A Systematic Approach to Pregnancy-Specific Liver Disorders.

Consultation for liver disease during pregnancy is challenging for both the hepatologist and gynecologist, as normal physiologic changes during pregnancy can mimic chronic liver disease. Pregnancy-specific liver disorders are leading causes of abnormal liver function tests during pregnancy. Moreover, up to 3% of all pregnant women in developed countries experience liver diseases nonspecific to pregnancy. When severe, pregnancy-specific liver disorders are associated with significant morbidity and mortality for both the mother and the fetus. The main factors that determine maternal prognosis are the type of liver disease; degree of impaired synthetic, metabolic, and excretory liver function; and timing of delivery. This article focuses on a systematic approach to diagnosing and managing pregnancy-specific liver disorders, which includes understanding normal findings in pregnancy, excluding liver diseases nonspecific to pregnancy, factoring in trimester status, and using clinical clues to make a diagnosis and provide treatment in a timely fashion.

Emerging risk factors for nonalcoholic fatty liver disease associated hepatocellular carcinoma.

Worldwide, nonalcoholic fatty liver disease (NAFLD) has reached epidemic proportions and in parallel, hepatocellular carcinoma (HCC) has become one of the fastest growing cancers. Epidemiological studies have not only shed light on the prevalence and incidence of the disease but have also unmasked important environmental risk factors, including the role of diabetes and dyslipidemia in disease pathogenesis. Genetic association studies have identified single nucleotide polymorphisms implicated in NAFLD-HCC, many of which are part of lipid metabolism pathways. Through these clinical studies and subsequently, translational and basic research, the role of statins as a chemoprotective agent has also emerged with ongoing clinical trials assessing their utility in HCC prevention and treatment. In this review, we summarize the recent epidemiological studies describing the burden of NAFLD-HCC in different patient populations and countries. We discuss the genetic and environmental risk factors for NAFLD-HCC and highlight the chemoprotective role of statins and aspirin. We also summarize what is known about NAFLD-HCC in the cirrhosis and non-cirrhosis populations and briefly address the role of surveillance in NAFLD-HCC patients.

HBV/HCV Coinfection in the Era of HCV-DAAs.

Epidemiologic studies suggest that 10% to 15% of patients infected with hepatitis C virus (HCV) are coinfected with hepatitis B virus (HBV) in the United States as a result of the shared modality of transmission, but the true prevalence is not known. The progression of liver disease to cirrhosis and hepatocellular carcinoma is generally faster in patients who are coinfected, and HCV is usually more predominant. Immunosuppression of the host or eradication of hepatitis C can change this paradigm, causing hepatitis B reactivation. This review describes HCV-HBV viral interactions, risks for reactivation, screening, and society guidelines for surveillance and treatment.

Transjugular Liver Biopsy: Safe Even in Patients With Severe Coagulopathies and Multiple Biopsies.

OBJECTIVES: To investigate the safety profile and diagnostic efficacy of transjugular liver biopsy (TJLB), with a focus on patients with severe coagulopathies and with multiple biopsies. METHODS: Clinical, laboratory, and demographic information was collected on 1,321 TJLBs in 932 patients (mean age 43.5 ± 23.2 years) performed between January 2009 and May 2017 to determine the diagnostic success rate and incidence of both major and minor complications in the 3-day and 30-day period post-biopsies. These outcomes were also analyzed for severely coagulopathic patients and a subgroup of patients who underwent multiple biopsies. RESULTS: The overall success rate (diagnostic yield) of the TJLB procedure was 97.7% (1,291/1,321). Overall, the major and minor complication rates were 1.0% (13/1,321) and 9.5% (126/1,321), respectively. In patients with multiple biopsies, the overall complication rate was similar to the entire study cohort, which was 10.4% (57/550). Patients were also stratified according to the platelet counts of 0-50, 51-100, 101-200, 201-300 and >300 × 10 platelets/µL. The overall complication rates were 8.0% (10/124), 11.6% (36/310), 9.9% (54/547), 11.9% (28/235), and 14.3% (11/77), respectively, and these were not statistically significant from each other. Patients were also stratified by international normalized ratio into 0-1, 1.1-2, 2.1-3, and >3. The overall complication rates of these patients were 8.0% (19/237), 11.8% (113/954), 16.3% (7/43), and 0% (0/9), respectively, and were not statistically significant from each other. DISCUSSION: TJLB is a highly efficacious, well-tolerated and safe procedure. It can be safely performed multiple times in the same patient or in critically ill, severely coagulopathic patients with no significant increase in the rate of complication while maintaining an extremely favorable diagnostic yield.

Hyperlipidemia and Nonalcoholic Steatohepatitis Predispose to Hepatocellular Carcinoma Development Without Cirrhosis.

BACKGROUND: Hepatocellular carcinoma (HCC) accounts for 90% of primary hepatic malignancies. With the exception of chronic hepatitis B (CHB), other etiologies of chronic liver disease require progression to cirrhosis before HCC development. Case reports have described HCC in noncirrhotic patients with hepatitis C (HCV) and nonalcoholic fatty liver disease. GOAL: The aim of this study was to determine the prevalence of patients without cirrhosis and CHB who developed HCC among a large cohort of HCC patients and to identify independent variables that are associated with no cirrhosis among patients with HCC. STUDY: From 2005 to 2015, hepatobiliary cancer patients seen in our liver cancer and liver transplant clinics were evaluated. Patients were included if above18 years old and had histologically confirmed HCC from liver biopsy, resection specimen, or explanted livers. Patients with CHB, non-HCC tumors, or missing paired tumor and nontumor liver histology were excluded. Demographic information, pertinent laboratory values, and comorbid conditions were recorded. Potential predictors were evaluated using both backward stepwise logistic regression model and classification tree model. RESULTS: Of the 1927 patients screened, 545 HCC patients (411 transplanted, 43 resected, 74 transarterial chemoembolization/radiofrequency ablation, 17 untreated) included, 29 (5.3%) patients had no cirrhosis histologically. Eleven patients had HCV, 3 had alcoholic liver disease, 3 had nonalcoholic fatty liver, and 12 had cryptogenic liver disease. Logistic regression models show that patients with hyperlipidemia and elevated serum alanine aminotransferase are more likely to develop HCC without cirrhosis (odds ratio, 1.73 and 0.40; P<0.05). CONCLUSIONS: This large cohort, histology-confirmed case-controlled study shows that patients with nonalcoholic fatty liver disease and hyperlipidemia with elevated serum alanine aminotransferase (most likely nonalcoholic steatohepatitis) are significantly associated with the development of HCC in the absence of cirrhosis.

Elimination of Hepatitis C in Liver Transplant Recipients.

Background and Aims: Recurrent hepatitis C (HCV) disease in liver transplant (LT) recipients is associated with significant morbidity and mortality. With the availability of noninterferon-based therapy, eliminating HCV may be achievable in LT recipients. Methods: We studied all consecutive recipients who underwent LT at the University of California Los Angeles between January 2005 and June 2017. We collected data on date of transplant and last follow-up, as well as laboratory values. We also recorded type and timing of antiviral therapy relative to LT. Analyses were performed to assess the proportion of LT recipients who are viremic after transplant. Results: Six hundred thirty-four patients underwent LT with a diagnosis of HCV. There was a statistically significant trend for patients to be cured before (p < 0.001) and after liver transplantation (p < 0.001) for the study period of 2014 to 2016 relative to 2005 and 2013, respectively. Of the 634 recipients eligible for therapy, 8% and 74% were treated within 12 months of transplant for the study periods 2005 to 2013 and 2014 to 2016, respectively. There was a significant decrease between the two study periods in the proportion of patients undergoing re-LT 1 year after the original LT: 5.5% (n = 28/510) and 1.5% (n = 2/124) respectively for study periods 2005 to 2013 and 2014 to 2016 respectively (p = 0.011). Conclusions: The proportion of LT recipients who are viremic has decreased over time. Eliminating HCV in LT recipients is feasible after the introduction of direct-acting agents. Curing HCV should translate to improved clinical outcomes in LT recipients who were transplanted for HCV infection with longer follow-up. Preliminary results suggest the decreased need for transplant in the direct-acting agents era.

Impact of Sustained Viral Response With Direct-Acting Agents on Glycemic Control and Renal Function in Hepatitis C Liver Transplant Recipients.

OBJECTIVES: The impact of achieving a sustained viral response on extrahepatic manifestations after liver transplant is unclear. In this study, our aim was to evaluate whether sustained viral responses in hepatitis C-positive liver transplant recipients can lead to improved nonhepatic outcomes. MATERIALS AND METHODS: We studied 84 consecutive liver transplant recipients who achieved a sustained viral response with direct-acting antiviral agents at the University of California Los Angeles. We collected laboratory data before and after the sustained viral response was achieved. Paired t tests were performed. RESULTS: The mean age and standard deviation of our cohort was 62.4 ± 7.6 years. The mean time from achieving a sustained viral response to last follow-up in our cohort was 19.5 ± 10.8 months. In the entire cohort, there were no changes in mean fasting blood glucose (123 ± 42 vs 120 ± 35 mg/dL; P = .49). We observed a significant improvement in renal function in recipients with stage 1 and 2 chronic kidney disease (82 ± 15 vs 71.16 ± 16 mL/min/1.73 m2; P ⟨ .001) and in those treated within 3 months of liver transplant (75 ± 28 vs 61 ± 16 mL/min/1.73 m2; P = .035). Fasting blood glucose decreased in recipients with a diagnosis of impaired fasting blood glucose (109 ± 16 vs 103 ± 13 mg/dL; P = .001). CONCLUSIONS: The benefits on glucose metabolism and renal function after a sustained viral response in liver transplant recipients appear to be limited to those with early chronic kidney disease and those treated soon after transplant. The potential benefits from direct-acting antiviral agents on these parameters may be overshadowed by the effects of immunosuppressant therapy.

Hepatitis C Virus Prevalence in Egyptian Americans in Southern California.

BACKGROUND: Hepatitis C virus (HCV) is a global medical health concern. Egypt has the highest HCV prevalence. Few studies have assessed the HCV prevalence rates among Egyptian-born expatriates. We sought to define the HCV prevalence Egyptian-born individuals residing in the Southern California area. PATIENTS AND METHODS: We screened Egyptian-born individuals in houses of worship in the Southern California area using a point of care test HCV antibody test. Results were confirmed by testing the blood for viral load. Demographic information including risk factors were also collected. Individuals were contacted with their results, and those found to be detectable HCV antibodies were referred for further testing and additional care. RESULTS: Three hundred twenty-six Egyptian expatriates from 7 houses of worship in Southern California were screened for the HCV infection. Most of the participants were screened at Coptic Churches. Nine of these individuals were found to be HCV infected (2.8%). We found an increased HCV seroprevalence in subjects were male and born in Egyptian urban areas. Five of the 9 subjects (56%) who tested positive were not baby boomers and only 2 of these 9 subjects (22%) had recognized Center for Disease Control risk factors. CONCLUSIONS: The HCV prevalence rate of Egyptian-born individuals living in the Southern California area was lower compared with the prevalence rate in the general Egyptian population, but higher than that seen in the general US population. The utility of using Center for Disease Control risk factors to define individuals at risk of HCV among Egyptian expatriates is not applicable.

Clinical Food Addiction Is Not Associated with Development of Metabolic Complications in Liver Transplant Recipients.

Background and Aims: Given the increased risk of post-transplant metabolic syndrome (PTMS; defined by hypertension, diabetes mellitus and hyperlipidemia), we aimed to identify the potential role of food addiction in the development of metabolic complications in the post-liver transplant population. Methods: Inclusion criteria included adult liver transplant recipients followed at our institution between June 2016 and November 2016. Participants were administered a demographic survey as well as the Yale Food Assessment Scale 2.0, a 35-item questionnaire used to assess frequency of food addiction in accordance with the DSM-V guidelines of substance use disorders. Demographic and clinical data were collected. Results: Our study included 236 liver transplant recipients (139 males, 97 females). The median (interquartile range [IQR]) BMI of participants was 26.8 kg/m2 (24.2, 30.4), and median (IQR) time since transplantation was 50.9 months (19.6, 119.8). The prevalence rates of hypertension, hypercholesterolemia and diabetes mellitus were 54.7%, 25.0% and 27.1%, respectively. Twelve participants (5.1%) were found to have a diagnosis of food addiction. A diagnosis of food misuse was made in 94 (39.8%) of the transplant recipients. Conclusions: Our findings are consistent with prior data that indicate high prevalence of metabolic complications among liver transplant recipients. Food addiction was not predictive of metabolic complications within this population. Nevertheless, we found that this population was at high risk of demonstrating symptoms of food misuse, and they were not likely to appreciate the risks of pathologic patterns of eating. Given the increasing risk of cardiovascular morbidity and mortality in this population, efforts should be made to identify risk factors for the development of PTMS.

Decrease of Alpha-fetoprotein in Patients with Cirrhosis Treated with Direct-acting Antivirals.

Background and Aims: The lack of specificity has limited the role of serum alpha-fetoprotein (AFP) for hepatocellular carcinoma (HCC) screening among patients with cirrhosis related to hepatitis C virus (HCV) infection. We sought to examine whether AFP may decrease after achieving a sustained virological response (SVR) in patients with HCV-related cirrhosis. Methods: We performed a retrospective study of patients with HCV-related cirrhosis who were cured with direct-acting antiviral (DAA) therapy at the University of California, Los Angeles. Laboratory values, including serum AFP, were measured before and after completing the DAA treatment. Results: Fifty-six patients met the inclusion criteria, with median (interquartile range [IQR]) age of 67 (58-69) years and with 51.8% being male. All patients received DAA therapy without interferon. AFP decreased from median (IQR) 7.2 (4.2-13.4) ng/mL before DAAs to 4.2 (2.7-6.3) ng/mL at the end of treatment and 4.2 (2.9-6.8) ng/mL at 12 weeks after treatment (p < 0.001). Model for end-stage liver disease (MELD), fibrosis-4 (FIB4), and aspartate transaminase (AST) to platelet ratio index (APRI) scores at baseline were not significantly associated with AFP reduction. On multivariate analysis, platelet count, AST and total bilirubin at baseline were significantly correlated to AFP reduction (p = 0.04, 0.009 and 0.04, respectively). The higher the baseline AFP, the greater the reduction in AFP. There was no statistically significant correlation between baseline AFP and MELD, FIB4 or APRI scores. Conclusion: There was a significant decrease in AFP in patients with cirrhosis who achieved a SVR with DAAs. Given a reduction in AFP after DAA treatment, AFP should be further studied as a screening modality for HCC in patients with cirrhosis.

Nationwide trends and predictors of inpatient mortality in 83884 transjugular intrahepatic portosystemic shunt.

AIM: To evaluate and validate the national trends and predictors of in-patient mortality of transjugular intrahepatic portosystemic shunt (TIPS) in 15 years. METHODS: Using the National Inpatient Sample which is a part of Health Cost and Utilization Project, we identified a discharge-weighted national estimate of 83884 TIPS procedures performed in the United States from 1998 to 2012 using international classification of diseases-9 procedural code 39.1. The demographic, hospital and co-morbility data were analyzed using a multivariant analysis. Using multi-nominal logistic regression analysis, we determined predictive factors related to increases in-hospital mortality. Comorbidity measures are in accordance to the Comorbidity Software designed by the Agency for Healthcare Research and Quality. RESULTS: Overall, 12.3% of patients died during hospitalization with downward trend in-hospital mortality with the mean length of stay of 10.8 ± 13.1 d. Notable, African American patients (OR = 1.809 vs Caucasian patients, P < 0.001), transferred patients (OR = 1.347 vs non-transferred, P < 0.001), emergency admissions (OR = 3.032 vs elective cases, P < 0.001), patients in the Northeast region (OR = 1.449 vs West, P < 0.001) had significantly higher odds of in-hospital mortality. Number of diagnoses and number of procedures showed positive correlations with in-hospital death (OR = 1.249 per one increase in number of procedures). Patients diagnosed with acute respiratory failure (OR = 8.246), acute kidney failure (OR = 4.359), hepatic encephalopathy (OR = 2.217) and esophageal variceal bleeding (OR = 2.187) were at considerably higher odds of in-hospital death compared with ascites (OR = 0.136, P < 0.001). Comorbidity measures with the highest odds of in-hospital death were fluid and electrolyte disorders (OR = 2.823), coagulopathy (OR = 2.016), and lymphoma (OR = 1.842). CONCLUSION: The overall mortality of the TIPS procedure is steadily decreasing, though the length of stay has remained relatively constant. Specific patient ethnicity, location, transfer status, primary diagnosis and comorbidities correlate with increased odds of TIPS in-hospital death.

Limited Knowledge of Acetaminophen in Patients with Liver Disease.

Background and Aims: Unintentional acetaminophen overdose remains the leading cause of acute liver failure in the United States. Patients with underlying liver disease are at higher risk of poor outcomes from acetaminophen overdose. Limited knowledge of acetaminophen may be a preventable contributor to elevated rates of overdose and thus acute liver failure. The purpose of this study is to assess knowledge of acetaminophen dosing and presence of acetaminophen in common combination products in patients with liver disease. Methods: We performed a cross-sectional study of patients with liver disease at the Pfleger Liver Institute at the University of California, Los Angeles between June 2015 and August 2016. Patients completed a demographic questionnaire and an acetaminophen knowledge survey. Additional information was obtained from the medical record. Results: Of 401 patients with liver disease, 30 (15.7%) were able to correctly identify that people without liver disease can safely take up to 4 g/day of acetaminophen. The majority of patients (79.9%-86.8%) did not know that Norco® (hydrocone/acetaminophen), Vicodin® (hydrocone/acetaminophen) and Percocet® (oxycodone/acetaminophen) contained acetaminophen. Only 45.3% of the patients knew that Tylenol® #3 contained acetaminophen. Conclusions: We conclude that patients with liver disease have critically low levels of knowledge of acetaminophen, putting them at risk both of acetaminophen overdose, as well as undermedication, and inadequate management of chronic pain. We recommend an increase in education efforts regarding acetaminophen dosage and its safety in the setting of liver disease. Increasing education for those at risk of low acetaminophen knowledge is essential to minimizing acetaminophen overdose rates and optimizing pain management.

Timing of Antiviral Therapy in Candidates for Liver Transplant for Hepatitis C and Hepatocellular Carcinoma.

OBJECTIVES: Hepatitis C virus infection is the most common underlying reason for hepatocellular carcinoma and indication for liver transplant. The increased availability of non-interferon-based therapy has expanded the number of treatment-eligible patients. MATERIALS AND METHODS: We used a decision analysis model to compare 2 strategies of treating hepatitis C virus. Included patients were followed for 1 year after liver transplant. The probabilities and costs were obtained from a literature review, an expert panel, and our institution's experience. Sensitivity analyses were performed on all variables. RESULTS: Our model demonstrated that it would be less costly to treat patients after liver transplant than to treat patients while they wait for transplant. When we compared baseline values, the cost difference between the 2 strategies was $25,011 per patient and $41,535 per sustained viral response. Overall survival was 60.1% for both strategies. Our model was robust across most of the variables tested in the sensitivity analysis. CONCLUSIONS: Our results indicated that there is no substantial pharmacoeconomic or survival advantage of treating hepatitis C virus in patients with compensated cirrhosis and hepatocellular carcinoma before liver transplant versus after transplant.