of chronic hepatitis B have been identified, namely the "classical" HBeAg positive form and the "atypical" HBeAg negative, anti-HBe positive variant which is due to infection by a mutant HBV having a pre-core stop codon that makes the virus unable to produce HBeAg. The anti-HBe positive form is currently the prevalent type of chronic hepatitis B in the Mediterranean area, being associated with a more severe clinical course compared to HBeAg positive cases. The response to interferon therapy in patients with anti-HBe positive chronic hepatitis B has been recently investigated in control trials. These studies have shown that normalization of ALT with efficient suppression of virus activity can be achieved in 50-80% of patients while treated with interferon alpha indicating that also the pre-core mutant of HBV is sensitive to the antiviral effect of interferon. However, reactivation of hepatitis occurs in a variable percentage of initial responders when interferon is stopped. The probability of reactivation increases when the disease is of long duration, when cirrhosis is present and particularly if the pre-core mutant of HBV has become the predominant type of circulating virus, indicating that this HBV variant is more resistant to immunoclearance compared to wild type HBV.
OBJECTIVES: The purpose of this study was to assess the reliability of echocardiography in the noninvasive diagnosis of acute rejection in heart transplant recipients. BACKGROUND: Although echocardiographic results seem to correlate well with allograft rejection, published data are limited and contradictory. METHODS: In 130 transplant recipients, 1,400 serial echocardiograms were recorded within 24 h of endomyocardial biopsy. Increased wall thickness, myocardial echogenicity, pericardial effusion, shorter pressure half-time, isovolumetric relaxation time and a decrease in left ventricular ejection fraction were considered markers of rejection. RESULTS: The distribution of echocardiographic markers revealed highly significant differences between bioptically graded moderate, mild and no rejection and between untreated and treated rejection episodes (both chi-square test, p < 0.0001). Specificity was 98.6% for two markers, but sensitivity was good (80%) for only moderate rejection because of the large number of false negatives in untreated patients with mild rejection. In untreated patients, there was a highly significant difference in the number of echocardiographic criteria between a benign and nonbenign outcome (chi-square test, p < 0.0001). In treated patients, the significant difference in the variation in echocardiographic criteria between favorable and unfavorable responses after 1 week was more pronounced after 2 weeks (t test, p < 0.01 vs. < 0.001). Diastolic indexes and pericardial effusion at 2 weeks seemed to be predictive of therapeutic response. CONCLUSIONS: Poor sensitivity to mild rejection indicates that serial echocardiography cannot supplant endomyocardial biopsy in the early diagnosis of acute rejection, but it seems to be a reliable noninvasive means of identifying acute rejection requiring intensified immunosuppressive therapy and of evaluating outcome.
Strategies of treatment of chronic hepatitis type B are currently based on the use of either antiviral or immunomodulatory agents. A randomized, controlled trial was performed to assess the safety and efficacy of 6-month thymopentin therapy in 30 patients with chronic hepatitis B. Inclusion criteria were biopsy-proven chronic hepatitis, elevated alanine aminotransferase and serum HBsAg and HBV-DNA positivity for at least 12 months. At the conclusion of the study (1 year), HBV-DNA was negative and alanine aminotransferase had normalized in 13% and 20% of treated cases and in 20% and 27% of controls. None of the ten treated and one of the nine control patients who were initially HBeAg positive subsequently cleared HBeAg. None became HBsAg negative. A histologic improvement was noted in 27% of the treated patients compared with 18% of controls. These results indicate that this regimen of thymopentin therapy is not effective in treating chronic hepatitis B.
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)
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