Association between Metabolic-Dysfunction-Associated Steatotic Liver Disease and Hepatic Cancer: Current Concepts and Future Challenges.

Background: This study systematically reviewed the association between metabolic-dysfunction-associated steatotic liver disease (MASLD) and the development of hepatic cancer. Previous research has highlighted MASLD as a predisposing condition. Aim: To collect recent global data on the relationship between MASLD and hepatic cancer. Methods: A systematic review was conducted, which included an analysis of studies on the relationship between MASLD and the incidence of hepatic cancers, focusing on the role of fibrosis and MASLD severity as predictors of cancer risk. Following standard methodological frameworks for the assessment of longitudinal studies, the review gathered information on fibrosis scores, hepatocellular carcinoma (HCC) incidence, and other types of hepatic neoplasms. Results: A total of 522 studies were initially identified, of which 6 studies were appropriate for the review. They collectively revealed that the stage of fibrosis in MASLD is a significant independent predictor of mortality and liver-related events, with higher fibrosis stages correlating with greater risk. Longitudinal data showed that increases in FIB-4 scores were linked to a higher risk of developing HCC and cirrhosis. MASLD was also associated with an increased risk of non-hepatic cancers such as colorectal cancer in males and breast cancer in females. The severity of MASLD was found to be a modifiable risk factor for biliary tract cancer (BTC), with the risk further amplified by diabetes. Moreover, lifestyle factors and comorbidities, such as smoking and diabetes, were identified as modifiers of cancer risk in MASLD patients. Conclusions: The systematic review identified the association between MASLD and an elevated risk of hepatic cancer, establishing a clear link between the severity of liver fibrosis and the incidence of HCC and other hepatic neoplasms. This supports the need for screening for hepatic cancer in patients with MASLD, particularly in the presence of advanced fibrosis or other risk-modifying factors.

Maternal, obstetrical, and neonatal outcomes in celiac disease.

OBJECTIVES: Some studies have suggested a link between celiac disease (CD) and adverse maternal, obstetrical, and neonatal outcomes. Using a large database, we evaluated the effect of CD on pregnancy outcomes. METHODS: We conducted a retrospective cohort study using the National Inpatient Sample (NIS) of all deliveries from 2015 to 2019 in the United States. Using ICD-10 codes, we identified pregnant patients who had CD and those who did not. A multivariate logistic regression was used to generate odds ratios (ORs) with 95% confidence intervals (CIs) for maternal, obstetrical, and neonatal outcomes. RESULTS: Of 12,039,222 deliveries between 2015 and 2019, there were 10,555 births in women with CD. Pregnant women with CD were more likely to be white and older compared to those without CD. Pregnant women with CD were significantly more likely to carry a diagnosis of gestational hypertension (OR 1.26; 95% CI 1.04-1.52), preeclampsia (1.28; 1.08-1.53), and severe preeclampsia (1.62; 1.25-2.09). They were less likely to have a full-term uncomplicated delivery (OR 0.11; 95% CI, 0.05-0.20), while being more likely to require device-assisted delivery (1.25; 1.04-1.50) and sustain 3rd or 4th degree vaginal lacerations (1.56; 1.21-2.02). Babies of pregnant women with CD were more likely to be small for gestational age (SGA) (OR 1.29; 95% CI 1.03-1.61). CONCLUSIONS: CD in pregnancy appears to be associated with increased adverse maternal, obstetrical, and neonatal outcomes. Clinicians should discuss these increased risks with CD patients who are planning to conceive.

Uncovering the Burden of Immune-Related Adverse Events in Immunotherapy: Insights from a Nationally Representative Sample.

BACKGROUND: Immune checkpoint inhibitors have shown promising efficacy in multiple malignancies and, therefore, have been increasingly used over the past decade. Clinical data have suggested anti-cancer efficacy associated with immune-related adverse events that could have added healthcare resource utilization and costs. OBJECTIVE: We used a nationwide dataset to investigate the association between immune-related adverse events and healthcare resource utilization, charges, and mortality among patients receiving various immune checkpoint inhibitors for indicated cancers. METHODS: We performed a retrospective analysis of the National Inpatient Sample to identify patients hospitalized in the USA for immunotherapy between October 2015 and 2018. Data between patients who developed immune-related adverse events were compared to those who did not. Baseline characteristics, inpatient complications, and associated charges were collected and analyzed between these two groups. RESULTS: Patients who developed immune-related adverse events in the hospital had high incidences of acute kidney injury, non-septic shock, and pneumonia, and managing these complications significantly contributed to higher healthcare resource utilization. The average charge of admission was highest in patients who developed an infusion reaction, followed by colitis, and adrenal insufficiency. In terms of cancer type, renal cell carcinoma had the highest charges, followed by Merkel cell carcinoma. CONCLUSIONS: Immune checkpoint inhibitor-based regimens have shifted the treatment landscape among multiple malignancies and their use continues to expand. However, a significant proportion of patients still develop severe adverse effects leading to increased healthcare costs and impacting patients' quality of life. Closer attention should be given to recognizing and managing immune-related adverse events according to guidelines across healthcare facilities and clinical practice settings.

Relationship Between Body Mass Index and Outcomes in Acute Myocardial Infarction.

Background: The prevalence of obesity in the United States is high. Obesity is one of the leading risk factors in the development of acute myocardial infarction (AMI). Nevertheless, how obesity impacts AMI in-hospital outcomes remains controversial. Methods: Using National Inpatient Sample (NIS) database, we identified patients diagnosed with AMI from the year 2015 to 2018. We divided these patients into five subgroups based on their body mass index (BMI). We compared outcomes such as mortality, length of inpatient stay, and inpatient complications between our subgroups. Statistical analysis was done using the program STATA. Our nationally representative analysis included 561,535 patients who had an AMI event across various weight classes. Results: Most of our sample was obese (BMI > 30 kg/m2) and male. Obese patients were significantly younger than the rest. Length of stay (LOS) for AMI was highest for those with a BMI of less than 24 kg/m2. In-hospital mortality is highest for those with a BMI of < 30 kg/m2 and lowest for those with a BMI of 30 - 40 kg/m2. Inpatient complications are highest in the lower BMI population (BMI < 24 kg/m2). Conclusion: The current analysis of a nationally representative sample showed the clinical implications of BMI in patients with AMI. Patients with a BMI of 30 - 40 kg/m2 had more favorable LOS, inpatient complications, and in-hospital mortality when compared to those with an ideal body weight. Hence, this supports and expands on the concept of the "obesity paradox". Further studies are needed to further investigate the possible mechanism behind this.

Disparities in the Prescription of Statins in the Primary Care Setting: A Retrospective Observational Study.

Despite the high disease burden of atherosclerosis, evidence exists for the disparity in the prescription of guideline-indicated medications between genders, racial groups, socioeconomic groups, and ages. We aim to perform a retrospective study looking at the disparity in statin prescription for primary and secondary prevention in these groups. Data were collected from a single center and included patients with an LDL level >190 mg/dL, diagnosis of diabetes mellitus with LDL level >70 mg/dL, and diagnosis of cardiovascular disease regardless of LDL level. Patients older than 75 or younger than 21 were excluded from the study. Complex samples multivariable logistic and linear regression models were used to calculate the adjusted odds ratio and 95% confidence interval. The total study population was n = 56,995. Of those, 57.89% (n = 32,992) were female. Only 59.56 % of these patients for whom statin therapy was indicated received it. Most patients were White (53.21%) followed by African Americans (35.98%), Asians (2.43%), American Indian/Native Alaskans (0.40%), and Native Hawaiian/Pacific Islander (0.18%). There is a clear disparity in statin prescription favoring males, the elderly, and people of white ethnicity. Interestingly, Asians were more likely to be prescribed statins as opposed to whites. Self-pay patients were more likely to receive statins than patients on Medicare.Despite being indicated, Statins are under prescribed. Disparities based on race, gender, and insurance type mirror previous trends in the literature. Some results have shown a reversal in trends such as the higher prescription for Asian-Americans. Multiple patient-specific, provider-related, institutional factors might explain these disparities and must be investigated.

B-type natriuretic peptide (BNP) predicts 90-day mortality and need for paracentesis in cirrhotic patients without systolic heart failure.

Fluid overload is a common complication in patients with cirrhosis. B-type natriuretic peptide (BNP) is a marker of increased blood volume, commonly used in heart failure, that has been shown to be elevated in patients with liver disease. This study examined if BNP levels can be used to determine prognosis and predict worsening of ascites in patients with cirrhosis without concomitant heart disease. A retrospective study was performed at a large urban hospital in Chicago, Illinois and included 430 patients with cirrhosis who had BNP levels ordered during their hospital stay. Patients with clinical heart failure, arrhythmias or pulmonary hypertension were excluded. The primary outcome was 90-day mortality and the secondary outcome was a requirement for therapeutic paracentesis in the 90 days following BNP results. 53 patients (12%) had BNP levels ≥ 300 pg/mL. They had significantly increased serum levels of creatinine, bilirubin, and International Normalized Ratio (INR) when compared to those with BNP < 300 pg/mL. Patients with higher BNP had significantly higher mortality rates (HR 3.49; p = 0.037) and were more likely to require therapeutic paracentesis (HR 2.26; p = 0.02) in the next 90 days. A BNP ≥ 300 pg/mL had specificity of 88.2% in predicting 90-day mortality. BNP may serve as a practical and reliable marker of underlying disease severity in patients with cirrhosis, with potential to be included in prognostication tools for assessment of end-stage liver disease.

Prognostic Value of Neutrophil-lymphocyte Ratio in Patients with Severe Alcoholic Hepatitis.

Background Prednisolone is considered the cornerstone treatment for severe alcoholic hepatitis (AH). However, its use is limited by the increased risk of infection in an already immunocompromised patient population. Among patients with severe AH, there exists a group of non-responders who do not benefit from prednisolone therapy. Day-4 Lille score is a widely employed prognostic model used to identify this non-responder subgroup. The present study evaluates the prognostic ability of the inflammatory marker, the neutrophil-lymphocyte ratio (NLR), as a stand-alone model and in conjunction with the day-4 Lille score. Methods We retrospectively reviewed the electronic medical records of patients diagnosed with AH. Demographic and biochemical data at diagnosis were collected to calculate Maddrey's discriminant function (MDF) and model for end-stage liver disease (MELD) score upon admission and also on day 4. Receiver operating characteristic (ROC) curves were plotted for day-4 NLR and day-4 Lille score for prediction of 90-day mortality, and optimal cut-off values were determined. Patients were then subcategorized into groups based on the generated optimal cut-off values. Categorization was validated by comparing the mortality rate in each group with the chi-squared test. We then performed a multivariate analysis for prediction of 90-day mortality using day-4 Lille score and day-4 NLR, constructing a new prediction score based on the odds ratio (OR). The ROC curve of the new score was plotted and the area under a curve (AUC) was reported and compared with previously validated scores. Results Our analysis demonstrated that both day-4 NLR and Lille score individually predicted 90-day mortality with statistical significance (p: 0.049, p: <0.001, respectively). The ROC analysis of day-4 Lille score for the prediction of 90-day mortality revealed an AUC of 0.819 with an optimal cut-off value of 0.45 (sensitivity: 83.3%, specificity: 76.1%). Day-4 NLR had an AUC of 0.756 with an optimal cut-off value of 12.3 (sensitivity: 66.7%, specificity: 78.1%) The combined day-Lille-NLR model with a cut-off of 0.55 had an AUC of .889, which was higher than day-4 Lille score and NLR independently. Conclusion Day-4 NLR is an easily assessed prognostic model of mortality in alcoholic hepatitis. However, it often underperforms relative to day-4 Lille score. Combining these two models to create a "modified" Lille score adds increased performance characteristics to the prediction of outcomes/mortality. The "modified" Lille score presented in this study can be used to further cut down the number of non-responders who are often forced to undergo costly and potentially harmful treatment courses.

Safety and Efficacy of Infliximab in Severe Alcoholic Hepatitis: A Systematic Review.

Severe alcoholic hepatitis (SAH) is associated with significant morbidity and mortality, yet the treatment options available are very limited. Past studies have evaluated the efficacy of infliximab in such patients; however, they were limited by sample size. Our aim was to perform a systematic review of these studies to assess the role of infliximab in patients with SAH. We conducted a literature search using electronic database engines including Ovid, PubMed, Scopus, MEDLINE and Cochrane Library from inception to October 2018 to identify published articles addressing outcomes in patients treated for alcoholic hepatitis with infliximab. The primary outcome reviewed was one-month mortality. Secondary outcomes included rate and type of infection; cause of mortality; levels of aspartate aminotransferase, alanine aminotransferase, bilirubin and tumor necrosis factor-α; and Maddrey discriminant function. Five studies including two randomized controlled trials and three case series were included in our analysis with a total sample size of 70 patients. One-month mortality ranged from 10% to 17% in patients who received a single dose of infliximab with or without prednisone compared to 38% in patients who received three doses of infliximab in combination with prednisone. A single dose of infliximab was associated with an infection rate of 10% to 26% in contrast to an 89% rate with three doses of infliximab. Infliximab, when used in a single dose, could potentially be an alternative agent for the management of SAH in a large group of patients who have contraindications such as gastrointestinal bleeding, uncontrolled diabetes or an active hepatitis infection. It might also have a role in the prevention of hepatorenal syndrome. There is a need for larger trials to evaluate the role of infliximab in a cohort of patients who are not candidates for prednisolone therapy.

Revised Marshall Score: A New Approach to Stratifying the Severity of Acute Pancreatitis.

BACKGROUND: Modified Marshall Score is one of the severity scores for acute pancreatitis (AP) and is included in the Revised Atlanta Classification, but given its utilization of a set serum creatinine level (sCr), it may misclassify stable patients with chronic kidney disease (CKD) to a more severe class just due to their elevated sCr. AIMS: Our study aims to evaluate the role of CKD in AP and the possibility of utilizing acute kidney injury (AKI) into developing a new scoring system. METHODS: We retrospectively reviewed the electronic medical records of three hundred consecutive patients who were diagnosed with AP during hospitalization. Multiple demographic variables and clinical course indices were collected. Univariate logistic regression was then applied to predict mortality and ICU admission. Finally, receiver operating curve was utilized to compare original versus New Revised Marshall Score. RESULTS: Two hundred and eight-four (284) patients had a definitive diagnosis of AP. When comparing patients who had AKI on admission to those without AKI, the AKI group showed statistically significant higher mortality rate (5.6% vs. 1.1%, p = 0.04). Finally, we substituted the renal part of Marshall Score with our AKIN and we plotted the New "Revised" Marshall Score, which showed a higher AUROC compared to the original modified version (C-statistics 0.93 vs. 0.89, p < 0.05). CONCLUSION: We found that AKI predicts mortality and outperforms the use of a fixed sCr value alone. The use of our New Revised Marshall Score can accurately classify AP severity, avoiding misclassification of AP severity and providing better patient care.

Thin Patient, Fatty Liver.

A 49-year-old lady with no past medical history presented with dysphagia and 40-pound weight loss, which occurred over eight months. On physical examination, she had proximal muscle weakness and crackles in basilar regions of the lungs. Labs were significant for low albumin, elevated transaminases, and high aldolase. Imaging suggested aspiration pneumonitis in both lungs and hepatic steatosis. A swallow evaluation revealed oropharyngeal dysphagia and muscle biopsy confirmed a rare form of myositis. A liver biopsy showed steatohepatitis and a diagnosis of starvation-induced steatohepatitis was made. The patient succumbed to hypoxic respiratory failure from aspiration pneumonitis before the treatment for myositis could be initiated. We report the first case of starvation-induced steatohepatitis in a patient with dysphagia from myositis affecting the oropharyngeal musculature.

Pseudohyponatremia in Hypertriglyceridemia-Induced Acute Pancreatitis: A Tool for Diagnosis Rather Than Merely a Laboratory Error?

OBJECTIVES: The relative rarity of hypertriglyceridemia (HTG) as the etiology for acute pancreatitis (AP) delays the final diagnosis of hypertriglyceridemia-induced AP (HTG-AP). This study aimed to explore the diagnostic and prognostic value of pseudohyponatremia in this clinical entity. METHODS: We retrospectively compared 140 patients with HTG-AP and 266 patients of AP of other etiologies. The correlation of presenting hyponatremia and a final diagnosis of HTG-AP is evaluated. RESULTS: Presenting hyponatremia had an area under curve of 0.926 for predicting the diagnosis of HTG-AP. After dichotomization by the optimal cutoff value of 130 mEq/dL, patients with hyponatremia had a higher prevalence of acute kidney injury (61.9% vs 38.1%, P < 0.001), systemic inflammatory response syndrome (52.2% vs 47.8%, P < 0.001), a higher Ranson criteria (3.0 vs 1.4, P < 0.001), and a higher Bedside Index for Severity of Acute Pancreatitis score (0.69 vs 0.55, P = 0.011). CONCLUSIONS: Presenting hyponatremia is highly efficient in differentiating hypertriglyceridemia from other etiologies of AP. It also demonstrated promising prognostic values in both AP and HTG-AP patients. Therefore, initial serum sodium could potentially provide the first clue of HTG-AP, as well as facilitate risk-stratifying patients to determine treatment allocation.

Single institution experience of sorafenib for advanced HCC in a US tertiary care hospital.

BACKGROUND: Sorafenib is first line chemotherapy for advanced hepatocellular carcinoma (HCC). There are little real-world experiences with sorafenib done on US population except for the US arm of the GIDEON study, a phase IV multi-national study. In this context, we present a single institution experience with sorafenib for HCC in a tertiary inner-city safety-net hospital of Chicago. METHODS: We retrospectively analyzed electronic medical records of patients with HCC (confirmed with radiographic criteria and/or biopsy) who received sorafenib from 2009 to 2016. We collected data regarding the demographics, characteristics of tumor, liver cirrhosis, duration of treatment with sorafenib, reported adverse effects with sorafenib and laboratory investigations done at the time of sorafenib initiation. Overall survival was calculated from the time of sorafenib initiation and cases were censored at the date of last follow up, if date of death was not known. Kaplan-Meier curves were estimated to evaluate the prognostic significance of various clinical variables. RESULTS: Fifty-nine patients received sorafenib in the study period and the median overall survival was 7 months (25-75 percentile =3-15 months). Alcohol was the leading cause of cirrhosis, 64% of them had Child-Turcotte-Pugh (CTP) class A cirrhosis or did not have cirrhosis and 73% had Barcelona stage C HCC at the time of sorafenib initiation. Close to half of them suffered from adverse effects of sorafenib, most common being those involving skin and gut. Patients with CTP class A cirrhosis or no cirrhosis (median OS 39 vs. 16 months, log rank test 3.913, P=0.048), absence of extrahepatic spread (EHS) (median OS 39 vs. 9 months, log rank test 5.632, P=0.018) and hepatitis C virus (HCV) infection (median OS 39 vs. 9 months, log rank test 5.015, P=0.025) had better survival. CONCLUSIONS: Overall survival of patients with HCC treated with sorafenib in US is lower than those observed in cohorts from Europe or Japan. HCV infection could be a marker of benefit in those treated with sorafenib for HCC. Further studies to confirm this association and understand it's pathophysiologic basis could be useful in development of other therapeutic options for advanced HCC.