A Brief Intervention on Alcohol Use Disorder Is Associated With Treatment Access for Inpatients With Alcohol-Associated Liver Disease.

BACKGROUND: Alcohol-associated liver disease (ALD) is the most common indication for liver transplantation in the United States. Alcohol use disorder (AUD) treatment is recommended in all patients with ALD and AUD, but it remains underutilized. AIMS: To identify predictors of AUD treatment and to assess 30-day readmission, return to drinking, and 1-year transplant-free survival. METHODS: Retrospective single-center cohort study of consecutive patients hospitalized with ALD and AUD between 2018 and 2020. Patients who died or were lost to follow-up at 90 days after hospitalization were excluded. AUD treatment was defined as receiving medication or participating in residential, outpatient, or support groups within 90 days of discharge. RESULTS: One hundred nine patients were included. Mean age was 51.7 years, and 63% were male. Fifty-six (51%) patients received AUD treatment, and 23 (21%) patients received more than one treatment. Predictors of AUD treatment were younger age (OR, 1.07 [95% CI, 1.04-1.12]; P < 0.001), gastroenterology/hepatology consult (AOR, 8.54 [95% CI, 2.55-39.50]; P = 0.0002), addiction psychiatry consult (AOR, 2.77 [95% CI, 1.16-6.84]; P = 0.02), and a brief AUD intervention (AOR, 18.19 [95% CI, 3.36-339.07]; P = 0.0001). Cirrhosis decompensation, MELD-Na score, and insurance status were not associated with treatment. Thirty-one patients (28.4%) were readmitted, and 29 (26.6%) remained abstinent 30 days from discharge. Patients who received treatment had improved transplant-free survival (HR, 0.44, P = 0.04). CONCLUSION: A brief intervention on AUD had the strongest association with receiving AUD treatment in our cohort. Further efforts to incorporate brief interventions when offering AUD treatment to patients with ALD may be beneficial.

You can't handle the truth! Comparing serum phosphatidylethanol to self-reported alcohol intake in chronic liver disease patients.

BACKGROUND: Serum phosphatidylethanol (PEth) testing has emerged as a promising biomarker for assessing recent alcohol consumption, surpassing the limitations of self-reported data. Limited clinical data exists comparing PEth levels and patients' reported alcohol intake. AIMS: Compare PEth testing results with self-reported alcohol intake and assesses variables associated with underreporting. METHODS: Single-center retrospective cohort of patients with a diagnosis of chronic liver disease and serum PEth. A patient's first positive PEth (>/=10 ng/mL) and self-reported alcohol consumption was used. PEth results were categorized as mild (10-20), moderate (20-200), or heavy (>200). Severity measures between self-report and PEth were assessed using Bhapkar's test and Bonferroni-adjusted McNemar's tests. Demographic data was analyzed using Chi-Square tests. RESULTS: 279 patients were included. 94 (33.7%) patients had consistency with self-report, and 185 patients had inconsistencies in their report (66.3%, p < 0.001). Of 279 patients, 161 (57.7%) underreported their alcohol consumption, and 55 (19.7%) heavy PEth patients underreported alcohol consumption as light. 58% of alcohol-related and 56.4% of non-alcohol-related cirrhotic patients underreported their alcohol use. CONCLUSION: In our cohort, only one third of self-reported alcohol consumption was consistent with the PEth level. Notably, 57.7% underreported alcohol intake. Our study reinforces the clinical importance of PEth testing as an objective clinical measure.

Antibiotic point prevalence survey and antimicrobial resistance in hospitalized patients across Peruvian reference hospitals.

BACKGROUND: Peru reports higher levels than other countries in Latin America of resistance to antimicrobials among Gram-positive and Gram-negative bacteria, however data on antibiotic use in Peru are scarce. This study aims to estimate the prevalence and quality of antibiotic prescription in hospitalized patients and to determine the antibiotic susceptibility rates of bacteria causing key bacterial infections. METHODS: We carried out a point prevalence survey of antibiotic prescription at ten public hospitals in nine regions of Peru. Data was collected from patients hospitalized during a 3-week period, with details about antibiotic use, patient information, and antimicrobial susceptibility. RESULTS: 1620 patient charts were reviewed; in 924 cases antibiotics were prescribed (57.0 %, range 45.9-78.9 %). Most of the antibiotics (74.2 %) were prescribed as empirical treatment, only 4.4 % as targeted treatment. For 9.5 % of cases the reason for antibiotic use was unknown. Cephalosporins were the most prescribed (30.0 %), followed by carbapenems (11.3 %). Ninety-four blood cultures were positive for bacterial growth, 48.8 % of the Staphylococcus aureus were methicillin-resistant, among Escherichia coli and Klebsiella pneumoniae, 51.7 % and 72.7 % were resistant to third-generation cephalosporins (3GC), 3.4 % and 18.2 % were resistant to carbapenems, respectively. Among bacteria isolated from urine cultures (n = 639), 43.9 % of E. coli and 49.2 % of K. pneumoniae were resistant to 3GC, and 0.9 % of E. coli and 3.2 % of K. pneumoniae were resistant to meropenem. CONCLUSIONS: The overall proportion of hospitalized patients receiving antibiotics in hospitals from different regions in Peru was high, with only a small proportion receiving targeted treatment. Cephalosporins and carbapenems were the most frequently prescribed antibiotics, reflecting high resistance rates against 3GC and carbapenems in Enterobacterales isolated from blood and urine.

Methicillin-Resistant Staphylococcus aureus Bloodstream Infections in Hospitalized Patients in Peru.

There is a knowledge gap in the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) causing bloodstream infections (BSIs) in Peru. Through a surveillance study in 13 hospitals of 10 Peruvian regions (2017-2019), we assessed the proportion of MRSA among S. aureus BSIs as well as the molecular typing of the isolates. A total of 166 S. aureus isolates were collected, and 36.1% of them were MRSA. Of note, MRSA isolates with phenotypic and genetic characteristics of the hospital-associated Chilean-Cordobes clone (multidrug-resistant SCCmec I, non-Panton-Valentine leukocidin [PVL] producers) were most commonly found (70%), five isolates with genetic characteristics of community-associated MRSA (CA-MRSA)-SCCmec IV, PVL-producer-(8.3%) were seen in three separate regions. These results demonstrate that hospital-associated MRSA is the most frequent MRSA found in patients with BSIs in Peru. They also show the emergence of S. aureus with genetic characteristics of CA-MRSA. Further studies are needed to evaluate the extension of CA-MRSA dissemination in Peru.

Liver Segment Disposition of Hepatocellular Carcinoma Predicts Microvascular Invasion.

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer morbidity and mortality. Findings of microvascular invasion (MVI) in patients with HCC have emerged as an important prognostic factor for poor survival after tumor resection. Aim: This study evaluated the relation between MVI and HCC within various anatomical Couinaud's segments of the liver. Method: A multicenter retrospective review of HCC records was conducted from 2012 to 2017. HCC cases were identified using ICD-9 and 10 codes 155, C22.0, and C22.8. HCC patients who underwent liver transplants were included in this study. Liver segment of the location of HCC was obtained from radiographic records, and MVI information was obtained from pathology reports. Segmental distributions of HCC in MVI versus non-MVI groups were compared using Wilcoxon rank sum tests. p value was set at <0.05. Results: We analyzed 120 HCC patients who underwent liver transplantation. The mean age of our cohort was 57 years, and the most common etiology of liver disease was hepatitis C at 58.3%. The median HCC size was 3.1 cm, and MVI was present in 23.3% of the explanted specimens. MVI was 2 to 3 times significantly higher in patients with HCC affecting segments 2 and 3 and segments 4b and 5 (p = 0.01). Moreover, median survival was significantly lower in patients with MVI versus those without MVI (50 vs. 137 months, p < 0.05). Conclusion: MVI was significantly higher in HCC tumors located in liver segments 2 and 3 and 4b and 5, and survival was lower in patients with MVI compared with those without.

Bile acid indices as biomarkers for liver diseases II: The bile acid score survival prognostic model.

BACKGROUND: Cholestatic liver diseases are characterized by an accumulation of toxic bile acids (BA) in the liver, blood and other tissues which lead to progressive liver injury and poor prognosis in patients. AIM: To discover and validate prognostic biomarkers of cholestatic liver diseases based on the urinary BA profile. METHODS: We analyzed urine samples by liquid chromatography-tandem mass spectrometry and investigated the use of the urinary BA profile to develop survival models that can predict the prognosis of hepatobiliary diseases. The urinary BA profile, a set of non-BA parameters, and the adverse events of liver transplant and/or death were monitored in 257 patients with cholestatic liver diseases for up to 7 years. The BA profile was characterized by calculating BA indices, which quantify the composition, metabolism, hydrophilicity, formation of secondary BA, and toxicity of the BA profile. We have developed and validated the bile-acid score (BAS) model (a survival model based on BA indices) to predict the prognosis of cholestatic liver diseases. RESULTS: We have developed and validated a survival model based on BA (the BAS model) indices to predict the prognosis of cholestatic liver diseases. Our results demonstrate that the BAS model is more accurate and results in higher true-positive and true-negative prediction of death compared to both non-BAS and model for end-stage liver disease (MELD) models. Both 5- and 3-year survival probabilities markedly decreased as a function of BAS. Moreover, patients with high BAS had a 4-fold higher rate of death and lived for an average of 11 mo shorter than subjects with low BAS. The increased risk of death with high vs low BAS was also 2-4-fold higher and the shortening of lifespan was 6-7-mo lower compared to MELD or non-BAS. Similarly, we have shown the use of BAS to predict the survival of patients with and without liver transplant (LT). Therefore, BAS could be used to define the most seriously ill patients, who need earlier intervention such as LT. This will help provide guidance for timely care for liver patients. CONCLUSION: The BAS model is more accurate than MELD and non-BAS models in predicting the prognosis of cholestatic liver diseases.

Bile acid indices as biomarkers for liver diseases I: Diagnostic markers.

BACKGROUND: Hepatobiliary diseases result in the accumulation of toxic bile acids (BA) in the liver, blood, and other tissues which may contribute to an unfavorable prognosis. AIM: To discover and validate diagnostic biomarkers of cholestatic liver diseases based on the urinary BA profile. METHODS: We analyzed urine samples by liquid chromatography-tandem mass spectrometry and compared the urinary BA profile between 300 patients with hepatobiliary diseases vs 103 healthy controls by statistical analysis. The BA profile was characterized using BA indices, which quantifies the composition, metabolism, hydrophilicity, and toxicity of the BA profile. BA indices have much lower inter- and intra-individual variability compared to absolute concentrations of BA. In addition, BA indices demonstrate high area under the receiver operating characteristic curves, and changes of BA indices are associated with the risk of having a liver disease, which demonstrates their use as diagnostic biomarkers for cholestatic liver diseases. RESULTS: Total and individual BA concentrations were higher in all patients. The percentage of secondary BA (lithocholic acid and deoxycholic acid) was significantly lower, while the percentage of primary BA (chenodeoxycholic acid, cholic acid, and hyocholic acid) was markedly higher in patients compared to controls. In addition, the percentage of taurine-amidation was higher in patients than controls. The increase in the non-12α-OH BA was more profound than 12α-OH BA (cholic acid and deoxycholic acid) causing a decrease in the 12α-OH/ non-12α-OH ratio in patients. This trend was stronger in patients with more advanced liver diseases as reflected by the model for end-stage liver disease score and the presence of hepatic decompensation. The percentage of sulfation was also higher in patients with more severe forms of liver diseases. CONCLUSION: BA indices have much lower inter- and intra-individual variability compared to absolute BA concentrations and changes of BA indices are associated with the risk of developing liver diseases.

Impact of sarcopenia on mortality in patients undergoing liver re-transplantation.

BACKGROUND: Sarcopenia, which is a loss of skeletal muscle mass, has been reported to increase post-transplant mortality and morbidity in patients undergoing the first liver transplant. Cross-sectional imaging modalities typically determine sarcopenia in patients with cirrhosis by measuring core abdominal musculatures. However, there is limited evidence for sarcopenia related outcomes in patients undergoing liver re-transplantation (re-OLT). AIM: To evaluate the risk of mortality in patients with pre-existing sarcopenia following liver re-OLT. METHODS: This is a retrospective study of all adult patients who had undergone a liver re-OLT at the University of Nebraska Medical Center from January 1, 2007 to January 1, 2017. We divided patients into sarcopenia and no sarcopenia groups. "TeraRecon AquariusNet 4.4.12.194" software was used to evaluate computed tomography or magnetic resonance imaging of the patients done within one year prior to their re-OLT, to calculate the Psoas muscle area at L3-L4 intervertebral disc. We defined cutoffs for sarcopenia as < 1561 mm2 for males and < 1464 mm2 for females. The primary outcome was to compare 90 d, one, and 5-year survival rates. We also compared complications after re-OLT, length of stay, and re-admission within 30 d. Survival analysis was performed with Kaplan-Meier survival analysis. Continuous variables were evaluated with Wilcoxon rank-sum tests. Categorical variables were evaluated with Fisher's exact tests. RESULTS: Fifty-seven patients were included, 32 males: 25 females, median age 50 years. Two patients were excluded due to incomplete information. Overall, 47% (26) of patients who underwent re-OLT had sarcopenia. Females were found to have significantly more sarcopenia than males (73% vs 17%, P < 0.001). Median model for end stage liver disease at re-OLT was 28 in both sarcopenia and no sarcopenia groups. Patients in the no sarcopenia group had a trend of longer median time between the first and second transplant (36.5 mo vs 16.7 mo). Biological markers, outcome parameters, and survival at 90 d, 1 and 5 years, were similar between the two groups. Sarcopenia in re-OLT at our center was noted to be twice as common (47%) as historically reported in patients undergoing primary liver transplantation. CONCLUSION: Overall survival and outcome parameters were no different in those with and without the evidence of sarcopenia after re-OLT.

Urinary bile acids as biomarkers for liver diseases I. Stability of the baseline profile in healthy subjects.

The role of bile acids (BAs) as biomarkers for liver injury has been proposed for decades. However, the large inter- and intra-individual variability of the BA profile has prevented its clinical application. To this end, we investigated the effect of covariates such as food, gender, age, BMI, and moderate alcohol consumption on the BA profile in healthy human subjects. The BA profile was characterized by the calculation of indices that describe the composition, sulfation, and amidation of total and individual BAs. Both inter- and intra-individual variabilities of BA indices were low in serum and even lower in urine compared with those of absolute concentrations of BAs. Serum BA concentrations increased with consumption of food, whereas urinary BA concentrations were mildly affected by food. Gender differences in the urinary and serum BA profile were minimal. The serum and urinary BA profiles were also not affected by age. BMI showed minimal effect on the urine and serum BA profile. Moderate alcohol consumption did not have a significant effect on the BA profile in both urine and serum. When the effect of the type of alcohol was studied, the results indicate that moderate drinking of beer does not affect BA concentrations and has minimal effect on BA indices, whereas moderate wine consumption slightly increases BA concentrations without affecting the BA indices. In summary, urinary BA indices showed lower variability and higher stability than absolute BA concentrations in serum and showed minimal changes to covariate effects suggesting their utility as biomarkers in clinic.

Urinary bile acids as biomarkers for liver diseases II. Signature profiles in patients.

Hepatobiliary diseases result in the accumulation of bile acids (BAs) in the liver, systemic blood, and other tissues leading to an unfavorable prognosis. The BA profile was characterized by the calculation of indices that describe the composition, sulfation, and amidation of total and individual BAs. Comparison of the urinary BA profiles between healthy subjects and patients with hepatobiliary diseases demonstrated significantly higher absolute concentrations of individual and total BAs in patients. The percentage sulfation of some individual BAs were different between the two groups. The percentage amidation of overall and most individual BAs was higher in patients than controls. The percentage of primary BAs (CDCA and CA) was higher in patients, whereas the percentage of secondary BAs (DCA and LCA) was lower in patients. BA indices belonging to percentage amidation and percentage composition were better associated with the severity of the liver disease as determined by the model for end-stage liver disease (MELD) score and disease compensation status compared with the absolute concentrations of individual and total BAs. In addition, BA indices corresponding to percentage amidation and percentage composition of certain BAs demonstrated the highest area under the receiver operating characteristic (ROC) curve suggesting their utility as diagnostic biomarkers in clinic. Furthermore, significant increase in the risk of having liver diseases was associated with changes in BA indices.

The profile of bile acids and their sulfate metabolites in human urine and serum.

The role of sulfation in ameliorating the hepatotoxicity of bile acids (BAs) in humans remains unknown due to the lack of proper analytical methods to quantify individual BAs and their sulfate metabolites in biological tissues and fluids. To this end, a simple and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to characterize the detailed BA profile in human urine and serum. The limit of quantification was 1ng/mL and baseline separation of all analytes was achieved within in a run time of 32min. The method was validated over the dynamic range of 1-1000ng/mL. The LC-MS/MS method was more accurate, precise, and selective than the commercially available kits for the quantification of sulfated and unsulfated BAs, and the indirect quantification of individual sulfated BAs after solvolysis. The LC-MS/MS method was applied to characterize the BA profile in urine and serum of healthy subjects. Thirty three percent of serum BAs were sulfated, whereas 89% of urinary BAs existed in the sulfate form, indicating the role of sulfation in enhancing the urinary excretion of BAs. The percentage of sulfation of individual BAs increased with the decrease in the number of hydroxyl groups indicating the role of sulfation in the detoxification of the more hydrophobic and toxic BA species. Eighty percent of urinary BAs and 55% of serum BAs were present in the glycine-amidated form, whereas 8% of urinary BAs and 13% of serum BAs existed in the taurine-amidated form.

Risk of cytomegalovirus disease in high-risk liver transplant recipients on valganciclovir prophylaxis: a systematic review and meta-analysis.

Valganciclovir (VGC) was approved by the Food and Drug Administration in 2004 as cytomegalovirus (CMV) prophylaxis except for liver transplant recipients because of their high incidence of CMV disease with this drug. However, surveys have shown its common off-label use for CMV prophylaxis in liver transplant recipients. We aimed to evaluate the risk of CMV disease with VGC prophylaxis in liver transplant recipients. All studies that evaluated liver transplant recipients and used VGC (900 or 450 mg daily) for the prevention of CMV disease were included. Five controlled studies (n = 483) were pooled with a random effects model; five single-arm studies (n = 380) were pooled for the prevalence rate of CMV disease. The risk of CMV disease with VGC versus ganciclovir was 1.81 [95% confidence interval (CI) = 1.00-3.29, P = 0.05, I(2) = 0%]. For high-risk (donor-positive/recipient-negative) patients, the risk of CMV disease was 1.96 (95% CI = 1.05-3.67, P = 0.035, I(2) = 0%). The risk of CMV disease remained significant with 900 mg of VGC daily (P = 0.04) but not with 450 mg of VGC daily (P = 0.76). The risk of leukopenia with VGC was 1.87 (95% CI = 1.03-3.37, P = 0.04, I(2) = 0%). In single-arm trials, the overall CMV disease rate was 12% (95% CI = 9%-16%, P < 0.001), and the rate for high-risk patients was 20% (95% CI = 10%-38%, P = 0.002). In conclusion, 900 mg of VGC daily may not be safe as CMV prophylaxis in high-risk liver transplant recipients because of the significant 2-fold increase in the risk of CMV disease and the 1.9-fold increase in the risk of leukopenia. Alternative CMV prophylaxis should be used for liver transplant recipients.

Intrahepatic bilioenteric anastomosis after biliary complications of liver transplantation: operative rescue of surgical failures.

BACKGROUND: Biliary complications after orthotopic liver transplantation (OLT) are multifactorial in origin. In most series, the frequency of such complications ranges from 5-20%. Most can be treated by endoscopy and/or interventional radiology. For cases in which this option is not successful, surgical approach is indicated. We report the results of reoperation using an intrahepatic bilioenteric anastomosis. METHODS: The medical charts of patients with biliary complications after OLT during a 10-year period (1997-2007), who failed to respond to nonsurgical treatment and were surgically treated, were reviewed. Roux-en-Y hepatojejunostomy was performed. Segments IV and V were partially removed after cutting the hilar plate, thus obtaining healthy ducts without ischemic or inflammatory reaction and allowing a wide hepatojejunostomy. RESULTS: Five cases (8.4%) with biliary complications after duct-to-duct anastomosis not amenable to further endoscopic management or interventional radiology were identified. Hepaticojejunostomy was achieved in all cases (wide, tension-free, nonischemic, fine hydrolyzable sutures), and segments IV and V were partially removed. No cholangitis, jaundice, and liver function test abnormalities were present in the postoperative. Mean follow-up was 24 months. Only one patient died of causes not related to bile duct reconstruction during follow-up. CONCLUSIONS: Intrahepatic hepatojejunostomy with partial resection of segments IV and V offers an excellent therapeutic alternative for biliary complications that require a surgical approach after OLT.

Prevalencia de anticuerpos antinucleares en cirrosis biliar primaria, con anticuerpos antimitocondriales negativos / Primary biliar cirrhosis: patients eith autoimmune cholangitis ANA positive and AMA negative

Recientemente se describió en la literatura una subpoblación de pacientes con cirrosis biliar primaria (CBP) y anticuerpos antimitocondriales negativos [AAM(-)], que puede corresponder a pacientes con colangitis autoinmune con AAN(+). En este trabajo encontramos 25 casos (23 mujeres) con CBP y AAM(-), en las que 14 (56 por ciento) tuvieron AAN(+) a una dilución 1:40. Se determinaron bilirrubinas totales, transaminasas, AAM y AAN por inmunofluorescencia indirecta, considerándose como positivos títulos de 1:40. Cien por ciento tenían elevación de la fosfatasa alcalina (641 ñ 389 U/I). La bilirrubina estuvo por debajo de 2.5 en 59 por ciento. Trece pacientes tenían várices esofágicas. El estadio histológico fue I-II en once y III-IV en 14 casos. Corroboramos la existencia de una subpoblación de pacientes con CBP, AAM(-) y ANN(+) y confirmamos las observaciones de otros grupos con respecto a alteraciones inmunológicas diversas en pacientes con CBP.