The Interplay of Microbiome Dysbiosis and Cardiovascular Disease.

The intricate ecosystem of the mammalian gut, which hosts a diverse microbiome, plays a vital role in various physiological functions. Trillions of bacteria within the gut contribute to host metabolism, immune modulation, energy homeostasis, and more. Emerging research highlights the gut microbiota's significant impact on cardiovascular diseases (CVDs), with intestinal dysbiosis identified as a risk factor for conditions such as obesity and diabetes, both linked to atherosclerosis. Chronic inflammation, pivotal in atherosclerosis, is influenced by the gut microbiome, where microbial signals, such as lipopolysaccharides, can translocate from the gut to trigger inflammatory responses. Diet has major effects on the gut microbiota, with the Western diet, rich in saturated fats, contributing to dysbiosis and elevated cardiovascular risks. Probiotics and prebiotics offer therapeutic potential in CVD management. Probiotics, or live microorganisms, exhibit antioxidant, anti-inflammatory, and cholesterol-lowering effects. Probiotics are most effective when given with prebiotics, with the former acting on the latter as substrate. Understanding the dynamic interplay between diet, gut microbiota, and CVD provides insights into preventive and therapeutic strategies.

Disseminated histoplasmosis in an HIV/AIDS transgender male-to-female with atypical and persistent GI manifestations.

Disseminated histoplasmosis is a rare complication of infection due to Histoplasma capsulatum. Typically, histoplasmosis is self-limiting and asymptomatic in infected individuals with immunocompetence. Disseminated disease, however, can arise in high-risk populations with primary or acquired cellular immunodeficiency including HIV/AIDS, transplant recipients, and those undergoing immunosuppressive therapy. Here we describe a unique case of extrapulmonary gastrointestinal histoplasmosis by infiltrative Peyer's patch disease with bone marrow involvement in a transgender HIV-infected woman.

The Delta Delta: Gaps in screening and patient assessment for hepatitis D virus infection.

Hepatitis D virus (HDV) infection is highly prevalent in patients with chronic hepatitis B (CHB). AASLD guidelines recommend a risk-based screening approach. Our aim was to ascertain if the risk-based approach leads to appropriate HDV screening, identify targets to improve screening rates, and study HDV clinical burden. CHB patients screened for HDV from 01/2016 to 12/2021 were identified. Level of training and specialty of providers ordering HDV screening tests were determined. HDV seropositive (HDV+) patient charts were reviewed for the presence of individual risk factors per the AASLD guidelines to determine if they met screening criteria. The severity of liver disease at the time of HDV screening was compared between the HDV+ group and a matched (based on age, hepatitis B e antigen status, BMI and sex) HDV seronegative (HDV-) group. During the study period, 1444/11,190 CHB patients were screened for HDV. Most screening tests were ordered by gastroenterology (90.2%) specialists and attending physicians (80.5%). HDV+ rate was 88/1444 (6%), and 72 HDV+ patients had complete information for analysis. 18% of HDV+ patients would be missed by a risk-based screening approach due to unreported or negative risk factors (see Table). A significantly higher number of HDV+ patients had developed significant fibrosis (p = 0.001) and cirrhosis (p < 0.01) by the time of screening than HDV- (n = 67) patients. In conclusion, targeted interventions are needed towards trainees and primary care clinics to improve screening rates. Current risk-based criteria do not appropriately screen for HDV. It is time for universal screening of HDV in CHB patients.

Pregnancy Outcomes After Liver Transplantation: A Systematic Review and Meta-Analysis.

INTRODUCTION: Liver transplantation (LT) remains the gold standard for treatment of end-stage liver disease. Given the increasing number of liver transplantation in females of reproductive age, our aim was to conduct a systematic review and meta-analysis evaluating pregnancy outcomes after LT. METHODS: MEDLINE, Embase, and Scopus databases were searched for relevant studies. Study selection, quality assessment, and data extraction were conducted independently by 2 reviewers. Estimates of pregnancy-related outcomes in LT recipients were generated and pooled across studies using the random-effects model. RESULTS: A comprehensive search identified 1,430 potential studies. Thirty-eight studies with 1,131 pregnancies among 838 LT recipients were included in the analysis. Mean maternal age at pregnancy was 27.8 years, with a mean interval from LT to pregnancy of 59.7 months. The live birth rate was 80.4%, with a mean gestational age of 36.5 weeks. The rate of miscarriages (16.7%) was similar to the general population (10%-20%). The rates of preterm birth, preeclampsia, and cesarean delivery (32.1%, 12.5%, and 42.2%, respectively) among LT recipients were all higher than the rates for the general US population (9.9%, 4%, and 32%, respectively). Most analyses were associated with substantial heterogeneity. DISCUSSION: Pregnancy outcomes after LT are favorable, but the risk of maternal and fetal complications is increased. Large studies along with consistent reporting to national registries are necessary for appropriate patient counseling and to guide clinical management of LT recipients during pregnancy.

Risk factors and incidence of 90-day readmission for diverticulitis after an acute diverticulitis index admission.

OBJECTIVES: Acute diverticulitis is the third most frequent cause of gastrointestinal admission in the USA. We sought to determine the incidence of recurrence within a 90-day period and determine its impact on mortality and hospital utilization. METHODS: Nationwide Readmission Database (NRD) 2016 was used to identify patients ≥ 18 years old with a principal diagnosis of acute diverticulitis who were readmitted for recurrence within 90 days. The primary outcome was 90-day readmission rate for acute diverticulitis, and predictors were analyzed using a multivariate regression analysis. Secondary outcomes were mortality and hospital resource utilization. RESULTS: A total of 171,238 admissions were included which met inclusion criteria. Ninety-day readmission for acute diverticulitis after index diverticulitis hospitalization was 8.9%. Readmissions were associated with in-hospital additional total cost of $444,726,560 and 65,685 total hospital days and mortality rate of 4.69% compared with mortality rate of 5.20% on index hospitalization (p < 0.01). In multivariable analysis, increased odds of readmission were associated with disposition against medical advice (OR 1.75, 95% CI 1.31-2.33), younger age (OR 0.98, 95% CI 0.98-0.99), and shorter length of stay (OR 0.99, CI 0.98-0.99). CONCLUSIONS: Acute diverticulitis is frequently associated with recurrence within 90 days and bears a substantial financial and mortality burden. Targeted interventions are needed to minimize readmissions in identified subpopulations.

Impact of a digital medicine programme on hepatitis C treatment adherence and efficacy in adults at high risk for non-adherence.

BACKGROUND: Direct-acting anti-virals (DAA) are highly effective for hepatitis C virus (HCV) treatment, but perceived risks of medication non-adherence may restrict access to care. Digital medicine programme (DMP) has improved adherence and outcomes for some conditions. AIMS: To conduct a prospective, single-arm, open-label study across the United States to assess the impact of DMP on adherence and efficacy in adults with chronic HCV infection at high risk for non-adherence. METHODS: Eligible participants were placed on the DMP to evaluate real-time adherence; primary outcome was sustained virological response (SVR) at ≥10 weeks post-treatment. RESULTS: Between August 2017 and April 2019, 288 participants (Medicaid, 64.9%; psychiatric disorders, 61.1%; homeless, 9.4%) received DAAs for 8-12 weeks (sofosbuvir/velpatasvir or ledipasvir, 45%; glecaprevir/pibrentasvir, 55%). SVR was achieved in 99.1% of 218 participants who had HCV RNA assessed at ≥10 weeks post-treatment; of the 70 participants who did not have SVR assessed, 17 had SVR4 with HCV RNA assessed at a median (IQR; interquartile range) 5.6 weeks (4.1, 7.9) post-treatment; one completed treatment but did not have HCV RNA assessed, and 52 discontinued treatment early without assessment. Overall, the primary analysed participants (n = 218) actively used the DMP for median (range) 92.9% (12.5%, 100%) of their prescribed treatment time, and overall pill-taking adherence was 95.0% (57.1%, 100%). Participants reported the programme was useful and easy to use through satisfaction surveys. CONCLUSIONS: HCV treatment with DMP was accepted by patients and clinicians and may support HCV treatment outcomes among patients at high risk for treatment non-adherence (Clinical trials.gov NCT03164902).

Portal vein thrombosis prevalence and mortality among alcoholic cirrhosis in a nationwide inpatient cohort.

OBJECTIVES: Portal vein thrombosis is commonly associated with cirrhosis. The effect of alcoholic cirrhosis on portal vein thrombosis prevalence and mortality has not been well studied. METHODS: We conducted a retrospective cohort study utilizing the 2000-2014 National Inpatient Sample Database. We included patients older than 18 years with decompensated cirrhosis without a history of liver transplantation or hepatocellular carcinoma. We further identified patients with alcoholic cirrhosis vs. non-alcoholic cirrhosis. Primary outcomes included the risk and mortality of portal vein thrombosis in alcoholic cirrhosis. Secondary outcomes included trends of portal vein thrombosis prevalence and mortality in alcoholic cirrhosis, implications of portal vein thrombosis on complications in alcoholic cirrhosis vs. non-alcoholic cirrhosis, and risk of venous thromboembolism in alcoholic cirrhosis. RESULTS: Among 1 892 271 patients with decompensated alcoholic cirrhosis, portal vein thrombosis prevalence was 1.3%. Alcoholic cirrhosis was associated with lower risk of portal vein thrombosis (odds ratio 0.76, P < 0.001) and venous thromboembolism (odds ratio 0.69, P < 0.001) compared to non-alcoholic cirrhosis. Portal vein thrombosis contributed to increased mortality (odds ratio 1.19, P < 0.001) in alcoholic cirrhosis. Portal vein thrombosis prevalence among alcoholic cirrhosis increased while mortality declined during the study period. CONCLUSION: Thrombotic events including portal vein thrombosis and venous thromboembolism were found in less frequent association with alcoholic cirrhosis compared with non-alcoholic cirrhosis. Despite this, the higher in-hospital mortality found among portal vein thrombosis with alcoholic cirrhosis should prompt careful consideration of management.

Colonic Mucosubmucosal Elongated Polyp in the Sigmoid Colon on Surveillance Colonoscopy.

Colonic mucosubmucosal elongated polyp (CMSEP) is a newly designated colorectal polyp. It has unique endoscopic features of a worm- or drumstick-shaped appearance. Histologically, it is composed of normal colonic mucosa and expanded submucosa with a prominent vascular component and no significant inflammation. CMSEP is usually detected incidentally on screening colonoscopy or colonoscopy for other causes. Differential diagnoses that need to be considered include mucosal prolapse syndrome, filiform polyposis, hamartomatous polyp, colon leiomyoma, inverted diverticulum, and residual stalk of a pedunculated adenoma. We present a case of CMSEP on surveillance colonoscopy and literature review.

The role of transjugular intrahepatic portosystemic shunt in the management of portal vein thrombosis: a systematic review and meta-analysis.

BACKGROUND: The role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of portal vein thrombosis (PVT) remains controversial. This study aimed to conduct a systematic review and meta-analysis to evaluate the role of TIPS for the management of PVT in adult patients with liver disease. PATIENTS AND METHODS: Multiple databases were searched through April 2017. Data were gathered to estimate the rates of technical success, portal vein recanalization, portal patency, hepatic encephalopathy, and mean change in portal pressure gradient in patients with PVT who underwent TIPS. Estimates were pooled across studies using the random effects model. RESULTS: Eighteen studies were included in the analysis. The pooled technical success rate was 86.7% [95% confidence interval (CI)=78.6-92.1%]. Rate of portal vein recanalization was 84.4% (95% CI=78.4-89.0%). The rate of complete recanalization was 73.7% (95% CI=64.3-81.3%). Portal patency was 86.9% (95% CI=79.7-91.8%). Mean change in portal pressure gradient was 14.5 mmHg (95% CI=11.3-17.7 mmHg). Hepatic encephalopathy was 25.3% (95% CI=19.2-32.6%). The number of major adverse events reported across studies was low. The majority of the analyses were not associated with substantial heterogeneity. CONCLUSION: The use of TIPS in the management of PVT is feasible and effective in achieving a significant and sustainable reduction in clot burden with a low risk of major complications. TIPS should be considered as a viable treatment option in patients with PVT. Given the limited amount of randomized comparative studies reported, additional trials are warranted to assess the safety and efficacy of TIPS as a treatment modality in PVT, in comparison to other treatment options, such as anticoagulation.

Hemochromatosis: pathophysiology, evaluation, and management of hepatic iron overload with a focus on MRI.

INTRODUCTION: Hereditary hemochromatosis (HH) is an autosomal recessive disorder that occurs in approximately 1 in 200-250 individuals. Mutations in the HFE gene lead to excess iron absorption. Excess iron in the form of non-transferrin-bound iron (NTBI) causes injury and is readily uptaken by cardiomyocytes, pancreatic islet cells, and hepatocytes. Symptoms greatly vary among patients and include fatigue, abdominal pain, arthralgias, impotence, decreased libido, diabetes, and heart failure. Untreated hemochromatosis can lead to chronic liver disease, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Many invasive and noninvasive diagnostic tests are available to aid in diagnosis and treatment. MRI has emerged as the reference standard imaging modality for the detection and quantification of hepatic iron deposition, as ultrasound (US) is unable to detect iron overload and computed tomography (CT) findings are nonspecific and influenced by multiple confounding variables. If caught and treated early, HH disease progression can significantly be altered. Area covered: The data on Hemochromatosis, iron overload, and MRI were gathered by searching PubMed. Expert commentary: MRI is a great tool for diagnosis and management of iron overload. It is safe, effective, and a standard protocol should be included in diagnostic algorithms of future treatment guidelines.

Primer on Hepatitis C Virus Resistance to Direct-Acting Antiviral Treatment: A Practical Approach for the Treating Physician.

Treatment of hepatitis C virus has been vastly transformed by the arrival of all-oral, interferon-free, direct-acting antiviral regimens. Despite the high rate of success with these agents, a small portion of treated patients fail therapy and the emergence of viral resistance is the most common cause of treatment failure. Given the error-prone hepatitis C virus polymerase, baseline resistance-associated substitutions (RASs) may be present before direct-acting antiviral exposure. Clinicians need to understand the role of baseline RAS testing and the settings and manner in which the treatment regimens need to be customized based on the presence of RASs.

Viral hepatitis screening in transgender patients undergoing gender identity hormonal therapy.

BACKGROUND AND AIM: Viral hepatitis is a global health issue and can lead to cirrhosis, liver failure, and hepatocellular carcinoma. Guidelines for viral hepatitis screening in the transgender population do not exist. Transgender patients may be at higher risk for contracting viral hepatitis due to socioeconomic and behavioral factors. The aim of this study was to measure the quality of screening, prevalence, and susceptibility of viral hepatitis, and to identify barriers to screening in transgender patients undergoing gender identity hormonal therapy. METHODS: LGBTQ-friendly clinic visits from transgender patients older than 18 years in New York City from 2012 to 2015 were reviewed. RESULTS: Approximately 13% of patients were screened for any viral hepatitis on initial consultation. Screening rates for hepatitis C virus (HCV), hepatitis B virus (HBV), and hepatitis A virus (HAV) at any point were 27, 22, and 20%. HAV screening was performed in 28% of the female to male (FtM) patients and 16% of male to female (MtF) (P<0.05) patients. HBV screening was performed in 30% of FtM patients and 18% of MtF patients (P<0.05). Thirty-one percent of FtM, 24% of MtF, and 17% of genderqueer patients were tested for HCV (P>0.05). Prevalence of HCV, HBV, and HIV in FtM was 0, 0, and 0.44% and that in MtF was 1.78, 0.89, and 1.78%, respectively. Percentage of patients immune to hepatitis A in FtM and MtF subgroups were 55 and 47% (P>0.05). Percentage of patients immune to HBV in FtM and MtF subgroups were 54 and 48% (P>0.05). CONCLUSION: This study indicates a significant lack of hepatitis screening in the transgender population and a concerning proportion of patients susceptible to disease.

A pangenotypic, single tablet regimen of sofosbuvir/velpatasvir for the treatment of chronic hepatitis C infection.

INTRODUCTION: Hepatitis C virus (HCV) infects nearly 170 million people worldwide and is a leading cause of progressive liver damage, cirrhosis, and hepatocellular carcinoma. Curative therapies have historically relied on interferon-based treatments and were limited by significant toxicity and poor response rates, particularly among patients with prior treatment failure and advanced hepatic fibrosis. The recent advent of direct acting antiviral (DAA) agents which target key steps in the HCV viral life cycle has transformed the landscape of HCV treatment by offering highly effective and well tolerated interferon-free treatments. However, current therapies are genotype-specific and have variable efficacy amongst less prevalent HCV variants. Areas covered: This review covers the preclinical and clinical development of sofosbuvir/velpatasvir (SOF/VEL), an interferon-free, once daily, pangenotypic treatment for the treatment of chronic hepatitis C virus (HCV) infection. All relevant literature from 2014 through September of 2016 is included. Expert opinion: SOF/VEL offers the promise of a single tablet, interferon- and ribavirin-free treatment that has extremely high efficacy in persons with chronic HCV infection regardless of genotype, subtype, treatment history or fibrosis status. It is expected to play a major role on a global scale in the therapeutic armamentarium against this ubiquitous threat to human health.

Impact of depressive symptoms and hepatic encephalopathy on health-related quality of life in cirrhotic hepatitis C patients.

Depression, common in chronic medical conditions, and hepatic encephalopathy (HE), a reversible neuropsychiatric syndrome due to liver dysfunction, are associated with impaired health-related quality of life (HRQOL) in cirrhosis and hepatitis C (HCV). This study investigated the impact of depression and HE on HRQOL in cirrhotic patients with HCV. A convenience sample of 43 ambulatory patients, with varying degrees of cirrhosis secondary to HCV, was prospectively enrolled in this study. Participants were assessed for any current depressive, fatigue, and daytime sleepiness symptoms and underwent a psychometric evaluation to determine the presence of HE symptoms. Participants reported current HRQOL on general health and liver disease-specific questionnaires. Diagnosis and current health status were confirmed via medical records. The associations between disease severity, depressive symptoms, HE, fatigue, and daytime sleepiness were measured. Predictors of HRQOL in this sample were determined. Depressive symptoms (70 %) and HE (77 %) were highly prevalent in this sample, with 58 % actively experiencing both conditions at the time of study participation. A significant positive association was found between depressive symptoms and HE severity (P = .05). Depressive symptoms were significantly associated with fatigue (P < .001), daytime sleepiness (P < .001), general HRQOL (P < .001), and disease-specific HRQOL (P < .001). HE was significantly associated with fatigue (P = .02), general HRQOL (P < .001), and disease-specific HRQOL (P < .001). Depressive symptoms and HE were significant predictors of reduced HRQOL (P < .001), with depressive symptoms alone accounting for 58.8 % of the variance. Depressive symptoms and HE accounted for 68.0 % of the variance. Findings suggest a possible pathophysiological link between depression and HE in cirrhosis, and potentially a wider-reaching benefit of treating minimal and overt HE than previously appreciated.

Fatal hepatitis B reactivation due to everolimus in metastatic breast cancer: case report and review of literature.

Hepatitis B reactivation can occur with cytotoxic chemotherapy in patients with hepatitis B and cancer. Reactivation can occur in a patient with chronic hepatitis, an inactive carrier, or one with resolved hepatitis. Clinical presentation may range from subclinical elevation of liver enzymes to fatal fulminant hepatic failure. Mammalian target of rapamycin inhibitors, which include everolimus, are a new generation of targeted agents that are currently approved for many cancers (since March 2009) including advanced hormone receptor positive, human epidermal growth factor receptor 2-negative breast cancer, in conjunction with exemestane (as of July 2012). We are therefore still learning the various adverse events that occur with this new class of agents. Here, we present an unfortunate case of fatal hepatitis B reactivation in a woman with metastatic breast cancer treated with everolimus and exemestane. We have detailed the controversies around hepatitis B screening prior to immunosuppressive therapy. Clinicians and patients should be aware of this rare but fatal complication prior to everolimus use, and a detailed history, screening for hepatitis B and prophylactic antiviral treatment should be considered.

Cardiovascular diseases and the liver.

The dual blood supply of the liver, originating from the portal vein and the hepatic artery, makes it relatively resistant to minor circulatory disturbances. However, hepatic manifestations of common cardiovascular disorders are frequently encountered in both the inpatient and outpatient setting. Beginning with the macro- and microcirculation of the liver, this article reviews the pathophysiology of hepatic blood flow and gives a detailed appraisal of ischemic hepatitis, congestive hepatopathy, and other less common hepatic conditions that arise when cardiovascular function is impaired.

Telaprevir: hope on the horizon, getting closer.

Standard therapy with pegylated interferon and ribavirin for chronic hepatitis C is effective in 40% to 50% of individuals with genotype 1 hepatitis C virus (HCV) infection and is associated with significant treatment-related toxicities. Newly developed small molecules that target key enzymes essential for HCV replication are in development. Telaprevir, a peptidomimetic inhibitor of the HCV NS3/4A protease, has shown great promise in early trials and is currently in advanced stages of clinical development. In treatment-naïve patients and those with previous treatment failure, the addition of telaprevir to standard interferon and ribavirin therapy is well tolerated and enhances rates of sustained virologic response while shortening the treatment duration. In this report, the current experience using telaprevir to treat chronic HCV infection as monotherapy and in combination with other agents is reviewed.