Role of Probiotics in Non-alcoholic Fatty Liver Disease: Does Gut Microbiota Matter?

Non-alcoholic fatty liver disease (NAFLD) is the hepatic consequence of metabolic syndrome, which often also includes obesity, diabetes, and dyslipidemia. The connection between gut microbiota (GM) and NAFLD has attracted significant attention in recent years. Data has shown that GM affects hepatic lipid metabolism and influences the balance between pro/anti-inflammatory effectors in the liver. Although studies reveal the association between GM dysbiosis and NAFLD, decoding the mechanisms of gut dysbiosis resulting in NAFLD remains challenging. The potential pathophysiology that links GM dysbiosis to NAFLD can be summarized as: (1) disrupting the balance between energy harvest and expenditure, (2) promoting hepatic inflammation (impairing intestinal integrity, facilitating endotoxemia, and initiating inflammatory cascades with cytokines releasing), and (3) altered biochemistry metabolism and GM-related metabolites (i.e., bile acid, short-chain fatty acids, aromatic amino acid derivatives, branched-chain amino acids, choline, ethanol). Due to the hypothesis that probiotics/synbiotics could normalize GM and reverse dysbiosis, there have been efforts to investigate the therapeutic effect of probiotics/synbiotics in patients with NAFLD. Recent randomized clinical trials suggest that probiotics/synbiotics could improve transaminases, hepatic steatosis, and reduce hepatic inflammation. Despite these promising results, future studies are necessary to understand the full role GM plays in NAFLD development and progression. Additionally, further data is needed to unravel probiotics/synbiotics efficacy, safety, and sustainability as a novel pharmacologic approaches to NAFLD

Then and now: the progress in hepatitis B treatment over the past 20 years.

The ultimate goals of treating chronic hepatitis B (CHB) is prevention of hepatocellular carcinoma (HCC) and hepatic decompensation. Since the advent of effective antiviral drugs that appeared during the past two decades, considerable advances have been made not only in controlling hepatitis B virus (HBV) infection, but also in preventing and reducing the incidence of liver cirrhosis and HCC. Furthermore, several recent studies have suggested the possibility of reducing the incidence of recurrent or new HCC in patients even after they have developed HCC. Currently, six medications are available for HBV treatment including, interferon and five nucleoside/nucleotide analogues. In this review, we will examine the antiviral drugs and the progresses that have been made with antiviral treatments in the field of CHB

Coronary Artery Disease and Nonalcoholic Fatty Liver Disease: Clinical Correlation Using CT Coronary Calcium Scans

Introduction: Nonalcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD) have been explored with coronary angiography which showed a link between severe NAFLD and CVD risk. This study’s aim is to determine if CT coronary artery calcium (CAC) scores used to determine CAD severity in asymptomatic populations can help predict presence of NAFLD. Methods: Retrospective cross-sectional study of positive CT CAC scores and liver imaging with either CT, ultrasound, or MRI of the abdomen or CT of the chest. Drinking 7 or 14 drinks per week for a woman or man respectively and chronic viral hepatitis diagnosis were excluding criteria. CT CAC scores and hepatic steatosis were correlated by chi-squared analysis. Age, sex, lipid and liver panels, weight, blood pressure, and hemoglobin A1c were correlated to CAD severity and NAFLD by logistic regression. Results: 134 patients with a median age of 63 years (IQR 57-69), 65% male, BMI 28.5 (IQR 23.9-31.3), and 8% diabetes. CAD severity was not associated with presence of hepatic steatosis (p = 0.36). Multivariate logistic regression showed a link between hepatic steatosis, CAD severity, BMI over 30 (p = 0.02), and diabetes (p = 0.01). There were associations between hepatic steatosis with triglycerides (p = 0.03) and CAD severity with AST (p = 0.02). Discussion: In patients with CAD detected using a positive CAC CT scan, we determined that BMI over 30 and diabetes were markers of increased NAFLD risk. We determined there was no direct relationship between CAD and hepatic steatosis presence

Presence and Implications of Sarcopenia in Non-alcoholic Steatohepatitis.

Sarcopenia, defined as the loss of muscle strength, mass, and functionality, confers a poor prognosis in the setting of cirrhosis. Given its clinical significance, a better understanding of the underlying mechanisms leading to cirrhosis, sarcopenia, and their co-occurrence may improve these patients\u27 outcomes. Non-alcoholic steatohepatitis (NASH) shares many of the same etiologies as sarcopenia, including insulin resistance, chronic inflammation, and ectopic adipocyte deposition, which are hallmarks of metabolic syndrome (MS). NASH thus serves as a prime candidate for further exploration into the underlying pathophysiology and relationship between these three conditions. In this review, we discuss the natural history of NASH and sarcopenia, explore the interplay between these conditions in the scope of MS, and seek to better define how an assessment of muscle mass, strength, and functionality in this population is key to improved diagnosis and management of patients with sarcopenia and NASH

Hepatitis B Virus-Associated Hepatocellular Carcinoma and Chronic Stress

The Hepatitis B virus is one of the most significant hepatocarcinogens globally. The carcinogenic mechanisms of this virus are complex, and may include interactions with the host\u27s immune system. Certain factors, such as stress on the body, can also potentiate these mechanisms. Stress, although adaptive in an acute form, is deleterious to health when chronic and can both suppress and activate the host\u27s defense system. In hepatocellular carcinoma, this can lead to tumor initiation and progression. Those that are more prone to stress, or exposed to situations that incite stress, may be at higher risk of developing cancer. Racial disparities, for example, are a source of chronic psychosocial stress in America and predispose minorities to poorer outcomes. As it remains perplexing why some individuals with chronic hepatitis B develop feared complications while others do not, it is important to recognize as many risk factors as possible, including those often overlooked such as chronic stress

Obstetricians\u27 and gynecologists\u27 knowledge, education, and practices regarding chronic hepatitis B in pregnancy.

Background: In pregnant women with high viral loads, third-trimester initiation of antiviral agents can reduce the risk of vertical transmission. We aimed to assess obstetricians\u27 and gynecologists\u27 (OB-GYN) knowledge and clinical practice when treating pregnant women with chronic hepatitis B virus (HBV). Methods: All program directors (PDs) from 250 US OB-GYN residency programs were invited to anonymously complete an 18-item questionnaire. Descriptive statistics were calculated and analyzed. Results: A total of 323 participants responded, including both PDs (n=51, response rate 21%) and residents (n=272, response rate 11%). Responding PDs (62% university-based vs. 32% community-based) came from various practice types. All PDs and 95.2% of residents reported screening for chronic HBV in pregnant patients on the first prenatal visit. A majority of PDs (85.5%) and residents (85%) correctly interpreted HBV serologies. Referral patterns showed that 66.7% of PDs and 65.5% of residents refer to a specialist regardless of viral load. A minority of respondents (19.6% PDs and 12.6% residents) knew that third-trimester antiviral therapy is recommended for women with high viral loads (\u3e200,000 IU/mL). Few respondents had prescribed HBV antivirals (9.8% PDs and 6.0% residents), with residents more commonly prescribing tenofovir and less frequently lamivudine. Half the PDs believed trainees from their programs were comfortable managing HBV in pregnancy, but only 41.8% of residents reported being comfortable managing pregnant patients with HBV. Conclusion: OB-GYNs report screening almost all pregnant patients for chronic HBV, though significant gaps still exist in practitioner comfort and training regarding the management of HBV during pregnancy

Pharmacotherapy for Primary Biliary Cholangitis: An Assessment of Medication Candidacy and Rates of Treatment

BACKGROUND: Ursodeoxycholic acid is the preferred first-line therapy for primary biliary cholangitis. Alternative therapies, such as obeticholic acid, are recommended for patients who cannot tolerate ursodeoxycholic acid or who have an inadequate response to ursodeoxycholic acid monotherapy. Prior investigations have suggested that as many as 30% of patients with primary biliary cholangitis may have never received treatment with ursodeoxycholic acid. No prior investigations have examined usage rates of obeticholic acid in the treatment of primary biliary cholangitis. METHODS: All patients with an ICD-10 diagnosis of primary biliary cholangitis who had any records within the health system were included. A review of medical records was performed to confirm the diagnosis of primary biliary cholangitis and determine which medications had been prescribed for treatment, as well as candidacy for second-line therapies. RESULTS: A total of 495 patients met inclusion criteria. Notably, 95% of patients were taking ursodeoxycholic acid for treatment of their primary biliary cholangitis, with 67% of patients having disease that was well-controlled on ursodeoxycholic acid monotherapy. In total, 8% of patients were taking obeticholic acid (either as combination or monotherapy). Only 3% would benefit from the addition of a second line therapy but had not yet been offered medication. Only 3% of patients were not on any medication for management of their primary biliary cholangitis. CONCLUSIONS: Ursodeoxycholic acid is a readily available and generally well-tolerated medication that should be offered to all patients with primary biliary cholangitis as first-line therapy. While prior investigations have suggested that up to 30% of patients with primary biliary cholangitis may never have received treatment for the disorder, the present study suggests that patients are generally being managed according to guidelines. Moreover, a significant proportion of patients with primary biliary cholangitis will qualify for second line therapies and prescribers should be aware of the indications to use these medications

The Use of Palliative Performance Score in Patients with End-Stage Liver Disease

● Palliative Care services are often underutilized in patients with End-Stage Liver Disease (ESLD) and often only initiated at the end of life ● The Palliative Performance Score (PPS) is an important tool used in Palliative Care to assess functional status ● PPS has five functional dimensions: ambulation, activity level and evidence of disease, self-care, oral intake, and level of consciousness ● The aim of this study is to determine if there is a correlation between Model for End-Stage Liver Disease (MELD) score and PPS in ESLD patients ● MELD is used to predict mortality and to prioritize liver transplant allocation in ESLD patientshttps://jdc.jefferson.edu/medposters/1011/thumbnail.jp

Limited sampling estimates of epigallocatechin gallate exposures in cirrhotic and noncirrhotic patients with hepatitis C after single oral doses of green tea extract.

BACKGROUND: Epigallocatechin-3-gallate (EGCG) has antiangiogenic, antioxidant, and antifibrotic properties that may have therapeutic potential for the treatment of cirrhosis induced by hepatitis C virus (HCV). However, cirrhosis might affect EGCG disposition and augment its reported dose-dependent hepatotoxic potential. OBJECTIVE: The safety, tolerability, and disposition of a single oral dose of EGCG in cirrhotic patients with HCV were examined in an exploratory fashion. METHODS: Eleven patients with hepatitis C and detectable viremia were enrolled. Four had Child-Pugh (CP) class A cirrhosis, 4 had Child-Pugh class B cirrhosis, and 3 were noncirrhotic. After a single oral dose of green tea extract 400 mg containing 94% pure EGCG, blood for EGCG levels and safety parameters was ascertained at 2, 4, and 10 hours. RESULTS: C(max) and AUC to EGCG overlapped among the 3 groups, which suggests that the disposition of EGCG was not significantly altered in these patients with cirrhosis. CONCLUSIONS: A single 400-mg oral dose of EGCG was safe and well tolerated by all of the patients in the study. These results provide guidance for the continued investigation of the long-term safety and antitumor potential of EGCG in cirrhotic patients with HCV

The Long Game: A Functional Cure Is Possible with Nucleoside Analogues and the Tincture of Time

Chronic hepatitis B is still prevalent globally. Many patients are treated for many years with nucleos(t)ide analogues to prevent the virus from actively replicating. However, although it typically requires consecutive treatment for more than 10 years, patients can achieve a functional cure from this virus. This case series presents details of functional cures in patients who received varying nucleos(t)ide therapies for an average of 15.3 years before losses of hepatitis B surface antigen and viral load were observed. It is imperative to understand that abbreviating therapy once a functional cure is achieved may be a possibility in treating patients in order to limit the associated costs and side effects of an otherwise lifelong therapy until other cure drugs are approved