Safety of Nonselective Beta-Blockers in Decompensated Liver Cirrhosis and Their Role in Inducing Hepatorenal Syndrome.

Background Nonselective beta-blockers (NSBBs) have been used in the management of portal hypertension and the prevention of initial and recurrent variceal bleeding in patients with liver cirrhosis. However, there is controversy regarding the use of NSBBs in patients with decompensated cirrhosis (DC) due to concerns over potential adverse effects, such as worsening of hepatic function and risk of hepatorenal syndrome (HRS). HRS is a serious complication of DC characterized by acute kidney injury (AKI) and progressive renal failure, and its development can lead to significant morbidity and mortality in this setting. Therefore, using NSBBs in patients with DC remains an area of ongoing research and debate. Our study aims to investigate the potential effect of NSBBs on HRS development. Methodology A retrospective chart review of 404 patients with cirrhosis was performed across all Northwell Health institutions between January 01, 2019, and December 31, 2020. An analysis was done on 516 patient encounters. Inclusion criteria included patients with an established International Classification of Diseases 10th Revision code of cirrhosis and AKI. After adjusting for clinical predictors, the Student's t-test or Mann-Whitney U-test was used to compare variables between the two outcome groups (HRS vs. no HRS) for the continuous variables. Pearson's chi-square test or Fisher's exact test was used for the categorical variables to test if an association existed between the use of NSBBs at home and HRS. A two-sided p-value <0.05 was considered statistically significant. SAS 9.4 (SAS Institute Inc., Cary, NC, USA) was used for statistical analysis. Results The primary outcome was the development of HRS during the hospital stay. With a total of 109 visits with HRS, we had 21 (23.60%) reported HRS in the 89 visits where NSBBs were used at home before the hospitalization, while 88 (20.61%) HRS were observed in the 427 visits with no NSBB use at home. The use of NSBBs at home was not significantly associated with the development of HRS (odds ratio = 1.1, 95% confidence interval = 0.6-1.9, p = 0.7321). We also found that higher serum albumin on admission is associated with lower odds of HRS. In contrast, increased serum creatinine, bilirubin, presence of ascites, and use of pressors were associated with a higher risk of HRS. Conclusions Our study highlights the relevant safety of NSBB use in end-stage liver disease. Their use did not appear to increase the risk of developing HRS during hospitalization with DC. Further randomized controlled trials are warranted to shed more light on the efficacy, dose tolerance limits, and safety of NSBBs in decompensated end-stage liver disease.

A Diagnosis of Gastric Inflammatory Myofibroblast Tumor: A Challenge Like No Other!

Inflammatory myofibroblastic tumors (IMTs) are mesenchymal tumors of intermediate malignant potential. Gastric IMTs are rare and commonly affect young adults. They are typically confused with gastrointestinal stromal tumors, inflammatory fibroid polyps, and leiomyosarcomas. The etiology of IMTs remains unclear, but is theorized to be due to hyperinflammatory response to chronic infections. We present a middle-aged woman found to have a gastric mass positive for Helicobacter pylori, underwent multiple endoscopies with endoscopic ultrasound, and a definitive diagnosis of gastric IMT was only made after a partial gastrectomy with immunohistochemistry negative for CD-117, S-100, ALK-1, and positive for vimentin and SMA.

Granulocyte-colony stimulating factor in decompensated liver cirrhosis: a meta-analysis of four randomized controlled trials.

BACKGROUND: Decompensated liver cirrhosis (DC) has high mortality, but liver transplantation is limited due to organ scarcity and contraindications for transplantation. Granulocyte-colony stimulating factor (GCSF) shows potential for liver disease treatment with its regenerative and immunomodulatory properties. To assess the controversial use of GCSF in DC, a meta-analysis of randomized controlled trials (RCTs) compared survival benefits in patients receiving GCSF plus standard medical therapy (SMT) versus SMT alone. METHODS: A literature search was performed in four databases from data inception up to December 2022, and all registered randomized controlled (RCTs) evaluating GCSF-based therapies for cirrhotic patients were included. RESULTS: A study combining four RCTs assessed the impact of GCSF with SMT in 595 patients with decompensated cirrhosis. The results indicated that GCSF + SMT led to higher odds of survival compared to SMT alone [risk ratio 1.28, 95% CI (1.08-1.5)]. Heterogeneity existed among the studies, but overall, GCSF showed potential in improving survival. The intervention group exhibited improved Child-Pugh-Turcotte scores [-2.51, CI (-4.33 to -0.70)], and increased CD34 levels, but no significant improvement in MELD scores. These findings suggest GCSF may benefit patients with decompensated cirrhosis in terms of survival and liver function. CONCLUSION: These results suggest that the combination of GCSF and SMT may have a positive impact on the survival rate and improvement in CPT score in patients with DC. Further RCTs are needed to shed more light on this promising modality in end-stage liver disease.

Statin Use in Patients With Chronic Liver Disease and Cirrhosis: Current Evidence and Future Directions.

Chronic liver disease (CLD) and its complications constitute a significant cause of mortality and morbidity worldwide. Most deaths are secondary to the decompensation of cirrhosis and evolution of portal hypertension (PHTN). Since disease progression reversal is hardly attainable after decompensated cirrhosis develops, it is essential to intervene early with a therapeutic agent or regimen that could prevent or slow disease evolution. Thus far, there has been no agreed-upon medication to help in the fight against the development of cirrhosis or its decompensation. While early data depicted statins as harmful agents for the liver, current evidence from preclinical and clinical studies suggests that they might have positive impact on CLD. Low-quality evidence supports the fact that statins reduce mortality in CLD. Moderate-quality evidence suggests that statins reduce the risk of hepatic decompensation, variceal bleeding, and mortality, especially among patients with compensated cirrhosis. Combining this data with the long track-record of safety and tolerability of statins and their potential benefits in hepatocellular carcinoma (HCC) risk reduction, hepatologists might soon rely on statins to achieve better outcomes in their CLD and cirrhotic patients without significant additional costs. This review describes the rationale behind the use of statins in patients with CLD and cirrhosis. It sheds light on the current preclinical and clinical studies that reflect beneficial effects of the use of different types and doses of statins in the treatment of patients with different types and stages of CLD and cirrhosis. It also emphasizes the need for designing and developing additional large prospective interventional randomized control trials (RCTs) to better evaluate the association between statin exposure and the risk of fibrosis progression and development of cirrhosis in patients with non-cirrhotic CLDs, the risk of progression of PHTN in patients with cirrhosis, and the mortality rates in patients with cirrhotic or non-cirrhotic CLDs.

Proton Pump Inhibitors Use and Increased Risk of Spontaneous Bacterial Peritonitis in Cirrhotic Patients: A Retrospective Cohort Analysis.

Background: Since their introduction in the early 1980s, proton pump inhibitors (PPIs) have been used worldwide for a broad range of indications. Unfortunately, however, PPIs have become overly prescribed by healthcare providers, sometimes in the absence of clear indications. Although PPIs were initially presumed to have an excellent safety profile, emerging studies have shed light on the association between their long-term use and a myriad of side effects, including the possibility of an increased risk of spontaneous bacterial peritonitis (SBP). Data available to date regarding the association between PPI use and SBP development in cirrhotic patients is conflicting. While some observational studies provide no association between PPI use in cirrhotic patients and an increased risk of SBP development, many others support this association. As a result of the conflicting conclusions from case controls, cohorts, and meta-analyses, we aimed to carry out this retrospective cohort analysis of data from cirrhotic patients included in the electronic medical record-based commercial database, EXPLORYS (IMB-WATSON, Cleveland, Ohio). Our aim was to evaluate for a possible association between PPIs use and the risk of SBP development in cirrhotic patients and to compare the prevalence of SBP development between cirrhotic patients who were actively using PPIs and those who were not. Methods: A retrospective cohort analysis with chart review was conducted on patients with cirrhosis who were included in the electronic medical record-based commercial database, EXPLORYS (IMB-WATSON, Cleveland, Ohio). Using this database, records were reviewed between December 2017 and 2020. Included patients were adults aged 30 to 79 years with a Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT) diagnosis of liver cirrhosis. Included patients with a SNOMED-CT diagnosis of liver cirrhosis were divided into two groups: the first group included all cirrhotic patients who did not use PPIs and the second group included all cirrhotic patients who were on PPIs at home. Results: In our analysis, SBP occurred in 1.7% (1,860 patients) of the included cirrhotic patients whether they were actively taking PPIs or not. Among the 40,670 cirrhotic patients who were on PPIs at home, 1,350 (3.3%) patients developed SBP. On multivariate analysis, PPI use was the strongest predictor for SBP in cirrhotic patients (odds ratio (OR) = 4.24; 95% confidence interval (CI): 3.83 - 4.7, P value < 0.0001), with cirrhotic patients taking PPIs being 4.24 more likely to develop SBP than those not on PPIs. In addition, PPI use, history of bleeding varices, age, race, and gender were found to be independent predicting factors for SBP, in descending order of importance. Conclusions: Our retrospective cohort analysis has shown that the use of PPIs in patients with liver cirrhosis is an independent predicting risk factor for SBP development. It solidified the argument that cirrhotic patients receiving this form of therapy seem to have a higher risk of developing SBP. In the setting of the emerging evidence that PPIs might impose health risks in cirrhotic patients, further studies are needed to settle the current debate between supporters and opponents of this proposition. In addition, future studies may help clarify the relationship between the occurrence of SBP in cirrhotic patients and the type, dose, and duration of PPIs used. We recommend that unless it is clearly indicated, PPI therapy should be avoided or administered with caution in patients with cirrhosis.

The Incidence of Venous Thromboembolism and Practice of Deep Venous Thrombosis Prophylaxis Among Hospitalized Cirrhotic Patients.

Background: Patients with liver cirrhosis have altered hepatic synthetic functions which theoretically result in reduced levels of pro-and anti-coagulant factors as well as thrombocytopenia. Initially, cirrhotic patients were thought to be at an increased risk of bleeding and a reduced risk of thrombosis. Several studies have recently reported an increased occurrence of venous thromboembolism (VTE) in cirrhotic patients. In this study, we aimed to assess the current practice of deep venous thrombosis (DVT) prophylaxis, the incidence and predictors of VTE, and the associated bleeding sequelae in patients with liver cirrhosis. Methods: A retrospective cohort study was performed. We included all adult patients with a diagnosis of liver cirrhosis from January 2010 to June 2019 admitted to the hospital. Our cohort patients were divided into two groups, cirrhotic patients with pharmacological VTE prophylaxis and those with mechanical or no VTE prophylaxis. Results: We included 601 cirrhotic patients in our study. The incidence of VTE occurring within the first 6 months of their admission was 1.5%. Seven patients (1.49%) developed VTE with the majority being DVTs while not on pharmacologic prophylaxis, and two patients developed VTE despite being on pharmacologic prophylaxis; however, there was no statistical difference. Alcohol use was the most common underlying cause of liver cirrhosis (40.4%), followed by chronic hepatitis C (21.1%), and nonalcoholic steatohepatitis (11.3%). Out of the 601 patients included, 69 patients received neither pharmacologic nor mechanical VTE prophylactic agent (11.48%), while the remaining majority received either pharmacological or mechanical prophylaxis (88.52%). Conclusions: Our study did not show a statistically significant association between the use of pharmacological VTE prophylactic agents and a reduction in the risk of VTE in cirrhotic patients. The rates of usage of DVT prophylactic agents among our Northwell hospitals during the study period appeared to be no longer suboptimal when compared to prior studies. Low albumin appears to be a predictor factor to develop VTE. There was a statistically significant increase in bleeding risk and transfusion requirement in cirrhotic patients receiving no pharmacological VTE prophylactic agents. Further prospective trials are needed to shed more light on this subject and identify the group of cirrhotic patients who could safely benefit from pharmacologic VTE prophylaxis.

Epidemiology of Depressive Disorders in Patients With Liver Cirrhosis: A Population-Based Study in the United States.

Objective: Major depressive disorder (MDD) is a chronic, debilitating mood disorder associated with poor medical outcomes. MDD has a multifactorial etiology with numerous biopsychosocial factors implicated as risk factors. Functional and psychiatric impairments have been evaluated in patients with liver cirrhosis; however, less is known about the prevalence and risk factors for the development of MDD in those patients. The objective of this study was to evaluate the risk of developing depression among adult patients with liver cirrhosis in the United States.Methods: Data were collected using a commercial database, an aggregate of electronic health record data from 26 major integrated US health care systems consisting of 360 hospitals in the US from 1999 to 2019.The study cohort was retrieved by searching the database for a Systematized Nomenclature of Medicine-Clinical Terms diagnosis of "cirrhosis of liver" during the designated period of the study.The following factors were adjusted for in the analyses: age, sex, race, smoking, alcohol, substance abuse, underlying mental disorders, and comorbidities.Results: 56,197,690 adults were identified between 1999 and 2019. Of those, 293,150 had a diagnosis of liver cirrhosis. The prevalence of depression among those cirrhotic patients was 23.93% versus 7.61% in the noncirrhotic control group (95% CI, 16.1836%-16.4770%; P < .0001). By applying a multivariate analysis model, cirrhotic patients were found to be more likely to develop depression (odds ratio = 2.172; 95% CI, 2.159-2.185; P < .0001) compared to patients with no prior history of liver cirrhosis.Conclusions: Liver cirrhosis is associated with increased risk of depression and is likely to be an independent risk factor in its development. Future efforts should focus on the identification and treatment of this debilitating condition in those with liver cirrhosis via an integrated care model.

The Association Between Gastroesophageal Reflux Disease and Non-Small Cell Lung Cancer: A Retrospective Case-Control Study.

Background: Lung cancer is a leading cause of mortality in the USA. Non-small cell lung cancer (NSCLC) contributes to 85% of all lung cancers. It is the most prevalent subtype amongst non-smokers, and its incidence has risen in the last 20 years. In addition, gastroesophageal reflux disease (GERD) has been associated with several lung pathologies, namely idiopathic pulmonary fibrosis and asthma. We aimed to investigate the association between GERD and NSCLC by performing a retrospective, multicenter, case-control study. This is the first study of this nature to be carried out in the USA. Methods: Data were retrieved from 17 Northwell health care facilities in the New York area between the years 2010 and 2018. Inclusion criteria were patients > 18 years of age with NSCLC (large cell, adenocarcinoma, and squamous cell). They were appropriately matched with controls based on age, gender, weight, comorbidities, and medication use. Our exposure group had a diagnosis of GERD based on the International Classification of Diseases, Ninth/10th Revision (ICD 9/10) codes and endoscopic, in addition to histological evidence if present. We excluded patients with secondary lung cancers, esophageal adenocarcinoma, other primary malignancies, Barrett's esophagus, and smokers. Logistic regression was conducted to determine the adjusted odds ratio (OR) and corresponding 95% confidence interval (CI) for the association between NSCLC and GERD. Results: A total of 1,083 subjects were included in our study: 543 (50%) patients were diagnosed with NSCLC. In this population, GERD was twice as prevalent compared to controls (20.4% vs. 11.6%, P < 0.001). Multivariate analysis demonstrated that GERD was associated with a higher risk of NSCLC compared to matched controls (OR = 1.86, 95% CI = 1.26 - 2.73). In addition, GERD patients treated with either antihistamines or proton pump inhibitors did not demonstrate an overall reduced risk of NSCLC (OR = 1.01, 95% CI = 0.48 - 2.12). Conclusions: Our study demonstrates that GERD is associated with a higher risk of NSCLC, irrespective of GERD treatment. We postulate that GERD patients suffer from chronic micro-aspirations leading to a prolonged inflammatory state within the lung parenchyma, triggering specific proliferative signaling pathways that may lead to malignant transformation.

Predictors of Development of Hepatorenal Syndrome in Hospitalized Cirrhotic Patients with Acute Kidney Injury.

Hepatorenal syndrome (HRS) is a type of acute kidney injury (AKI), occurring in patients with decompensated liver cirrhosis and is associated with high mortality. We aim to describe the predictors associated with the development of HRS in cirrhotic patients with AKI. We retrospectively analyzed 529 cirrhotic patient encounters with AKI across all Northwell Health institutions between 1 January 2015 and 31 December 2018. We performed multivariate analyses to determine independent predictors of development of HRS. Alcoholic cirrhosis was the most common identified etiology of cirrhosis. The mean Model for End-Stage Liver Disease Scorewas18 (±7). Ascites was the most commonly identified clinical feature of portal hypertension. Infection was identified in 38.4% of patients with urinary tract infection/pyelonephritis being the most common. Spontaneous bacterial peritonitis occurred in 5.9% of patients. The most common cause of AKI was pre-renal. Hepatorenal syndrome was identified in 9.8% of patient encounters. Predictors of HRS were history of ascites, serum creatinine >2.5 mg/dL, albumin <3 g/dL, bilirubin >2 mg/dL and spontaneous bacterial peritonitis. We demonstrate strong predictors for the development of HRS which can aid clinicians to attain an early diagnosis of HRS, leading to prompt and targeted management and improving outcomes.

Colorectal Metastasis from Ovarian Neoplasm Mimicking Primary Colon Cancer.

Metastasis to the colon from another primary internal malignancy is an untypical and a seldom reported entity. Direct visualization during colonoscopy is considered the gold standard of diagnosis. Pathologic diagnosis with immunohistochemical staining is essential to differentiate primary colorectal malignancy from secondary metastasis to the colon. We, hereby, present a case of a 53-year-old female status-post resection of left-sided papillary serous ovarian neoplasm who presented 2 years later with a single rectosigmoid intraluminal ulcerative mass imitating a primary colon cancer. Biopsies of the mass were consistent with metastasis from her primary ovarian carcinoma. We believe this case is unique because of the rarity of ovarian cancer metastasizing to the colon intraluminally rather than through direct locoregional invasion. Furthermore, it highlights the importance of considering secondary metastasis in patients with previous history of another primary internal malignancy.

A Comprehensive Review of Infectious Granulomatous Diseases of the Gastrointestinal Tract.

A granuloma is defined as a localized inflammatory reaction or a hypersensitive response to a nondegradable product leading to an organized collection of epithelioid histiocytes. Etiologies of granulomatous disorders can be divided into two broad categories: infectious and noninfectious (autoimmune conditions, toxins, etc.) causes. The endless list of causalities may prove challenging for gastroenterologists and pathologists to formulate a list of clearly defined differentials. This is true when distinguishing these etiologies based on various clinical presentations and endoscopic and histological findings. We aim to provide a comprehensive review of some of the frequent and rare infectious granulomatous diseases of the gastrointestinal tract documented in the literature to date. We provide an overview of each infectious pathology with an emphasis on epidemiology, clinical presentation, and endoscopic and histologic findings, in addition to treatment.

Is the Use of Proton Pump Inhibitors a Predisposing Factor for Pyogenic Liver Abscesses?

BACKGROUND: Proton pump inhibitors (PPIs) increase gastric pH by reducing acid production. The resulting alkaline milieu in the stomach increases the risk of bacterial translocation. This study aimed to investigate if there is a correlation between PPI use and developing pyogenic liver abscesses. METHODS: In this retrospective case-control analysis, we studied adult patients diagnosed with cryptogenic liver abscess at Northwell hospitals between 2015 and 2019. Adult patients with the diagnosis of liver abscess were included. We excluded patients with history of liver abscess prior to admission, biliary disease, hepatobiliary malignancy, or intra-abdominal infections. A group of randomly selected patients without liver abscess from the same hospitals' database were enrolled as the control group. A multivariate logistic regression analysis was performed to adjust for potential confounding factors. RESULTS: We identified 277 patients diagnosed with first episode of pyogenic liver abscess. Cases were compared to 554 controls. Klebsiella pneumonia was the most common pathogen. PPI use was associated with an increased risk of developing a first episode of pyogenic liver abscess in univariate (odds ratio (OR): 2.36, 95% confidence interval (CI): 1.70 - 3.27), and multivariate analysis (adjusted OR: 2.27, 95% CI: 1.55 - 3.32). CONCLUSION: This study is the first US population-based analysis to demonstrate that PPI use is associated with increased risk of developing pyogenic liver abscesses. Further prospective studies are needed to shed more light on this association and better evaluate the impact of dose and duration of PPI exposure.

Beyond Pain Relief: Is Opioids Use Safe in Clostridium difficile Infection?

BACKGROUND: Clostridium difficile infection (CDI) is a common condition in hospitalized patients. In the USA, there has been an alarming rise in the use of opioids for analgesia during hospitalization. Due to their antiperistalsis effect, opioids can increase absorption of bacterial toxins. Our study aimed to highlight any correlation between opioids use in CDI and morbidity, mortality, and duration of hospitalization. METHODS: A retrospective study was performed, and data were collected from 321 hospitalized patients with CDI. The dosage of opioids received in the first 4 days following diagnosis was calculated. Patients were divided into two groups (control group vs. opioid group). Reassessment of severity of disease on day 4 was performed. Complications, hospital mortality, readmissions for CDI within 3 months, length of stay, and disposition at discharge were compared. RESULTS: The opioid arm consisted of 169 patients, and 152 patients served as controls. On day 4, the number of patients with severe disease was significantly higher in the opioid group versus controls (78 (46.1%) vs. 37 (24%), respectively, P < 0.01), and complications including ileus, high white blood cell count, and need for vasopressors were significantly higher in the opioid group (27.8% versus 16.4%, P = 0.01). Control group patients were more likely to be discharged home (47% vs. 33%, P = 0.04), while opioid group required predominantly long-term facilities care after discharge. CONCLUSION: Opioid usage for analgesia in CDI increases the risk for severe disease, complications, longer hospitalization, readmission rates, hospital mortality and discharge to a long-term facility.