Pharmacologic Management of Hepatic Encephalopathy.

Hepatic encephalopathy is a common cause of morbidity and mortality among patients with decompensated liver cirrhosis. In this article, we review the history, mechanism, and evidence for first-line pharmacologic therapies for hepatic encephalopathy including nonabsorbable disaccharides, antibiotics, and electrolyte management. We also review newer, second-line therapies including polyethylene glycol, albumin, branched-chain amino acids, probiotics and fecal microbiota transplant, zinc, and l-ornithine-l-aspartate.

Serum Ammonia Levels Do Not Correlate With Overt Hepatic Encephalopathy Severity in Hospitalized Patients With Cirrhosis.

Although ammonia is involved in the pathophysiology of hepatic encephalopathy (HE), the use of ammonia levels in clinical practice is problematic.1-3 For example, in a study of 551 patients with overt HE (OHE) receiving lactulose who had ammonia levels tested, only 60% had an increased ammonia level (defined as >72 µmol/L).2 Overall, there was no correlation observed between lactulose dose and whether ammonia levels were obtained (ie, presence/absence of increased ammonia level did not guide therapy), or between time to OHE resolution and ammonia levels.2 Additionally, there is substantial interlaboratory variability in sample handling and processing, which may affect ammonia measurements.4.

Hepatocellular Carcinoma Incidence and Mortality in the USA by Sex, Age, and Race: A Nationwide Analysis of Two Decades.

Background and Aims: While the incidence rates of hepatocellular carcinoma (HCC) are increasing, there are limited comprehensive data on demographic-specific incidence and mortality trends in the USA. We aimed to evaluate recent trends in HCC incidence and mortality among different demographic groups in the USA. Methods: Age-adjusted HCC incidence rates were calculated from the Centers for Disease Control's United States Cancer Statistics database, which combines incidence data on newly diagnosed cancer cases and covers approximately 98% of the population in the USA. Additionally, age-adjusted HCC mortality rates were obtained from the Centers for Disease Control's National Center for Health Statistics database, which offers comprehensive coverage spanning nearly 100% of deaths attributed to HCC in the USA. Rates were stratified by sex, age (older [≥55 years] and younger [<55 years] adults), race and ethnicity (Non-Hispanic White, Non-Hispanic Black, Hispanic, Non-Hispanic Asian/Pacific Islander, and Non-Hispanic American Indian/Alaska Native), and tumor stage at diagnosis (early and late). Annual and average annual percentage change (AAPC) were calculated using joinpoint regression. A sex-specific pairwise comparison was conducted. Results: Between 2001 and 2020, there were 467,346 patients diagnosed with HCC (26.0% women), with increasing incidence in both sexes without significant difference (p=0.65). In younger adults (78,169 patients), the incidence decreased in men but not in women (AAPC difference=-2.39, p=0.002). This was seen in various racial and ethnic groups, mostly driven by early-stage tumors (AAPC difference=-2.65, p=0.02). There were 329,973 deaths attributed to HCC between 2000 and 2020 (28.4% women). In younger adults (43,093 deaths), mortality decreased in men at a greater rate than in women (AAPC difference=1.61, p=0.007). This was seen in various racial and ethnic groups, most notably in non-Hispanic American Indian/Alaska Natives (AAPC difference=-4.51, p=0.01). Conclusions: Nationwide USA data, covering nearly all HCC cases, show an increasing incidence and mortality over the last two decades. In younger adults, there was a decreasing incidence in men but not in women, due to early-stage tumors. Mortality improved in younger men at a greater rate than in women, especially in Non-Hispanic American Indian/Alaska Natives. Future studies are warranted to identify the risk factors associated with the occurrence and outcomes of HCC in demographic-specific populations, especially younger women.

Trends of Hepatocellular Carcinoma (HCC) Inpatients Mortality and Financial Burden From 2011 to 2017: A Nationwide Analysis.

INTRODUCTION: Liver cancer, including Hepatocellular carcinoma (HCC) is the seventh most common tumor worldwide. Previously, the financial burden of HCC in the United States between 2002 and 2011 was noted to be continuously increasing. This study aims to evaluate temporal trends of hospitalizations due to HCC. METHOD: This is a retrospective analysis utilizing the National Inpatient Sample (NIS) database. All subjects admitted between 2011 and 2017 with a diagnosis of HCC were identified. The primary trend characteristics were in-hospital mortality, hospital charges, and length of stay. RESULTS: An increase in hospitalization from 67,779 (0.18%) admissions in 2011 to 84,580 (0.23%) admissions in 2017( P <0.05) was noted. Most patients were 45 to 64 years old (median 50%), predominantly men (median 68%) ( P <0.05). The primary health care payer was Medicare (Median 49%) and Medicaid (Median 18%) ( P <0.05). The most common geographical location was the south (Median 36%) ( P <0.05). Most patients were admitted to large hospitals (Median 62%) in urban areas ( P <0.05). The median inpatient mortality was estimated to be 9% in 2017 ( P <0.05), which has decreased from 10%( P <0.05) in 2011. The total charges per admission have increased steadily from $58,406 in 2011 to $78,791 in 2017 ( P <0.05). The median length of stay has increased from 5.79 (SD 6.93) in 2011 to 6.07 (SD 8.3) in 2017( P <0.05). The most common mortality risk factor was sepsis, Acute renal failure, and GI hemorrhage. CONCLUSION: HCC-related admissions continue to be on the rise. HCC mortality has decreased across the years with earlier diagnoses and advances in therapy. However, we observed a significant increase in financial burden on health care with increasing in-hospital costs, a finding that needs to be verified in prospective trials.

Chronic Liver Disease and Cirrhosis Mortality Rates Are Disproportionately Increasing in Younger Women in the United States Between 2000-2020.

BACKGROUND & AIMS: Previous studies show that mortality from chronic liver disease (CLD) and cirrhosis is increasing in the United States. However, there are limited data on sex-specific mortality trends by age, race, and geographical location. The aim of this study was to conduct a comprehensive time-trend analysis of liver disease-related mortality rates in the National Center of Health Statistics (NCHS) database. METHODS: CLD and cirrhosis mortality rates between 20002020 (age-adjusted to the 2000 standard U.S. population) were collected from the NCHS database and categorized by sex and age into older adults (≥55 years) and younger adults (<55 years), race (Non-Hispanic-White, Non-Hispanic-Black, Hispanic, Non-Hispanic-American-Indian/Alaska-Native, and Non-Hispanic-Asian/Pacific-Islander), U.S. state, and cirrhosis etiology. Time trends, annual percentage change (APC), and average APC (AAPC) were estimated using Joinpoint Regression using Monte Carlo permutation analysis. We used tests for parallelism and identicalness for sex-specific pairwise comparisons of mortality trends (two-sided P value cutoff = .05). RESULTS: Between 20002020, there were 716,651 deaths attributed to CLD and cirrhosis in the U.S. (35.68% women). In the overall population and in older adults, CLD and cirrhosis-related mortality rates were increasing similarly in men and women. However, in younger adults (246,149 deaths, 32.72% women), the rate of increase was greater in women compared with men (AAPC = 3.04 vs 1.08, AAPC-difference = 1.96; P < .001), with non-identical non-parallel data (P values < .001). The disparity was driven by Non-Hispanic-White (AAPC = 4.51 vs 1.79, AAPC-difference = 2.71; P < .001) and Hispanic (AAPC = 1.89 vs -0.65, AAPC-difference = 2.54; P = .001) individuals. The disparity varied between U.S. states and was seen in 16 states, mostly in West Virginia (AAPC = 4.96 vs 0.88, AAPC-difference = 4.08; P < .001) and Pennsylvania (AAPC = 2.81 vs -1.02, AAPC-difference = 3.84; P < .001). Etiology-specific analysis did not show significant sex disparity in younger adults. CONCLUSIONS: Mortality rates due to CLD and cirrhosis in the U.S. are increasing disproportionately in younger women. This finding was driven by higher rates in Non-Hispanic White and Hispanic individuals, with variation between U.S. states. Future studies are warranted to identify the reasons for these trends with the ultimate goal of improving outcomes.

Classification and Epidemiologic Aspects of Acute-on-Chronic Liver Failure.

The three most common definitions of acute-on-chronic liver failure (ACLF) are derived from data from North America, Europe, and the Asian-Pacific Region. All three definitions identify patients with underlying liver disease who are at increased risk for mortality who develop a syndrome often characterized by associated organ failures. The epidemiology of ACLF differs throughout various regions globally and is driven by the cause of the underlying chronic liver disease and the triggers of ACLF.

Emerging Pharmacotherapies in Alcohol-Associated Hepatitis.

The incidence of alcoholic-associated hepatitis (AH) is increasing. The treatment options for severe AH (sAH) are scarce and limited to corticosteroid therapy which showed limited mortality benefit in short-term use only. Therefore, there is a dire need for developing safe and effective therapies for patients with sAH and to improve their high mortality rates.This review article focuses on the current novel therapeutics targeting various mechanisms in the pathogenesis of alcohol-related hepatitis. Anti-inflammatory agents such as IL-1 inhibitor, Pan-caspase inhibitor, Apoptosis signal-regulating kinase-1, and CCL2 inhibitors are under investigation. Other group of agents include gut-liver axis modulators, hepatic regeneration, antioxidants, and Epigenic modulators. We describe the ongoing clinical trials of some of the new agents for alcohol-related hepatitis. Conclusion: A combination of therapies was investigated, possibly providing a synergistic effect of drugs with different mechanisms. Multiple clinical trials of novel therapies in AH remain ongoing. Their result could potentially make a difference in the clinical course of the disease. DUR-928 and granulocyte colony-stimulating factor had promising results and further trials are ongoing to evaluate their efficacy in the large patient sample.

Early treatment with terlipressin in patients with hepatorenal syndrome yields improved clinical outcomes in North American studies.

Hepatorenal syndrome type 1 (HRS-1) is a serious complication of advanced cirrhosis and a potentially reversible form of acute kidney injury that is associated with rapidly deteriorating kidney function. Liver transplantation remains the only curative treatment for decompensated cirrhosis. However, terlipressin, a vasopressin analog, successfully reverses HRS-1, and may improve patient survival while awaiting liver transplantation. Patients with higher baseline serum creatinine have a reduced response to treatment with terlipressin. These post hoc analyses examined pooled data from 352 patients with HRS-1 treated with terlipressin in 3 North American-centric, Phase III, placebo-controlled clinical studies (i.e. OT-0401, REVERSE, and CONFIRM)-across 3 serum creatinine subgroups (i.e. <3, ≥3-<5, and ≥5 mg/dL)-to further delineate their correlation with HRS reversal, renal replacement therapy-free survival, and overall survival. Serum creatinine was significantly associated with HRS reversal in univariate and multivariate logistic regression analyses (P<0.001). The incidence of HRS reversal inversely correlated with serum creatinine subgroup (<3 mg/dL, 49.2%; ≥3-<5 mg/dL, 28.0%; ≥5 mg/dL, 9.1%). At Day 30 follow-up, renal replacement therapy-free survival was significantly higher for patients with HRS-1 in the lower serum creatinine subgroups than in the higher subgroup (<5 vs. >5 mg/dL; p=0.01). Terlipressin-treated patients with HRS-1, with a lower baseline serum creatinine level, had a higher overall survival (p<0.001) and higher transplant-free survival at Day 90 (p=0.04). Patients with HRS-1 and lower serum creatinine levels who were treated with terlipressin had higher HRS reversal and survival outcomes, highlighting the significant need to identify and treat patients with HRS-1 early when they often have lower serum creatinine levels, and likely a greater response to terlipressin.

Dosing of Rifaximin Soluble Solid Dispersion Tablets in Adults With Cirrhosis: 2 Randomized, Placebo-controlled Trials.

BACKGROUND & AIMS: Cirrhosis-related complications are a major burden. Rifaximin soluble solid dispersion (SSD) tablets (immediate-release [IR]; sustained extended-release [SER]) were designed to increase rifaximin water solubility. These analyses evaluate dosing for prevention of cirrhosis complication-related hospitalizations/mortality and overt hepatic encephalopathy (OHE) treatment. METHODS: Two phase II, randomized, double-blind, placebo-controlled trials were conducted. Trial 1: outpatients with early decompensated cirrhosis randomized to placebo or rifaximin SSD once-nightly: IR 40 or 80 mg, SER 40 or 80 mg, or IR 80 mg plus SER 80 mg, for 24 weeks. Trial 2: inpatients with OHE randomized to lactulose plus placebo or rifaximin SSD: IR 40 mg once or twice daily or SER 80 mg once or twice daily for ≤14 days. Primary efficacy endpoint: time to cirrhosis complication-related hospitalization/all-cause mortality (Trial 1) or time to OHE resolution (Trial 2). RESULTS: In Trial 1 (n = 516), no significant difference in time to cirrhosis complication-related hospitalization/all-cause mortality vs placebo. In a post hoc analysis, time to all-cause hospitalization/all-cause mortality was improved with IR 40 mg vs placebo (15.4% [12/78] vs 27.7% [26/94]; P = .03). A Trial 2 prespecified interim analysis (n = 71) showed lactulose plus rifaximin SSD IR 40 mg bid significantly reduced median time to OHE resolution (21.1 hours) vs lactulose plus placebo (62.7 hours; P = .02). Trial 2 was subsequently terminated. CONCLUSION: Rifaximin SSD IR 40 mg may reduce hospitalizations in patients with cirrhosis and shorten duration of OHE during hospitalization-considered a negative finding, yet also hypothesis-generating. (ClinicalTrials.govNCT01904409; NCT03515044).

Improving Outcomes in Hepatorenal Syndrome-Acute Kidney Injury With Early Diagnoses and Implementation of Approved Treatment Regimens.

Decompensated cirrhosis, defined by the overt manifestations of liver failure and portal hypertension (eg, ascites, hepatic encephalopathy, variceal bleeding), is the inflection point associated with increased morbidity and mortality in chronic liver disease. Acute kidney injury in the setting of cirrhosis (hepatorenal syndrome-acute kidney injury [HRS-AKI]) is a severe and often fatal complication. The goals of treatment of HRS-AKI are to reverse renal failure and prolong survival in these critically ill patients or perhaps to allow the transplant team to complete the pretransplant evaluation and bridge the patient to transplant. Historically, in the United States, standard-of-care treatments for HRS-AKI were chosen by default despite lack of data, off-label use, and suboptimal results. Terlipressin represents the first drug in the United States indicated for the treatment of HRS-AKI. This review provides an up-to-date overview of HRS-AKI, discusses terlipressin and how to incorporate this new treatment into patient care and streamline society guidelines on HRS diagnosis and treatment in a practical way for clinical use, and concludes with a sample order set that highlights the recommendations discussed throughout the supplement.

Hypoglycemia Is Associated With Worse Outcomes in Patients With Cholangitis Despite Undergoing Endoscopic Retrograde Cholangiopancreatography.

Background Hypoglycemia has been associated with poorer outcomes in hospitalized patients undergoing surgical interventions. In cholangitis, endoscopic retrograde cholangiopancreatography (ERCP) is often a critical adjunct to surgery, capable of diagnosing and treating various biliary and pancreatic pathologies. While technically less invasive than surgery, the effect of hypoglycemia on clinical outcomes of patients with cholangitis undergoing ERCP has not been elucidated. Methodology Data were extracted from the National Inpatient Sample (NIS) database from 2016 to 2019. Using the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes, patients diagnosed with cholangitis and underwent ERCP were identified. Baseline demographic data, comorbidities, in-hospital mortality, hospital charges, and hospital length of stay (LOS) were extracted and compared based on the presence or absence of hypoglycemia. Statistical analysis was done using t-test and chi-square analyses. A multivariate analysis for the mortality odds ratio (OR) was calculated to adjust for possible confounders. Results A total of 256,540 patients with cholangitis who underwent ERCP were identified, and 2,810 of them had hypoglycemia during their hospitalization. The mean age of the hypoglycemia group was 64.41 years. Most patients were females (54%) and whites (57%). More patients in the hypoglycemia group had a history of alcoholism and congestive heart failure (CHF). Hypoglycemia was associated with higher odds of in-hospital mortality (OR = 6.71, confidence interval (CI) = 5.49-8.2; p < 0.0001). In addition to hypoglycemia, age >65 years, non-white race, and CHF were independently associated with higher mortality. Moreover, patients with hypoglycemia had higher total hospital charges ($87,147 vs. $133,400; p < 0.0001) and a significant increase in the LOS (9.7 vs. 6.7 days; p < 0.0001). Conclusions Previous studies in the surgical literature have linked hypoglycemia to increased incidence of atrial fibrillation, usage of mechanical ventilation, and application of circulatory support. Hypoglycemia may also affect the metabolism of the heart, leading to myocardial ischemia and malignant arrhythmias. However, it is unclear if hypoglycemia represents a proxy for the severity of patient illness as septic shock and renal insufficiency are common etiologies that may strongly impact mortality. Therefore, careful glycemic control during hospitalization should be practiced as hypoglycemia serves as a poor prognostic indicator that should not be overlooked.

The Impact of Cirrhosis on Outcomes of Patients Admitted With Diabetic Ketoacidosis: A Nationwide Study.

Introduction Diabetic ketoacidosis (DKA) is the most common acute hyperglycemic emergency in people with diabetes mellitus (DM). Cirrhosis is a consequence of chronic inflammation that is followed by hepatic fibrosis. It has been noted that cirrhosis is associated with an increased risk of developing type II DM due to altered glucose homeostasis. The prognostic value of DM in cirrhotic patients has been studied before and was found to be associated with lower survival. However, the risk of mortality and adverse events in cirrhotic patients admitted with DKA needs further evaluation. The aim of this study is to compare outcomes in patients with cirrhosis admitted to the hospital with DKA compared to non-cirrhotic patients. Methods The data for this study were extracted from the National Inpatient Sample (NIS) 2016-2019. The NIS was queried for all patients who had a discharge diagnosis of DKA. Patients with cirrhosis were identified and subclassified into compensated and decompensated cirrhosis using the International Classification of Diseases 10th revision, Clinical Modification (ICD-10-CM) codes. Patients without cirrhosis were the control group. ICD-10-CM codes that have been validated for cirrhosis were utilized. The primary outcome was in-hospital mortality. Secondary outcomes were hospital charges, length of stay (LOS), and in-hospital complications, including shock, mechanical ventilation, and acute kidney injury (AKI) requiring dialysis. Results We included 1,098,875 hospitalizations with a discharge diagnosis of DKA. Overall, 9,190 patients had compensated cirrhosis and 4,355 had decompensated cirrhosis. Cirrhotic patients had overall worse outcomes compared to non-cirrhotics. Decompensated cirrhotics had the highest mortality (11.26%; 95% confidence interval [CI]: 9.36% to 13.49%) compared to compensated cirrhotics (3.54%; 95% CI: 2.79% to 4.48%) and non-cirrhotics (2.15%; 95% CI: 1.89% to 2.43%). Similarly, decompensated cirrhotics also had the highest LOS, total charges, and in-hospital complications among the groups. On multivariate analysis, decompensated cirrhosis, rather than compensated cirrhosis, was an independent predictor of higher mortality (adjusted odds ratio [AOR]: 2.30; 95% CI: 1.81 to 2.92), LOS (regression coefficient: +1.82 days; 95% CI: +1.19 to +2.44 days), hospital charges (regression coefficient: +$28,497; 95% CI: +$18,107 to +$38,887), shock (AOR: 2.31; 95% CI: 1.68 to 3.18), mechanical ventilation (AOR: 1.91; 95% CI: 1.58 to 2.29), and AKI requiring dialysis (AOR: 2.31; 95% CI: 1.68 to 3.18). Conclusion This study showed that patients with decompensated liver cirrhosis who were admitted with DKA had the worst in-hospital outcomes. Additionally, only decompensated cirrhosis was an independent predictor of worse outcomes. Decompensated cirrhotics who develop DKA should be approached with more caution with a probable lower threshold for intensive care unit admission for a higher level management.

Liver transplant allocation policies and outcomes in United States: A comprehensive review.

Liver transplant allocation policies in the United States has evolved over 3 decades. The donor liver organs are matched, allocated and procured by the Organ Procurement and Transplantation Network which is administered by the United Network of Organ Sharing (UNOS), a not-for-profit organization governed by the United States human health services. We reviewed the evolution of liver transplant allocation policies. Prior to 2002, UNOS used Child-Turcotte-Pugh score to list and stratify patients for liver transplantation (LT). After 2002, UNOS changed its allocation policy based on model for end-stage liver disease (MELD) score. The serum sodium is the independent indicator of mortality risk in patients with chronic liver disease. The priority assignment of MELD-sodium score resulted in LT and prevented mortality on waitlist. MELD-Sodium score was implemented for liver allocation policy in 2016. Prior to the current and most recent policy, livers from adult donors were matched first to the status 1A/1B patients located within the boundaries of the UNOS regions and donor-service areas (DSA). We reviewed the disadvantages of the DSA-based allocation policies and the advantages of the newest acuity circle allocation model. We then reviewed the standard and non-standard indications for MELD exceptions and the decision-making process of the National Review Liver Review Board. Finally, we reviewed the liver transplant waitlist, donation and survival outcomes in the United States.

Interferon drives HCV scarring of the epigenome and creates targetable vulnerabilities following viral clearance.

BACKGROUND AND AIMS: Chronic HCV infection is a leading etiologic driver of cirrhosis and ultimately HCC. Of the approximately 71 million individuals chronically infected with HCV, 10%-20% are expected to develop severe liver complications in their lifetime. Epigenetic mechanisms including DNA methylation and histone modifications become profoundly disrupted in disease processes including liver disease. APPROACH AND RESULTS: To understand how HCV infection influences the epigenome and whether these events remain as "scars" following cure of chronic HCV infection, we mapped genome-wide DNA methylation, four key regulatory histone modifications (H3K4me3, H3K4me1, H3K27ac, and H3K27me3), and open chromatin in parental and HCV-infected immortalized hepatocytes and the Huh7.5 HCC cell line, along with DNA methylation and gene-expression analyses following elimination of HCV in these models through treatment with interferon-α (IFN-α) or a direct-acting antiviral (DAA). Our data demonstrate that HCV infection profoundly affects the epigenome (particularly enhancers); HCV shares epigenetic targets with interferon-α targets; and an overwhelming majority of epigenetic changes induced by HCV remain as "scars" on the epigenome following viral cure. Similar findings are observed in primary human patient samples cured of chronic HCV infection. Supplementation of IFN-α/DAA antiviral regimens with DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine synergizes in reverting aberrant DNA methylation induced by HCV. Finally, both HCV-infected and cured cells displayed a blunted immune response, demonstrating a functional effect of epigenetic scarring. CONCLUSIONS: Integration of epigenetic and transcriptional data elucidate key gene deregulation events driven by HCV infection and how this may underpin the long-term elevated risk for HCC in patients cured of HCV due to epigenome scarring.

In-Hospital Outcomes of Patients With Non-Alcoholic Fatty Liver Disease Who Underwent Percutaneous Coronary Intervention: A Nationwide Inpatient Sample Analysis.

Background Non-alcoholic fatty liver disease (NAFLD) is prevalent in almost 25% of the Western population and is predicted to become one of the leading causes of end-stage liver disease. There is increasing evidence that NAFLD is a risk factor for cardiovascular disease, specifically for coronary artery disease, via disruption of the metabolism of glucose and lipids in the body, leading to a state of systemic inflammation that promotes atherosclerosis. This study aims to explore outcomes in patients who underwent percutaneous coronary intervention (PCI) with or without placement of drug-eluting stents (DES) to determine whether the concurrent diagnosis of NAFLD led to worse in-hospital outcomes. Methods We used the National Inpatient Sample, Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality 2016 to conduct a cross-sectional study that included all adult patients who underwent PCI with or without placement of DES during hospital admission. Patients with NAFLD were identified and compared to patients without NAFLD. Patients were selected by using ICD-10-CM and ICD-10-PCS codes. Outcomes included mortality, length of stay and total hospital charges, and major adverse cardiac events (MACE). Data on patient demographics, inpatient statistics, and comorbidities were obtained and analyzed using cross-tabulation, Pearson χ2 test, and independent samples t-test. Data were adjusted for confounders using logistic and linear regression. Results Among 429,855 patients who underwent PCI with or without placement of DES, 2,560 patients (0.6%) had a diagnosis of NAFLD. There was no significant difference with regard to mortality and MACE. The NAFLD group had a higher proportion of females, a longer average length of hospital stay, and patients presented at a younger average age. Regarding comorbidities, more patients in the NAFLD group had diabetes mellitus type II, obesity, obstructive sleep apnea (OSA), chronic kidney disease (CKD), and peripheral vascular disease (PVD). Conclusion NAFLD is emerging as a risk factor for cardiovascular disease. Increasing evidence suggests that the disease contributes to systemic atherosclerosis and thus coronary artery disease. We found that among patients who underwent PCI in 2016, those with NAFLD had a longer length of stay, were admitted at a younger age, and had significantly more cardiovascular comorbidities than those without NAFLD. Increasing evidence has shown that advanced liver disease due to NAFLD will continue to place a significant burden on the healthcare system and is, therefore, an area that the medical community should continue to focus on, especially, regarding preventative and therapeutic efforts.

Bacterial Infections in Cirrhotic Patients in a Tertiary Care Hospital.

BACKGROUND AND AIMS: Patients with cirrhosis are immunocompromised and at higher risk of developing infections compared to the general population. The aim of this study was to assess the incidence of infections in cirrhotic patients in a large academic liver center and investigate potential associations between infections, bacteria isolated, therapeutic regimens used, and mortality. METHODS: This was a retrospective chart review study, including 192 patients. All patients had a diagnosis of cirrhosis and were admitted to University Hospital. Information collected included demographics, etiology of cirrhosis, identification of bacteria from cultures, multidrug-resistant (MDR) status, antibiotics administered, intensive care unit (ICU) admission, and patient mortality. RESULTS: Infections were present in 105 (54.6%) patients, and 60 (31.2%) patients had multiple infections during a hospitalization(s) for infections. A total of 201 infections were identified. Urinary tract infections (UTIs) were the most common infection (37.8%), followed by bacteremia (20.4%), pneumonia (12.9%), spontaneous bacterial peritonitis (SBP) (11.9%), abscess/cellulitis (6.0%), infectious diarrhea (6.0%), and other (5.0%). Escherichia coli was the most common bacteria isolated (13.4%), both among sensitive and MDR infections. MDR bacteria were the cause for 41.3% of all infections isolated. Fungi accounted for 9.5% of infections. 21.9% of patients had decompensation from their infection(s) that required ICU care, and 14.6% of patients died during hospitalization or soon after discharge. CONCLUSIONS: The incidence of infections in cirrhotic patients is much higher than in their non-cirrhotic counterparts (54.6%), even higher than prior studies suggest. As many of these infections are caused by MDR bacteria and fungal organisms, stronger empiric antibiotics and antifungals should be considered when initially treating this immunocompromised population. However, once organism sensitivities are discovered, narrowing of antibiotic regimens must occur to maintain good antibiotic stewardship.

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.

Cannabis use history is associated with increased prevalence of ascites among patients with nonalcoholic fatty liver disease: A nationwide analysis.

BACKGROUND: Recent studies have revealed the endocannabinoid system as a potential therapeutic target in the management of nonalcoholic fatty liver disease (NAFLD). Cannabis use is associated with reduced risk for NAFLD, we hypothesized that cannabis use would be associated with less liver-related clinical complications in patients with NAFLD. AIM: To assess the effects of cannabis use on liver-related clinical outcomes in hospitalized patients with NAFLD. METHODS: We performed a retrospective matched cohort study based on querying the 2014 National Inpatient Sample (NIS) for hospitalizations of adults with a diagnosis of NAFLD. The NIS database is publicly available and the largest all-payer inpatient database in the United States. The patients with cannabis use were selected as cases and those without cannabis were selected as controls. Case-control matching at a ratio of one case to two controls was performed based on sex, age, race, and comorbidities. The liver-related outcomes such as portal hypertension, ascites, varices and variceal bleeding, and cirrhosis were compared between the groups. RESULTS: A total of 49911 weighed hospitalizations with a diagnosis of NAFLD were identified. Of these, 3820 cases were selected as the cannabis group, and 7625 non-cannabis cases were matched as controls. Patients with cannabis use had a higher prevalence of ascites (4.5% vs 3.6%), with and without cannabis use, P = 0.03. The prevalence of portal hypertension (2.1% vs 2.2%), varices and variceal bleeding (1.3% vs 1.7%), and cirrhosis (3.7% vs 3.6%) was not different between the groups, with and without cannabis use, all P > 0.05. Hyperlipidemia, race/ethnicity other than White, Black, Asian, Pacific Islander or Native American, and higher comorbidity score were independent risk factors for ascites in the cannabis group. Among non-cannabis users, obesity and hyperlipidemia were independent protective factors against ascites while older age, Native American and higher comorbidity index were independent risk factors for ascites. CONCLUSION: Cannabis was associated with higher rates of ascites, but there was no statistical difference in the prevalence of portal hypertension, varices and variceal bleeding, and cirrhosis.