A Randomized Trial of Albumin Infusions in Hospitalized Patients with Cirrhosis.

BACKGROUND: Infection and increased systemic inflammation cause organ dysfunction and death in patients with decompensated cirrhosis. Preclinical studies provide support for an antiinflammatory role of albumin, but confirmatory large-scale clinical trials are lacking. Whether targeting a serum albumin level of 30 g per liter or greater in these patients with repeated daily infusions of 20% human albumin solution, as compared with standard care, would reduce the incidences of infection, kidney dysfunction, and death is unknown. METHODS: We conducted a randomized, multicenter, open-label, parallel-group trial involving hospitalized patients with decompensated cirrhosis who had a serum albumin level of less than 30 g per liter at enrollment. Patients were randomly assigned to receive either targeted 20% human albumin solution for up to 14 days or until discharge, whichever came first, or standard care. Treatment commenced within 3 days after admission. The composite primary end point was new infection, kidney dysfunction, or death between days 3 and 15 after the initiation of treatment. RESULTS: A total of 777 patients underwent randomization, and alcohol was reported to be a cause of cirrhosis in most of these patients. A median total infusion of albumin of 200 g (interquartile range, 140 to 280) per patient was administered to the targeted albumin group (increasing the albumin level to ≥30 g per liter), as compared with a median of 20 g (interquartile range, 0 to 120) per patient administered to the standard-care group (adjusted mean difference, 143 g; 95% confidence interval [CI], 127 to 158.2). The percentage of patients with a primary end-point event did not differ significantly between the targeted albumin group (113 of 380 patients [29.7%]) and the standard-care group (120 of 397 patients [30.2%]) (adjusted odds ratio, 0.98; 95% CI, 0.71 to 1.33; P = 0.87). A time-to-event analysis in which data were censored at the time of discharge or at day 15 also showed no significant between-group difference (hazard ratio, 1.04; 95% CI, 0.81 to 1.35). More severe or life-threatening serious adverse events occurred in the albumin group than in the standard-care group. CONCLUSIONS: In patients hospitalized with decompensated cirrhosis, albumin infusions to increase the albumin level to a target of 30 g per liter or more was not more beneficial than the current standard care in the United Kingdom. (Funded by the Health Innovation Challenge Fund; ATTIRE EudraCT number, 2014-002300-24; ISRCT number, N14174793.).

Skeletal muscle protein turnover responses to parenteral nutrition in patients with alcoholic liver cirrhosis and sarcopenia.

Alcoholic liver cirrhosis (ALC) is accompanied by sarcopenia. The aim of this study was to investigate the acute effects of balanced parenteral nutrition (PN) on skeletal muscle protein turnover in ALC. Eight male patients with ALC and seven age- and sex-matched healthy controls were studied for 3 h of fasting followed by 3 h of intravenous PN (SmofKabiven 1,206 mL: amino acid = 38 g, carbohydrates = 85 g, and fat = 34 g) 4 mL/kg/h. We measured leg blood flow and sampled paired femoral arteriovenous concentrations and quadriceps muscle biopsies while providing a primed continuous infusion of [ring-2d5]-phenylalanine to quantify muscle protein synthesis and breakdown. Patients with ALC exhibited shorter 6-min walking distance (ALC: 487 ± 38 vs. controls: 722 ± 14 m, P < 0.05), lower hand-grip strength (ALC: 34 ± 2 vs. controls: 52 ± 2 kg, P < 0.05), and computed tomography (CT)-verified leg muscle loss (ALC: 5,922 ± 246 vs. controls: 8,110 ± 345 mm2, P < 0.05). Net leg muscle phenylalanine uptake changed from negative (muscle loss) during fasting to positive (muscle gain) in response to PN (ALC: -0.18 ± +0.01 vs. 0.24 ± 0.03 µmol/kg muscle·min-1; P < 0.001 and controls: -0.15 ± 0.01 vs. 0.09 ± 0.01 µmol/kg muscle·min-1; P < 0.001) but with higher net muscle phenylalanine uptake in ALC than controls (P < 0.001). Insulin concentrations were substantially higher in patients with ALC during PN. Our results suggest a higher net muscle phenylalanine uptake during a single infusion of PN in stable patients with ALC with sarcopenia compared with healthy controls.NEW & NOTEWORTHY Muscle protein turnover responses to parenteral nutritional (PN) supplementation have not previously been studied in stable alcoholic liver cirrhosis (ALC). We applied stable isotope tracers of amino acids to directly quantify net muscle protein turnover responses to PN in sarcopenic males with ALC and healthy controls. We found a higher net muscle protein gain in ALC during PN, thereby providing the physiological rationale for future clinical trials of PN as a potential countermeasure to sarcopenia.

Alcohol treatment discussions and clinical outcomes among patients with alcohol-related cirrhosis.

BACKGROUND: Alcohol cessation is the cornerstone of treatment for alcohol-related cirrhosis. This study evaluated associations between medical conversations about alcohol use disorder (AUD) treatment, AUD treatment engagement, and mortality. METHODS: This retrospective cohort study included all patients with ICD-10 diagnosis codes for cirrhosis and AUD who were engaged in hepatology care in a single healthcare system in 2015. Baseline demographic, medical, liver disease, and AUD treatment data were assessed. AUD treatment discussions and initiation, alcohol cessation, and subsequent 5-year mortality were collected. Multivariable models were used to assess the factors associated with subsequent AUD treatment and 5-year mortality. RESULTS: Among 436 patients with cirrhosis due to alcohol, 65 patients (15%) received AUD treatment at baseline, including 48 (11%) receiving behavioral therapy alone, 11 (2%) receiving pharmacotherapy alone, and 6 (1%) receiving both. Over the first year after a baseline hepatology visit, 37 patients engaged in AUD treatment, 51 were retained in treatment, and 14 stopped treatment. Thirty percent of patients had hepatology-documented AUD treatment recommendations and 26% had primary care-documented AUD treatment recommendations. Most hepatology (86%) and primary care (88%) recommendations discussed behavioral therapy alone. Among patients with ongoing alcohol use at baseline, AUD treatment one year later was significantly, independently associated with AUD treatment discussions with hepatology (adjusted odds ratio (aOR): 3.23, 95% confidence interval (CI): 1.58, 6.89) or primary care (aOR: 2.95; 95% CI: 1.44, 6.15) and negatively associated with having Medicaid insurance (aOR: 0.43, 95% CI: 0.18, 0.93). When treatment was discussed in both settings, high rates of treatment ensued (aOR: 10.72, 95% CI: 3.89, 33.52). Over a 5-year follow-up period, 152 (35%) patients died. Ongoing alcohol use, age, hepatic decompensation, and hepatocellular carcinoma were significantly associated with mortality in the final survival model. CONCLUSION: AUD treatment discussions were documented in less than half of hepatology and primary care encounters in patients with alcohol-related cirrhosis, though such discussions were significantly associated with receipt of AUD treatment.

Patients with alcohol-related liver disease hospitalized during the COVID-19 pandemic experienced worse outcomes.

INTRODUCTION AND OBJECTIVES: Psychosocial stressors related to the coronavirus-19 (COVID-19) pandemic increased alcohol consumption. The effect on patients with alcohol-related liver diseases remains unclear. MATERIALS AND METHODS: Hospitalizations at a tertiary care center due to alcohol-related liver disease from March 1 through August 31 in 2019 (pre-pandemic cohort) and 2020 (pandemic cohort) were reviewed retrospectively. Differences in patient demographics, disease features, and outcomes were estimated in patients with alcoholic hepatitis utilizing T-tests, Mann-Whitney tests, Chi-square and Fisher Exact Tests and Anova models and logistic regression models in patients with alcoholic cirrhosis. RESULTS: 146 patients with alcoholic hepatitis and 305 patients with alcoholic cirrhosis were admitted during the pandemic compared to 75 and 396 in the pre-pandemic cohort. Despite similar median Maddrey Scores (41.20 vs. 37.45, p=0.57), patients were 25% less likely to receive steroids during the pandemic. Patients with alcoholic hepatitis admitted during the pandemic were more likely to have hepatic encephalopathy (0.13; 95% CI:0.01, 0.25), variceal hemorrhage (0.14; 95% CI:0.04, 0.25), require oxygen (0.11; 95% CI:0.01, 0.21), vasopressors (OR:3.49; 95% CI:1.27, 12.01) and hemodialysis (OR:3.70; 95% CI:1.22, 15.13). On average, patients with alcoholic cirrhosis had MELD-Na scores 3.77 points higher (95% CI:1.05, 13.46) as compared to the pre-pandemic and had higher odds of experiencing hepatic encephalopathy (OR:1.34; 95% CI:1.04, 1.73), spontaneous bacterial peritonitis (OR:1.88; 95% CI:1.03, 3.43), ascites (OR:1.40, 95% CI:1.10, 1.79), vasopressors (OR:1.68, 95% CI:1.14, 2.46) or inpatient mortality (OR:2.00, 95% CI:1.33, 2.99) than the pre-pandemic. CONCLUSIONS: Patients with alcohol-related liver disease experienced worse outcomes during the pandemic.

Identifying Alcohol Use Disorder in Patients With Cirrhosis Reduces 30-Days Readmission Rate.

AIMS: Readmission is frequent among patients with cirrhosis and is a complex multifactorial process. To examine the association of alcohol use disorder (AUD) and risk of readmission in patients with alcohol-associated cirrhosis. METHODS AND RESULTS: National Readmission Dataset (2016-2017) was used to extract a retrospective cohort of 53,348 patients with primary or secondary discharge diagnosis code of alcohol-associated cirrhosis with their first admission (26,674 patients with vs. propensity matched 26,674 without a primary or secondary discharge diagnosis code of AUD). Readmission within 30-day was lower (43.9 vs. 48%, P < 0.001) among patients identified to have AUD at the time of discharge. In a conditional logistic regression model, a diagnosis of AUD was associated with 15% reduced odds of 30-day readmission, 0.85 (0.83-0.88). Furthermore, the reason for readmission among patients identified vs. not identified to have AUD was less likely to be liver disease complication. The findings remained similar in a matched cohort of patients where the AUD diagnosis at discharge was listed as one of the secondary diagnoses only. CONCLUSION: Although, our study findings suggest that identification of AUD at the time of discharge among patients hospitalized for alcohol-associated cirrhosis reduces the risk of 30-day readmission, unavailable information on patient counseling, referral for mental health specialist and treatment received for AUD limit the causality assessment. Future studies are needed overcoming the inherent limitations of the database to establish the role of identification and treatment of AUD in reducing readmission and liver decompensation in patients with alcohol-associated cirrhosis.

Alcohol use disorder in the COVID-19 era: Position paper of the Italian Society on Alcohol (SIA).

Coronavirus disease 2019 (COVID-19) first emerged in China in November 2019. Most governments have responded to the COVID-19 pandemic by imposing a lockdown. Some evidence suggests that a period of isolation might have led to a spike in alcohol misuse, and in the case of patients with alcohol use disorder (AUD), social isolation can favour lapse and relapse. The aim of our position paper is to provide specialists in the alcohol addiction field, in psychopharmacology, gastroenterology and in internal medicine, with appropriate tools to better manage patients with AUD and COVID-19,considering some important topics: (a) the susceptibility of AUD patients to infection; (b) the pharmacological interaction between medications used to treat AUD and to treat COVID-19; (c) the reorganization of the Centre for Alcohol Addiction Treatment for the management of AUD patients in the COVID-19 era (group activities, telemedicine, outpatients treatment, alcohol-related liver disease and liver transplantation, collecting samples); (d) AUD and SARS-CoV-2 vaccination. Telemedicine/telehealth will undoubtedly be useful/practical tools even though it remains at an elementary level; the contribution of the family and of caregivers in the management of AUD patients will play a significant role; the multidisciplinary intervention involving experts in the treatment of AUD with specialists in the treatment of COVID-19 disease will need implementation. Thus, the COVID-19 pandemic is rapidly leading addiction specialists towards a new governance scenario of AUD, which necessarily needs an in-depth reconsideration, focusing attention on a safe approach in combination with the efficacy of treatment.

A notable proportion of liver transplant candidates with alcohol-related cirrhosis can be delisted because of clinical improvement.

BACKGROUND & AIMS: To what extent patients with alcohol-related decompensated cirrhosis can improve until recovery from decompensation remains unclear. We aimed to investigate the probability of recovery and delisting due to improvement in patients with alcohol-related decompensated cirrhosis on the waiting list (WL) for liver transplantation (LT). METHODS: We conducted a registry-based, multicenter, retrospective study including all patients admitted to the LT WL in Catalonia (Spain) with the indication of alcohol-, HCV-, cholestasis- or non-alcoholic steatohepatitis-related decompensated cirrhosis between January 2007 and December 2018. Competing-risk analysis was used to investigate variables associated with delisting due to improvement in patients with alcohol-related decompensated cirrhosis. Criteria for delisting after improvement were not predefined. Outcomes of patients after delisting were also studied. RESULTS: One-thousand and one patients were included, 420 (37%) with alcohol-related decompensated cirrhosis. Thirty-six (8.6%) patients with alcohol-related decompensated cirrhosis were delisted after improvement at a median time of 29 months after WL admission. Lower model for end-stage liver disease (MELD) score, higher platelets and either female sex or lower height were independently associated with delisting due to improvement, while time of abstinence did not reach statistical significance in multivariate analysis (p = 0.055). Five years after delisting, the cumulative probability of remaining free from liver-related death or LT was 76%, similar to patients with HCV-related decompensated cirrhosis delisted after improvement. CONCLUSIONS: A significant proportion of LT candidates with alcohol-related cirrhosis can be delisted due to improvement, which is predicted by low MELD score and higher platelet count at WL admission. Women also have a higher probability of being delisted after improvement, partially due to reduced early access to LT for height discrepancies. Early identification of patients with potential for improvement may avoid unnecessary transplants. LAY SUMMARY: Patients with alcohol-related cirrhosis can improve until being delisted in approximately 9% of cases. Low model for end-stage liver disease score and high platelet levels at admission predict delisting after improvement, and women have higher probabilities of being delisted due to improvement. Long-term outcomes after delisting are generally favorable.

miRNA expression profiles in liver grafts of HCV and HIV/HCV-infected recipients, 6 months after liver transplantation.

In hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infected patients, HIV enhances HCV replication and liver damage. Several microRNAs (miRNAs), active in pro-fibrotic and inflammatory pathways, have been implicated in the pathogenesis of this phenomenon. However, these miRNAs have been tested only in explanted cirrhotic livers, when the liver damage has become chronic and irreversible. No data are available on the early phase of viral infection, such as early after liver transplantation (LT). In the present study, the expression of miR-101, miR-122, miR-155, miR-192, miR-200c, miR-338, and miR-532 was determined by quantitative real-time polymerase chain reaction in liver biopsies of HCV (n = 19) and HCV/HIV-infected (n = 20) LT recipients, as well as in a control group (n = 18) of noninfected patients, transplanted for alcoholic cirrhosis. The timing of liver biopsy was 6 months post-LT. None of the patients was treated with direct-acting anti-HCV drugs. All co-infected recipients had suppressed HIV viral load. Grading and staging were assessed according to the Ishak Classification. HCV and HIV viral load were measured in the sera. miR-101 (p = .03), miR-122 (p = .012), and miR-192 (p = .038) were significantly downregulated in HCV/HIV co-infected and HCV mono-infected recipients when compared with noninfected recipients, and such downregulation was more pronounced in co-infected ones. Moreover, in co-infected recipients but not in mono-infected ones, miR-101 inversely correlated with the peripheral HCV-RNA levels (r = .41, p = .04) and miR-122 inversely correlated with peripheral HCV-RNA levels (r = .49, p = .03) and with the histological grading (r = .51, p = .02).  In conclusion, as early as 6 months after LT, the presence of HIV-HCV co-infection enhanced a significant downregulation of certain miRNAs that showed a direct correlation with HCV viral load and liver inflammation.

Acute on chronic liver failure from novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious viral disease that predominantly causes respiratory symptoms. Elevated liver enzymes have been reported during the course of disease and appear to be common. We present a 56-year-old woman with a history of decompensated alcoholic cirrhosis who presented with abdominal pain, fever and diarrhoea and was found to have acute on chronic liver failure secondary to SARS-CoV-2 infection. The patient was treated with empiric antibiotic and supportive care with subsequent improvement.

Accuracy of the Enhanced Liver Fibrosis Test vs FibroTest, Elastography, and Indirect Markers in Detection of Advanced Fibrosis in Patients With Alcoholic Liver Disease.

BACKGROUND & AIMS: Alcohol is the leading cause of cirrhosis and liver-related mortality, but we lack serum markers to detect compensated disease. We compared the accuracy of the Enhanced Liver Fibrosis test (ELF), the FibroTest, liver stiffness measurements (made by transient elastography and 2-dimensional shear-wave elastography), and 6 indirect marker tests in detection of advanced liver fibrosis (Kleiner stage ≥F3). METHODS: We performed a prospective study of 10 liver fibrosis markers (patented and not), all performed on the same day. Patients were recruited from primary centers (municipal alcohol rehabilitation, n = 128; 6% with advanced fibrosis) and secondary health care centers (hospital outpatient clinics, n = 161; 36% with advanced fibrosis) in the Region of Southern Denmark from 2013 through 2016. Biopsy-verified fibrosis stage was used as the reference standard. The primary aim was to validate ELF in detection of advanced fibrosis in patients with alcoholic liver disease recruited from primary and secondary health care centers, using the literature-based cutoff value of 10.5. Secondary aims were to assess the diagnostic accuracy of ELF for significant fibrosis and cirrhosis and to determine whether combinations of fibrosis markers increase diagnostic yield. RESULTS: The ELF identified patients with advanced liver fibrosis with an area under the receiver operating characteristic curve (AUROC) of 0.92 (95% confidence interval 0.89-0.96); findings did not differ significantly between patients from primary vs secondary care (P = .917). ELF more accurately identified patients with advanced liver fibrosis than indirect marker tests, but ELF and FibroTest had comparable diagnostic accuracies (AUROC of FibroTest, 0.90) (P = .209 for comparison with ELF). Results from the ELF and FibroTest did not differ significantly from those of liver stiffness measurement in intention-to-diagnose analyses (AUROC for transient elastography, 0.90), but did differ in the per-protocol analysis (AUROC for transient elastography, 0.97) (P = .521 and .004 for comparison with ELF). Adding a serum marker to transient elastography analysis did not increase accuracy. For patients in primary care, ELF values below 10.5 and FibroTest values below 0.58 had negative predictive values for advanced liver fibrosis of 98% and 94%, respectively. CONCLUSION: In a prospective, direct comparison of tests, ELF and FibroTest identified advanced liver fibrosis in alcoholic patients from primary and secondary care with high diagnostic accuracy (AUROC values of 0.90 or higher using biopsy as reference). Advanced fibrosis can be ruled out in primary health care patients based on an ELF value below 10.5 or a FibroTest value below 0.58.

The high burden of alcoholic cirrhosis in privately insured persons in the United States.

Alcoholic cirrhosis (AC) is a major cause of liver-related morbidity and mortality in the United States. Rising rates of alcohol use disorders in the United States will likely result in more alcoholic liver disease. Our aim was to determine the prevalence, health care use, and costs of AC among privately insured persons in the United States. We collected data from persons aged 18-64 with AC (identified by codes from the International Classification of Diseases, Ninth and Tenth Revisions) enrolled in the Truven MarketScan Commercial Claims and Encounters database (2009-2015). We determined yearly prevalence, weighted to the national employer-sponsored, privately insured population. Using competing risk analysis, we estimated event rates for portal hypertensive complications and estimated the association between AC and costs as well as admissions and readmissions. In 2015, 294,215 people had cirrhosis and 105,871 (36%) had AC. Mean age at AC diagnosis was 53.5 years, and 32% were women. Over the 7 years queried, estimated national cirrhosis prevalence rose from 0.19% to 0.27% (P < 0.001) and for AC from 0.07% to 0.10% (P < 0.001). Compared to non-AC, AC enrollees were significantly more likely to have portal hypertensive complications at diagnosis and higher yearly cirrhosis and alcohol-related admissions (25 excess cirrhosis admissions and 6.3 excess alcohol-related admissions per 100 enrollees) as well as all-cause readmissions. Per-person costs in the first year after diagnosis nearly doubled for AC versus non-AC persons (US$ 44,835 versus 23,319). CONCLUSION: In a nationally representative cohort of privately insured persons, AC enrollees were disproportionately sicker at presentation, were admitted and readmitted more often, and incurred nearly double the per-person health care costs compared to those with non-AC. (Hepatology 2018).

Gender Disparities in Alcohol Use Disorder Treatment Among Privately Insured Patients with Alcohol-Associated Cirrhosis.

BACKGROUND: The burden of alcohol-associated cirrhosis (AC) is high, and though alcohol cessation improves mortality, many patients fail to engage in alcohol use disorder (AUD) treatment and continue drinking. Our aim was to determine rates, predictors, and outcomes of AUD treatment utilization in AC patients with private insurance. METHODS: We collected data from persons with AC (diagnosed by ICD-9/ICD-10 codes), aged 18 to 64 years, enrolled in the Truven MarketScan Commercial Claims and Encounters database (2009 to 2016). We determined rates and predictors of substance abuse treatment visits as well as rates of alcohol relapse prevention medication prescriptions, weighted to the national employer-sponsored insured population. Effects of AUD treatment utilization on decompensation rates were calculated using proportional hazards regression with propensity score adjustment. RESULTS: A total of 66,053 AC patients were identified, 32% were female, and mean age at diagnosis was 54.5 years. About 72% had insurance coverage for substance abuse treatment. Overall, AUD treatment utilization rates were low, with only 10% receiving a face-to-face mental health or substance abuse visit and only 0.8% receiving a Food and Drug Administration (FDA)-approved relapse prevention medication within 1 year of index diagnosis. Women were less likely to receive a face-to-face visit (hazard ratio [HR] 0.84, p < 0.001) or an FDA-approved relapse prevention medication (0.89, p = 0.05) than men. AC patients who had a clinic visit for AUD treatment or used FDA-approved relapse medication showed decreased risk of decompensation at 1 year (HR 0.85, p < 0.001 for either). CONCLUSIONS: AUD treatment utilization is associated with lower decompensation rates among privately insured patients with AC. Women were less likely to utilize AUD treatment visits. Efforts to reduce gender-specific barriers to treatment are urgently needed to improve outcomes.

Charges for Alcoholic Cirrhosis Exceed All Other Etiologies of Cirrhosis Combined: A National and State Inpatient Survey Analysis.

BACKGROUND: Inpatient charges for patients with cirrhosis are substantial. We aimed to examine trends in inpatient charges among patients with cirrhosis to determine the drivers of healthcare expenditures. We hypothesized that alcoholic cirrhosis (AC) was a significant contributor to overall expense. METHODS: We performed a retrospective analysis of the Health Care Utilization Project Nationwide Inpatient Sample Database 2002-2014 (annual cross-sectional data) and New York and Florida State Inpatient Databases 2010-2012 (longitudinal data). Adult patients with cirrhosis of the liver were categorized as AC versus all other etiologies of cirrhosis combined. Patient characteristics were analyzed using ordinary least squares regression modeling. A random effects model was used to evaluate 30-day readmissions. RESULTS: In total, 1,240,152 patients with cirrhosis were admitted between 2002 and 2014. Of these, 567,510 (45.8%) had a diagnosis of AC. Total charges for AC increased by 95.7% over the time period, accounting for 59.9% of all inpatient cirrhosis-related charges in 2014. Total aggregate charges for AC admissions were $28 billion and increased from $1.4B in 2002 to $2.8B by 2014. In the NIS and SID, patients with AC were younger, white and male. Readmission rates at 30, 60, and 90 days were all higher among AC patients. CONCLUSIONS: Inpatient charges for cirrhosis care are high and increasing. Alcohol-related liver disease accounts for more than half of these charges and is driven by sheer volume of admissions and readmissions of the same patients. Effective alcohol addictions therapy may be the most cost-effective way to substantially reduce inpatient cirrhosis care expenditures.

Incidence and Outcomes for Patients With Cirrhosis Admitted to the United Kingdom Critical Care Units.

OBJECTIVE: To assess the epidemiology and outcome of patients with cirrhosis following critical care unit admission. DESIGN: Retrospective cohort study. SETTING: Critical care units in England, Wales, and Northern Ireland participating in the U.K. Intensive Care National Audit and Research Centre Case Mix Programme. PATIENTS: Thirty-one thousand three hundred sixty-three patients with cirrhosis identified of 1,168,650 total critical care unit admissions (2.7%) admitted to U.K. critical care units between 1998 and 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Ten thousand nine hundred thirty-six patients had alcohol-related liver disease (35%). In total, 1.6% of critical care unit admissions in 1998 had cirrhosis rising to 3.1% in 2012. The crude critical care unit mortality of patients with cirrhosis was 41% in 1998 falling to 31% in 2012 (p < 0.001). Crude hospital mortality fell from 58% to 46% over the study period (p < 0.001). Mean(SD) Acute Physiology and Chronic Health Evaluation II score in 1998 was 20.3 (8.5) and 19.5 (7.1) in 2012. Mean Acute Physiology and Chronic Health Evaluation II score for patients with alcohol-related liver disease in 2012 was 20.6 (7.0) and 19.0 (7.2) for non-alcohol-related liver disease (p < 0.001). In adjusted analysis, alcohol-related liver disease was associated with increased risk of death (odds ratio, 1.51 [95% CI, 1.42-1.62; p < 0.001]) with a year-on-year reduction in hospital mortality (adjusted odds ratio, 0.95/yr, [0.94-0.96, p < 0.001]). CONCLUSIONS: More patients with cirrhosis are being admitted to critical care units but with increasing survival rates. Patients with alcohol-related liver disease have reduced survival rates partly explained by higher levels of organ failure at admission. Patients with cirrhosis and organ failure warrant a trial of organ support and universal prognostic pessimism is not justified.

Osmotic Demyelination Unrelated to Hyponatremia.

Osmotic demyelination unrelated to hyponatremia is rarely reported. We present a case of osmotic demyelination in a patient with hypernatremia in the absence of preceding hyponatremia and review previously reported cases of osmotic demyelination in nonhyponatremic patients. We conclude that a rapid increase in serum sodium concentration and plasma tonicity even in the absence of preceding hyponatremia may surpass the brain's capacity for adaptation to hypertonicity and lead to osmotic demyelination in predisposed individuals. Risk factors for osmotic demyelination in patients with chronic hyponatremia and without hyponatremia are probably similar and are usually associated with states of limited brain osmolyte response, such as alcoholism, liver disease (including those undergoing orthotopic liver transplantation), malnutrition, malignancy, pregnancy/postpartum state, severe illness/sepsis, adrenal insufficiency, and metabolic derangements. Clinicians should be vigilant in identifying individuals who may, even in the absence of hyponatremia, have increased susceptibility to osmotic demyelination and avoid rapid fluctuations in serum sodium concentrations in such patients.

Alcohol Consumption Influences Clinical Outcome in Patients Admitted to a Referral Center for Liver Disease.

INTRODUCTION AND AIM: Excessive alcohol consumption is a public health concern worldwide and has been associated with high mortality rates. This study aimed to determine the prevalence of alcohol consumption and its influence on the prognosis of hospitalized cirrhotic patients in a tertiary care hospital. MATERIAL AND METHODS: We reviewed the medical records of all patients with hepatic cirrosis admitted between January 2009 and December 2014, in a referral center for liver disease in southern Brazil. Data on clinical outcomes, associated conditions, infections, and mortality were collected and compared between alcoholic and nonalcoholic patients. RESULTS: The sample consisted of 388 patients; 259 (66.7%) were men. One hundred fifty-two (39.2%) were classified as heavy use of alcohol. Most alcoholic patients were men (n = 144; 94.7%). Mean age was 55.6 ± 8.9 years. Hepatic decompensations and infections were more prevalent in alcoholic patient. Spontaneous bacterial peritonitis and respiratory tract infection accounted for most of the infections. Excessive alcohol consumption was associated with mortality (P = 0.009) in multivariate analysis. CONCLUSION: On the present study, the prevalence of heavy use of alcohol was high and associated with a poorer prognosis in hospitalized cirrhotic patients, increasing the risk of infection and death.

[Ruptured ascending colonic varices in a patient with alcoholic liver cirrhosis treated using topical skin adhesive:a case study].

A 59-year-old man had been admitted to our hospital because of general malaise and abdominal fullness caused by massive ascites. He was diagnosed with alcoholic liver cirrhosis. Following the removal of ascites, he was referred to our department because of hematochezia. Emergent colonoscopy revealed the rupture of ascending colonic varices. Endoscopic variceal sclerotherapy using topical skin adhesive (75% Histoacryl) was performed to treat the colonic varices, which proved to be an effective treatment. Enhanced computerized tomography performed 5 days after the treatment of ascending colonic varices showed complete obstruction of the ileocolic varices without complication. It is important to consider the possibility of ectopic varices when a patient with liver cirrhosis reports bloody stool.

Bidirectional Communication between Liver and Gut during Alcoholic Liver Disease.

Alcoholic liver disease is a major medical burden. Alcohol abuse is the cause for end-stage liver disease in approximately 50% of all patients with cirrhosis. Chronic alcohol consumption is associated with changes in the composition of the intestinal microbiota and gut barrier dysfunction. The portal vein is the major communication route between the intestine and the liver. Increased intestinal permeability allows microbial components, bacteria, and metabolites to translocate to the liver. The liver communicates with the intestine via mediators in the systemic circulation and the biliary system. In this review, the authors describe the changes that occur in the intestinal microbiota with chronic alcohol consumption. They further review the bilateral communication between the liver and the gut, and discuss how this interaction affects the progression of alcoholic liver disease.

A Comparative Study of Liver Disease Care in the USA and Urban and Rural China.

BACKGROUND: Chronic liver disease is a major cause of morbidity and mortality in the USA and China, but the etiology of liver disease, medical practice, and patient expectations in these two countries are different. AIMS: To compare patient knowledge about their liver disease, patient satisfaction with liver disease care, and patient medical decision-making preference in the USA and China. METHODS: Three cohorts of established adult patients with liver disease seen in liver clinics in Ann Arbor, USA, and Beijing (urban) and Hebei (rural), China, completed a survey between May and September 2014. RESULTS: A total of 990 patients (395 USA, 398 Beijing, and 197 Hebei) were analyzed. Mean liver disease knowledge score (maximum 5) in the USA, Beijing, and Hebei patients was 4.1, 3.6, and 3.0, respectively (p < 0.001). US patients had a greater preference for collaborative decision-making: 71.8 % preferred to make treatment decisions together with the doctor, while most Chinese patients (74.6 % Beijing and 84.8 % Hebei) preferred passive decision-making. Mean satisfaction score (maximum 85) in the USA was higher than in Beijing, which in turn was higher than in Hebei (78.2 vs. 66.5 vs. 60.3, p < 0.001). There was a positive correlation between liver disease knowledge score and satisfaction score (r = 0.27, p < 0.001) and with collaborative medical decision-making (r = 0.22, p < 0.001) when responses from all sites were combined. CONCLUSIONS: Liver disease knowledge and patient satisfaction were greatest in the USA, followed by Beijing and then Hebei patients. Understanding these differences and associated factors may help to improve patient outcomes.