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J Rodés

Publications and source records attributed to J Rodés.

At least 37 records · Page 2Linked to original sources
PubMed2001

Long-term follow-up of chronic hepatitis C in patients diagnosed at a tertiary-care center.

BACKGROUND/AIMS: The natural history of chronic hepatitis C (HCV) is not completely understood. This study was aimed to evaluate the long-term outcome of the disease over a prolonged period of time and to identify factors associated with progression. METHODS: One hundred and sixteen patients with non-cirrhotic chronic non-A, non-B hepatitis consecutively diagnosed at a tertiary hospital between 1971 and 1977 were followed until December 1998 or until death. Patients with significant alcohol intake were excluded from the study. Variables obtained at the time of diagnosis, including epidemiological, clinical, laboratory, and histological data were recorded to determine risk factors associated with the development of liver cirrhosis and hepatic decompensation. RESULTS: Based on complete follow-up data, the development of liver cirrhosis and hepatic decompensation was evaluated in 94 and 114 of the 116 patients, respectively. Thirty-seven (39.3%) of 94 patients developed liver cirrhosis; an aspartate aminotransferase (AST) value higher than 70 IU/L was associated with development of cirrhosis (odds ratio (OR) 4.22, 95% CI 1.3-13.8). Hepatic decompensation occurred in 12 (10.5%) of 114 patients, its cumulative probability being 2.8% at 10 years, 5.2% at 15 years and 19.8% at 20 years. The only factor independently associated to the development of hepatic decompensation was the presence of fibrosis (stage 2 or 3) in the initial liver biopsy (OR 4.1, IC 95% 1.22-13.9). Liver-related death occurred only in seven (6%) of 114 patients. In comparison with the 116 patients diagnosed in the 1970's, patients with chronic hepatitis C diagnosed in 1999 were younger, more often asymptomatic, had lower AST and alanine aminotransferase (ALT) values and had significantly lower grade and stage histological scores. CONCLUSIONS: In summary, chronic hepatitis C had a high rate of progression to liver cirrhosis over a prolonged follow-up. However, this might be related to the fact that two decades ago the diagnosis was made at a significantly more advanced stage of the disease. Patients at high risk of progression can be identified by biochemical and histological variables at the time of diagnosis.

Adult↗
PubMed2001

Human myofibroblastic hepatic stellate cells express Ca(2+)-activated K(+) channels that modulate the effects of endothelin-1 and nitric oxide.

BACKGROUND/AIMS: High-conductance Ca(2+)-activated K(+) (BK(Ca)) channels modulate the effects of vasoactive factors in contractile cells. It is unknown whether hepatic stellate cells (HSCs) contain BK(Ca) channels and what their role in the regulation of HSCs contractility is. METHODS: The presence of BK(Ca) channels in HSCs was assessed by the patch-clamp technique. The functional role of BK(Ca) channels was investigated by measuring intracellular calcium concentration ([Ca(2+)](i)) and cell contraction in individual cells after stimulation with endothelin-1 in the presence or absence of specific modulators of BK(Ca) channels. RESULTS: BK(Ca) channels were detected by patch-clamp in most of the activated HSCs studied. Incubation of cells with iberiotoxin, a BK(Ca) channel blocker, increased both the sustained phase of [Ca(2+)](i) elicited by endothelin-1 and the number of cells undergoing contraction, while the use of NS1619, a BK(Ca) channel opener, induced opposite effects. Stimulation of HSCs with S-nitroso-N-acetyl-penicillamine (SNAP), a nitric oxide (NO)-donor, increased the opening of BK(Ca) channels and reduced the effects of endothelin-1. Conversely, iberiotoxin abolished the inhibitory effect of SNAP on endothelin-induced [Ca(2+)](i) increase and cell contraction. CONCLUSIONS: Activated human HSCs contain BK(Ca) channels that modulate the contractile effect of endothelin-1 and mediate the inhibitory action of NO.

Benzimidazoles↗
PubMed2001

[Infectious complications associated with liver transplantation: analysis of 104 patients].

OBJECTIVE: Infectious complications are the main cause of morbidity and mortality during the first year after liver transplantation. The aim of the present study was to determine the incidence, microorganisms and factors associated with the development of infectious complications. PATIENTS AND METHOD: Retrospective analysis of infectious episodes during the first year after transplantation in 104 patients undergoing transplantation between April 1995 and December 1996. The various clinical variables related to the pre-transplant disease, the surgical intervention and post-transplant evolution were evaluated with the aim of identifying predictive factors for the development of bacterial infectious complications. RESULTS: During the first year, 51 patients (49%) presented 111 infectious episodes. The most frequent infections were bacterial (66%); 21% were cytomegalovirus infections and 22% were fungal. The incidence of bacterial infections was highest during the first month (80% of all infectious episodes in this period). Two variables were independently associated with the development of bacterial infections in the first month following transplantation: prolonged ischemia of the graft (p = 0.002) and length of stay in the intensive care unit (p = 0.002). Infectious complications caused 8 of the 11 deaths that occurred during the 1-year follow-up. Mortality associated with invasive fungal infections was 100%. CONCLUSIONS: Although the overall incidence of infections and associated mortality has decreased, it remains the main cause of mortality and morbidity in the first year after transplantation.

Female↗
PubMed2001

Desensitization to the effects of intravenous octreotide in cirrhotic patients with portal hypertension.

BACKGROUND & AIMS: Octreotide has been suggested for the treatment of variceal bleeding, but detailed dose-finding studies are not available. We performed a dose-finding study investigating the hemodynamic effects of several forms of intravenous octreotide administration. METHODS: Splanchnic hemodynamics and plasma glucagon levels were measured in 68 cirrhotics in baseline conditions and (1) after a double-blind intravenous injection of octreotide (50 microg [n = 9] or 500 microg [n = 8]) or placebo (n = 7); (2) after a 50-microg octreotide bolus followed by continuous infusion of 50 microg/h (n = 8), 250 microg/h (n = 8), or placebo (n = 6); (3) after repeated 50-microg injections of octreotide (n = 9) or placebo (n = 6) after an initial bolus (50 microg octreotide); and (4) after a placebo bolus and continuous octreotide infusion (50 microg/h; n = 7). RESULTS: Placebo caused no significant changes. Octreotide caused a marked and transient decrease in portal pressure and azygos blood flow and an increase in mean arterial pressure. These effects lasted only 5 minutes despite addition of continuous octreotide infusions. Repeated octreotide injections had shorter, less marked effects than the first bolus. A continuous octreotide infusion did not decrease portal pressure. Glucagon levels were markedly reduced by octreotide, but gradually returned to baseline despite continuous infusions or repeated injections of octreotide. CONCLUSIONS: Octreotide injection caused marked but transient reductions in portal pressure and azygos blood flow. Adding a continuous octreotide infusion neither maintained nor prolonged its effects. Repeated boluses caused significant tachyphylaxis. This rapid desensitization to the effects of octreotide may explain the divergent effects achieved with octreotide infusions in acute variceal bleeding.

Adult↗
PubMed2001

Collagen type Ialpha1 and vitamin D receptor gene polymorphisms and bone mass in primary biliary cirrhosis.

The potential influence of two gene polymorphisms, vitamin D receptor gene (VDR) and the gene encoding collagen type Ialpha1 (COLIA1) Sp1 polymorphisms, in the reduced bone mass observed in patients with primary biliary cirrhosis (PBC) was assessed in 61 women with PBC (age, 54.1 +/- 1.1 years) by restriction enzyme digestion of polymerase chain reaction (PCR)-amplified DNA extracted from whole blood. Bone mineral density (BMD) of the lumbar spine (L2-L4) and proximal femur were measured by X-ray absorptiometry. The severity of liver disease and cholestasis was also evaluated, and changes in BMD were calculated after a mean period of 2.9 +/- 0.3 years in 41 patients. Sixteen patients (26 %) had the BB, 20 the bb (33 %), and 25 Bb (41%) VDR genotypes. There were no significant baseline BMD differences among the 3 VDR genotypes. Forty-one patients (68%) had the SS, 16 the Ss (27%), and 3 the ss (5%) COLIA1 genotypes. The baseline lumbar BMD was significantly lower in patients having the s allele than in the homozygote SS patients (Z-score, -0.76 +/- 0.24 vs. -0.10 +/- 0.17, P =.02). The severity of cholestasis was not related to the VDR or COLIA1 1 polymorphisms. Lumbar bone loss was independent of VDR and COLIA1 genotypes, but it was associated with cholestasis. In conclusion, the COLIA1 but not VDR polymorphism is a genetic marker of peak bone mass in patients with PBC, although the severity of cholestasis is the main factor for osteoporosis since it is associated with the rate of bone loss.

Bone Density↗
PubMed2001

Effects of blood volume restitution following a portal hypertensive-related bleeding in anesthetized cirrhotic rats.

The aim of this study was to investigate the influence of different strategies of blood volume restitution in the outcome of portal hypertension-related bleeding in anesthetized cirrhotic rats. Gastrointestinal hemorrhage was induced by sectioning a first order branch of the ileocolic vein in 38 cirrhotic rats (common bile duct ligation and occlusion). The subsequent hypovolemic shock was treated with no transfusion (n = 17), moderate transfusion (50% of expected blood loss, 5 mL, n = 11), and total transfusion (100% of expected blood loss, 10 mL, n = 10). At the end of the blood transfusion period (minute 15), mean arterial pressure (MAP) partially recovered in rats receiving moderate transfusion or no transfusion but decreased in the 10-mL transfusion group ( downward arrow 12 +/- 43%, P < .05 vs. no transfusion and 5 mL transfusion). After transfusion, groups given no or 5 mL transfusion remained hemodynamically stable. However, rats receiving 10 mL transfusion continued to deteriorate with persistent bleeding and progressive fall in MAP ( downward arrow 65 +/- 12%; P < .05 vs. no transfusion and 5 mL transfusion). Collected blood loss was significantly greater in the 10-mL group (20.0 +/- 1.5 g) than in groups given 5 mL (15.9 +/- 2.8 g; P < .05) or no transfusion (13.2 +/- 2.1 g; P < .05 vs. 10 mL and 5 mL transfusion). Survival in the no transfusion group was 47%. Rats given 5-mL transfusion had 64% survival. The worst survival was observed in the 10-mL transfusion group (0% survival; P < .05). We concluded that a transfusion policy aimed at completely replacing blood loss worsens the magnitude of bleeding and mortality from portal hypertensive-related bleeding in cirrhotic rats. On the contrary, moderate blood transfusion allowed hemodynamic stabilization and increased survival.

Animals↗
PubMed2001

In vitro and in vivo activation of rat hepatic stellate cells results in de novo expression of L-type voltage-operated calcium channels.

Following chronic liver injury, hepatic stellate cells (HSCs) transdifferentiate into myofibroblast-like cells, which develop contractile properties and contribute to increased resistance to blood flow. We investigated whether this phenotypic activation includes changes in the expression of L-type voltage-operated Ca2+ channels (VOCC), which mediate Ca2+ influx and regulate cell contraction in vascular cell types. Rat HSCs were studied in the quiescent phenotype and after their activation in vitro (cultured on plastic for 14 days) and in vivo (isolated from rats with CCl(4)-induced cirrhosis). Patch-clamp studies showed Ca2+ currents through L-type VOCC in HSCs activated both in vitro and in vivo, whereas no currents were detected in quiescent HSCs. Moreover, binding studies with (3)H-isradipine, a specific L-type VOCC antagonist, showed a large number of binding sites in activated HSCs, while no specific binding was found in quiescent HSCs. Finally, messenger RNA (mRNA) encoding L-type VOCC was not detected in quiescent HSCs as assessed by reverse transcription-polymerase chain reaction (RT-PCR) and Northern blot analysis, whereas it was present in activated HSCs. Stimulation of L-type VOCC with KCl resulted in a marked increase in [Ca2+](i) followed by cell contraction in HSCs activated both in vitro and in vivo, whereas no effects were observed in quiescent HSCs. We conclude that the activation of HSCs is associated with up-regulation of L-type VOCC that mediate Ca2+ influx and cell contraction. These results may be relevant to the pathogenesis of portal hypertension.

Animals↗
PubMed2001

Increased risk of tumor seeding after percutaneous radiofrequency ablation for single hepatocellular carcinoma.

Radiofrequency (RF) ablation is an alternative to percutaneous ethanol injection (PEI) for single nonsurgical hepatocellular carcinoma (HCC) and is currently used as adjuvant therapy before liver transplantation. This phase II study assesses the treatment-related complications and response rate of RF for the treatment of single HCC < or = 5 cm. Percutaneous RF was performed under conscious sedation and ultrasound (US) guidance with an electrical generator connected to a single cooled-tip electrode. Neoplastic cells in peripheral blood (reverse transcription-polymerase chain reaction for alpha fetoprotein [AFP] messenger RNA) were analyzed before and after RF. Treatment response was assessed by spiral computed tomography (CT) at 1 month and every 3 months by US or spiral CT thereafter. Thirty-two patients (20 men; age 67 +/- 4 years; 78% hepatitis C virus; 24 Child-Pugh A) with a mean tumor size of 2.8 cm (25 patients < or = 3 cm) were treated by RF (1.25 sessions; mean time, 22.1 +/- 2 minutes). Adjuvant PEI was performed in 9 cases. Complete response was achieved in 21 patients (65%), being significantly higher for HCC < or = 3 cm (76% vs. 29%, P = .03). After a median follow-up of 10 months, 8 patients showed treatment-related morbidity. Four of them (12.5%) showed biopsy-proven needle-track seeding detected between 4 to 18 months. Neoplastic seeding was related to subcapsular location (P = .009), poor differentiation degree (P = .02), and baseline AFP levels (P = .02). Thus, RF ablation with cooled-tip needle for HCC is associated with a high risk of neoplastic seeding. Iatrogenic dissemination was related to subcapsular location or an invasive tumoral pattern, and has to be considered when selecting curative treatments for HCC or adjuvant therapies before liver transplantation.

Aged↗
PubMed2001

High amino acid variability within the NS5A of hepatitis C virus (HCV) is associated with hepatocellular carcinoma in patients with HCV-1b-related cirrhosis.

Interferon therapy may decrease the risk of hepatocellular carcinoma in patients with hepatitis C virus (HCV)-related liver cirrhosis. Interaction of the cellular protein kinase PKR with the PKR-binding domain (PKR-bd) of HCV-NS5A protein may affect cellular growth control and viral resistance to interferon therapy. Mutations within the PKR-bd, which comprises the interferon sensitivity determining region (ISDR), have been associated with interferon sensitivity. To determine whether or not there is an association between HCV heterogeneity and the presence of hepatocellular carcinoma, HCV-1b genomic regions were amplified and directly sequenced from serum samples obtained from 82 patients with liver cirrhosis, 53 with, and 29 without hepatocellular carcinoma. None of them had received antiviral therapy. When compared with the deduced consensus sequence, the median number of amino acid changes in the PKR-bd was higher among samples from patients with (4.22) than from those without hepatocellular carcinoma (1.62; P <.001), and isolates with 3 or more amino acid changes were significantly more common among the former (60%) than among the later (6%, P <.001). No such differences were observed in other viral regions, including Core, E2-HVR-1, E2-PePHD, NS3, and the 5' and 3' PKR-bd flanking regions. In addition, amino acid variation in viral regions other than HVR-1 did not accumulate over time in the analyzed sequential serum samples obtained from patients with or without hepatocellular carcinoma. Therefore, a mutated HCV-PKR-bd phenotype is very common in cirrhotic patients with hepatocellular carcinoma.

Aged↗
PubMed2001

Increased production of vascular endothelial growth factor in peritoneal macrophages of cirrhotic patients with spontaneous bacterial peritonitis.

Spontaneous bacterial peritonitis (SBP) is a common complication of cirrhotic patients with ascites that usually results in renal failure and death despite the efficacy of the current antibiotic therapy. The pathogenesis of these phenomena is poorly known but it has been related to the production of vasoactive cell mediators locally acting on the splanchnic vasculature. Because previous studies showed that peritoneal macrophages of cirrhotic patients may produce high quantities of vascular endothelial growth factor (VEGF), a powerful vessel permeabilizing agent, when stimulated by cytokines and bacterial lipopolysaccharide, the present study was aimed to seek whether peritoneal macrophages of SBP patients are induced to produce increased amounts of VEGF. Our results indicate that the production rate and the messenger RNA (mRNA) and protein expression of this substance are increased in macrophages of patients with SBP in comparison with those of noninfected cirrhotic patients. This characteristic feature is absent in circulating monocytes of these patients. Moreover, enhanced endothelial cell proliferation induced by conditioned medium of macrophages isolated from the ascites of patients with SBP is abolished by anti-VEGF antibody, and peritoneal tissue of cirrhotic patients expresses both VEGF receptors, Flt-1 and KDR. These results, therefore, are consistent with the concept that locally released macrophage-derived VEGF may result in increased vascular permeability and plasma leakage in the peritoneal vessels of cirrhotic patients with SBP.

Bacterial Infections↗
PubMed2001

Renal failure after upper gastrointestinal bleeding in cirrhosis: incidence, clinical course, predictive factors, and short-term prognosis.

To assess the incidence, clinical course, predictive factors, and prognosis of renal failure in patients with cirrhosis and gastrointestinal bleeding, 175 consecutive episodes of gastrointestinal bleeding in 161 patients were analyzed. Renal failure occurred in 20 (11%) episodes and was transient in 8 episodes and nontransient in 12. Renal failure was more common in patients with cirrhosis than in a control population of bleeding patients without cirrhosis matched by age and severity of the bleeding episode. Among 39 clinical and laboratory variables obtained at admission or during hospitalization related with the bleeding episode or with liver and renal function, the presence of hypovolemic shock, number of packed red blood cells transfused, Child-Pugh class at admission, and baseline platelet count were independent predictors of renal failure. The development of renal failure and hypovolemic shock was the only independent predictors of in-hospital mortality. Mortality rate among the 20 episodes with renal failure was 55% (11 deaths) as compared with only 3% (5 deaths) in the 155 episodes without renal failure (P <.01). The development of nontransient renal failure entailed a much greater mortality as compared with transient renal failure (10 of 12 [83%] vs. 1 of 8 [12%]; P <.01). In conclusion, renal failure is a common event in patients with cirrhosis and gastrointestinal bleeding, the occurrence of which is mainly related to the severity of bleeding and baseline liver function. Renal failure is a strong predictor of mortality in patients with cirrhosis and gastrointestinal bleeding.

Adolescent↗
PubMed2001

Propranolol for the prevention of first esophageal variceal hemorrhage: a lifetime commitment?

Although beta blockers have had significant impact in the treatment of portal hypertension, the question of how long they should be continued for prevention of variceal hemorrhage remains unknown. Prospective studies on beta blockers to prevent variceal hemorrhage lack long-term follow-up, and indefinite administration of beta blockers for primary prevention of variceal bleeding has become standard practice. The aim of this study was to determine the outcomes of patients in whom beta blocker therapy was discontinued. Patients completing a prospective, randomized, double-blind, placebo-controlled trial of propranolol for the primary prevention of variceal hemorrhage were tapered off of propranolol and placebo and followed prospectively for subsequent events. Of the 49 patients in the follow-up study (25 former propranolol, 24 former placebo), 9 experienced variceal hemorrhage (6 former propranolol, 3 former placebo). Following withdrawal of propranolol, the freedom from variceal bleeding was not significantly different between these 2 groups of patients, suggesting that the protective effect of propranolol against variceal hemorrhage, noted previously, was no longer present. Seventeen patients died (12 former propranolol, 5 former placebo) during the follow-up study. Cumulative survival was longer in the placebo group. These trends for EVH and survival were opposite to those observed in the original study population while patients were taking medication. When propranolol is withdrawn, the risk of variceal hemorrhage returns to what would be expected in an untreated population. Patients who discontinue beta blockers experience increased mortality compared with an untreated population. These observations support the current practice of indefinite prophylactic therapy.

Adrenergic beta-Antagonists↗
PubMed2001

Stenosis of the suprahepatic inferior vena cava as a complication of transjugular intrahepatic portosystemic shunt in Budd-Chiari patients.

We report 2 patients with Budd-Chiari (BC) syndrome secondary to thrombogenic conditions who underwent transjugular intrahepatic portosystemic shunt (TIPS) placement because of refractory ascites and impending liver failure. After TIPS placement, there was marked symptomatic relief and improvement in liver function, but the courses of both patients were complicated by the development of an inferior vena cava (IVC) syndrome caused by segmental stenosis of the suprahepatic IVC just at the outflow jet of the TIPS at 11 and 9 months later. One patient underwent liver transplantation, and the other patient, caval angioplasty and stenting. Stenosis of the IVC represents an unrecognized complication of TIPS in patients with BC syndrome.

Adult↗
PubMed2001

Hepatocellular carcinoma in primary biliary cirrhosis: similar incidence to that in hepatitis C virus-related cirrhosis.

OBJECTIVES: The prevalence of hepatocellular carcinoma (HCC) in primary biliary cirrhosis (PBC) is not well established, as some reports suggest a low risk, whereas others indicate that HCC may be no less frequent than in other types of cirrhosis. METHODS: We compared the incidence of HCC in a series of 140 patients with PBC (five men, 135 women, mean age 54 +/- 1.6 yr) followed-up for a mean of period of 5.6 +/- 0.4 yr with a group of patients with cirrhosis related to hepatitis C virus (HCV) who were matched for age, sex, and follow-up period. In all patients, HCC was prospectively screened by clinical, laboratory, and ultrasound procedures. RESULTS: Five patients with PBC (3.6%) developed HCC. All were in stage IV of the disease. The incidence of HCC in the 45 patients with late stages of the disease (III or IV) was 11.1%, similar to that found in patients with HCV-related cirrhosis, which was 15.0%. The relative risk for HCC in late stages of PBC was of 0.812 (95% CI, 0.229-2.883) with respect to HCV-related cirrhosis. The probability for developing HCC was significantly higher in patients with HCV-related cirrhosis than in PBC patients overall (p = 0.001), but was similar in patients with HCV-related cirrhosis and in patients with PBC in stages III and IV (p = ns). CONCLUSION: The risk for HCC in patients with late stages of PBC is similar to that in patients with HCV-related cirrhosis.

Carcinoma, Hepatocellular↗
PubMed2001

Hepatic familial amyloidosis caused by a new mutation in the apolipoprotein AI gene: clinical and pathological features.

OBJECTIVE: Recently, we reported a nondescribed deletion/insertion mutation in the apolipoprotein AI gene as the cause of hereditary amyloidosis with hepatic presentation. We describe the clinical and pathological features of this type of amyloidosis in one affected family. METHODS: Demographic, clinical, and biochemical data were obtained from 33 members of the family in whom the apolipoprotein AI gene was studied. Diagnosis was based on the detection of the apolipoprotein AI gene mutation, scintigraphy using radioionated serum amyloid P component, and histological and immunohistochemical studies. RESULTS: Eight members with the mutation had hepatic involvement. Six patients were practically asymptomatic, presented with an elevation of alkaline phosphatase and gamma-glutamyl transpeptidase, and remained stable during follow-up (7.6 +/- 4.9 yr). One patient had jaundice, developed ascites and encephalopathy, and died of hepatorenal syndrome a few months after diagnosis. Jaundice and portal hypertension appeared in the remaining patient, who died 4 yr later. CONCLUSION: This form of familial amyloidosis is characterized by elevation in serum alkaline phosphatase and gamma-glutamyl transpeptidase secondary to amyloid deposits in the portal tracts. Patients remain stable and asymptomatic for many years, but portal hypertension and liver failure can develop later in life and lead to death. Thus, patients should be observed regularly and liver transplantation should be indicated when progression is detected.

Adult↗