During acute rejection (AR), the endothelial targeting seen in the mucosal vessels of the intestinal allograft (IA) could impair the blood supply and response to luminal stimuli. To study the effect of AR in the perfusion and reactivity of the IA mucosa, we measured the mucosal blood flow in the ileum (IL) of 2 groups of control rats (Lewis and ACI) and in the native and grafted IL of syngeneic (ACI to ACI) and allogeneic (donor ACI to recipient Lewis) rats. Using reflectance spectrophotometry and laser-Doppler flowmetry, parameters of mucosal oxygen saturation (ISO2), hemoglobin content (IHB), and blood flow (FLOW) were obtained at baseline and after saline and 50% dextrose (D50) stimulation. When compared to controls, the isograft IL had similar perfusion (ISO2, IHB, and FLOW). The allograft IL showed ischemia (similar ISO2, and lower ISO2 and FLOW). In the allografts, the ISO2 and FLOW were lower than in the isografts. In response to D50, the native IL of all groups showed an increased IHB and FLOW (hyperemia); the isografts showed an increase only in IHB (partial response); the allografts did not show any response at all. In summary, the mucosal perfusion in the rejecting allografts, but not in the isografts, showed ischemia. The response to D50 seen in the native ilea was only partial in the isografts and absent in the allografts. Because these changes occurred before the onset of mucosal ulcerations, we postulate that they could be used as early indicators of AR.

Animals↗

PubMed1995

Acute liver failure: results of a 5-year clinical protocol.

This investigation summarizes and evaluates the results of a clinical protocol that we designed to care for patients with acute liver failure (ALF). Adult patients with ALF were enrolled in the protocol. Grade II portal-systemic encephalopathy prompted admission to the intensive care unit (ICU). Patients who met the clinical criterion were activated for liver transplantation. Intracranial pressure (ICP) was monitored in patients with grade III encephalopathy. An increase in ICP was treated with hyperventilation, diuretics, barbiturates, or a combination thereof. Survival was considered to have occurred if the patient left the hospital alive. Our series included 25 patients. Orthotopic liver transplantation (OLT) was performed on 19 patients, 12 of whom survived. Only 2 of 6 patients who did not undergo transplantation survived. Ten of 11 patients who underwent transplantation before reaching grade IV encephalopathy survived. Only 2 of 8 patients who underwent transplantation after reaching grade IV survived (P = .006). The causes of death included cerebral edema (3 patients), disseminated aspergillosis (3 patients), and other (5 patients). ICP was monitored in 11 patients. Increased pressure was documented by seven of the monitors placed. There was one focal hemorrhage secondary to a subdural monitor. Outcome is improved if transplantation occurs before grade IV encephalopathy. ICP monitoring can be accomplished without significant risk of hemorrhage. In our series, infection with aspergillus occurred frequently and with fatal outcome.

Adolescent↗

PubMed1995

Liver transplantation for hepatitis B: what have we learned and what does the future hold?

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Animals↗

PubMed1995

Hepatitis C genotypes in liver transplant recipients: distribution and 1-year follow-up.

Chronic hepatitis C infection (CH-C) accounts for a significant number of patients undergoing orthotopic liver transplantation (OLT). Recently, hepatitis C virus (HCV) genotype-dependent differences in disease outcome and therapeutic responses have been suggested. The objectives of our study were to determine (1) the recurrence of HCV infection after OLT; (2) distribution of HCV genotypes in patients with CH-C who required liver transplantation compared with those who did not; and (3) the 1-year transplantation outcome in patients infected with different hepatitis C genotypes. RNA was extracted from sera of 20 patients who underwent OLT for end-stage liver disease secondary to CH-C (group I) and 52 patients with CH-C who did not require OLT (group II). For viral RNA detection, reverse transcriptase and polymerase chain reaction (RT/PCR) of 5'UT region was performed on all OLT patients both before and after OLT. For genotyping, RT-PCR of the NS 5 region was performed, followed by automated sequencing of the amplification products. Nineteen OLT patients had viral RNA detected by PCR both before and after OLT. One patient had no RNA detected before OLT but became viremic after OLT. The prevalence of HCV genotype 1b was significantly higher in group I patients compared with group II (53% v 23% respectively, P = .01). Examination of outcome at 1 year after OLT showed that 9 of 10 patients with HCV genotype 1b had histological evidence of hepatitis compared with 4 of 9 patients with other genotypes (non-1b) (P = .06). However, the number of patients who had one or more episodes of rejection, underwent retransplantation, or died at 1 year after OLT were similar. Recurrence of HCV infection after OLT was shown in all studied patients. Hepatitis C genotype 1b is more prevalent in our patients who underwent transplantation compared with a group with chronic hepatitis C who did not require transplantation (P = .01). Patients infected with HCV genotype 1b may have a higher risk of histological hepatitis after transplantation.

DNA Primers↗

PubMed1995

Nucleotide sequence analysis of precore and proximal core regions in patients with chronic hepatitis B treated with interferon.

The aim of the study was to estimate the prevalence of HBeAg defective mutants among patients with chronic hepatitis B (CHB) in the United States and to study the effect of interferon-alpha (IFN-alpha) on determining the occurrence of mutations in the HBV precore and proximal core regions. Twenty CHB patients who were treated with IFN-alpha were studied. Initially, all were HBV DNA positive by dot-blot hybridization; 17/20 were HBeAg positive, and 3/20 were anti-HBe positive. The precore (87 nt) and proximal core (81 nt) regions were sequenced after PCR amplification by the dideoxy chain termination method. In pretreatment sera, 15/20 patients harbored wild-type HBV only, while in 5/20 at least one nucleotide substitution was found. Mutations that prevent HBeAg synthesis were found in three patients, all of whom had G-to-A substitution at nt 1896 and two of them were anti-HBe positive. Follow-up sera were available in 18 patients. With respect to pretreatment specimen, 15/18 patients had no changes in the sequenced regions after therapy. Sequence changes were observed in the remaining three patients: In one an HBeAg defective strain was replaced by a wild-type strain; in the second a wild-type strain was replaced by an HBeAg defective strain; and in the third two mutations changing the deduced amino acid sequence of the core protein developed in the wild-type strain. In conclusion, most of our patients (85%) were initially infected by HBV strains having no mutations that prevented HBeAg synthesis. IFN-alpha therapy infrequently resulted in the appearance of mutations in the precore and proximal core regions.

Adult↗

PubMed1995

Hepatitis B virus core promoter sequence analysis in fulminant and chronic hepatitis B.

BACKGROUND & AIMS: It was recently reported that two point mutations within the hepatitis B virus (HBV) core promoter region (A to T at position 1762 and G to A at position 1764) are associated with fulminant hepatitis and lead to hepatitis B e antigen (HBeAg)-negative phenotype. The aim of this study was to correlate core promoter sequence variations with HBeAg status and clinical outcome in various forms of HBV infection. METHODS: Core promoter region of HBV was amplified by polymerase chain reaction and directly sequenced in 94 patients: 37 patients with fulminant hepatitis, 20 with acute self-limited hepatitis, 30 with chronic hepatitis, and 7 patients with end-stage cirrhosis. RESULTS: Core promoter region was found to be heterogenous and no specific changes correlated with HBeAg/anti-HBeAg status or survival in patients with fulminant hepatitis. Substitutions at positions 1762 and 1764 were found in HBV strains from 4 patients (10%) with fulminant hepatitis, 2 patients (10%) with self-limited hepatitis, 8 patients (27%) with chronic hepatitis, and in 5 of 7 patients with end-stage cirrhosis. The majority of these patients were HBeAg positive. CONCLUSIONS: Mutations at positions 1762 and 1764 are rarely observed in HBV strains from patients with fulminant hepatitis B in the United States but are common in patients with chronic hepatitis. Even when present, they seem to be insufficient to lead to the HBeAg-negative phenotype.

Base Sequence↗

PubMed1995

Blood donors who are repeatedly reactive for hepatitis C virus on enzyme immunoassay and positive on recombinant immunoblot assay: evidence of failure to identify some risk factors.

BACKGROUND: Despite the introduction of surrogate testing and subsequent antibody testing of donor blood, transmission of hepatitis C virus (HCV) still occurs. The institution from which this report originates is a medical center, and many of the blood donors have also been seen as patients at the institution. This provided an opportunity for comparison of donor questionnaire responses and medical history information and for correlation of those findings with HCV test results. STUDY DESIGN AND METHODS: HCV polymerase chain reaction (PCR) testing was performed on nine stored frozen sera from donors or former donors with previous positive results on HCV enzyme immunoassay (EIA) (first- or second-generation) and recombinant immunoblot assay (RIBA) (first- or second-generation). The medical histories were also reviewed for 22 of 23 such HCV EIA-repeatedly reactive, RIBA-positive donors and 88 randomly chosen HCV-negative donors. The lifestyle information was compared with the donors' responses on the blood donation questionnaires. The data were then correlated with available clinical and laboratory evidence of HCV transmission to transfusion recipients. RESULTS: For eight donors, there were no recipients of their blood to be assessed. For 9 of the remaining 15 donors, there were recipients who were tested for HCV. Recipients of blood from 5 of these 9 donors were repeatedly reactive for HCV; while recipients of blood from 4 donors were not. Donor PCR positivity correlated with apparent transmission (p = 0.047). Twelve of 20 HCV EIA-positive donors for whom history and questionnaires were available for comparison had at least one suggestive lifestyle or established risk factor in their medical records, while none of 88 HCV-negative controls did (p < 0.0001). The data did not indicate that paid donation correlated with failure to disclose these factors. CONCLUSION: Despite more explicit and intrusive donor questioning, it is still not possible to identify all possible risk factors at donations, though many donors who do not disclose all their risk factors are eliminated from the pool by the increasingly sensitive donor tests. As long as tests are not completely foolproof, workers must be vigilant regarding the ability to elicit complete information on a donor's risk. Further study is required to determine the best way(s) to do so.

Blood↗

PubMed1995

Clinical and radiologic features of cerebral edema in fulminant hepatic failure.

OBJECTIVE: To describe a series of consecutive patients with fulminant hepatic failure (FHF) and to present a new classification system for brain edema, an important cause of mortality in such patients. DESIGN: We reviewed 22 computed tomographic (CT) scans of the brain in 12 patients with FHF and classified the severity of cerebral edema by using predefined criteria. RESULTS: No cerebral edema was detected on CT scans in four patients with stage 1 or 2 hepatic encephalopathy at the time of admission, but it was noted in seven of eight patients with stage 3 or 4 hepatic encephalopathy. The severity of brain edema on CT scans was significantly correlated (P < 0.001) with the stage of hepatic encephalopathy. Three of the four patients who had stage 1 or 2 hepatic encephalopathy at the time of initial assessment ultimately had a good outcome. Of seven patients with stage 3 encephalopathy, two had rapid deterioration to brain death, three died of nonneurologic causes, and two had a good outcome after liver transplantation. One patient with stage 4 hepatic encephalopathy died, and autopsy showed cerebral edema. CONCLUSION: Stage 3 or 4 hepatic encephalopathy is associated with cerebral edema that can be detected on CT scans. The clinical and radiologic signs of cerebral edema in patients who have progression to stage 3 hepatic encephalopathy can be reversed with conventional treatment of increased intracranial pressure. Whether early recognition and treatment of cerebral edema result in increased survival of patients with FHF remains to be determined.

Adolescent↗

PubMed1995

Genotype-dependent serologic reactivities in patients infected with hepatitis C virus in the United States.

OBJECTIVE: To evaluate the serologic reactivities in patients infected with different hepatitis C virus (HCV) genotypes to four HCV proteins that are components of the second-generation recombinant immunoblot assay. MATERIAL AND METHODS: Serum samples from 36 patients with chronic HCV infection were obtained. RNA was extracted by using chaotropic lysis and isopropanol precipitation. Reverse-transcriptase polymerase chain reaction of the NS-5 region was performed, followed by automated single-pass dideoxy sequencing of desalted amplification products. Classification of isolated HCV subtypes was based on Simmonds' system. All samples were tested for antibodies to proteins 5-1-1, C100-3, C33c, and C22-3 with the second-generation recombinant immunoblot assay. RESULTS: Reactivity to protein 5-1-1 was significantly lower for patients with genotypes 2b and 3a than for those infected with HCV types 1a or 1b (P < 0.05). Antibody reactivity to the C100-3 protein was also reduced in patients infected with HCV types 2b and 3a. CONCLUSION: These data indicate that the genotype-dependent differences in serologic reactivities are substantial among patients with chronic HCV infection.

Base Sequence↗

PubMed1995

Pittsburgh University questions paper.

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Child↗

PubMed1995

Epidemiology and natural history of hepatitis C infections in liver transplant recipients.

Hepatitis C infection is common in patients undergoing liver transplantation. Few studies have focused on the prevalence and epidemiology of hepatitis C infection among liver transplant recipients since the implementation of donor screening for antibodies against the hepatitis C virus (anti-HCV). Using reverse transcription-polymerase chain reaction (RT-PCR) and genomic sequencing methods, we sought to determine the prevalence, epidemiology, and natural history of hepatitis C infections among 44 consecutive liver transplant patients between January and December 1991. All patients and donors were screened for antibodies against HCV with a first-generation test. Laboratory tests and liver biopsies were routinely done 12 months after transplantation. Serum samples from all organ donors and transplant recipients were analyzed for the presence of HCV-RNA. From four of the six HCV-RNA-positive patients, pre- and post-transplant serum samples were available for sequence analysis. No donor had detectable HCV-RNA. Six of 44 (13.6%) patients had detectable HCV-RNA before and after liver transplantation. Recurrent infection was documented in all who were infected before transplantation and was confirmed by genotype analysis in the four patients who were analyzed. No acquired infections were identified. After transplantation, the HCV-RNA-positive recipients had higher mean alanine aminotransferase (207 +/- 85 U/l vs 37 +/- 7 U/l; p < 0.0001) and were more likely to have chronic hepatitis (50% vs 6%; p < 0.03) than the HCV-RNA-negative recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

PubMed1995

Hepatitis B virus (HBV) re-infection following liver transplantation: theory and practice.

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Antiviral Agents↗

PubMed1995

Interferon therapy in hepatitis C.

Interferon is effective for the treatment of hepatitis C infection in some patients. Although its effectiveness is established in patients with chronic hepatitis C infection, more work need to be done before it can be recommended for the treatment of patients with acute HCV infection. The currently recommended therapeutic regimen is 3 MU three times weekly, but higher dosages and longer duration of therapy may be more beneficial. Multiple factors including the degree of inflammation and fibrosis, HCV-RNA titer, and HCV genotype may influence the response to therapy. Therefore proper patient selection will improve response rate, and make interferon treatment more cost-effective. No controlled studies have yet evaluated the use of interferon in children with chronic HCV infection. Many questions are yet to be answered regarding interferon therapy in patients with chronic hepatitis C, thus we recommend all patients who belong to these categories be enrolled in clinical trials.

Acute Disease↗

PubMed1994

The stem-loop structure of the cis-encapsidation signal is highly conserved in naturally occurring hepatitis B virus variants.

The region encoding the stem-loop structure of the HBV cis-encapsidation signal was sequenced in 87 patients with various forms of hepatitis. Altogether, 20 nucleotide substitutions were found; 15/20 were predicted to increase the stability of the stem-loop structure. Substitutions likely to decrease the stability of the cis-encapsidation signal were not observed.

Base Sequence↗