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.

American Association for the Study of Liver Diseases Expert Panel Consensus Statement: Vaccines to Prevent Coronavirus Disease 2019 Infection in Patients With Liver Disease.

The aim of this document is to provide a concise scientific review of the currently available COVID-19 vaccines and those in development, including mRNA, adenoviral vectors, and recombinant protein approaches. The anticipated use of COVID-19 vaccines in patients with chronic liver disease (CLD) and liver transplant (LT) recipients is reviewed and practical guidance is provided for health care providers involved in the care of patients with liver disease and LT about vaccine prioritization and administration. The Pfizer and Moderna mRNA COVID-19 vaccines are associated with a 94%-95% vaccine efficacy compared to placebo against COVID-19. Local site reactions of pain and tenderness were reported in 70%-90% of clinical trial participants, and systemic reactions of fever and fatigue were reported in 40%-70% of participants, but these reactions were generally mild and self-limited and occurred more frequently in younger persons. Severe hypersensitivity reactions related to the mRNA COVID-19 vaccines are rare and more commonly observed in women and persons with a history of previous drug reactions for unclear reasons. Because patients with advanced liver disease and immunosuppressed patients were excluded from the vaccine licensing trials, additional data regarding the safety and efficacy of COVID-19 vaccines are eagerly awaited in these and other subgroups. Remarkably safe and highly effective mRNA COVID-19 vaccines are now available for widespread use and should be given to all adult patients with CLD and LT recipients. The online companion document located at https://www.aasld.org/about-aasld/covid-19-resources will be updated as additional data become available regarding the safety and efficacy of other COVID-19 vaccines in development.

Incidence of Complications from Percutaneous Biopsy in Chronic Liver Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Approaches to liver biopsy have changed over the past decade in patients with chronic liver disease. AIMS: We conducted a systematic review and meta-analysis on the incidence of all complications and technical failure associated with percutaneous liver biopsy. METHODS: We systematically searched PubMed and the Cochrane Library for cohort studies reporting on complications resulting from liver biopsy published between 2010 and 2020. Studies on participants of any age and sex, who underwent any percutaneous biopsy for non-focal liver disease, were selected. All events except mild pain, minor hematoma, vasovagal episodes, fever and fistula were defined as major complications. Random-effect model meta-analyses with and without covariates were performed, to examine the effect of publication year, patient characteristics, outcome collection, and biopsy type on incidences. RESULTS: We identified 30 studies reporting on complications resulting from percutaneous liver biopsy procedures (n = 64,356). Incidence of major complications was 2.44% (95% CI 0.85, 6.75), with mortality at 0.01% (95% CI 0.00, 0.11), hospitalization at 0.65% (95% CI 0.38, 1.11), major bleeding at 0.48% (95% CI 0.22, 1.06), and moderate/severe pain at 0.34% (95% CI 0.08, 1.37). Minor complications at 9.53% (95% CI 3.68, 22.5) were mainly pain at 12.9% (95% CI 5.34, 27.9). Technical failure was high at 0.91% (95% CI 0.27, 3.00). Decreasing patient age significantly increased incidence of hospitalization and major bleeding (P < 0.0001). Hospitalization incidence also significantly increased with disease severity. CONCLUSIONS: Incidence of major (2.4%) and minor (9.5%) complications, and technical failure (0.91%) in percutaneous liver biopsies continues.

ACG Clinical Guideline: Liver Disease and Pregnancy.

Consultation for liver disease in pregnant women is a common and oftentimes vexing clinical consultation for the gastroenterologist. The challenge lies in the need to consider the safety of both the expectant mother and the unborn fetus in the clinical management decisions. This practice guideline provides an evidence-based approach to common diagnostic and treatment challenges of liver disease in pregnant women.

Generic medications for hepatitis C.

The recent development and approval of expensive but highly effective oral agents against hepatitis C has led to restrictions and access limitations in many countries with limited healthcare budgets. Generic formulations of many of these agents are available at a fraction of the retail price in several countries because of generic licensure agreements. The discounted alternatives are only accessible in developing countries and require manufacturing and distribution regulations to ensure the quality and bioequivalence of the new drug formulations. The continued medication access limitations have driven great interest in the practice of personal drug importation of the generic formulations. This review and debate will address the medical and legal issues involved in the purchase and importation of these medicines.

The benefit of paracentesis on hospitalized adults with cirrhosis and ascites.

BACKGROUND AND AIM: The aim of this study is to assess paracentesis utilization and outcomes in hospitalized adults with cirrhosis and ascites. METHODS: The 2011 Nationwide Inpatient Sample was used to identify adults, non-electively admitted with diagnoses of cirrhosis and ascites. The primary endpoint was in-hospital mortality. Variables included patient and hospital demographics, early (Day 0 or 1) or late (Day 2 or later) paracentesis, hepatic decompensation, and spontaneous bacterial peritonitis. RESULTS: Out of 8 023 590 admissions, 31 614 met inclusion criteria. Among these hospitalizations, approximately 51% (16 133) underwent paracentesis. The overall in-hospital mortality rate was 7.6%. There was a significantly increased mortality among patients who did not undergo paracentesis (8.9% vs 6.3%, P < 0.001). Patients who did not receive paracentesis died 1.83 times more often in the hospital than those patients who did receive paracentesis (95% confidence interval 1.66-2.02). Patients undergoing early paracentesis showed a trend towards reduction in mortality (5.5% vs 7.5%) compared with those undergoing late paracentesis. Patients admitted on a weekend demonstrated less frequent use of early paracentesis (50% weekend vs 62% weekday) and demonstrated increased mortality (adjusted odds ratio 1.12 95% confidence interval 1.01-1.25). Among patients diagnosed with spontaneous bacterial peritonitis, early paracentesis was associated with shorter length of stay (7.55 vs 11.45 days, P < 0.001) and decreased hospitalization cost ($61 624 vs $107 484, P < 0.001). CONCLUSION: Paracentesis is under-utilized among cirrhotic patients presenting with ascites and is associated with decreased in-hospital mortality. These data support the use of paracentesis as a key inpatient quality measure among hospitalized adults with cirrhosis. Future studies are needed to investigate the barriers to paracentesis use on admission.

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.

Chronic Viral Hepatitis: Current Management and Future Directions.

The past decade has seen transformation in the strategies for identifying and managing viral hepatitis, most dramatically the transformation of hepatitis C virus from a mostly chronic affliction to a curable disease that is accessible to wide populations through direct-acting antiviral therapies. More recently, shifting of hepatitis C virus burden to younger patients driven by intravenous drug use has shaped screening recommendations. Future work focusing on effective screening, linkage to care, treatment initiation, and post-cure management will allow countries to work toward meeting goals of eliminating viral hepatitis as a major public health threat. Concurrently, hepatitis B virus has also seen advances in management using oral nucleos(t)ide therapies with high-resistance barriers. However, virologic cure remains elusive in the setting of viral genetic persistence within the hepatocyte nucleus, even with suppressive antiviral therapy. Future directions include a refined definition of "cure," new biomarkers, and development of therapies targeting multiple pathways in the viral pathogenic and replication pathway. Progress is additionally being made on the management of hepatitis D infection. This review summarizes the recent evolution in disease characteristics, associated affected population, and changes in our understanding of management for these infections. We also discuss future directions in the management of viral hepatitis, including discussion on issues related to management before and after antiviral therapy. Conclusion: We summarize recent advances in the identification and management of viral hepatitis, which hold the potential to markedly reduce disease burden and therefore associated liver-related complications. However further work is needed to adequately identify and manage these diseases.

Vanishing bile duct syndrome.

Perhaps no condition associated with chronic cholestasis is less understood than vanishing bile duct syndrome, a term that refers loosely to the group of acquired disorders associated with progressive destruction and disappearance of the intrahepatic bile ducts and, ultimately, cholestasis. Although the array of insults resulting in poor bile flow is vast, most adult patients who have chronic cholestasis have either primary biliary cirrhosis (or primary sclerosing cholangitis; in some cases, however, a cause cannot be identified. This article reviews the multiple causes, postulated pathophysiology, clinical features, and treatment options for this syndrome.

Should NS5A inhibitors serve as the scaffold for all-oral anti-HCV combination therapies?

Chronic hepatitis C virus (HCV) infection represents a global health problem that affects up to 130-150 million people worldwide. The HCV treatment landscape has been transformed recently by the introduction of direct-acting antiviral (DAA) agents that target viral proteins, including the NS3 protease, the NS5B polymerase, and the NS5A protein. Treatment with multiple DAAs in combination has been shown to result in high rates of sustained virologic response, without the need for pegylated interferon, and a shorter duration of therapy compared with interferon-based regimens; however, the optimal combination of DAAs has yet to be determined. The class of NS5A inhibitors has picomolar potency with pangenotypic activity, and recent clinical studies have shown these inhibitors to be an important component of DAA combination regimens. This review discusses the rational design of an optimal anti-HCV DAA cocktail, with a focus on the role of NS5A in the HCV life cycle, the attributes of the NS5A class of inhibitors, and the potential for NS5A inhibitors to act as a scaffold for DAA-only treatment regimens.

Hepatitis C virus: a critical appraisal of new approaches to therapy.

The HCV council 2011 convened 11 leading clinicians and researchers in hepatitis C virus from academic medical centers in the United States to provide a forum for the practical and comprehensive evaluation of current data regarding best practices for integrating new direct-acting antiviral agents into existing treatment paradigms. The council investigated 10 clinical practice statements related to HCV treatment that reflect key topical areas. Faculty members reviewed and discussed the data related to each statement, and voted on the nature of the evidence and their level of support for each statement. In this new era of DAAs, a comprehensive and critical analysis of the literature is needed to equip clinicians with the knowledge necessary to design, monitor, and modify treatment regimens in order to optimize patient outcomes.