Autoimmune hepatitis: Current and future therapies.

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that can lead to cirrhosis and liver failure. AIH can present in all ages, races, and ethnicities, but it predominantly affects women. As a heterogeneous disease, AIH presents variably in different patients, making diagnosis and treatment a challenge. Currently, the standard treatment for AIH comprises immunosuppressants; however, their long-term use is associated with adverse effects. The pathogenesis of AIH is complex, involving T cells, macrophages, and plasma cells that invade the periportal parenchyma and lead to an inflammatory cascade that can result in liver damage. Due to the complexity of AIH pathogenesis, treatment targets several inflammatory pathways. However, unlike other autoimmune diseases in which targeted treatments have been approved, there has been little progress made in advancing the treatment paradigm for AIH. Major obstacles to progress include challenges in conducting clinical trials, particularly patient recruitment and ensuring a diverse range of backgrounds; poorly defined outcomes to assess treatment response and improved quality of life; and a lack of study designs that account for the stage of disease and variations in treatment. A focus on individualized and steroid-free treatment approaches is needed to improve AIH prognosis and minimize steroid-associated adverse effects.

Rifaximin plus lactulose versus lactulose alone for reducing the risk of HE recurrence.

BACKGROUND: The aim was to examine rifaximin plus lactulose efficacy in patients with cirrhosis at a risk of developing overt HE who were stratified by important baseline characteristics such as comorbid ascites or diabetes. METHODS: Pooled post hoc subgroup analysis of adults receiving rifaximin 550 mg twice daily plus lactulose or lactulose alone for 6 months in a phase 3 randomized, double-blind trial and a phase 4 open-label trial was conducted. RESULTS AND CONCLUSION: Rifaximin plus lactulose was more efficacious than lactulose alone for reducing the risk of overt HE recurrence and HE-related hospitalization in adults grouped by select baseline disease characteristics.

The delta in management of HDV/HBV coinfection: Lessons from a case.

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Could the answer to NAFLD be hidden in diabetic therapy? The impact of T2DM treatment on NAFLD.

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Patients With Autoimmune Hepatitis and Nonalcoholic Fatty Liver Disease: Characteristics, Treatment, and Outcomes.

GOAL: The objective of this study was to characterize an autoimmune hepatitis (AIH)/nonalcoholic fatty liver disease (NAFLD) overlap cohort, determine if they received standard of care treatment, and delineate their outcomes in comparison with patients with AIH or NAFLD alone. BACKGROUND: AIH is a relatively rare and heterogeneously presenting liver disease of unknown etiology. NAFLD is a leading cause of liver disease worldwide. AIH treatment includes steroids, which have adverse metabolic effects that can worsen NAFLD. No treatment guidelines are available to mitigate this side on AIH/NAFLD overlap patients. Few studies to date have examined these patients' characteristics, management practices, and outcomes. MATERIALS AND METHODS: A single-center, retrospective chart review study examining biopsy-proven AIH/NAFLD, AIH, and NAFLD patients. Characteristics, treatment, and 1- and 3-year outcomes (all-cause mortality, need for liver transplantation, or decompensated cirrhosis) were evaluated. RESULTS: A total of 72 patients (36.1% AIH/NAFLD, 34.7% AIH, and 29.2% NAFLD) were included. AIH/NAFLD patients were found to be more often Hispanic/Latino, female, and with lower liver aminotransaminases, immunoglobulin G, and anti-smooth muscle antibody positivity. AIH/NAFLD patients were less likely to receive standard of care treatment. No significant differences in outcomes were seen between AIH/NAFLD and either AIH or NAFLD. CONCLUSIONS: Our study demonstrated that AIH/NAFLD patients have unique characteristics and are less likely to receive standard of care treatment compared with patients with AIH alone. Despite this, no difference in outcomes (all-cause mortality, need for liver transplantation, or decompensated cirrhosis) was seen. Given NAFLD's rising prevalence, AIH/NAFLD cases will likely increase, and may benefit from alternative treatment guidelines to prevent worsening of NAFLD.

What Is the Real Epidemiology of Hepatitis D Virus and Why so Many Mixed Messages?

The disease burden of HDV is poorly understood. Our review identified multiple reasons: (1) HDV infection rates are overestimated in the general population due to limited sample sizes, sampling high-risk populations, and significant regional variations, (2) estimates are based on chronic HBV populations, but HBV burden itself is uncertain, (3) there is a lack of testing in at-risk populations, (4) prevalence testing is based on HDV antibody testing and not HDV RNA, which distinguishes between active infection versus prior exposure, (5) older studies used less reliable testing and (6) HBV vaccination programs have affected HDV prevalence, but is often not accounted for.

Improving the Management of Hepatorenal Syndrome-Acute Kidney Injury Using an Updated Guidance and a New Treatment Paradigm.

Cirrhosis, or advanced scarring of the liver, represents the end stage of chronic liver disease and is associated with high morbidity and mortality. Hepatorenal syndrome-acute kidney injury (HRS -AKI), a condition causing functional and progressive kidney failure, is a complication of cirrhosis that contributes to its high mortality rate. In the United States, the standard-of-care treatments for HRS -AKI have historically been suboptimal. Recently, terlipressin became the first drug approved for HRS -AKI in the United States, and the American Association for the Study of Liver Diseases updated its guidance document on HRS diagnosis and management. Clinical practice guidelines and guidance documents have a variable effect on physician behavior owing to a lack of awareness, familiarity, and education. The imple mentation of standardized order sets can improve guidance adherence and the quality of care delivered by encouraging data-driven treatment administration, especially for new therapies. This review seeks to facilitate improvements in the management of HRS -AKI by discussing early HRS -AKI interventions, which will streamline diagnosis and treatment in a practical way for clinical use, and how to incorporate new treatments into patient care to improve survival in this subset of patients. Finally, these recommendations are integrated into a sample order set developed by members of the Chronic Liver Disease Foundation and experts in the management of HRS-AKI.

Real-World Effectiveness of 8-Week Glecaprevir/Pibrentasvir in Treatment-Naïve, Compensated Cirrhotic HCV Patients.

INTRODUCTION: The EXPEDITION-8 clinical trial has demonstrated that treatment-naïve patients with compensated cirrhosis (TN/CC) of HCV genotypes 1-6 can achieve a 98% intent-to-treat sustained virologic response rate 12 weeks post-treatment with an 8-week glecaprevir/pibrentasvir (G/P) regimen. Further real-world evidence is needed to support the effectiveness of 8-week G/P in a clinical practice setting and to consolidate these treatment recommendations. The aim of this study is to contribute real-world evidence for the effectiveness of an 8-week G/P treatment in TN/CC patients with HCV genotypes 1-6. METHODS: Retrospective real-world data from 494 TN/CC patients with HCV genotypes 1-6 were collected between August 2017 to December 2020 from the Symphony Health Solutions administrative claims database. Demographic and clinical characteristics were collected at baseline. Patients were required to have a follow-up HCV ribonucleic acid level at least 8 weeks or more after the end of treatment. The percentage of patients achieving a sustained virologic response (SVR) is reported. RESULTS: The majority of patients were male (58%) and Caucasian (40%), with a mean age of 58 years; 74%, 12%, 12%, and 1% of patients were HCV genotype 1, 2, 3, and 4-6 infected, respectively. SVR was achieved in 95.5% of all patients. Across patient subgroups, SVR was achieved in 95.6% of patients with HCV genotype 3 and in 93% of HCV patients with a recent diagnosis of illicit drug use or abuse (within 6 months prior to G/P initiation). CONCLUSION: Early real-world evidence indicates high effectiveness of the 8-week G/P regimen in TN/CC patients of HCV genotypes 1-6 from a large US claims database.

Clinical advances: pregnancy in gastroenterologic and hepatic conditions.

The fields of gastroenterology and hepatology, along with endoscopic practice, have seen significant changes and innovations to practice in just the past few years. These practice changes are not limited to gastroenterology, but maternal fetal medicine and the care of the pregnant person have become increasingly more sophisticated as well. Gastroenterologists are frequently called on to provide consultative input and/or perform endoscopy during pregnancy. To be able to provide the best possible care to these patients, gastroenterologists need to be aware of (and familiar with) the various nuances and caveats related to the care of pregnant patients who either have underlying gastrointestinal (GI) conditions or present with GI and liver disorders. Here, we offer a clinical update with references more recent than 2018, along with a few words about SARS-CoV-2 infection and its relevance to pregnancy.

The Spectrum of Hepatic Critical Care During Pregnancy: A Clinical Review.

Hepatic disease during pregnancy can result in the development of critical illness requiring special attention from a multidisciplinary team with a low threshold for tertiary care transfer to provide access to liver transplantation. Management of this population requires taking into consideration the benefit and risks of both mother and fetus. A myriad of diseases has been recognized, some being unique to pregnancy while others are common to the general population. We present a review of the literature on the diagnosis, management, and prognosis of these diseases to aid in the optimization of care in this special population.

Evaluation of Liver Disease in Pregnancy.

Liver disease in pregnancy often requires diagnostic and therapeutic considerations that are unique to pregnancy. Liver disease in pregnancy is commonly thought of as either liver disease unique to pregnancy, chronic liver disease, or liver disease coincidental to pregnancy. This review summarizes the approach to evaluation of liver disease in pregnancy.

Improving Outcomes in Hepatorenal Syndrome-Acute Kidney Injury With Early Diagnoses and Implementation of Approved Treatment Regimens.

Decompensated cirrhosis, defined by the overt manifestations of liver failure and portal hypertension (eg, ascites, hepatic encephalopathy, variceal bleeding), is the inflection point associated with increased morbidity and mortality in chronic liver disease. Acute kidney injury in the setting of cirrhosis (hepatorenal syndrome-acute kidney injury [HRS-AKI]) is a severe and often fatal complication. The goals of treatment of HRS-AKI are to reverse renal failure and prolong survival in these critically ill patients or perhaps to allow the transplant team to complete the pretransplant evaluation and bridge the patient to transplant. Historically, in the United States, standard-of-care treatments for HRS-AKI were chosen by default despite lack of data, off-label use, and suboptimal results. Terlipressin represents the first drug in the United States indicated for the treatment of HRS-AKI. This review provides an up-to-date overview of HRS-AKI, discusses terlipressin and how to incorporate this new treatment into patient care and streamline society guidelines on HRS diagnosis and treatment in a practical way for clinical use, and concludes with a sample order set that highlights the recommendations discussed throughout the supplement.