Determinants of clinical response to empirical antibiotic treatment in patients with cirrhosis and bacterial and fungal infections-Results from the ICA "Global Study" (EABCIR-Global Study).

BACKGROUND: The administration of an appropriate empirical antibiotic treatment is essential in cirrhosis and severe bacterial infections. We aimed to investigate the predictors of clinical response of empirical antibiotic treatment in a prospective cohort of patients with cirrhosis and bacterial and fungal infections included in the International Club of Ascites "Global Study." METHODS: Patients hospitalized with cirrhosis and bacterial/fungal infection were prospectively enrolled at 46 centers. Clinical response to antibiotic treatment was defined according to changes in markers of infection/inflammation, vital signs, improvement of organ failure, and results of cultures. RESULTS: From October 2015 to September 2016, 1302 patients were included at 46 centers. A clinical response was achieved in only 61% of cases. Independent predictors of lack of clinical response to empirical treatment were C-reactive protein (OR = 1.16; 95% CI = 1.02-1.31), blood leukocyte count (OR = 1.39;95% CI = 1.09-1.77), serum albumin (OR = 0.70; 95% CI = 0.55-0.88), nosocomial infections (OR = 1.96; 95% CI = 1.20-2.38), pneumonia (OR = 1.75; 95% CI = 1.22-2.53), and ineffective treatment according to antibiotic susceptibility test (OR = 5.32; 95% CI = 3.47-8.57). Patients with a lack of clinical response to first-line antibiotic treatment had a significantly lower resolution rate of infections (55% vs. 96%; p < 0.001), a higher incidence of second infections (29% vs. 15%; p < 0.001), shock (35% vs. 7%; p < 0.001) and new organ failures (52% vs. 19 %; p < 0.001) than responders. Clinical response to empirical treatment was an independent predictor of 28-day survival ( subdistribution = 0.20; 95% CI = 0.14-0.27). CONCLUSIONS: Four out of 10 patients with cirrhosis do not respond to the first-line antibiotic therapy, leading to lower resolution of infections and higher mortality. Broader-spectrum antibiotics and strategies targeting systemic inflammation may improve prognosis in patients with a high degree of inflammation, low serum albumin levels, and severe liver impairment.

Development and external validation of a model to predict multidrug-resistant bacterial infections in patients with cirrhosis.

With the increasing rate of infections caused by multidrug-resistant organisms (MDRO), selecting appropriate empiric antibiotics has become challenging. We aimed to develop and externally validate a model for predicting the risk of MDRO infections in patients with cirrhosis. METHODS: We included patients with cirrhosis and bacterial infections from two prospective studies: a transcontinental study was used for model development and internal validation (n = 1302), and a study from Argentina and Uruguay was used for external validation (n = 472). All predictors were measured at the time of infection. Both culture-positive and culture-negative infections were included. The model was developed using logistic regression with backward stepwise predictor selection. We externally validated the optimism-adjusted model using calibration and discrimination statistics and evaluated its clinical utility. RESULTS: The prevalence of MDRO infections was 19% and 22% in the development and external validation datasets, respectively. The model's predictors were sex, prior antibiotic use, type and site of infection, MELD-Na, use of vasopressors, acute-on-chronic liver failure, and interaction terms. Upon external validation, the calibration slope was 77 (95% CI .48-1.05), and the area under the ROC curve was .68 (95% CI .61-.73). The application of the model significantly changed the post-test probability of having an MDRO infection, identifying patients with nosocomial infection at very low risk (8%) and patients with community-acquired infections at significant risk (36%). CONCLUSION: This model achieved adequate performance and could be used to improve the selection of empiric antibiotics, aligning with other antibiotic stewardship program strategies.

Norfloxacin prophylaxis effect on multidrug resistance in patients with cirrhosis and bacterial infections.

It is unclear whether norfloxacin predisposes to infections by multidrug-resistant organisms (MDROs). We aimed to evaluate if patients with cirrhosis receiving norfloxacin prophylaxis at the time of the diagnosis of bacterial infections were more likely to present a multidrug-resistant isolate than those without prophylaxis. This is a cross-sectional study of hospitalized patients with cirrhosis and bacterial infections from Argentina and Uruguay (NCT03919032) from September 2018 to December 2020. The outcome variable was a multidrug-resistant bacterial infection. We used inverse probability of treatment weighting to estimate the odds ratio (OR) of norfloxacin on infection caused by MDROs considering potential confounders. Among the 472 patients from 28 centers, 53 (11%) were receiving norfloxacin at the time of the bacterial infection. Patients receiving norfloxacin had higher MELD-sodium, were more likely to have ascites or encephalopathy, to receive rifaximin, beta-blockers, and proton-pump inhibitors, to have a nosocomial or health-care-associated infection, prior bacterial infections, admissions to critical care units or invasive procedures, and to be admitted in a liver transplant center. In addition, we found that 13 (24.5%) patients with norfloxacin and 90 (21.5%) of those not receiving it presented infections caused by MDROs (adjusted OR 1.55; 95% CI: 0.60-4.03; p = 0.360). The use of norfloxacin prophylaxis at the time of the diagnosis of bacterial infections was not associated with multidrug resistance. These results help empiric antibiotic selection and reassure the current indication of norfloxacin prophylaxis in well-selected patients.Study registration number: NCT03919032.

Nitrofurantoin-induced liver injury: long-term follow-up in two prospective DILI registries.

Nitrofurantoin is a synthetic antibiotic that is recommended as first-choice treatment for uncomplicated urinary tract infections. The prescription of this drug has increased dramatically, especially in Latin American countries. We described the demographics, clinical characteristics, biochemical features, and outcome of nitrofurantoin-induced liver injury. We analyzed 23 cases from the Latin American DILI Network (LATINDILI) and the Spanish DILI Registry. Causality was assessed with the RUCAM and RECAM scale. Of the 23 DILI cases included in our series, 96% patients were women, and the mean age of the whole cohort was 61 years. The median time of drug exposure was 175 days (interquartile range [IQR] 96-760), with 11 patients who were prescribed nitrofurantoin for more than six months. Hepatocellular damage was the most frequent pattern of liver injury (83%), and nearly half of the patients had an asymptomatic presentation (52%). Neither death nor liver transplantation was documented in this series. Overall, 65% of the patients (n = 15) presented with positive autoantibody titres. The median time to resolution was 81 days (IQR 57-141), and 15 patients (83%) recovered within six months. Five patients (22%) developed nitrofurantoin-induced autoimmune-like hepatitis (NI-AILH), of whom two were characterized by a persistent increase in transaminases that required immunosuppressive treatment to achieve normalization of liver enzymes. Clinicians who prescribe nitrofurantoin should be aware that patients who had taken nitrofurantoin for a long term may be at risk of developing nitrofurantoin-induced autoimmune-like hepatitis.

Clinical and microbiological characteristics of bacterial infections in patients with cirrhosis. A prospective cohort study from Argentina and Uruguay.

INTRODUCTION AND OBJECTIVES: there is insufficient data regarding bacterial infections in patients with cirrhosis to support recommendations for empiric antibiotic treatments, particularly in Latin America. This study aimed to evaluate bacterial infection's clinical impact and microbiological characteristics, intending to serve as a platform to revise current practices. MATERIALS AND METHODS: multicenter prospective cohort study of patients with cirrhosis and bacterial infections from Argentina and Uruguay. Patient and infection-related information were collected, focusing on microbiology, antibiotic susceptibility patterns, and outcomes. RESULTS: 472 patients were included. Spontaneous bacterial infections and urinary tract infections (UTIs) were registered in 187 (39.6%) and 116 (24.6%) patients, respectively, representing the most common infections. Of the 256 culture-positive infections, 103 (40.2%) were caused by multidrug-resistant organisms (reaching 50% for UTI), and 181 (70.7%) received adequate initial antibiotic treatment. The coverage of cefepime and ceftriaxone was over 70% for the empirical treatment of community-acquired spontaneous infections, but ceftazidime´s coverage was only 40%. For all UTI cases and for healthcare-associated or nosocomial spontaneous bacterial infections, the lower-spectrum antibiotics that covered at least 70% of the isolations were imipenem and meropenem. During hospitalization, a second bacterial infection was diagnosed in 9.8% of patients, 23.9% required at least one organ support, and 19.5% died. CONCLUSIONS: short-term mortality of bacterial infections in patients with cirrhosis is very high, and a high percentage were caused by multidrug-resistant organisms, particularly in UTIs. The information provided might serve to adapt recommendations, particularly related to empirical antibiotic treatment in Argentina and Uruguay. The study was registered in Clinical Trials (NCT03919032).

Clinical features and evolution of bacterial infection-related acute-on-chronic liver failure.

BACKGROUND & AIMS: Bacterial infections can trigger the development of organ failure(s) and acute-on-chronic liver failure (ACLF). Geographic variations in bacteriology and clinical practice could lead to worldwide differences in ACLF epidemiology, phenotypes and associated outcomes. Herein, we aimed to evaluate regional differences in bacterial infection-related ACLF in patients with cirrhosis admitted to hospital. METHODS: This post hoc analysis included 1,175 patients with decompensated cirrhosis (with bacterial infection on admission or nosocomial infection) from 6 geographic regions worldwide. Clinical, laboratory and microbiological data were collected from the diagnosis of infection. Patients were followed-up for organ failure(s) and ACLF development according to the EASL-CLIF criteria from enrolment to discharge/death. RESULTS: A total of 333 patients (28%) had ACLF at diagnosis of infection, while 230 patients developed ACLF after diagnosis of infection, resulting in an overall rate of bacterial infection related-ACLF of 48%, with rates differing amongst different geographic regions (38% in Southern Europe vs. 75% in the Indian subcontinent). Bacterial infection related-ACLF more frequently developed in younger patients (55 ± 13 vs. 58 ± 14 years), males (73% vs. 62%), patients with alcohol-related cirrhosis (59% vs. 45%) and those with a higher baseline MELD score (25 ± 11 vs. 16 ± 5) (all p <0.001). Spontaneous bacterial peritonitis, pneumonia or infections caused by extensively drug resistant (XDR) bacteria were more frequently associated with ACLF development. More patients with ACLF had a positive quick sequential organ failure assessment score and septic shock, resulting in a lower infection resolution rate (all p <0.001). CONCLUSIONS: Bacterial infections, especially with XDR organisms, are associated with the highest risk of ACLF development, accounting for almost half of cases globally. Geographic differences result in variable epidemiology and clinical outcomes. LAY SUMMARY: Bacterial infections can trigger a sudden deterioration in an otherwise stable cirrhotic patient, a condition known as acute-on-chronic liver failure or ACLF. This study has found that the development of ACLF following bacterial infection occurs most commonly in the Indian subcontinent and less so in Southern Europe. The common infections that can trigger ACLF include infection of the abdominal fluid, known as spontaneous bacterial peritonitis, pneumonia and by bacteria that are resistant to multiple antibiotics. Patients who develop ACLF following a bacterial infection have high death rates and are frequently unable to clear the infection.

Epidemiology and Effects of Bacterial Infections in Patients With Cirrhosis Worldwide.

BACKGROUND & AIMS: Bacterial infections are common and life-threatening in patients with cirrhosis. Little is known about the epidemiology of bacterial infections in different regions. We performed a multicenter prospective intercontinental study to assess the prevalence and outcomes of bacterial and fungal infections in patients with cirrhosis. METHODS: We collected data from 1302 hospitalized patients with cirrhosis and bacterial or fungal infections at 46 centers (15 in Asia, 15 in Europe, 11 in South America, and 5 in North America) from October 2015 through September 2016. We obtained demographic, clinical, microbiology, and treatment data at time of diagnosis of infection and during hospitalization. Patients were followed until death, liver transplantation, or discharge. RESULTS: The global prevalence of multidrug-resistant (MDR) bacteria was 34% (95% confidence interval 31%-37%). The prevalence of MDR bacteria differed significantly among geographic areas, with the greatest prevalence in Asia. Independent risk factors for infection with MDR bacteria were infection in Asia (particularly in India), use of antibiotics in the 3 months before hospitalization, prior health care exposure, and site of infection. Infections caused by MDR bacteria were associated with a lower rate of resolution of infection, a higher incidence of shock and new organ failures, and higher in-hospital mortality than those caused by non-MDR bacteria. Administration of adequate empirical antibiotic treatment was independently associated with improved in-hospital and 28-day survival. CONCLUSIONS: In a worldwide study of hospitalized patients, we found a high prevalence of infection with MDR bacteria in patients with cirrhosis. Differences in the prevalence of MDR bacterial infections in different global regions indicate the need for different empirical antibiotic strategies in different continents and countries. While we await new antibiotics, effort should be made to decrease the spread of MDR bacteria in patients with cirrhosis.

A Latin American survey on demographic aspects of hospitalized, decompensated cirrhotic patients and the resources for their management.

INTRODUCTION & OBJECTIVES: Liver cirrhosis is a major cause of mortality worldwide. Adequate diagnosis and treatment of decompensating events requires of both medical skills and updated technical resources. The objectives of this study were to search the demographic profile of hospitalized cirrhotic patients in a group of Latin American hospitals and the availability of expertise/facilities for the diagnosis and therapy of decompensation episodes. METHODS: A cross sectional, multicenter survey of hospitalized cirrhotic patients. RESULTS: 377 patients, (62% males; 58±11 years) (BMI>25, 57%; diabetes 32%) were hospitalized at 65 centers (63 urbans; 57 academically affiliated) in 13 countries on the survey date. Main admission causes were ascites, gastrointestinal bleeding, hepatic encephalopathy and spontaneous bacterial peritonitis/other infections. Most prevalent etiologies were alcohol-related (AR) (40%); non-alcoholic-steatohepatitis (NASH) (23%), hepatitis C virus infection (HCV) (7%) and autoimmune hepatitis (AIH) (6%). The most frequent concurrent etiologies were AR+NASH. Expertise and resources in every analyzed issue were highly available among participating centers, mostly accomplishing valid guidelines. However, availability of these facilities was significantly higher at institutions located in areas with population>500,000 (n=45) and in those having a higher complexity level (Gastrointestinal, Liver and Internal Medicine Departments at the same hospital (n=22). CONCLUSIONS: The epidemiological etiologic profile in hospitalized, decompensated cirrhotic patients in Latin America is similar to main contemporary emergent agents worldwide. Medical and technical resources are highly available, mostly at great population urban areas and high complexity medical centers. Main diagnostic and therapeutic approaches accomplish current guidelines recommendations.

Alcohol-Related Liver Disease Is Rarely Detected at Early Stages Compared With Liver Diseases of Other Etiologies Worldwide.

BACKGROUND & AIMS: Despite recent advances in treatment of viral hepatitis, liver-related mortality is high, possibly owing to the large burden of advanced alcohol-related liver disease (ALD). We investigated whether patients with ALD are initially seen at later stages of disease development than patients with hepatitis C virus (HCV) infection or other etiologies. METHODS: We performed a cross-sectional study of 3453 consecutive patients with either early or advanced liver disease (1699 patients with early and 1754 with advanced liver disease) seen at 17 tertiary care liver or gastrointestinal units worldwide, from August 2015 through March 2017. We collected anthropometric, etiology, and clinical information, as well as and model for end-stage liver disease scores. We used unconditional logistic regression to estimate the odds ratios for evaluation at late stages of the disease progression. RESULTS: Of the patients analyzed, 81% had 1 etiology of liver disease and 17% had 2 etiologies of liver disease. Of patients seen at early stages for a single etiology, 31% had HCV infection, 21% had hepatitis B virus infection, and 17% had nonalcoholic fatty liver disease, whereas only 3.8% had ALD. In contrast, 29% of patients seen for advanced disease had ALD. Patients with ALD were more likely to be seen at specialized centers, with advanced-stage disease, compared with patients with HCV-associated liver disease (odds ratio, 14.1; 95% CI, 10.5-18.9; P < .001). Of patients with 2 etiologies of liver disease, excess alcohol use was associated with 50% of cases. These patients had significantly more visits to health care providers, with more advanced disease, compared with patients without excess alcohol use. The mean model for end-stage liver disease score for patients with advanced ALD (score, 16) was higher than for patients with advanced liver disease not associated with excess alcohol use (score, 13) (P < .01). CONCLUSIONS: In a cross-sectional analysis of patients with liver disease worldwide, we found that patients with ALD are seen with more advanced-stage disease than patients with HCV-associated liver disease. Of patients with 2 etiologies of liver disease, excess alcohol use was associated with 50% of cases. Early detection and referral programs are needed for patients with ALD worldwide.

Recommendations on the Diagnosis and Initial Management of Acute Variceal Bleeding and Hepatorenal Syndrome in Patients with Cirrhosis.

Cirrhosis is a serious and life-threatening condition which imposes a significant socioeconomic burden on affected individuals and healthcare systems. Cirrhosis can result in portal hypertension, which may lead to major complications, including acute variceal bleeding and hepatorenal syndrome. Without prompt treatment, these complications may be life-threatening. Over the past 2 decades, new treatment modalities and treatment strategies have been introduced, which have improved patients' prognosis, but the initial management of these severe complications continues to present a challenge. The present recommendations aim to increase clinicians' knowledge on the importance of early diagnosis and treatment, and to provide evidence-based management strategies to potentially, further improve patient outcomes. Special attention was given to the role of terlipressin. A comprehensive non-systematic literature search was undertaken to evaluate the evidence for the diagnosis and initial management of acute variceal bleeding and hepatorenal syndrome in patients with cirrhosis. Recommendations on the diagnosis and initial management of acute variceal bleeding and hepatorenal syndrome in patients with cirrhosis have been developed based on the best available evidence and the expert opinion of the consensus panel following a comprehensive review of the available clinical data. Prompt identification and timely treatment of acute variceal bleeding and hepatorenal syndrome are essential to reduce the burden.

Ombitasvir/paritaprevir/ritonavir/dasabuvir ± ribavirin is safe and effective in HCV-infected patients in a real-life cohort from Latin America.

Information about the use of ombitasvir/paritaprevir/ritonavir/dasabuvir ± ribavirin (OBV/PTV/r/DSV ± RBV) in real-clinical practice in Latin America is scarce. We aimed to confirm safety and effectiveness of OBV/PTV/r/DSV ± RBV therapy in real-world setting. We analyzed a cohort of patients with genotype 1 infection treated with OBV/PTV/r/DSV ± RBV. Data on demographics, clinical features, safety, and virological response were retrospectively collected from 21 centers in Latin America. A total of 96 patients received OBV/PTV/r/DSV, associated with RBV in 68% of the cases. Most were genotype 1b (80%), 56 (58%) had cirrhosis, and 45 (47%) failed prior HCV treatment. Adverse events occurred in 62% of patients. The most common adverse events were pruritus (21%), hyperbilirubinemia (17%), and asthenia (17%). Five patients discontinued therapy prematurely due to hepatic decompensation, three of them were Child-Pugh B at baseline and one patient died due to multi-organ failure. Follow up HCV-RNA 12 weeks after completion of therapy was evaluated in all the patients and sustained virologic response rate was 97%. No virologic breakthrough was detected. Our study confirms that OBV/PTV/r/DSV treatment is highly effective in patients with chronic HCV without cirrhosis or with Child-Pugh A cirrhosis in non-European populations. Adverse events were often mild and rarely led to treatment discontinuation except for patients with Child-Pugh B cirrhosis or with previous history of hepatic decompensation. These results can support the development of public strategies to expand the access of OBV/PTV/r + DSV and other DAAs combinations in order to reduce the burden of HCV infection in our region.

Prevention of portal hypertension: from variceal development to clinical decompensation.

Pharmacological treatment of portal hypertension (PH) has been exclusively devoted to gastroesophageal varices-related events at different frameworks, including prophylactic, emergency, or preventive therapy. The goals of treatment are to avoid the first bleeding episode, stop active bleeding, and prevent bleeding recurrence, respectively. The objective of preprimary prophylaxis (PPP) is to avoid variceal development, and therefore it necessarily deals with patients with cirrhosis at earlier stages of the disease. At these earlier stages, nonselective beta-blockers (NSBBs) have been ineffective in preventing the development of varices and other complications of PH. Therefore, treatment should not rely on NSBB. It is possible that, at these earlier stages, etiological treatment of liver disease itself could prevent progression of PH. This review will focus mainly on early treatment of PH, because, if successful, it may translate into histological-hemodynamic improvements, avoiding not only variceal development, but also other PH-related complications, such as ascites and portosystemic encephalopathy. Moreover, the advent of new therapies may allow not only the prevention of the complications of PH, but also the chance of a substantial degree of regression in the cirrhotic process, with the possible prevention of hepatocellular carcinoma (HCC).

Hepatic venous pressure gradient measurement in pre-primary and primary prophylaxis of variceal hemorrhage.

Pharmacological therapy of portal hypertensión can be accomplished according to different objectives. Among them, pre-primary prophylaxis aims to avoid / delay esophageal varices development while the target of primary prophylaxis is protection against first variceal bleeding. Hepatic venous pressure gradient (HVPG) measurement closely reflects portal pressure in most liver diseases whith predominant sinusoidal network involvement. Clinical-hemodynamic correlations have been demonstrated in both pre-primary and primary prophylatic therapy, allowing to establish HVPG measurement as a predictive parameter, not only regarding variceal growth and bled but also of liver disease evolution and other portal hypertensive related complications.

Natural history of hepatitis C virus infection in a cohort of asymptomatic post-transfused subjects.

UNLABELLED: BACKGROUND & AIMS. Studies about the natural history of hepatitis C virus (HCV) infection report variable progression to cirrhosis depending on study design. Retrospective cross-sectional liver clinic studies overestimate the rate of fibrosis progression due to inclusion of patients with more severe disease leaving mild and asymptomatic patients underrepresented. We evaluated fibrosis progression in a group of "healthy" asymptomatic subjects, attending to a voluntary campaign for the detection of HCV infection. MATERIAL AND METHODS: A detection campaign was launched on subjects transfused before 1993. Of 1699 volunteers, 61(3.6%) had HCV infection. A liver biopsy was performed in 40 (65%). Assessed risk factors for liver fibrosis were: sex, body mass index, alcohol consumption (> 20 g/d - > 40g/d ), genotype, HLA-DRB1 alleles, present age, age at infection and duration of infection. RESULTS: 25 (62.5%) were women with a median age of 52.5 years. The median duration of infection was 21.5 years with a median age at infection of 27 years. As regards fibrosis, 25 (62.5%) had a Low Stage (F0-F1), 8 patients, 20%, had severe fibrosis, one patient (2.5%) had cirrhosis. Alcohol consumption was the only risk factor associated with fibrosis progression. CONCLUSIONS: The low progression to cirrhosis may be explained by the clinical characteristics of our population: asymptomatic middle-aged "healthy" subjects infected at young age. The progression to severe fibrosis was noticeable; hence a longer follow-up might demonstrate changes in this outcome. Significant alcohol consumption clearly worsens the natural history of HCV infection; this is no so evident for occasional or mild alcohol consumers.

Measurement of portal pressure: when, how, and why to do it.

Many of the clinical complications of cirrhosis are the direct consequences of the evaluation of portal venous pressure (PVP). The degree of portal hypertension has been shown to correlate with the severity of liver disease, both functionally and histologically. Direct measurement of PVP, however, is invasive and cannot be routinely performed. As a surrogate, the hepatic venous pressure gradient (HVPG) has been widely accepted as a measurement of PVP. The ease, accuracy, and safety of HVPG measurement has made it a valuable tool in the research arena and, increasingly, in clinical practice.

Hepatic venous pressure in practice: how, when, and why.

Hepatic venous pressure gradient (HVPG) measurement has evolved into an extremely useful procedure for the assessment of portal hypertensive patients and in the prediction and management of portal hypertension-related events. Although invasive and not widely available, its safety and reproducibility can be warranted when performed in referral centers and following accepted guidelines. Well-established manometric HVPG cut off are reliable targets in the therapy of portal hypertension. When adequately indicated and performed, HVPG measurement provides valuable information allowing to establish diagnosis, elaborate prognosis, evaluate therapy and, most importantly, to make therapeutic decisions in portal hypertensive patients.

Octreotide enhances portal pressure reduction induced by propranolol in cirrhosis: a randomized, controlled trial.

BACKGROUND: In vitro, octreotide potentiates vasoconstriction in isolated, preconstricted, mesenteric arterial vessels. In cirrhotic patients, portal pressure (HVPG) reduction induced by propranolol is partly due to splanchnic vasoconstriction. AIM: To evaluate HVPG effects of octreotide administration in cirrhotic patients receiving long-term propranolol. PATIENTS AND METHODS: A randomized, controlled trial. First study: a total of 28 patients were studied at baseline and 30 and 60 minutes after octreotide (200 mug) (N = 14) or placebo (N = 14) and then treated with propranolol for approximately 30 days (106 +/- 5 mg/day). Second study: after baseline evaluation patients received octreotide or placebo as they were assigned to in the first study and measurements repeated 30 and 60 minutes later. RESULTS: In the first study baseline HVPG was 18.7 +/- 0.9 mmHg and decreased to 17.1 +/- 1.1 mmHg and 17.1 +/- 1.0 mmHg (both P < 0.05 vs baseline) at 30 and 60 minutes after octreotide, respectively. Eight patients decreased their HVPG after octreotide. In the second study baseline HVPG was 15.6 +/- 1.3 mmHg (P < 0.01 vs baseline HVPG in first study) and decreased to 14.1 +/- 1.2 mmHg and 14.1 +/- 1.3 mmHg (25.7 +/- 5% lower than baseline HVPG in the first study, P < 0.01) (both P < 0.05 vs baseline) at 30 and 60 minutes after octreotide, respectively. Nine patients (2 responders/7 nonresponders to propranolol) decreased their HVPG after octreotide. Octreotide effects may be mediated by potentiation and additive mechanisms. CONCLUSIONS: Octreotide enhances HVPG reduction induced by propranolol in cirrhotic patients.

Effects of long-term propranolol and octreotide on postprandial hemodynamics in cirrhosis: a randomized, controlled trial.

BACKGROUND & AIMS: Postprandial increases in portal pressure may influence esophageal variceal rupture. The effects of chronic propranolol and octreotide (100 and 200 microg subcutaneously in a single dose) on postprandial hemodynamics were evaluated. METHODS: FIRST STUDY: 36 cirrhotic patients were studied at baseline and 30 and 60 minutes after a standard meal and then treated with propranolol (139 +/- 9 mg/d during 39 +/- 2 days). SECOND STUDY: After baseline measurements, patients were randomized into 3 groups: (1) placebo, (2) octreotide (100 microg), or (3) octreotide (200 microg) (n = 12 for each group). Thirty minutes postinjection a new baseline was established and measurements were repeated 30 and 60 minutes after the meal. RESULTS: First study: Baseline portal pressure was 18.1 +/- 1.2 mm Hg, 30 and 60 minutes after the meal it was 21.5 +/- 0.8 mm Hg and 20.5 +/- 0.8 mm Hg, respectively (both P < 0.01 vs. baseline). Cardiac index (CI) was 4.5 +/- 0.2, 4.8 +/- 0.2, and 4.9 +/- 0.2 L x min(-1) x m(-2), respectively (both P < 0.05 vs. baseline). Peripheral vascular resistance was 1012 +/- 56, 902 +/- 51 (P = NS), and 884 +/- 49 dynes x sec x cm(-5) (P< 0.05 vs. baseline), respectively. Second study: Propranolol and placebo did not blunt postprandial increase in portal pressure. Octreotide (100 microg) partially ameliorated postprandial increase in portal pressure. Octreotide (200 microg) significantly enhanced the portal hypotensive effect of propranolol and blunted the postprandial increase in portal pressure. CONCLUSIONS: Octreotide blunts postprandial increase in portal pressure not prevented by long-term propranolol administration.