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J Guardia

Publications and source records attributed to J Guardia.

At least 55 records · Page 3Linked to original sources
PubMed1999

Rapid detection of lamivudine-resistant hepatitis B virus polymerase gene variants.

The amino acid substitution from methionine to valine or isoleucine at the YMDD (tyrosine, methionine, aspartate, aspartate) motif of the HBV polymerase gene is the main mutation responsible for resistance to lamivudine treatment. Detection of emerging HBV variants by direct sequencing of the HBV genome is excessively time-consuming for studying large numbers of clinical samples. The aim of the study was to analyse the emergence of lamivudine-resistant HBV genotypes by means of restriction fragment length polymorphism (RFLP) of the PCR product generated from a fragment of domain C of the polymerase gene, in clinical samples from patients receiving treatment. The results with this method were compared with those obtained with a direct sequencing technique. In total, 139 serum samples were studied from 37 patients with chronic hepatitis B, obtained at pre-treatment and at 9, 12, 18 and 24 months of treatment. Variants were detected by cleavage of the products of the three PCRs with the following enzymes: FokI (identifies the normal variant, YMDD, and the mutant variant YVDD), SspI (identifies the mutant variant, YIDD) and Alw44I (identifies the variant, YVDD). The digested fragments were separated by electrophoresis in 3% agarose gel. Of the 139 serum samples analysed, the wild-type YMDD sequence was detected in 106 (76%), the YVDD variant in 20 (15%) and the YIDD variant in 13 (9%) cases. The non-mutated variant, YMDD, was detected in all the pre-treatment samples. After 9 months of treatment the mutant variant was detected in four of 37 serum samples analysed (11%) (two YVDD and two YIDD). At 12 months, 12 of the 37 serum samples (32%) showed mutations in the YMDD sequence (seven YVDD and five YIDD). Among the 16 serum samples obtained at 18 months, nine had the YMDD variant (56%) (seven YVDD and two YIDD). At 24 months, variants in the YMDD sequence were detected in eight of the 12 patients treated (66%) (four YVDD and four YIDD). HBV genotypes were confirmed by direct sequencing, with consistent results. In 45% of cases, the emergence of HBV variants was not associated with ALT breakthrough. The PCR-RFLP assay used in this study, in perfect concordance with direct sequencing, is an accurate method for genotyping lamivudine-resistant HBV variants. Since it is a rapid low-cost technique, PCR- RFLP is suitable for large-scale screening of these polymorphisms in clinical samples.

Antiviral Agents↗
PubMed1999

Adrenomedullin, a vasodilator peptide implicated in hemodynamic alterations of liver cirrhosis: relationship to nitric oxide.

This prospective cohort study was aimed at investigating the role of adrenomedullin, a potent vasodilator peptide, in liver cirrhosis and its relationship with nitric oxide and cytokines. Overall, 66 consecutive patients with liver cirrhosis and 15 controls matched for age and sex distribution were included. Adrenomedullin levels in patients with cirrhosis were higher than in controls [28.1 (23.5-34.8) vs 21.9 (21.1-26.4) pmol/liter, P = 0.002]. Child class A patients had adrenomedullin levels similar to those of controls, but lower than patients in class B and C, respectively (P = 0.01). Patients with ascites showed more elevated adrenomedullin levels than patients without (P = 0.001). Adrenomedullin levels had significant correlations with aldosterone (r = 0.55; P < 0.001), plasma renin activity (r = 0.49; P < 0.001) and nitrates-nitrites levels (r = 0.52; P < 0.001). Weak correlations were found with tumor necrosis factor-alpha and interleukin-6. This study shows that high levels of adrenomedullin in liver cirrhosis correlate with features associated with plasma volume expansion, and suggests that, in late stages of cirrhosis, adrenomedullin might contribute to vasodilatation by increasing the generation of nitric oxide.

Adrenomedullin↗
PubMed1999

Evaluation of RNA and E2 antibodies in prospectively followed recipients of hepatitis G virus-infected blood.

BACKGROUND: Hepatitis G virus (HGV) has recently been cloned and tests for HGV RNA and envelope antibodies (anti-E2) have been developed. HGV infection is widespread among blood donors worldwide, but the clinical and serologic outcome of transfusion-associated HGV infection has not been fully characterized. STUDY DESIGN AND METHODS: Consecutive blood donors (n = 2210) were investigated for HGV markers (RNA and anti-E2). The recipients of HGV RNA-positive blood were followed for 1 year after transfusion. RESULTS: Forty-two blood donors (1.9%) were positive for HGV RNA. Eight recipients of HGV RNA-positive blood were retrospectively identified within 2 weeks of transfusion and prospectively followed. In four patients, the presence of anti-E2 before transfusion or an early antibody response protected them from reinfection or prevented HGV persistence, while, in the remaining four patients, transient or persistent viremia was detected shortly after exposure. None of the infected recipients had any evidence of liver disease. CONCLUSION: These results do not support the screening of donors to prevent transfusion-associated HGV infection.

Blood Donors↗
PubMed1999

Genetic alterations in the S gene of hepatitis B virus in patients with acute hepatitis B, chronic hepatitis B and hepatitis B liver cirrhosis before and after liver transplantation.

BACKGROUND: Several studies have shown that hepatitis B immunoglobulin (HBIG) imposes a selection pressure on the hepatitis B virus (HBV) S gene, and that the emergence of mutations in this region would make reinfection after orthotopic liver transplantation (OLT) possible. AIMS: This study was undertaken to analyze the presence of HBV S-gene mutations in the different stages of HBV infection and the relationship between HBIG therapy and the emergence of mutations in liver transplant recipients. METHODS: The frequency and location of mutations in the coding region of the HBV S gene were studied by PCR and direct sequencing in 30 patients (7 with acute self-limited hepatitis B, 16 with chronic hepatitis B and 7 recipients of (OLT) for HBV-related end stage liver disease who became reinfected). RESULTS: The average number of amino acid changes was higher in patients with a more advanced stage of disease, 0.57 mutations/100 positions in acute hepatitis B and 1.57 in chronic hepatitis B (1.28 in HBeAg-positive and 1.8 in anti-HBe-positive patients). The average number of substitutions in the transplanted patients was 2.7 before OLT and 3 after OLT. No amino acid substitutions were detected in the "a" determinant of HBsAg in acute hepatitis B, however, 8 substitutions were observed in 6 chronic patients. In 3 OLT patients, 4 substitutions were observed in samples before and after OLT. One of these patients, who had protective levels of anti-HBs, showed 3 additional new amino acid substitutions after OLT, suggesting escape mutant selection by the effect of HBIG therapy. No changes were observed between the consensus sequences obtained several years before and after transplantation, indicating consensus sequence stability. CONCLUSION: These results show that there is an accumulation of HBV S-gene mutations in HBV-related end-stage liver disease. Prophylaxis with HBIG mainly obtained from acute self-limited hepatitis patients who have a highly homogeneous viral population, may be one factor underlying the reinfection after liver transplantation.

Acute Disease↗
PubMed1999

Interleukin-6, nitric oxide, and the clinical and hemodynamic alterations of patients with liver cirrhosis.

OBJECTIVE: Nitric oxide has been proposed as a mediator of hyperdynamic circulation in cirrhosis. Endotoxin and cytokines induce the synthesis of nitric oxide. The aim of this study was to investigate the relationship between endotoxemia, cytokines, and nitric oxide in patients with cirrhosis, and to correlate these findings with clinical, biochemical, and hemodynamic parameters. METHODS: Clinical, biochemical, and hemodynamic parameters were assessed in 66 patients with cirrhosis and 15 controls. Levels of antidiuretic hormone, plasma renin activity, aldosterone, interferon gamma, interleukin-1, interleukin-6, tumor necrosis factor alpha, endotoxin, and nitrates-nitrites were determined. RESULTS: Mean arterial pressure was lower and interleukin-6, tumor necrosis factor alpha, nitrites-nitrates levels, and endotoxin positivity rates were higher in cirrhotics than in controls (p < 0.005). Mean arterial pressure decreased and interleukin-6 levels increased with worsening of Child score (p < 0.005). Patients with ascites had higher levels of interleukin-6, tumor necrosis factor alpha, and nitrates-nitrites than patients without ascites (p < 0.01). Elevated levels of interleukin-6 were found in patients with encephalopathy grade I, compared with patients without (p < 0.001); this association was independent of the severity of liver disease. In patients with low mean arterial pressure, interleukin-6 levels were higher than in patients with high mean arterial pressure (p = 0.001), whereas tumor necrosis factor alpha and nitrates-nitrites levels were not different. By multivariate analysis, high interleukin-6 levels showed independent associations with the presence of ascites, encephalopathy, and low mean arterial pressure. Only interleukin-6 levels had significant correlations with Child score, plasma renin activity, serum and urinary sodium, and mean arterial pressure (r > or = 0.4, p < 0.005). CONCLUSIONS: Although the activity of the nitric oxide pathway is increased in patients with cirrhosis and might contribute to the hemodynamic alteration, other factors are involved. Interleukin-6, possibly through nitric oxide-independent mechanisms, also might play a role in the vasodilatation of cirrhosis and the pathogenesis of hepatic encephalopathy.

Aged↗
PubMed1999

High-throughput real-time reverse transcription-PCR quantitation of hepatitis C virus RNA.

We describe a rapid and reproducible method for assessment of the hepatitis C virus (HCV) load in serum samples. The method combines Taqman technology (Roche) and the ABI Prism 7700 (Perkin Elmer) real-time sequence detection system. We have optimized a single-tube reverse transcription-PCR (RT-PCR) that contains a dual-labeled fluorogenic probe to quantify the 5' noncoding region (5' NCR) of HCV. The probe contains a fluorescent reporter at the 5' end and a fluorescent quencher at the 3' end. The use of such a probe combined with the 5'-3' nuclease activity of Taq polymerase allows direct quantitation of the PCR product by the detection of a fluorescent reporter released in the course of the exponential phase of the PCR. For accurate quantitation of the number of copies of HCV in samples containing unknown quantities, we have used serial dilutions of a synthetic 5' NCR RNA standard of HCV that was previously quantified with an isotopic tracer. The method has a 5-log dynamic range (10(3) to 10(7)). The coefficient of regression of the standard curve was, on average, 0.98. The intra-assay and the interassay coefficients of variation of the threshold cycle were 1% and 6.2%, respectively. Seventy-nine RNA samples from the sera of infected patients were quantified by this method. Comparison of the results with those obtained by other quantitation methods (the Quantiplex 2.0 branched-DNA assay and the Superquant assay from the National Genetics Institute) revealed a significant correlation with all of the results. The mean values were also statistically comparable. In conclusion, the high sensitivity, simplicity, and reproducibility of the real-time HCV RNA quantitation which allows the screening of large numbers of samples, combined with its wide dynamic range, make this method especially suitable for monitoring of the viral load during therapy and tailoring of treatment schedules.

Adult↗
PubMed1999

[One year treatment with lamivudine in different hepatitis B virus related hepatic diseases].

BACKGROUND: Three month administration of lamivudine in patients with chronic hepatitis B produces a transitory inhibition of the DNA of the hepatitis B virus (HBV). AIM: The aim of this study was to evaluate the efficacy and safety of one year treatment with lamivudine in patients with chronic hepatitis B and liver transplantation (LTx) with recurrence of HBV infection. PATIENTS AND METHODS: Sixteen patients with chronic hepatitis B, 4 patients with decompensated hepatic cirrhosis and 4 patients having undergone LTx with recurrence of HVB infection were treated with the oral administration of 100 mg/day of lamivudine for one year. RESULTS: At 3 months of treatment, the HBV-DNA became negative in 94% of the cases of chronic hepatitis B, in 10% of those with decompensated hepatic cirrhosis and in 100% of the cases of LTx. At one year of treatment, the HBV-DNA was negative in 81% of the chronic hepatitis B, in 100% of the decompensated cirrhotics and in 100% of the LTX cases which survived. The tolerance to treatment was excellent in all the cases. In 34% of the cases, mutations were observed in the gene of the polymerase DNA at one year of treatment. CONCLUSIONS: Lamivudine produces intense, rapid inhibition in viral replication not only in chronic hepatitis B but also in cases of decompensated cirrhosis or recurrence following liver transplantation. Around 30% of the patients undergoing one year of treatment with lamivudine developed gene mutations of the HBV polymerase.

Adult↗
PubMed1999

Profiles of GBV-C/hepatitis G virus markers in patients coinfected with hepatitis C virus.

GBV-C/Hepatitis G virus (GBV-C/HGV) is a newly discovered viral agent, found widely among healthy blood donors and among individuals at risk of parenterally transmitted infections. GBV-C/HGV is found frequently in coinfection with HCV. A population of 109 HCV positive patients was examined for the presence of GBV-C/HGV RNA and antibodies to E2. Of the 109 patients, 23 (21%) had serum GBV-C/HGV RNA in serum, 39 (36%) had only antibodies to E2 and 8 (7%) were positive for both markers, with an overall prevalence of 64%. Different serologic and virological patterns were observed in GBV-C/HGV exposed patients according to their infection status. Active infection was characterized by positive RT/PCR signal with primers for both the 5'UTR and NS5 genomic regions, viremia levels above 10(4) copies/mL by real time quantitative RT/PCR and absence of detectable anti-E2. In the transition phase between active infection and recovery, GBV-C/HGV RNA was only detectable by RT/PCR using primers from the 5' untranslated region and viremia levels were below 10(4) copies/ml by quantitative PCR, with or without simultaneous presence of anti-E2 antibodies. Resolved infection was characterized by absence of detectable viremia and, in most patients, by the presence of anti-E2.

5' Untranslated Regions↗
PubMed1999

Regional cerebral blood flow changes in chronic alcoholic patients induced by naltrexone challenge during detoxification.

UNLABELLED: The recent introduction of the opioid antagonist naltrexone for alcohol-dependence therapy has been mainly based on behavioral animal models that provide evidence of the involvement of the endogenous opioid system in alcohol drinking and dependence. However, the neurophysiological mechanisms of the effect of naltrexone in alcoholic patients remain unknown. This study investigates the effects of a naltrexone challenge on regional cerebral blood flow (rCBF) in chronic alcoholic patients during detoxification. METHODS: Sixteen alcoholic inpatients underwent two 99mTc-hexamethyl propyleneamine oxime (HMPAO) brain SPECTs: a basal SPECT on day 10 of abstinence and a second SPECT on day 12 of abstinence after oral administration of 150 mg naltrexone. Region-to-cerebellar ratios were obtained for the orbitary frontal, prefrontal, lateral temporal and mesial temporal regions, basal ganglia and thalamus in each hemisphere. A percentage of rCBF change between both SPECTs was calculated for each region as 100 x (naltrexone - baseline)/ baseline. Values from 13 brain SPECTs of age-matched normal volunteers including test-retest measurements were used for statistical comparison. RESULTS: In baseline conditions, alcoholics showed lower rCBF than controls in left orbitofrontal cortex (84.0+/-5.1 versus 89.8+/-5.0, P < 0.01) and prefrontal cortex (left hemisphere: 87.4+/-5.2 versus 96.2+/-3.6, P < 0.001; right hemisphere: 87.0+/-4.9 versus 95.8+/-4.2, P< 0.001). After naltrexone, a significant rCBF decrease was found versus test-retest values in left basal ganglia (-3.3%+/-4.0% versus 1.5%+/-4.1%, P< 0.05), right basal ganglia (-4.2%+/-4.9% versus 0.6%+/-2.7%, P < 0.01) and left mesial temporal region (-4.5%+/-6.8% versus 2.2%+/-2.9%, P < 0.01). CONCLUSION: The rCBF decrease detected by SPECT after naltrexone challenge in structures rich in opioid receptors, such as the basal ganglia and the left mesial temporal region, may reflect a naltrexone-induced decreased metabolic activity in these areas. These results support the involvement of the opioid system in alcohol dependence. Furthermore, the localization of naltrexone-induced rCBF changes in mesial temporal structures and in basal ganglia supports the implication of emotional memory and obsessive-compulsive phenomena in craving.

Adult↗
PubMed1998

Recurrent hepatitis C virus infection after liver transplantation: immunohistochemical assessment of the viral antigen.

BACKGROUND: The value of immunohistochemical methods to identify hepatitis C virus antigen (HCVAg) in liver tissue has not been established. We have evaluated the significance of HCVAg expression in livers of patients with transplants and recurrent hepatitis C virus (HCV) infection. METHODS: Forty-two liver biopsy specimens from 32 liver-transplant recipients with recurrent HCV infection were tested for HCVAg using fluorescein isothiocyanate-labeled polyclonal, polyreactive human immunoglobulin. Histologic assessment of liver and quantitation of HCV RNA in sera were carried out in specimens obtained simultaneously with biopsies. RESULTS: HCVAg was found in 33% of the liver specimens obtained during the first month after transplantation and in all liver specimens obtained between 1 and 18 months after transplantation. Amounts of the antigen were significantly greater in specimens obtained more than 1 month after transplantation. A statistically significant increase of the average HCV RNA level in serum was observed in samples tested after the first month after the transplantation, and some decrease in the HCV RNA level was found in those obtained between 6 and 18 months after transplantation. Larger amounts of HCVAg were observed in specimens corresponding to episodes of acute or chronic hepatitis than in those associated with minimal parenchymal evidence of rejection. CONCLUSIONS: OBSERVATIONS of HCVAg expression in liver biopsy specimens indicated that the presence of viral antigens in hepatocytes is a constant finding in specimens obtained 1 month or longer after transplantation. Although large amounts of HCVAg correlated with acute or chronic hepatitis, the nature of this association with the development of pathologic changes remains to be established.

Adult↗
PubMed1998

Transient emergence of hepatitis B variants in a patient with chronic hepatitis B resistant to lamivudine.

BACKGROUND: Lamivudine is a cytosine nucleoside analogue that inhibits hepatitis B virus replication. Resistance to lamivudine monotherapy has been reported in patients who received lamivudine to prevent recurrent hepatitis B virus infection after liver transplantation. No cases of resistance have been described in patients who did not clear HBV DNA during lamivudine therapy. METHODS: We report the case of an adult patient with chronic HBeAg-positive hepatitis B who had a hepatitis flare during lamivudine therapy. The patient did not respond to lamivudine and, at 4 months of treatment, developed a significant serum alanine aminotransferase elevation. Alanine aminotransferase levels remained elevated for 4 months and returned to baseline spontaneously. Lamivudine therapy was administered for 1 year (52 weeks) and after withdrawal, alanine aminotransferase levels remained elevated. RESULTS: Sequencing studies of HBV DNA at week 52 showed the emergence of a lamivudine-resistant variant associated with two point mutations in the hepatitis B virus polymerase gene: one mutation led to amino acid substitution of methionine to valine at residue 552, in the highly conserved tyrosine-methionineaspartate-aspartate motif, part of the active site of the polymerase; the second mutation consisted of a substitution of leucine to methionine at residue 528. At week 54 of follow-up, both mutations were undetectable. CONCLUSION: This observation demonstrates the transient emergence of HBV variants in the course of therapy in a patient resistant to lamivudine therapy.

Adult↗
PubMed1998

Hepatitis delta genotypes in chronic delta infection in the northeast of Spain (Catalonia).

BACKGROUND/AIMS: Based on genetic analysis of variants obtained around the world, three genotypes of the hepatitis delta virus have been defined. Hepatitis delta virus variants have been associated with different disease patterns and geographic distributions. To determine the prevalence of hepatitis delta virus genotypes in the northeast of Spain (Catalonia) and the correlation with transmission routes and clinical disease, we studied the nucleotide divergence of the consensus sequence of HDV RNA obtained from 33 patients with chronic delta hepatitis (24 were intravenous drug users and nine had no risk factors), and four patients with acute self-limited delta infection. METHODS: Serum HDV RNA was amplified by the polymerase chain reaction technique and a fragment of 350 nucleotides (nt 910 to 1259) was directly sequenced. RESULTS: Genetic analysis of the nucleotide consensus sequence obtained showed a high degree of conservation among sequences (93% of mean). Comparison of these sequences with those derived from different geographic areas and pertaining to genotypes I, II and III, showed a mean sequence identity of 92% with genotype I, 73% with genotype II and 61% with genotype III. At the amino acid level (aa 115 to 214), the mean identity was 87% with genotype I, 63% with genotype II and 56% with genotype III. Conserved regions included the RNA editing domain, the carboxyl terminal 19 amino acids of the hepatitis delta antigen and the polyadenylation signal of the viral mRNA. CONCLUSIONS: Hepatitis delta virus isolates in the northeast of Spain are exclusively genotype I, independently of the transmission route and the type of infection. No hepatitis delta virus subgenotypes were found, suggesting that the origin of hepatitis delta virus infection in our geographical area is homogeneous.

Adolescent↗
PubMed1998

Epidemiological and clinical aspects of hepatitis C virus infection in the Russian Republic of Daghestan.

UNLABELLED: Hepatitis C virus (HCV) is a leading cause of chronic liver disease. The prevalence in blood donors in the USA and West Europe is around 0.3%. However, there are few studies performed in East Europe. We have studied the prevalence of hepatitis C virus infection and risk factors associated with it in the Russian Republic of Daghestan. POPULATION AND METHODS: We included 10,682 volunteer blood donors, 267 commercial blood donors, 97 high risk patients (22 haemophiliacs, 41 in haemodialysis program and 34 parenteral drug addicts), and 87 patients with chronic liver disease (61 chronic hepatitis, 20 cirrhosis and 6 hepatocellular carcinoma). Antibodies against HCV were detected by second generation ELISA. RESULTS: 0.93% of volunteer blood donors were found to be HCV reactive. Factors with stronger association with seropositivity were previous blood transfusion and parenteral drug addiction. 66% of seropositive blood donors had an elevated level of ALT. Alcohol use correlated with more marked deterioration in liver function tests. 7.5% of commercial blood donors were seropositive. Prevalence in high risk patients and in patients with chronic liver disease was very high (50-80% and 40-50%, respectively). CONCLUSION: The Russian Republic of Daghestan has one of the lowest rates of HCV infection in East Europe. Commercial blood donors have a very high prevalence of HCV infection. The risk factors associated with HCV infection are similar to those found in other epidemiological studies.

Adult↗
PubMed1998

Listeria monocytogenes-associated acute hepatitis in a liver transplant recipient.

We report a case of Listeria monocytogenes bacteriemia with liver involvement mimicking acute viral hepatitis in a liver transplant recipient. The patient presented with fever, jaundice and alanine aminotransferase levels ten times the upper limit of normal. Liver biopsy showed signs of acute hepatitis and occasional granulomas. Both blood and liver biopsy cultures were positive for Listeria monocytogenes. The patient received a 3 week course of ampicillin and gentamicin with clinical and biochemical recovery. Liver involvement during Listeria infections is unusual, and most cases occur in patients with underlying hepatic disease and impaired cell-mediated immunity. To our knowledge only one such case has previously been reported in a liver transplant patient. Furthermore, in the present case we isolated the causal agent from the liver biopsy specimen.

Ampicillin↗
PubMed1997

Tyrosine kinase inhibition ameliorates the hyperdynamic state and decreases nitric oxide production in cirrhotic rats with portal hypertension and ascites.

Tumor necrosis factor-alpha (TNF) causes vasodilatation and a hyperdynamic state by activating nitric oxide (NO) synthesis. Tyrphostins, specific inhibitors of protein tyrosine kinase (PTK), block the signaling events induced by TNF and NO production. A hyperdynamic circulatory syndrome (HCS) is often observed in portal hypertension (PHT). TNF and NO seem to mediate these hemodynamic changes. The aim of this work was to study the effect of PTK inhibition on the systemic and portal hemodynamics, TNF and NO production, in cirrhotic rats with portal hypertension. Rats with liver cirrhosis induced by chronic inhalation of carbon tetrachloride were used. Animals were treated daily with tyrphostin AG 126 (alpha-cyano-(3-hydroxy-4-nitro) cinnamonitrile) or placebo for 5 d. Mean arterial pressure (MAP), heart rate (HR), and portal pressure (PP) were measured by indwelling catheters. Cardiac output (CI) and stroke volume (SV) were estimated by thermodilution, systemic vascular resistance (SVR) was calculated (MAP/CI), and portal systemic shunting (PSS) was quantitated using radioactive microspheres. Serum and mesenteric lymph node (MLN) TNF levels were measured using an immunoassay kit, and serum NOx was determined photometrically by its oxidation products. The AG 126-treated group showed a statistically significant increase in MAP and SVR, and decreases in CI, SV, MLN TNF, and serum NO oxidation products nitrite and nitrate (NOx) in comparison with the placebo-treated rats. No significant differences were noticed in HR, PP, PSS, or serum TNF. Significant correlations were observed between MAP and NOx, MAP and MLN TNF, PSS and NOx, and serum TNF and serum NOx. The HCS observed in PHT seems to be mediated, at least in part, by TNF and NO by the activation of PTKs and their signaling pathways. PTK activity inhibition ameliorates the hyperdynamic abnormalities that characterize animals with cirrhosis and PHT.

Animals↗