Preoperative risk evaluation and optimization for patients with liver disease.

The prevalence of liver disease is rising and more patients with liver disease are considered for surgery each year. Liver disease poses many potential complications to surgery; therefore, assessing perioperative risk and optimizing a patient's liver health is necessary to decrease perioperative risk. Multiple scoring tools exist to help quantify perioperative risk and can be used in combination to best educate patients prior to surgery. In this review, we go over the various scoring tools and provide a guide for clinicians to best assess and optimize perioperative risk based on the etiology of liver disease.

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.

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.

Differential expression of hepatic cancer stemness and hypoxia markers in residual cancer after locoregional therapies for hepatocellular carcinoma.

Transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) treatment to hepatocellular carcinoma (HCC) are effective tools to control tumor growth, prolong survival, palliate symptoms, and improve quality of life for patients with intermediate-stage HCC. Nevertheless, there is high variability of local HCC responses to locoregional therapies; therefore, better and personalized prediction of tumor response to TACE is necessary for management of patients with HCC, especially when these modalities of treatment are used to bridge patients for liver transplant. Here, we investigated differential expression of hepatic cancer stem cell and hypoxia in residual HCC after TACE treatment in comparison with TARE. A publicly available gene data set was screened for differentially expressed genes (DEGs) in TACE_Response compared with TACE_Non-response HCC. Analysis of the GSE104580 data set displayed a total of 406 DEGs, including 196 down-regulated and 210 up-regulated DEGs. Of the 196 down-regulated DEGs, three hepatic cancer stem cell (CSC) markers and 11 hypoxia-related genes were identified. Immunohistochemical staining of hepatic CSC and hypoxia markers on explant liver tissues exhibited more intense positive staining of hepatic CSC markers (CD24, EpCAM) and hypoxia marker carbonic anhydrase 9 (CA9) in residual tumor nodule from patients with HCC treated with TACE compared with nontreated patients. Furthermore, Pearson's correlation analysis revealed the significant correlation between hepatic CSC markers and hypoxia marker, CA9. Conclusion: Hepatic CSC and hypoxia markers predict nonresponse to TACE and are differentially expressed in residual tumor after TACE compared with TARE. In the long term, TACE-induced hypoxia may select an aggressive HCC phenotype.

Late-Onset Acute Liver Injury From Azathioprine.

Azathioprine is a widely prescribed immunosuppressant. Although hepatotoxicity is rare, it commonly presents as mild asymptomatic liver enzyme elevation or acute cholestatic liver injury. We report a case of a 46-year-old woman who presented with jaundice, abdominal pain, fatigue, and elevated aminotransferases in a cholestatic pattern. Endoscopic retrograde cholangiopancreatogram demonstrated no abnormalities, and recently started medications were discontinued without improvement. Liver biopsy was performed, which was consistent with drug-induced liver injury. Despite multiple years of treatment without issue, after azathioprine was discontinued, symptoms and laboratory abnormalities resolved. This case highlights azathioprine's potential for hepatotoxicity even multiple years after initiation.

An international survey on patterns of practice in NAFLD and expectations for therapies-The POP-NEXT project.

BACKGROUND AND AIMS: Differences between countries in NAFLD patient care pathways and management need to be understood prior to defining supranational guidelines. APPROACH AND RESULTS: We conducted an anonymous survey in France, Germany, Hong Kong, Italy, Romania, Spain, the United Kingdom, and the United States among physicians providing specialist care for patients with NAFLD. Modalities of patient referral, patterns of practice (diagnosis, staging, monitoring, and indications for liver biopsy), therapeutic management, and expectations for future NASH pharmacotherapies were assessed, with 664 physicians completing the survey. Referral to surveyed physicians (SPs) mostly came from primary care. Prior to referral, NAFLD was rarely diagnosed, and noninvasive tests were not performed. Screening for comorbidities by SPs was incomplete and cardiovascular risk not calculated. Elastometry in combination with a serum biomarker was the most common first-line method for fibrosis staging. Liver biopsy, when performed, was often delayed by at least 1 year after diagnosis. It was, however, recommended even if noninvasive methods indicated advanced fibrosis. Frequent, biannual monitoring was conducted, including HCC surveillance in Stage 3 fibrosis. SPs rarely implemented and followed dietary and lifestyle changes themselves, and local availability of such programs was highly heterogenous. SPs favored pharmacotherapy based on mechanism of action adapted to the stage of the disease, including for early stages such as steatohepatitis with mild fibrosis. CONCLUSIONS: This international survey revealed major deficiencies and delays in referral pathways, suboptimal screening for comorbidities or managing of lifestyle modifications by SPs, and limited local availability for nonpharmacological interventions. Monitoring practices are not aligned with current guidelines.

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.

Disseminated AIDS-Related Kaposi Sarcoma Immune Reconstitution Inflammatory Syndrome With Infiltrative Liver Disease.

Clinically significant hepatic acquired immunodeficiency syndrome-related Kaposi sarcoma is rarely described in the literature. Kaposi sarcoma immune reconstitution inflammatory syndrome may play a role in the rapid progression of clinically insignificant to significant liver disease. We present an acquired immunodeficiency syndrome patient with disseminated Kaposi sarcoma that developed 3-6 weeks after initiation of highly active antiretroviral therapy.

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.

Cost-effectiveness of Antenatal Rescreening Among Pregnant Women for Hepatitis C in the United States.

To inform proposed changes in hepatitis C virus (HCV) screening guidelines in the United States, we assessed the cost-effectiveness of HCV antenatal rescreening for women without evidence of HCV during a prior pregnancy, using a previously published model. Universal HCV rescreening among pregnant women was cost-effective (incremental cost-effectiveness ratio, $6000 per quality-adjusted life-year) and should be recommended nationally.

Changing epidemiology, implications, and recommendations for hepatitis C in women of childbearing age and during pregnancy.

Despite the remarkable advances in HCV treatment brought about by the advent of direct-acting antivirals, HCV remains a global public health concern. One particular concern relates to the rising prevalence of HCV in women of childbearing age. Active HCV during pregnancy is associated with cholestasis of pregnancy as well as the risk of mother-to-child transmission. Guidelines are increasingly recommending universal screening during pregnancy, while the treatment of HCV during pregnancy is an area of ongoing research.

WGO Guidance for the Care of Patients With COVID-19 and Liver Disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the least deadly but most infectious coronavirus strain transmitted from wild animals. It may affect many organ systems. Aim of the current guideline is to delineate the effects of SARS-CoV-2 on the liver. Asymptomatic aminotransferase elevations are common in coronavirus disease 2019 (COVID-19) disease. Its pathogenesis may be multifactorial. It may involve primary liver injury and indirect effects such as "bystander hepatitis," myositis, toxic liver injury, hypoxia, and preexisting liver disease. Higher aminotransferase elevations, lower albumin, and platelets have been reported in severe compared with mild COVID-19. Despite the dominance of respiratory disease, acute on chronic liver disease/acute hepatic decompensation have been reported in patients with COVID-19 and preexisting liver disease, in particular cirrhosis. Metabolic dysfunction-associated fatty liver disease (MAFLD) has a higher risk of respiratory disease progression than those without MAFLD. Alcohol-associated liver disease may be severely affected by COVID-19-such patients frequently have comorbidities including metabolic syndrome and smoking-induced chronic lung disease. World Gastroenterology Organization (WGO) recommends that interventional procedures such as endoscopy and endoscopic retrograde cholangiopancreatography should be performed in emergency cases or when they are considered strictly necessary such as high risk varices or cholangitis. Hepatocellular cancer surveillance may be postponed by 2 to 3 months. A short delay in treatment initiation and non-surgical approaches should be considered. Liver transplantation should be restricted to patients with high MELD scores, acute liver failure and hepatocellular cancer within Milan criteria. Donors and recipients should be tested for SARS-CoV-2 and if found positive donors should be excluded and liver transplantation postponed until recovery from infection.

Hepatitis C remains leading indication for listings and receipt of liver transplantation for hepatocellular carcinoma.

BACKGROUND AND AIMS: With the availability of direct acting antivirals (DAA) for hepatitis C virus (HCV) infection, alcoholic liver disease (ALD) has evolved as the leading indication for listing and receipt of liver transplantation (LT) followed by non-alcoholic steatohepatitis and HCV infection. However, data are limited on etiology specific trends on listings and need for LT for hepatocellular carcinoma (HCC). METHODS: We analyzed UNOS database to examine etiology specific listings and receipt of LT for patients with and without HCC. Listings and receipt of LT in the pre-DAA (2007-2012) era were compared to the DAA (2013-2018) era. RESULTS: The analysis shows that among patients without HCV, there is a decreasing trend on the proportion of patients listed and transplanted for HCV, with simultaneous increase on listings and LT for NASH and ALD. Specifically for listings and transplants for HCC, the leading etiology remains HCV infection followed by NASH and ALD. The analysis also showed that LT for AH contributes to about 20% of increase in listings and receipt of LT for ALD.

Report from the International Conference on Viral Hepatitis - 2017.

The International Conference on Viral Hepatitis 2017 brought exciting news on the treatment of viral hepatitis. The most recent estimates of the burden for hepatitis B virus and hepatitis C virus (HCV) infections were presented. The current gaps and prospects for regional and global eradication of viral hepatitis were discussed on the light of the WHO roadmap until 2030. Debates focused on hepatitis C and expectations using the new approved HCV pan-genotypic, once daily, oral direct-acting antivirals (DAAs), glecaprevir-pibrentasvir, and sofosbuvir-velpatasvir-voxilaprevir. The management of difficult-to-cure HCV patients included individuals who had failed prior DAAs, people who inject drugs, patients with decompensated cirrhosis, or renal insufficiency. Special patient populations such as children, pregnant women, persons with acute hepatitis C, or HIV coinfection were addressed separately. The use of HCV treatment as prevention was subject to debate, balancing the benefits on halting transmission and the risk for HCV reinfections and high medication costs. Complementary efforts on behavioral interventions and harm reduction programs were highlighted. Data from both clinical trials and real-world experience (i.e., from the US Veterans) were compared. Further debates addressed hepatic conditions that may alter the management and outcome of viral hepatitis, such as hepatitis B reactivation, non-alcoholic fatty liver disease, liver transplantation, and hepatocellular carcinoma. Finally, the recent data on often neglected hepatitis D and E virus infections were reviewed.

Updates on hepatitis C virus therapy in the direct-acting antiviral era.

PURPOSE OF REVIEW: Hepatitis C virus (HCV) is a major cause of clinical burden in the United States and worldwide, as a percentage of patients can develop complications such as cirrhosis and hepatocellular carcinoma. RECENT FINDINGS: Therapy for chronic HCV infection was previously interferon-based, but with the advent of direct-acting antivirals (DAAs), there has been a dramatic improvement in eradicating the virus with favourable side effect profiles. SUMMARY: Emerging data are demonstrating new successful agents in difficult-to-manage populations. This review is aimed to provide a brief overview of currently accepted therapy, as well providing new information on upcoming therapeutic agents available for practioners going forward.

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.

Evaluation of Hepatitis C Patients in the Direct-Acting Antiviral Era.

Hepatitis C is a major worldwide cause of liver morbidity and mortality. A substantial proportion of infected patients will develop chronic disease, which may progress over decades to cirrhosis. This can lead to decompensation and hepatocellular carcinoma. With the advent of the direct-acting antivirals, hepatitis C has become increasingly curable with limited adverse events and a shorter duration of therapy. This review discusses the evaluation process of the hepatitis C patient in the direct-acting antiviral era, including screening, clinical evaluation, drug-drug interactions, treatment urgency, and counseling.

Screening for Zinc Deficiency in Patients with Cirrhosis: When Should We Start?

BACKGROUND: Zinc deficiency has been observed in cirrhosis, but management guidelines do not address screening for zinc deficiency. We aim to determine the prevalence of zinc deficiency in different stages of cirrhosis and to correlate zinc levels with complications of cirrhosis and clinical outcomes. Patients who had a diagnosis of cirrhosis and had serum zinc levels drawn from 2007 to 2011 were identified. Demographics, laboratory data, presence of ascites, encephalopathy, and infection were obtained; Child-Pugh and MELD scores were calculated. Stata software was used for data analysis. A total of 163 patients were included in the study. RESULTS: The median serum zinc level was 0.47 mcg/ml (IQR 0.37-0.63); 83 % of patients were zinc deficient. Zinc deficiency was more prevalent in patients with Child-Pugh score B or C, and with MELD scores ≥15. Zinc levels were lower in alcoholic, hepatitis C, and cholestatic diseases than in other etiologies of liver disease. Zinc levels correlated with INR (r = -0.56, p < 0.001), bilirubin (r = -0.51, p < 0.001), and albumin (r = 0.68, p < 0.001), and were lower in patients with ascites (0.40 vs. 0.57 mcg/ml, p < 0.001), encephalopathy (0.40 vs. 0.53 mcg/ml, p < 0.001), diuretic use (0.45 vs. 0.535 mcg/ml, p = 0.005), and infection (0.32 vs. 0.51 mcg/ml, p < 0.001). Ascites (p = 0.044) and infection (p = 0.009) were independently associated with zinc levels. Zinc-deficient patients had lower transplant-free survival rates than non-deficient patients. CONCLUSION: Zinc deficiency is highly prevalent in cirrhotic patients with Child-Pugh score B or C, and with MELD score ≥15. Zinc deficiency also correlates with disease severity, infection, and a worse transplant-free survival. Screening for zinc deficiency should be considered in this subset of patients.