The prognostic impact of acute kidney injury recovery patterns in critically ill patients with cirrhosis.

BACKGROUND: The prognostic impact of acute kidney injury (AKI) recovery patterns in critically ill patients with cirrhosis is unknown. We aimed to compare mortality stratified by AKI recovery patterns and identify predictors of mortality in patients with cirrhosis and AKI admitted to the intensive care unit. MATERIALS AND METHODS: Patients with cirrhosis and AKI from 2016 to 2018 at 2 tertiary care intensive care units were analyzed (N=322). AKI recovery was defined by Acute Disease Quality Initiative consensus: return of serum creatinine <0.3 mg/dL of baseline within 7 days of AKI onset. Recovery patterns were categorized by Acute Disease Quality Initiative consensus: 0-2 days, 3-7 days, and no-recovery (persistence of AKI >7 d). Landmark competing risk univariable and multivariable models (liver transplant as competing risk) was used to compare 90-day mortality between AKI recovery groups and to determine independent predictors of mortality. RESULTS: Sixteen percent (N=50) and 27% (N=88) achieved AKI recovery within 0-2 and 3-7 days, respectively; 57% (N=184) had no-recovery. Acute on chronic liver failure was prevalent (83%) and patients with no-recovery were more likely to have grade 3 acute on chronic liver failure (N=95, 52%) compared to patients with AKI recovery [0-2: 16% (N=8); 3-7: 26% (N=23); p<0.001]. Patients with no-recovery had significantly higher probability of mortality [unadjusted-sub-HR (sHR): 3.55; 95% CI: 1.94-6.49; p<0.001] compared to patients with recovery within 0-2 days, while the probability was similar between 3-7 and 0-2 days (unadjusted-sub-HR: 1.71; 95% CI: 0.91-3.20; p=0.09). On multivariable analysis, AKI no-recovery (sub-HR: 2.07; 95% CI: 1.33-3.24; p=0.001), severe alcohol-associated hepatitis (sub-HR: 2.41; 95% CI: 1.20-4.83; p=0.01), and ascites (sub-HR: 1.60; 95% CI: 1.05-2.44; p=0.03) were independently associated with mortality. CONCLUSION: AKI no-recovery occurs in over half of critically ill patients with cirrhosis and AKI and is associated with worse survival. Interventions that facilitate AKI recovery may improve outcomes in this patient population.

Severe Alcohol-Associated Hepatitis Is Associated With Worse Survival in Critically Ill Patients With Acute on Chronic Liver Failure.

Differences in mortality between critically ill patients with severe alcohol-associated hepatitis (sAH) and acute-on-chronic liver failure (ACLF) and non-sAH ACLF (i.e., ACLF not precipitated by sAH) are unknown. Such differences are important, as they may inform on prognosis and optimal timing of liver transplantation (LT). Thus, we aimed to compare short-term and longer-term mortality between patients with sAH ACLF and patients with non-sAH ACLF who were admitted to the intensive care unit. Patients with ACLF admitted from 2016-2018 at two tertiary care intensive care units were analyzed. SAH was defined by the National Institute on Alcohol Abuse and Alcoholism's Alcoholic Hepatitis Consortium and Model for End-Stage Liver Disease score >20. Mortality without LT was compared between sAH ACLF and non-sAH ACLF using Fine and Gray's competing-risks regression. A total of 463 patients with ACLF (18% sAH and 82% non-sAH) were included. Compared to patients with non-sAH ACLF, patients with sAH ACLF were younger (49 vs. 56 years; P < 0.001) and had higher admission Model for End-Stage Liver Disease (MELD) (35 vs. 25; P < 0.001) and Chronic Liver Failure Consortium (CLIF-C) scores (61 vs. 57; P = 0.002). There were no significant differences between the two groups for vasopressor, mechanical ventilation, and hemodialysis use. The cumulative incidence of death was significantly higher in patients with sAH ACLF compared to patients with non-sAH ACLF: 30-day 74.7% versus 45.3%; 90-day 81.9% versus 57.4%; 180-day 83.2% versus 63.0% (unadjusted subdistribution hazard ratio [sHR] 1.88 [95% confidence interval (CI) 1.44-2.46]; P < 0.001). After adjusting for CLIF-C score and infection in a multivariable competing-risk model, patients with sAH ACLF had significantly higher risk of death (sHR 1.57 [95% CI 1.20-2.06]; P = 0.001) compared to patients with non-sAH ACLF. Conclusion: Critically ill patients with sAH ACLF have worse mortality compared to patients with non-sAH ACLF. These data may inform prognosis in patients with sAH and ACLF, and early LT referral in potentially eligible patients.

Role of endotoxemia in causing renal dysfunction in cirrhosis.

Renal failure is a challenging problem in patients with cirrhosis since mortality increases with worsening renal function, hence the inclusion of serum creatinine in calculating the Model for End-Stage Liver Disease score for liver transplant evaluation. Among the various causes, infection is the leading etiology of mortality associated with cirrhosis. Bacterial infection frequently precipitates renal failure in patients with cirrhosis with the reported prevalence around 34%. Patients with cirrhosis are at increased risk of infections due to impaired immunity and increased gut permeability leading to bacterial translocation in the setting of portal hypertension. One of the most feared complications of severely decompensated liver and renal failure is hepatorenal syndrome, of which liver transplant may be the only available treatment. Furthermore, in those with spontaneous bacterial peritonitis and urinary tract infection, progressive renal failure occurs despite resolution of infection. Thus, the effects of endotoxemia on renal function in cirrhosis have become a major focus of research. The mechanisms of the damaging effects of endotoxin on renal function are complex but, in essence, involve dysregulated inflammation, circulatory dysfunction, poor clearance of endotoxin burden, as well as vasomotor nephropathy. In this article, we will review the mechanisms of endotoxemia-induced renal dysfunction in the setting of cirrhosis through the effects on renal blood flow, renal vascular endothelium, glomerular filtration rate, and tubular function.

Association between serum cotinine level and prevalence of non-alcoholic fatty liver disease: a cross-sectional study from the Third National Health and Nutrition Examination Survey.

The data on the effect of smoking on non-alcoholic fatty liver disease (NAFLD) has been controversial. The aim of this study was to investigate if an association exists between serum cotinine level (a tobacco biomarker) and NAFLD prevalence in the general US population. We conducted a cross-sectional analysis of data from the Third National Health and Nutrition Examination Survey (NHANES III). We included 11,003 adults aged 20-74 years who underwent ultrasonography. Of those, 4036 were identified as having NAFLD and 6967 were recognized as controls. The percentage of current smokers was significantly lower in subjects with NAFLD compared with those in controls (21.5% vs 26.0%, p<0.01). After adjustment for potential confounders, there was no association between current or former smokers with NAFLD. Additionally, no associations were observed between the levels of serum cotinine and NAFLD. No association between serum cotinine levels at each quartile level and NAFLD was observed regardless of smoking status. In this large US population-based study, we did not find an association between NAFLD and self-reported smoking status or measured serum cotinine level.

Management of alcohol misuse in patients with liver diseases.

Excessive alcohol use not only causes alcoholic liver disease (ALD) but also increases the risk of liver-related mortality in patients who already have other chronic liver diseases. Screening for alcohol misuse or alcohol use disorder (AUD) among patients with underlying liver disease is essential. This clinical review covers what is known about ALD, the impact of alcohol in patients with underlying liver diseases, current management of alcohol misuse and AUD, and the management of alcohol misuse and AUD specifically in patients with liver diseases. Several treatment options for alcohol misuse and AUD exist such as psychosocial intervention and behavioral and pharmacological therapies. The strategies used in the treatment of alcohol misuse and AUD are still applicable in those who consume alcohol and have underlying liver disease. However, certain medications still need to be carefully used due to potentially worsening already compromised liver function. Screening of ongoing alcohol use in subjects with liver disease is important, and prompt intervention is needed to prevent the associated morbidity and mortality from the detrimental effects of continued alcohol use on underlying liver disease. Considering alcoholism is a complex disease, probably a multidisciplinary approach combining psychotherapy and comprehensive medical care will be the most effective. Future research could focus on identifying additional treatment options for addressing the psychotherapy component since the self-determination and will to quit drinking alcohol can play such a crucial role in promoting abstinence.

Colonic Spirochetosis in a 60-Year-Old Immunocompetent Patient: Case Report and Review.

Spirochetes, a genetically and morphologically distinct group of bacteria, are thin, spiral-shaped, and highly motile. They are known causes of several human diseases such as syphilis, Lyme disease, relapsing fever, and leptospirosis. We report a case of colonic spirochetosis in a healthy patient presenting for surveillance colonoscopy. The diagnosis of intestinal spirochetosis was made accidentally during the histological examination of colonic polyps, which were removed during colonoscopy. We also performed an extensive review on intestinal spirochetosis with a focus on clinical presentation and outcomes of reported cases from the past two decades.

Multifocal Gastric Ulcers Caused by Diffuse Large B Cell Lymphoma in a Patient With Significant Weight Loss.

Primary gastrointestinal (GI) lymphoma is a heterogeneous disease with varied clinical presentations. The stomach is the most common GI site and accounts for 70% to 75% of GI lymphomas. We present a patient with gastric diffuse large B cell lymphoma (DLBCL) who presented with significant weight loss, early satiety, and multifocal ulcerated gastric lesions. Esophagoduodenoscopy should be performed in patients presenting with warning symptoms as in our case. Diagnosis is usually made by endoscopic biopsies. Multiple treatment modalities including surgery, radiotherapy, and chemotherapy have been used. Advancements in endoscopic and pathologic technology decrease turnaround time for diagnosis and treatment initiation, thus reducing the need for surgery. Health care providers should maintain a high level of suspicion and consider gastric DLBCL as part of the differential diagnosis, especially in those with warning symptoms such as weight loss and early satiety with abnormal endoscopic findings.