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Biomedical subjects

J Guardia

Publications and source records attributed to J Guardia.

At least 19 recordsLinked to original sources
PubMed2006

Hepatotoxicity of antiretroviral drugs in HIV HCV patients with congenital coagulopathies followed at an Haemophilia Unit during a decade.

The aim of the study was to assess the incidence and the cumulative probability of cytolytic and cholestatic hepatotoxicity during antiretroviral treatment in a group of HIV HCV haemophiliacs. We evaluated 47 patients that received 246 courses of antiretroviral treatment [98 courses of pre-highly active antiretroviral therapy (pre-HAART) and 148 HAART treatments]. Liver function tests were assessed at baseline of each treatment, after 1 month and at least every 4 months thereafter. Cytolytic and cholestatic hepatotoxicity was recorded. Of the 246 treatments, 28 (12.45%) were followed by cytolytic hepatotoxicity and 32 (13%) by cholestatic hepatotoxicity. Cytolytic hepatotoxicity was similar in HAART (16/148; 10.8%) and in pre-HAART treatment (12/98; 12.2%) and cholestatic hepatotoxicity was more frequent in HAART (29/148; 19.6%) than in pre-HAART treatment (3/98; 3.1%) (P < 0.001). The actuarial probability of developing cytolytic and cholestatic hepatotoxicity at 10 years of onset of antiretroviral treatments was 39% and 56%, respectively. Most enzyme elevations were asymptomatic, but in eight cases therapy was discontinued or changed and in one case a cirrhotic patient died of progressive liver failure. In HIV HCV haemophiliacs, the cumulative probability of developing hepatotoxicity during follow-up is high and although in the most cases the toxicity is mild, fatal cases can occur.

Adolescent↗
PubMed2006

Hepatitis B virus genotypes and G1896A precore mutation in 486 Spanish patients with acute and chronic HBV infection.

This study aims to determine the prevalence of hepatitis B virus (HBV) genotypes (A-F) and their association with the G1896A precore mutation in 486 patients positive for HBV surface antigen. Genotypes were determined by RFLP and precore mutation by real-time PCR. Genotypes D (48.1%) and A (39.5%) were the most common, followed by F (4.1%) and B, C and E (<1%). The A to D ratio (A:D) was 1.4 in HBeAg+ chronic hepatitis B (CHB), 0.6 in HBeAg- CHB and 1.4 in HBeAg- inactive carriers. Distribution of these genotypes was different between HBeAg+ CHB and HBeAg- CHB (P = 0.02), and between HBeAg- CHB and HBeAg- inactive carriers (P = 0.009). Genotype A was the most prevalent in HBeAg+ CHB with elevated alanine aminotransferase (ALT) (68.6%) and genotype D in HBeAg+ CHB with fluctuating ALT (60.7%). There was a difference in genotype prevalence between chronic and acute infection (P = 0.03). The precore mutant correlated with high levels of HBV-DNA in genotype d HBeAg- CHB. Genotype D is not as highly prevalent in Spanish patients as would be expected in a Mediterranean area. The unequal prevalence of genotypes between acute and chronic infection suggests that genotype A is associated with a higher tendency to cause chronic infection.

Adolescent↗
PubMed2005

Changes in different regions of hepatitis B virus gene in hepatitis B 'e' antigen-negative patients with chronic hepatitis B: the effect of long-term lamivudine therapy.

BACKGROUND: Lamivudine therapy for chronic hepatitis B has been associated with changes in different regions of the hepatitis B virus nucleotide sequence. AIM: To study changes in the sequences of polymerase and precore/core promoter regions of hepatitis B virus, before and during 5 years of therapy with lamivudine. METHODS: Eighty consecutive samples were taken from 10 chronic hepatitis B 'e' antigen-negative patients. RESULTS: Nine patients carried hepatitis B virus precore mutations during the study. Before therapy, wild type was replaced by A1896 in two (20%) cases. During treatment, A1896 reverted transitory to wild type in five cases (50%) and in one case wild type was replaced by A1896. The continuous detection of precore mutations during therapy was associated with a lower response rate. YMDD mutations were observed in nine cases and both, L180M and M204V/I mutations were simultaneously detected in six cases. About 75% of the patients with M204V mutations were responders and none with M204I or mixed pattern sustained response. CONCLUSION: Hepatitis B 'e' antigen-negative patients exhibit changes in the precore regions both spontaneously and under lamivudine therapy, the transitory reversion to wild type being most frequently witnessed. Patients carrying M204V mutations are more likely to respond to therapy. If, in further studies, these results are confirmed some patients with YMDD mutations could benefit from prolonging the duration of lamivudine therapy.

Adult↗
PubMed2004

Subtype mutations in the envelope 2 region including phosphorylation homology domain of hepatitis C virus do not predict effectiveness of antiviral therapy.

The aim of this study was to determine whether specific sequences of the phosphorylation homology domain (PePHD) region could be correlated with differences in response to antiviral therapy in patients infected with hepatitis C virus subtypes 1b, 2c, 3a and 4c/d. We included 43 patients (22 sustained responders and 21 nonresponders or relapsers) in the study, who were classified according to early viral decline during the first weeks of antiviral treatment and response at end of follow up. Type of mutations, mutation frequency, genetic diversity and phylogenetic relationships were compared at the PePHD and flanking regions. Phylogenetic trees showed that each sequence clustered together with those of the same subtype. Sequences from subtypes 1b and 4c/d resembled more closely the phosphorylation sites of protein kinase R and eIF2 alpha than sequences from genotypes 2c and 3a, the latter with higher response rates to interferon-alpha (IFN alpha) treatment. However, within specific subtypes, no separate clusters of responders and nonresponders were observed either at the beginning or at the end of follow up. We were not able to find any particular sequence or mutation in the PePHD region or in any other subregion of the fragment studied that allowed prediction of treatment response.

Adult↗
PubMed2003

Role of immunosuppression in the development of quinolone-resistant Escherichia coli spontaneous bacterial peritonitis and in the mortality of E. coli spontaneous bacterial peritonitis.

BACKGROUND: Norfloxacin decreases the incidence of spontaneous bacterial peritonitis in cirrhotics, but promotes the appearance of quinolone-resistant Escherichia coli. AIM: : To define the characteristics of quinolone-resistant E. coli spontaneous bacterial peritonitis. METHODS: E. coli-positive ascitic fluid cultures were identified during a 6-year period. Data on quinolone-sensitive and quinolone-resistant E. coli spontaneous bacterial peritonitis were compared. RESULTS: One hundred and two E. coli-positive ascitic fluid cultures were detected. Cirrhotics accounted for 67 cases. Spontaneous bacterial peritonitis was found in 47 of the 67 (70%) cases [35 (74%) caused by quinolone-sensitive and 12 (26%) caused by quinolone-resistant E. coli]. Norfloxacin prophylaxis was higher in the quinolone-resistant group (92% vs. 6%, P < 0.001). Compared with patients with quinolone-sensitive E. coli spontaneous bacterial peritonitis, those with quinolone-resistant E. coli spontaneous bacterial peritonitis showed a higher prevalence of associated immunosuppressive factors (immunosuppressive drugs, human immunodeficiency virus infection or cancer) (92% vs. 20%, P < 0.001). Steroid therapy was independently associated with quinolone-resistant E. coli spontaneous bacterial peritonitis (odds ratio, 49; 95% confidence interval, 3.4-699; P = 0.004). The Child-Pugh score (P = 0.03), immunosuppression (P = 0.02) and renal failure (P = 0.01) were independent predictors of E. coli spontaneous bacterial peritonitis-related mortality. CONCLUSIONS: Associated immunosuppression is an important co-factor for the development of quinolone-resistant E. coli spontaneous bacterial peritonitis and for E. coli spontaneous bacterial peritonitis-related mortality.

Anti-Infective Agents↗
PubMed2003

Increased tumour necrosis factor alpha production in mesenteric lymph nodes of cirrhotic patients with ascites.

BACKGROUND: Cytokines produced in mesenteric lymph nodes of cirrhotic rats with bacterial translocation may participate in circulatory alterations of cirrhosis. AIM: To investigate whether cirrhotic patients present an increased local generation of cytokines in mesenteric lymph nodes. METHODS: Mesenteric lymph nodes from 26 cirrhotic and 10 control patients were assessed for tumour necrosis factor alpha (TNF) and interleukin 6 mRNA and protein expression by competitive reverse transcription-polymerase chain reaction, and by enzyme immunoassay and immunohistochemistry, respectively. RESULTS: Interleukin 6 levels were not different between cirrhotics and controls. Protein and mRNA TNF levels in mesenteric lymph nodes from cirrhotics were higher than in controls (p<0.05). Tissue expression of TNF by immunohistochemistry was more abundant in cirrhotics. Ascitic patients showed higher TNF levels (47 (34-54) pg/mg protein) than patients without ascites (18 (17-25) pg/mg protein) (p<0.001). Elevated TNF levels (>28 pg/mg protein) in cirrhotics were associated with a higher Child-Pugh score, the antecedent of ascites, a lower prothrombin rate, and higher bilirubin and blood TNF levels. The strongest association, confirmed by multivariate analysis, was with the presence of ascites (p<0.001). Bacterial infections after transplantation, mainly by enteric bacteria, were only detected in patients with high TNF levels in mesenteric lymph nodes (33% of patients; p=0.05). CONCLUSION: Patients with advanced liver cirrhosis, and especially with ascites, have increased local production of TNF in mesenteric lymph nodes that, in common with experimental cirrhosis, may also be induced by bacterial translocation.

Ascites↗
PubMed2002

[Study of hepatitis B virus replication and infection by other hepatitis viruses in patients with chronic hepatitis B virus infection].

AIM: To study hepatitis B virus (HBV) replication in a series of patients with HBV infection and to analyze the frequency of associated hepatitis C virus (HCV) and hepatitis D (HDV) infection. PATIENTS AND METHOD: Serological markers of HBV, HCV and HDV, transaminase values and HBV DNA were studied in serum samples from 463 patients with chronic HBV infection. RESULTS: Three hundred ninety-six (85.5%) were classified as hepatitis B, 33 (7.1%) as hepatitis B and C, 17 (3.6%) as hepatitis B and D and 17 (3.6%) as hepatitis B, C and D. Sixty-seven percent of patients with hepatitis B and 33% of those with chronic hepatitis B were asymptomatic HBsAg carriers. HVB DNA was identified in 27.7% of patients with hepatitis B, in 24% of those with hepatitis B and C, in 11.7% of those with hepatitis B and D and in 29.4% of those with hepatitis B, C and D. HBV DNA and elevated transaminase levels were found in 63% of HBeAg-positive patients and in only 16% of those who were anti-HBe-positive. These latter were considered candidates for antiviral treatment. CONCLUSIONS: In our environment, most patients with HBV infection are asymptomatic HBsAg carriers. Viral replication and elevated alanine aminotransferase levels were found in 22% of the patients. Consequently, these patients are candidates for antiviral treatment. Between 3.6% and 7.1% of patients with hepatitis B presented coinfection with HCV or HDV, or both. No significant differences were found in HBV replication among the different groups.

Adult↗
PubMed2002

Early detection of nonresponse to interferon plus ribavirin combination treatment of chronic hepatitis C.

We have investigated the value of early hepatitis C virus (HCV) RNA decline (DeltaHCV RNA) to predict response to combination therapy in 66 chronic hepatitis C patients treated with IFN-alpha2b (3 MU thrice weekly) and ribavirin (800 mg daily) for 12 months [25 sustained responders (SR) and 41 nonresponders or relapsers (NR)]. Serum HCV RNA was retrospectively measured in samples obtained at baseline and 4, 8 and 12 weeks after treatment onset, using a commercially available quantitative RT-PCR assay. At 4 weeks, serum HCV RNA had decreased a mean of 2.6 +/- 0.8 logs among SR as compared with only 0.5 +/- 0.8 logs in NR (P < 0.001), and was already undetectable (< 600 IU/mL) in 12 (48%) of the SR but in none of the NR. At 8 weeks, HCV RNA was undetectable in 21 SR and in 2 NR and mean DeltaHCV RNA were 4.2 +/- 1.3 and 0.8 +/- 1.0 logs, respectively (P < 0.001). At week 12 all SR had undetectable HCV RNA as compared with only five NR (P < 0.001). Stepwise logistic regression analysis identified DeltaHCV RNA at 12 weeks as the strongest predictor of sustained response. Receiver operating characteristic (ROC) curves of DeltaHCV RNA for sustained response prediction identified sensitivity peaks with 100% negative predictive value corresponding to DeltaHCV RNA > 1 log at 4 weeks, > 2 logs at 8 weeks and > 3 logs at 12 weeks. Our results show that early changes in the HCV RNA level may reliably identify patients having no chance of a sustained virological response during the first 3 months of combination therapy, thus providing an excellent tool for optimizing antiviral treatment of chronic hepatitis C.

Adult↗
PubMed2002

Relation of Apo E and ACE genes to cognitive performance in chronic alcoholic patients.

Apolipoprotein E epsilon4 and ACE genes have been related to several conditions involving cognitive impairment, including Alzheimer's disease, normal ageing and cerebrovascular disease. However, it has not been established whether their genotypes are associated with alcoholism or its cognitive functioning. Genotypic distributions of 140 chronic alcoholic patients were compared with a non-alcoholic sample, and the cognitive performance of a subsample of the alcoholic subjects was assessed with standard neuropsychological tests. No differences in allele or genotype distributions of Apo E or ACE genes were found when comparing controls and alcoholics (Apo E epsilon2/2; patients 1.4%, controls 0% p < 0.06; epsilon2/epsilon3; patients 9.3%, controls 6.6% p < 0.29; epsilon2/epsilon4; patients 0%, controls 1% p < 0.31; epsilon3/epsilon3 patients 71.4%, controls 72% p < 0.89; epsilon3/epsilon4; patients 15.7%, controls 19.2%, p < 0.36; epsilon4/epsilon4; patients 2.1%, controls 1.2% p < 0.44; ACE D/D; patients 35%, controls 28.5% p < 0.14; I/D; patients 47.5%, controls 51.1% p < 0.51; I/I; patients 14.5%, controls 20.4% p < 0.19). In terms of cognitive performance, epsilon4/epsilon3 patients did better on visuoconstructive (p < 0.001) and visual memory (p < 0.04) functions compared with epsilon2/epsilon3 bearers. Furthermore, ACE D/D patients performed better on a test of abstract reasoning (p < 0.03) compared with the ACE I/I homozygous group. The cognitive results suggest that Apo E or ACE genotypes may modify the effects of ethanol on cognitive deterioration in alcoholic patients. However, the data do not support an association between the Apo E epsilon4 allele and reduced cognitive performance in alcoholism.

Adult↗
PubMed2001

(1)H-MR spectroscopy is sensitive to subtle effects of perinatal asphyxia.

The authors performed neuropsychological and (1)H-MRS studies in 18 subclinical patients with antecedents of perinatal asphyxia (PA) and in 18 matched control subjects. Patients with PA showed reduced values of N-acetylaspartate (NAA) in both the basal ganglia and the midtemporal region (MTR) and reduced NAA/choline values in the MTR. Neuropsychological testing showed group differences in tasks related to attention and memory. These results indicate persistent dysfunctions in cerebral structures vulnerable to hypoxia and demonstrate the utility of MRS for the long-term evaluation of cerebral sequelae of neonatal asphyxia.

Adolescent↗
PubMed2001

Quantitative hepatitis B virus DNA testing for the early prediction of the maintenance of response during lamivudine therapy in patients with chronic hepatitis B.

To determine whether a dramatic decrease in hepatitis B virus (HBV) DNA levels within the first months of lamivudine therapy can predict the emergence of YMDD variants in patients with chronic hepatitis B, quantitative testing was done every 3 months on serum samples from 35 patients who were treated with lamivudine for >1 year. The decline in HBV DNA levels from baseline to month 3 was higher in 22 responders than in 13 nonresponders (mean+/-SD, 4.16+/-1.06 vs. 2.88+/-1.77 log(10) copies; P=.002), whereas no differences were observed in patients with and without YMDD variants at 1 year of therapy. At 3 months, HBV DNA was undetectable in 77% of the responders, whereas, after 1 year, it was undetectable in 23% of nonresponders, 40% of patients with YMDD variants, and 74% of those without variants. Therefore, quantitative HBV DNA testing is very useful in deciding whether to continue therapy, because of the low likelihood of response in patients who remain HBV DNA positive at month 3 of treatment.

Adult↗
PubMed2001

Role of Doppler echocardiography in the assessment of portopulmonary hypertension in liver transplantation candidates.

BACKGROUND: Portopulmonary hypertension is a severe complication of liver cirrhosis that carries a high risk for posttransplantation mortality. We aimed at evaluating the utility of Doppler echocardiography in screening for portopulmonary hypertension in liver transplantation candidates. METHODS: One hundred seven cirrhotic patients candidates for liver transplantation were studied by Doppler echocardiography and subsequently, by cardiac catheterization at transplantation. Two parameters were estimated by Doppler: systolic pulmonary arterial pressure (SPAP) derived from tricuspid regurgitation and the pulmonary acceleration time. Portpulmonary hypertension was suspected when SPAP was > or = 40 mm Hg and/or pulmonary acceleration time < 100 ms. RESULTS: Portpulmonary hypertension was suspected by Doppler study in 17 patients (15%). However, portopulmonary hypertension (mean pulmonary arterial pressure > or = 25 mm Hg and pulmonary vascular resistance > 120 dynes.s/cm5) was confirmed by the hemodynamic study in five patients (4.7%). Sensitivity and specificity of Doppler echocardiography for detecting portopulmonary hypertension was 100 and 88%, respectively, with a positive predictive value of 30%. The diagnostic accuracy of pulmonary acceleration time alone (96%) was better than pulmonary arterial pressure alone (90%). CONCLUSIONS: Doppler echocardiography, and especially the determination of pulmonary acceleration time, is a useful screening method for portopulmonary hypertension in patients with liver cirrhosis who are candidates for liver transplantation.

Adult↗
PubMed2001

Evaluation of hepatitis C virus RNA RT/PCR qualitative and quantitative second generation assays.

Hepatitis C virus (HCV) RNA qualitative and quantitative second generation assays (Amplicor HCV v2.0 and Amplicor HCV Monitor v2.0, respectively) were evaluated by testing serum samples from 132 blood donors anti-HCV positive HCV RNA negative by first generation qualitative assay and 326 viremic patients. An HCV RNA transcript was synthesized and ten-fold dilutions were used to assess sensitivity. Second generation assays were one log more sensitive than their respective first generation tests (10(2) copies per ml vs. 10(3) for the qualitative tests; 10(3) copies per ml vs. 10(4) for the quantitative tests). From the 132 anti-HCV positive RNA negative subjects, 6 (5%) were positive by Amplicor v2.0. Quantification figures by Monitor v2.0 were similar in genotypes 1, 2 and 3, whereas Monitor 1.0 values were higher in genotype 1 than in genotype 2 or 3. In 114 patients, branched-DNA v2.0 obtained higher values than Monitor v2.0 and Monitor v1.0 (6.6+/-0.6 log RNA copies per ml, 6.4+/-0.6, and 5.3+/-0.7, respectively, P<0.001). HCV RNA qualitative and quantitative second generation assays are more sensitive and genotype independent than first generation assays.

Adult↗
PubMed2001

The development of low-grade cerebral edema in cirrhosis is supported by the evolution of (1)H-magnetic resonance abnormalities after liver transplantation.

BACKGROUND/AIMS: Liver failure may cause brain edema through an increase in brain glutamine. However, usually standard neuroimaging techniques do not detect brain edema in cirrhosis. We assessed magnetization transfer ratio and (1)H-magnetic resonance (MR) spectroscopy before and after liver transplantation to investigate changes in brain water content in cirrhosis. METHODS: Non-alcoholic cirrhotics without overt hepatic encephalopathy (n=24) underwent (1)H-MR of the brain and neuropsychological tests. (1)H-MR results were compared with those of healthy controls (n=10). In a subgroup of patients (n=11), the study was repeated after liver transplantation. RESULTS: Cirrhotic patients showed a decrease in magnetization transfer ratio (31.5+/-3.1 vs. 37.1+/-1.1, P<0.01) and an increase in glutamine/glutamate signal (2.22+/-0.47 vs. 1.46+/-0.26, P<0.01). The increase in glutamine/glutamate signal was correlated to the decrease in magnetization transfer ratio and to neuropsychological function. Following liver transplantation, there was a progressive normalization of magnetization transfer ratio, glutamine/glutamate signal and neuropsychological function. Accordingly, correlations between these variables were lost after liver transplantation. CONCLUSIONS: Cirrhotic patients show reversible changes in magnetization transfer ratio that are compatible with the development of low-grade cerebral edema. Minimal hepatic encephalopathy and low-grade cerebral edema appear to be the consequences of the metabolism of ammonia in the brain.

Ammonia↗
PubMed2001

[Assessment of the PCR-Southern blot technique for the analysis of viremia in patients with acute hepatitis A].

Assessment of viremia in hepatitis A virus (HAV) infection is not frequently performed with conventional methods because the techniques used are laborious, have low sensitivity are usually performed in feces. The aims of this study were to develop a polymerase chain reaction (PCR) and Southern blot technique to detect HAV-RNA in the serum of patients with acute HAV infection and to determine the relationship between HAV-RNA and anti-HAV IgM and alanine aminotransferase (ALT) levels. The presence of HAV-RNA was studied in 26 serum samples from 21 patients with acute hepatitis A. We also studied 11 samples from patients with acute hepatitis B and 15 samples from patients with non-A, non-E hepatitis. HAV-RNA was detected in 10 (38%) of the 26 serum samples from patients with acute hepatitis A. Simple PCR was positive in 5 samples and PRC-Southern blot was positive in 10. All the serum samples obtained during the first week of onset were HAV-RNA positive and 50% of those obtained during the second week were positive. None of the serum samples obtained after the second week of onset were HAV-RNA positive. None of the serum samples from the 11 patients with acute hepatitis B or from the 15 patients with non-A, non-E acute hepatitis were positive for HAV-RNA. No significant relationship was detected between HAV-RNA detection and an IgM anti-HAV or ALT positive result. In conclusion, the presence of HAV-RNA in acute hepatitis A is frequent but the PCR Southern blot technique is required for detection, which is transitory during the first weeks after onset.

Acute Disease↗
PubMed2001

Hemoperitoneum as a first manifestation of hepatocellular carcinoma in western patients with liver cirrhosis: effectiveness of emergency treatment with transcatheter arterial embolization.

Hemoperitoneum is a well-known form of hepatocellular carcinoma presentation and represents a frequent complication in countries with a high incidence of hepatocellular carcinoma, but it is rarely seen in Western countries. Our aim was to report the results and describe the arteriographic and CT-scan characteristics in a series of seven consecutive patients. They were admitted to our hospital because of hemoperitoneum due to ruptured tumor as a first manifestation of hepatocellular carcinoma, and the rupture was effectively controlled by transcatheter arterial embolization. From April 1989 to April 1998, 440 consecutive patients were admitted to our liver unit with the diagnosis of hepatocellular carcinoma and liver cirrhosis. Fourteen patients (3%) presented with acute hemoperitoneum due to tumor rupture as a first manifestation of hepatocellular carcinoma. We here report our experience in the group of patients treated by transcatheter arterial embolization. Mean age was 67.1+/-5 years (range, 61-73). All patients presented with sudden abdominal pain, abdominal distension, and four patients had symptoms of acute anemia. In all cases the ruptured tumor was subcapsular. The procedure was effective in the control of bleeding in all cases, without significant impairment in liver function or treatment-related deaths. In six of the seven patients, a self-limited postembolization syndrome was observed. Mean survival time was 273+/-488.7 days (range: 15-1290). Three patients survived more than six months but at the time of evaluation, only one patient was alive. In conclusion, the present results confirm that transcatheter arterial embolization is an effective and well-tolerated treatment in the management of hemoperitoneum due to ruptured hepatocellular carcinoma in patients with liver cirrhosis.

Aged↗
PubMed2001

Usefulness of magnetic resonance spectroscopy for diagnosis of hepatic encephalopathy in a patient with relapsing confusional syndrome.

Magnetic resonance spectroscopy allows the assessment of several metabolites in brain tissue. In patients with hepatic encephalopathy, this technique shows a rise in glutamine and a decrease in myoinositol in brain tissue. However, the role of magnetic resonance spectroscopy in the diagnosis of hepatic encephalopathy is not known. We report the case of a patient with a relapsing confusional syndrome who underwent magnetic resonance spectroscopy. Previously, hepatic encephalopathy was ruled out because of the negative results of a transjugular liver biopsy and normal hepatic venous pressure gradient. The results of magnetic resonance were characteristic of hepatic encephalopathy. Abdominal computed tomography demonstrated large portosystemic shunts associated with cirrhosis of the liver. This case shows that magnetic resonance spectroscopy is an useful technique for the diagnosis of hepatic encephalopathy in selected cases, such as those without clinical signs of cirrhosis and/or large portosystemic shunts.

Biopsy↗