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Biomedical subjects

Guadalupe Garcia-Tsao

Publications and source records attributed to Guadalupe Garcia-Tsao.

At least 19 recordsLinked to original sources

Prevention and treatment of infections in patients with cirrhosis.

Patients with cirrhosis have altered immune defenses and are considered immunocompromised individuals. Changes in gut motility, mucosal defense and microflora allow for translocation of enteric bacteria into mesenteric lymph nodes and the blood stream. Additionally, the cirrhotic liver is ineffective at clearing bacteria and associated endotoxins from the blood thus allowing for seeding of the sterile peritoneal fluid. Thus, hospitalised cirrhotic patients, particularly those with gastrointestinal hemorrhage, are at high risk of developing bacterial infections, the most common being spontaneous bacterial peritonitis. Given the significant morbidity and mortality associated with spontaneous bacterial peritonitis and the fact that half of the cases are community acquired, all hospitalised cirrhotic patients should have a diagnostic paracentesis to exclude infection. Those admitted with gastrointestinal bleed and a negative paracentesis require short-term prophylaxis with norfloxacin. A third generation cephalosporin is the treatment of choice for spontaneous bacterial peritonitis and, once the acute infection is resolved, secondary prophylaxis with oral norfloxacin is warranted. Patients who develop renal dysfunction at the time of active infection have the highest mortality and require adjunctive albumin therapy. This article reviews the pathogenesis of SBP, the evidence behind the antibiotics used, the rationale for adjunctive albumin therapy in the setting of acute renal failure, and the role of prophylactic antibiotics in specific high-risk populations.

Anti-Bacterial Agents↗

A commonsense approach to esophageal varices.

Variceal hemorrhage is one of the most serious complications of portal hypertension and cirrhosis and is associated with a mortality of at least 20% at 6 weeks, despite improvements in therapy over the last decade. Variceal hemorrhage predisposes cirrhotic patients to worsening hepatic decompensation, infection, or renal insufficiency, which contribute to mortality. Providing primary prophylaxis against first variceal hemorrhage, general management of an acute bleeding episode, and treatment after variceal hemorrhage--mainly prevention of rebleeding--are equally important components of care for the cirrhotic patient who has gastroesophageal varices. This article describes a practical approach to the management of cirrhotic patients who have gastroesophageal varices.

Adrenergic beta-Antagonists↗

The transjugular intrahepatic portosystemic shunt for the management of cirrhotic refractory ascites.

Cirrhotic ascites results from sinusoidal hypertension and sodium retention, which is secondary to a decreased effective arterial blood volume. Transjugular intrahepatic portosystemic shunt (TIPS) placement is currently indicated in cirrhotic patients with refractory ascites who require large-volume paracentesis (LVP) more than two or three times per month. TIPS placement is associated with normalization of sinusoidal pressure and a significant improvement in urinary sodium excretion that correlates with suppression of plasma renin activity, which is, itself, indicative of an improvement in effective arterial blood volume. Compared with serial LVP, placement of an uncovered TIPS stent is more effective at preventing ascites from recurring; however, increased incidence of hepatic encephalopathy and shunt dysfunction rates after TIPS placement are important issues that increase its cost. Although evidence suggests that TIPS placement might result in better patient survival, this needs to be confirmed, particularly in light of the development of polytetrafluoroethylene-covered stents. Favorable results apply to centers experienced in placing the TIPS, with the aim being to decrease the portosystemic gradient to <12 mmHg but >5 mmHg. This article reviews the pathophysiologic basis for the use of a TIPS in patients with refractory ascites, the results of controlled trials comparing TIPS placement (using uncovered stents) versus LVP, and a systematic review of predictors of death after TIPS placement for refractory ascites.

Ascites↗

Portal hypertension.

PURPOSE OF REVIEW: Significant advances in the pathophysiology, diagnosis and management of the complications of portal hypertension that have occurred in the last year are reported. RECENT FINDINGS: The specific areas reviewed are those that refer to experimental studies aimed at modifying the factors that lead to portal hypertension (increased intrahepatic vascular resistance and splanchnic vasodilatation) and recent advances in the diagnosis and management of the complications of portal hypertension. The specific complications reviewed in this paper are varices and variceal bleeding (primary prophylaxis, treatment of the acute episode and secondary prophylaxis), ascites and hepatorenal syndrome, spontaneous bacterial peritonitis and hepatic encephalopathy, as well as recent studies of predictors of death in cirrhosis. SUMMARY: Important studies, mostly prospective, regarding the management of the complications of portal hypertension are reviewed, including a trial of beta-blockers in the prevention of varices, a randomized trial of endoscopic variceal ligation plus nadolol in preventing recurrent variceal bleeding and several meta-analyses on trials comparing large-volume paracentesis with transjugular intrahepatic portosystemic shunt in the management of refractory ascites.

Animals↗

Liver involvement in hereditary hemorrhagic telangiectasia: CT and clinical findings do not correlate in symptomatic patients.

OBJECTIVE: The purpose of our study was to report the multiphasic CT findings in patients with symptomatic liver involvement by hereditary hemorrhagic telangiectasia (HHT) and to correlate the CT findings with the type of clinical presentation. CONCLUSION: Patients with symptomatic HHT liver disease have diffuse hepatic telangiectases, a dilated common hepatic artery, and a high incidence of biliary abnormalities. Multiphasic CT is useful in diagnosing liver involvement due to HHT; however, no strong correlation was seen between CT findings and the clinical subtype of HHT liver disease.

Adult↗

Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis.

BACKGROUND: Nonselective beta-adrenergic blockers decrease portal pressure and prevent variceal hemorrhage. Their effectiveness in preventing varices is unknown. METHODS: We randomly assigned 213 patients with cirrhosis and portal hypertension (minimal hepatic venous pressure gradient [HVPG] of 6 mm Hg) to receive timolol, a nonselective beta-blocker (108 patients), or placebo (105 patients). The primary end point was the development of gastroesophageal varices or variceal hemorrhage. Endoscopy and HVPG measurements were repeated yearly. RESULTS: During a median follow-up of 54.9 months, the rate of the primary end point did not differ significantly between the timolol group and the placebo group (39 percent and 40 percent, respectively; P=0.89), nor were there significant differences in the rates of ascites, encephalopathy, liver transplantation, or death. Serious adverse events were more common among patients in the timolol group than among those in the placebo group (18 percent vs. 6 percent, P=0.006). Varices developed less frequently among patients with a baseline HVPG of less than 10 mm Hg and among those in whom the HVPG decreased by more than 10 percent at one year and more frequently among those in whom the HVPG increased by more than 10 percent at one year. CONCLUSIONS: Nonselective beta-blockers are ineffective in preventing varices in unselected patients with cirrhosis and portal hypertension and are associated with an increased number of adverse events. (ClinicalTrials.gov number, NCT00006398.)

Adrenergic beta-Antagonists↗

Histological-hemodynamic correlation in cirrhosis-a histological classification of the severity of cirrhosis.

BACKGROUND/AIMS: While the definitive diagnosis of cirrhosis is histological, it is the degree of portal hypertension, as determined by the hepatic venous pressure gradient (HVPG), that is an important determinant of the severity of cirrhosis. An HVPG > or =10 mmHg (termed clinically significant portal hypertension or CSPH) is predictive of the development of complications of cirrhosis, including death. This study aimed to determine the relationship between specific histological parameters and HVPG in cirrhosis. METHODS: Forty-three patients with biopsy-proven cirrhosis and HVPG measurements within 6 months of the biopsy were included in the study. The following parameters were scored semiquantitatively and without knowledge of HVPG results: sinusoidal fibrosis, septal thickness, loss of portal tracts and central veins, nodule size, inflammation, steatosis, and iron. RESULTS: Septal thickness (p=0.03), small nodularity (p=0.003), loss of portal tracts (p=0.01), inflammation (p=0.04) and alcoholic etiology (p=0.01) correlated with the presence of CSPH. However, small nodularity and septal thickness were the only parameters independently predictive of CSPH (r=0.658, p<0.05). CONCLUSIONS: We describe a subclassification of histological cirrhosis based on the severity of portal hypertension that consists of a combination of nodule size and septal thickness, with small nodularity and thick septa being independent predictors of the presence of CSPH.

Biopsy↗

Patients' experiences related to anti-viral treatment for hepatitis C.

OBJECTIVE: To conduct a qualitative study to elicit patients' descriptions of their own experiences with treatment for hepatitis C (HCV). METHODS: Focus groups were conducted until thematic saturation was reached. RESULTS: A total of 40 patients (80% male) participated in eight focus groups. The themes that emerged most frequently during the focus groups centered on adverse effects and quality of care. The discussions highlighted discrepancies between patients' anticipated effects of drug toxicity versus their actual experiences, gaps in communication between physicians, and the lack of social support as important shortcomings in the healthcare of HCV patients. CONCLUSIONS: The issues raised by the participants in this study highlight several important areas that may lead to improved care for patients with HCV. PRACTICE IMPLICATIONS: This study suggests that care for patients with HCV might be improved by using patient testimonials to improve accuracy of expectations, having both the primary care physician and liver specialist devise a plan to treat symptoms arising during the course of therapy, and ensuring that patients have the option of participating in a support group.

Adaptation, Psychological↗

Bacterial translocation (BT) in cirrhosis.

Gut flora and bacterial translocation (BT) play an important role in the pathogenesis of the complications of cirrhosis. Research on the pathogenesis of BT and its clinical significance transcends established boundaries between microbiology, cell biology, intestinal pathophysiology, and immunology. This review delineates multiple mechanisms involved in the process of BT, with an emphasis on alterations in intestinal flora and mucosal barrier function, particularly immunological defense mechanisms. Current knowledge on the innate and adaptive immune response that allows a "friendly" communication between bacteria and host is summarized, and alterations occurring in cirrhosis that may facilitate BT are discussed. In addition, definition of a "pathological" BT is proposed together with an analysis of the anatomical site and route of BT. Finally, therapeutic approaches for the prevention of BT in experimental and human cirrhosis are reviewed. Future research in the field of BT in cirrhosis will allow the development of new therapeutic targets in the prevention of infections and other complications of cirrhosis.

Bacterial Translocation↗

Methotrexate (MTX) plus ursodeoxycholic acid (UDCA) in the treatment of primary biliary cirrhosis.

This placebo-controlled, randomized, multicenter trial compared the effects of MTX plus UDCA to UDCA alone on the course of primary biliary cirrhosis (PBC). Two hundred and sixty five AMA positive patients without ascites, variceal bleeding, or encephalopathy; a serum bilirubin less than 3 mg/dL; serum albumin 3 g/dL or greater, who had taken UDCA 15 mg/kg daily for at least 6 months, were stratified by Ludwig's histological staging and then randomized to MTX 15 mg/m2 body surface area (maximum dose 20 mg) once a week while continuing on UDCA. The median time from randomization to closure of the study was 7.6 years (range: 4.6-8.8 years). Treatment failure was defined as death without liver transplantation; transplantation; variceal bleeding; development of ascites, encephalopathy, or varices; a doubling of serum bilirubin to 2.5 mg/dL or greater; a fall in serum albumin to 2.5 g/dL or less; histological progression by at least two stages or to cirrhosis. Patients were continued on treatment despite failure of treatment, unless transplantation ensued, drug toxicity necessitated withdrawal, or the patient developed a cancer. There were no significant differences in these parameters nor to the time of development of treatment failures observed for patients taking UDCA plus MTX, or UDCA plus placebo. The trial was conducted with a stopping rule, and was stopped early by the National Institutes of Health at the advice of our Data Safety Monitoring Board for reasons of futility. In conclusion, methotrexate when added to UDCA for a median period of 7.6 years had no effect on the course of PBC treated with UDCA alone.

Adult↗

What do patients consider when making decisions about treatment for hepatitis C?

PURPOSE: There are few data describing decision-making in chronic hepatitis C infection from the patient's perspective. In this study, we sought to investigate the factors that influence patients' decisions as they consider treatment for hepatitis C infection. SUBJECTS: Consecutive patients attending outpatient liver clinics were recruited. Purposeful sampling was employed to include patients who were currently being treated or had recently been treated for chronic hepatitis C infection with pegylated-interferon and ribavirin as well as patients who had refused therapy. METHODS: We conducted focus groups until thematic saturation was reached. All focus groups were facilitated by the same PhD-level senior research scientist, and constant comparative methods were used to analyze the data. RESULTS: A total of 40 patients (80% male) participated in 8 focus groups. The factors influencing patients' decision-making that emerged most frequently during the focus groups were consideration of risk benefit tradeoffs, protected values, heuristics, participants' conceptualization of hepatitis C infection, social issues, and physicians' recommendations. CONCLUSION: Ideally, complex decision-making is based on careful consideration of the tradeoffs related to available options. Our findings suggest that patients' treatment decisions are influenced by multiple factors besides the risks and benefits of interferon and ribavirin. By being aware of these factors physicians can improve decision-making in hepatitis C infection by 1) determining whether patients' decisions are biased by heuristics or protect values, 2) understanding how patients' conceptualization of their illness influences their attitudes toward therapy, and by 3) ensuring that patients understand that social responsibilities need not necessarily preclude treatment because therapy can be discontinued if adverse effects become intolerable.

Adult↗

Portal hypertension.

PURPOSE OF REVIEW: Report on significant advances in the pathophysiology, diagnosis, and management of the complications of portal hypertension that have occurred in the last year. RECENT FINDINGS: The specific areas reviewed refer to experimental studies aimed at modifying the factors that lead to portal hypertension (increased intrahepatic vascular resistance and splanchnic vasodilatation) and recent advances in the diagnosis and management of the complications of portal hypertension. The specific complications reviewed in this paper are varices and variceal bleeding (primary prophylaxis, treatment of the acute episode, and secondary prophylaxis), ascites and some of its complications (hyponatremia, hepatic hydrothorax), hepatorenal syndrome, spontaneous bacterial peritonitis, and hepatic encephalopathy. SUMMARY: Important studies, mostly prospective, regarding the management of the complications of portal hypertension are reviewed, including trials that demonstrate the value of the hepatic venous pressure gradient in predicting these complications, a trial of beta-blockers in patients with small varices, a randomized trial of transjugular intrahepatic portosystemic shunt using covered stents and another pilot study using this shunt in the treatment of hepatorenal syndrome, a trial of antibiotic prophylaxis in preventing early variceal rebleeding, and a trial of synbiotic therapy in hepatic encephalopathy. These trials will contribute to advancing the practice of hepatology and defining future research areas.

Humans↗

Gut microflora in the pathogenesis of the complications of cirrhosis.

The gut flora plays an important role in the pathogenesis of the complications of cirrhosis. Cirrhotic patients are prone to develop bacterial infections, mainly the 'spontaneous' infection of ascites or spontaneous bacterial peritonitis. Other complications of cirrhosis, such as variceal haemorrhage and ascites, occur mostly or solely as a consequence of portal hypertension. Portal pressure increases initially as a consequence of an increased intrahepatic resistance but, once collaterals have formed, high portal pressure is maintained by an increased splanchnic blood inflow secondary to vasodilatation. Splanchnic vasodilatation is the initiating event in the hyperdynamic circulatory state that aggravates the complications of cirrhosis. The gut flora plays a role in both the development of infections and in the hyperdynamic circulatory state of cirrhosis and, although less prominently, it also plays a role in the pathogenesis of hepatic encephalopathy. This chapter presents evidence regarding gut flora and its modification in the pathogenesis and management of these complications of cirrhosis.

Ascites↗