ABSTRACT
Herbal and dietary supplements (HDS) are being used worldwide at an increasing rate. Mirroring this trend, HDS-induced liver injury, also known as HDS-induced liver injury (HILI), has increased significantly over the past three decades in the Drug-Induced Liver Injury Network (DILIN), now accounting for 20% of cases of drug-induced liver injury (DILI). There are significant challenges in the identification and prevention of HILI due to varying presentations, ability to make clear diagnosis, identification of the responsible ingredient, lack of treatment, and lack of regulatory oversight of HDS products to confirm their ingredients and ensure safety. The major implicated agents include anabolic steroids, green tea extract, garcinia cambogia, kratom, ashwagandha, turmeric and multi-ingredient nutritional supplements. Fortunately, with the formation of major DILI consortiums across the world, the last decade has seen advances in the identification of at-risk genetic phenotypes, the use of chemical analysis on multi-ingredient nutritional supplements, and the publication of data/injury patterns of potentially risky HDS.
ABSTRACT
BACKGROUND: Azithromycin (AZ) is a widely used antibiotic. The aim of this study was to characterise the clinical features, outcomes, and HLA association in patients with drug-induced liver injury (DILI) due to AZ. METHODS: The clinical characteristics of individuals with definite, highly likely, or probable AZ-DILI enrolled in the US Drug-Induced Liver Injury Network (DILIN) were reviewed. HLA typing was performed using an Illumina MiSeq platform. The allele frequency (AF) of AZ-DILI cases was compared to population controls, other DILI cases, and other antibiotic-associated DILI cases. RESULTS: Thirty cases (4 definite, 14 highly likely, 12 probable) of AZ-DILI were enrolled between 2004 and 2022 with a median age of 46 years, 83% white, and 60% female. Median duration of AZ treatment was 5 days. Latency was 18.5 days. 73% were jaundiced at presentation. The injury pattern was hepatocellular in 60%, cholestatic in 27%, and mixed in 3%. Ten cases (33%) were severe or fatal; 90% of these were hepatocellular. Two patients required liver transplantation. One patient with chronic liver disease died of hepatic failure. Chronic liver injury developed in 17%, of which 80% had hepatocellular injury at onset. HLA-DQA1*03:01 was significantly more common in AZ-DILI versus population controls and amoxicillin-clavulanate DILI cases (AF: 0.29 vs. 0.11, p = 0.001 and 0.002, respectively). CONCLUSION: Azithromycin therapy can lead to rapid onset of severe hepatic morbidity and mortality in adult and paediatric populations. Hepatocellular injury and younger age were associated with worse outcomes. HLA-DQA1*03:01 was significantly more common in AZ cases compared to controls.
ABSTRACT
Hepatocellular carcinoma (HCC) is often diagnosed at a late stage and frequently recurs despite curative intervention, leading to poor survival outcomes. Frontline systemic therapies include combination immunotherapy regimens and tyrosine kinase inhibitors. We report a case of a 38-year-old woman with chronic hepatitis B and C coinfection-associated non-cirrhotic HCC, which recurred in the peritoneum after initial resection of her primary tumor. Disease progression occurred on both atezolizumab/bevacizumab and lenvatinib, and she was subsequently treated with gemcitabine and oxaliplatin (GEMOX) chemotherapy and exhibited a profound clinical response on imaging with normalization of alpha fetoprotein (AFP) after several months. Following extensive multidisciplinary discussion, she underwent cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) that removed all visible macroscopic tumor. Her pathology demonstrated a complete pathologic response. She received two additional months of postoperative chemotherapy, and then proceeded with close monitoring off therapy. To our knowledge, this is the first reported case of a complete pathologic response to GEMOX chemotherapy in the context of CRS/HIPEC for peritoneal metastases in HCC, after progression on standard immunotherapy and tyrosine kinase inhibitor treatments. In this report, we review the current systemic treatment landscape in HCC. We highlight potential consideration of cytotoxic chemotherapy, which is less frequently utilized in current practice, in selected patients with HCC, and discuss the role of CRS/HIPEC in the management of peritoneal metastases. Further investigation regarding predictors of response to systemic treatments is strongly needed. Multidisciplinary management may ultimately prolong survival in patients with advanced HCC.
ABSTRACT
OBJECTIVE: To describe hepatotoxicity due to amiodarone and dronedarone from the DILIN and the US FDA's surveillance database. METHODS: Hepatotoxicity due to amiodarone and dronedarone enrolled in the U.S. Drug Induced Liver Injury Network (DILIN) from 2004 to 2020 are described. Dronedarone hepatotoxicity cases associated with liver biopsy results were obtained from the FDA Adverse Event Reporting System (FAERS) from 2009 to 2020. RESULTS: Among DILIN's 10 amiodarone and 3 dronedarone DILIN cases, the latency for amiodarone was longer than with dronedarone (388 vs 119 days, p = 0.50) and the median ALT at DILI onset was significantly lower with amiodarone (118 vs 1191 U/L, p = 0.05). Liver biopsies in five amiodarone cases showed fibrosis, steatosis, and numerous Mallory-Denk bodies. Five patients died although only one from liver failure. One patient with dronedarone induced liver injury died of a non-liver related cause. Nine additional cases of DILI due to dronedarone requiring hospitalization were identified in the FAERS database. Three patients developed liver injury within a month of starting the medication. Two developed acute liver failure and underwent urgent liver transplant, one was evaluated for liver transplant but then recovered spontaneously, while one patient with cirrhosis died of liver related causes. CONCLUSION: Amiodarone hepatotoxicity resembles that seen in alcohol related liver injury, with fatty infiltration and inflammation. Dronedarone is less predictable, typically without fat and with a shorter latency of use before presentation. These differences may be explained, in part, by the differing pharmacokinetics of the two drugs leading to different mechanisms of hepatotoxicity.
Subject(s)
Amiodarone , Chemical and Drug Induced Liver Injury , Humans , Dronedarone , Amiodarone/adverse effects , Amiodarone/pharmacokinetics , Anti-Arrhythmia Agents/adverse effects , Anti-Arrhythmia Agents/pharmacokinetics , DyphyllineABSTRACT
Chronic hepatitis B virus (HBV) infection is the largest global cause of hepatocellular carcinoma (HCC). Current HBV treatment options include pegylated interferon-alpha and nucleos(t)ide analogues (NAs), which have been shown to be effective in reducing HBV DNA levels to become undetectable. However, the literature has shown that some patients have persistent risk of developing HCC. The mechanism in which this occurs has not been fully elucidated. However, it has been discovered that HBV's covalently closed circular DNA (cccDNA) integrates into the critical HCC driver genes in hepatocytes upon initial infection; additionally, these are not targets of current NA therapies. Some studies suggest that HBV undergoes compartmentalization in peripheral blood mononuclear cells that serve as a sanctuary for replication during antiviral therapy. The aim of this review is to expand on how patients with HBV may develop HCC despite years of HBV viral suppression and carry worse prognosis than treatment-naive HBV patients who develop HCC. Furthermore, HCC recurrence after initial surgical or locoregional treatment in this setting may cause carcinogenic cells to behave more aggressively during treatment. Curative novel therapies which target the life cycle of HBV, modulate host immune response, and inhibit HBV RNA translation are being investigated.
ABSTRACT
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.
Subject(s)
Cholangitis , Liver Cirrhosis, Biliary , Humans , Cholagogues and Choleretics/therapeutic use , Cholangitis/drug therapy , Liver Cirrhosis, Biliary/drug therapy , Ursodeoxycholic Acid/therapeutic useABSTRACT
INTRODUCTION AND OBJECTIVES: Compared to premenopausal women, postmenopausal women are at greater risk of developing NAFLD and NASH, two common indications for liver transplantation (LT). We aim to determine the prevalence of NASH-related cirrhosis in postmenopausal women from a cohort of LT patients and investigate their post-LT complications. MATERIALS AND METHODS: Chart review of 1200 LT patients from 2002-2020 was performed. Postmenopausal women were defined as women over 51 and compared to a control group of men over 51. Prevalence of LT indications was determined. Subgroup analysis assessed cardiovascular disease risk. BMI and ASCVD risk scores were calculated at the time of LT and after 1 year. RESULTS: 510 patients met the inclusion criteria: 189 (37.1%) women and 321 (62.9%) men. The most common indication was NASH for women (26.5%, p<0.001) and alcohol-related cirrhosis for men (23.1%). 53 men and 46 women underwent subgroup analysis. There was no significant difference in BMI or ASCVD 10-year risk post-LT between sexes. MI occurred more in men (n=9.17%) than women (n=1, 2%, p=0.015), with no significant differences in CAD, CHF, or stroke. LT complications occurred less in men (n=5.9%) than women (n=20, 43%, p=0.0001). CONCLUSIONS: Postmenopausal women were significantly more likely to have NASH as an indication for LT than men. Postmenopausal women had greater weight gain and more noncardiac complications than men. Women did not have increased cardiovascular outcomes, ASCVD risk, or mortality. Diet education and weight control in postmenopausal women with existing risk factors for NASH should be encouraged to modulate health outcomes.
Subject(s)
Liver Transplantation , Non-alcoholic Fatty Liver Disease , Male , Humans , Female , Liver Transplantation/adverse effects , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/complications , Prevalence , Postmenopause , Retrospective Studies , Liver Cirrhosis/diagnosis , Liver Cirrhosis/epidemiology , Liver Cirrhosis/etiology , Risk Factors , Liver Cirrhosis, Alcoholic/complicationsABSTRACT
RATIONALE AND OBJECTIVES: Marked liver steatosis, steatohepatitis, and significant fibrosis are risk factors for unfavorable outcomes in non-alcoholic fatty liver disease (NAFLD). In this study, the diagnostic performance of attenuation coefficient (AC), liver stiffness (LS), and dispersion slope (DS) was evaluated separately and combined in the diagnosis of liver steatosis and fibrosis in NAFLD suspects using biopsy or magnetic resonance imaging (MRI) as a reference standard. MATERIALS AND METHODS: Seventy-four NAFLD suspects were prospectively imaged with an Aplio i800 ultrasound scanner (Canon Medical Systems, Tustin, CA). AC, LS, and DS measurements were obtained from the right liver lobe. RESULTS: Thirty-four patients underwent liver biopsy, and 40 had MRI. There were 32 patients (43%) with liver steatosis and fibrosis (S + F), 22 (30%) with steatosis (S), 5 (7%) with fibrosis (F), and 15 (20%) with normal liver (N). Mean ACs were significantly higher in steatotic livers (n = 54) than in non-steatotic livers (n = 20) (P < 0.0001). LS and DS were significantly higher in patients with liver fibrosis (n = 37) compared to non-fibrotic livers (n = 37) (P = 0.0004 and P = 0.0002, respectively). In detecting (S + F), the area under the receiver operating characteristic curve (AUROCC) was 0.87 for combined ultrasound parameters of LS and AC (negative predictive value [NPV]: 75%, positive predictive value [PPV]: 77%, P < 0.0001). In detecting patients with liver steatosis and fibrosis stage ≥2, LS had an AUROCC of 0.93 (NPV: 87%, PPV: 82%, P < 0.0001). In the biopsy group, 32% (11/34) were diagnosed with non-alcoholic steatohepatitis (NASH). DS values showed a significant difference among patients with (n = 23) or without (n = 11) hepatocellular ballooning (P = 0.02). AUROCC was 0.87 for combined ultrasound parameters of AC, LS, and DS with body mass index (BMI) in detecting NASH (NPV: 80%, PPV: 87%, P = 0.0006). CONCLUSION: AC and LS showed high diagnostic value in detecting liver steatosis and fibrosis, respectively. The combined AC and LS values further improved the diagnostic accuracy in detecting NAFLD and high-risk NAFLD patients.
Subject(s)
Elasticity Imaging Techniques , Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/complications , Elasticity Imaging Techniques/methods , Prospective Studies , Liver/diagnostic imaging , Liver/pathology , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/pathology , Fibrosis , BiopsyABSTRACT
BACKGROUND & AIMS: Pegbelfermin is a polyethylene glycol-conjugated analog of human fibroblast growth factor 21, a nonmitogenic hormone that regulates energy metabolism. This phase 2b study evaluated 48-week pegbelfermin treatment in patients with nonalcoholic steatohepatitis (NASH) with compensated cirrhosis. METHODS: FALCON 2 (NCT03486912) was a randomized (1:1:1:1), double-blind, placebo-controlled study. Eligible adults had biopsy-confirmed NASH and stage 4 fibrosis. Pegbelfermin (10, 20, or 40 mg) or placebo was injected subcutaneously once weekly. The primary endpoint was 1 or more stages of improvement in the NASH Clinical Research Network fibrosis score without NASH worsening at week 48; pegbelfermin dose response was assessed using a Cochran-Armitage trend test across proportions (1-sided α = .05). Additional endpoints included histologic and noninvasive measures of steatosis, fibrosis, and liver injury/inflammation. RESULTS: Overall, 155 patients were randomized, and 154 patients received treatment. At week 48, 24% to 28% of the pegbelfermin arms had primary endpoint responses vs 31% of the placebo arm (P = .361). Nonalcoholic fatty liver disease activity score improvements were more frequent with pegbelfermin vs placebo and were driven primarily by reduced lobular inflammation. Numerically higher proportions of the pegbelfermin arms had liver stiffness (magnetic resonance elastography) and steatosis (magnetic resonance imaging-proton density fat fraction) improvements vs placebo; these differences were not statistically significant. Mean N-terminal type III collagen propeptide, alanine aminotransferase, and aspartate aminotransferase values were numerically lower in the 20- and/or 40-mg pegbelfermin arms compared with placebo. Serious adverse events were more frequent with pegbelfermin vs placebo, although none were treatment related. One patient (40-mg pegbelfermin) discontinued treatment because of a treatment-emergent adverse event (worsening ascites). CONCLUSIONS: FALCON 2 did not meet its primary endpoint of 1 or more stages of improvement in the NASH Clinical Research Network fibrosis without NASH worsening assessed via biopsy. Pegbelfermin generally was well tolerated in this advanced NASH population.
Subject(s)
Non-alcoholic Fatty Liver Disease , Adult , Humans , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/pathology , Liver/pathology , Liver Cirrhosis/complications , Liver Cirrhosis/drug therapy , Polyethylene Glycols/adverse effects , Double-Blind Method , Inflammation/pathology , Treatment OutcomeABSTRACT
Mahvash disease is an exceedingly rare genetic disorder of glucagon signaling characterized by hyperglucagonemia, hyperaminoacidemia, and pancreatic α-cell hyperplasia. Although there is no known definitive treatment, octreotide has been used to decrease systemic glucagon levels. We describe a woman who presented to our medical center after three episodes of small-volume hematemesis. She was found to have hyperglucagonemia and pancreatic hypertrophy with genetically confirmed Mahvash disease and also had evidence of portal hypertension (recurrent portosystemic encephalopathy and variceal hemorrhage) in the absence of cirrhosis. These findings established a diagnosis of portosinusoidal vascular disease, a presinusoidal type of portal hypertension previously known as noncirrhotic portal hypertension. Liver transplantation was followed by normalization of serum glucagon and ammonia levels, reversal of pancreatic hypertrophy, and resolution of recurrent encephalopathy and bleeding varices.
Subject(s)
Genetic Diseases, Inborn , Glucagon , Hypertension, Portal , Liver Transplantation , Female , Humans , Esophageal and Gastric Varices/etiology , Esophageal and Gastric Varices/surgery , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/surgery , Glucagon/blood , Glucagon/genetics , Hypertension, Portal/blood , Hypertension, Portal/etiology , Hypertension, Portal/genetics , Hypertension, Portal/surgery , Hypertrophy/genetics , Liver Cirrhosis , Genetic Diseases, Inborn/blood , Genetic Diseases, Inborn/diagnosis , Genetic Diseases, Inborn/genetics , Genetic Diseases, Inborn/surgery , Pancreatic Diseases/genetics , Pancreatic Diseases/pathology , Pancreatic Diseases/surgery , Glucagon-Secreting Cells/pathologyABSTRACT
Patients with both achalasia and decompensated cirrhosis can often present a therapeutic challenge because portal hypertension has generally been considered a contraindication to definitive therapies for achalasia. This case report depicts a patient who presented with progressive dysphagia, weight loss, and large-volume ascites; was diagnosed with type II achalasia and decompensated cirrhosis without esophageal varices; and underwent peroral endoscopic myotomy after preprocedural transjugular intrahepatic portosystemic shunt placement. Our case highlights the importance of multidisciplinary care and need for definitive therapies for these complex patients at high risk of malnutrition and sarcopenia.
ABSTRACT
Sex and racial disparities in deceased donor liver transplantation (DDLT) have been described, but this has not been well studied in living donor liver transplantation (LDLT). We aim to examine these disparities in the US LDLT population and identify potential predictors of these differences. From 2002 to 2021, the Organ Procurement and Transplant Network database was queried to characterize the adult LDLT population and evaluate differences between LDLT and DDLT recipients with regard to sex and race. Donor demographics, Model for End-stage Liver Disease (MELD), and socioeconomic data were all included. Of the 4961 LDLT and 99,984 DDLT recipients, males received the majority of LDLT (55% vs. 45%, p < 0.001) and DDLT (67% vs. 33%, p < 0.001) compared to females. There was a significant difference in race between male and female LDLT recipients ( p < 0.001); 84% of male recipients were White and 78% of females. In both groups, females had lower levels of education and were less likely to have private insurance. There were more female living donors (N = 2545, 51%); 50% of female donors donated to males but only 40% of males donated to females. Donor-recipient relationships varied significantly by sex ( p < 0.001); males received more donations from spouses (62% vs. 39%) and siblings (60% vs. 40%). In the LDLT population, significant disparities exist with respect to sex and race that disadvantage women, but these disparities are less pronounced than in the DDLT population. Although further studies are needed, complex clinical and socioeconomic differences as well as donor factors may explain these variations.
Subject(s)
End Stage Liver Disease , Liver Transplantation , Adult , Humans , Male , Female , United States/epidemiology , Living Donors , Liver Transplantation/adverse effects , Liver Transplantation/methods , End Stage Liver Disease/surgery , Retrospective Studies , Severity of Illness Index , Treatment OutcomeABSTRACT
Hepatitis B virus (HBV)-host junction sequences (HBV-JSs) has been detected in the urine of patients with HBV infection. This study evaluated HBV-JSs as a marker of minimum residual disease (MRD) and tumor recurrence after treatment in HBV-hepatocellular carcinoma (HCC) patients. Archived serial urine DNA from two HBV-HCC with recurrence as confirmed by MRI and four HBV-related cirrhosis (LC) patients were used. Urinary HBV-JSs were identified by an HBV-targeted NGS assay. Quantitative junction-specific PCR assays were developed to investigate dynamic changes of the most abundant urinary HBV-JS. Abundant urinary HBV-JSs were identified in two cases of tumor recurrence. In case 1, a 78-year-old female with HBV- HCC underwent a follow-up MRI following microwave ablation. While MRI results were variable, the unique HBV-JS DNA, HBV-Chr17, steadily increased from initial diagnosis to HCC recurrence. In case 2, a 74-year-old male with HBV-HCC contained two HBV-JS DNA, HBV-Chr11 and HBV-TERT, that steadily increased after initial HCC diagnosis till recurrence. One LC examined had HBV-TERT DNA detected, but transiently in 3.5 years during HCC surveillance. HBV-JS DNA was persistently elevated prior to the diagnosis of recurrent HCC, suggesting the potential of urinary HBV-JS DNA to detect MRD and HCC recurrence after treatment.
ABSTRACT
Hepatitis B virus infections are prevalent worldwide, but the outcomes of infection vary greatly from host to host. In many endemic regions, vertical transmission from mother to child is most common. In this transmission setting, virus genotype and shared patient genetics make for an interesting comparison of outcome of chronic hepatitis B infection. This case series demonstrates four family clusters which display disparate outcomes among family members with hepatitis B virus infections, further stressing the role of host and non-genetic factors in the natural history of the disease. Many host factors have been theorized, from epigenetic mechanisms to the role of chronic stress, but more research is needed to better understand those at higher risk of feared complications such as hepatocellular carcinoma and cirrhosis.
ABSTRACT
Objective.While ultrasound image texture has been utilized to detect and quantify hepatic steatosis, the texture features extracted using a single (conventionally 1540 m s-1) beamforming speed of sound (SoS) failed to achieve reliable diagnostic performance. This study aimed to investigate if the texture features extracted using various beamforming SoSs can improve the accuracy of hepatic steatosis detection and quantification.Approach.Patients with suspected non-alcoholic fatty liver disease underwent liver biopsy or MRI proton density fat fraction (PDFF) as part of standard of care, were prospectively enrolled. The radio-frequency data from subjects' right and left liver lobes were collected using 6 beamforming SoSs: 1300, 1350, 1400, 1450, 1500 and 1540 m s-1and analyzed offline. The texture features, i.e. Contrast, Correlation, Energy and Homogeneity from gray-level co-occurrence matrix of normalized envelope were obtained from a region of interest in the liver parenchyma.Main results.Forty-three subjects (67.2%) were diagnosed with steatosis while 21 had no steatosis. Homogeneity showed the area under the curve (AUC) of 0.75-0.82 and 0.58-0.81 for left and right lobes, respectively with varying beamforming SoSs. The combined Homogeneity value over 1300-1540 m s-1from left and right lobes showed the AUC of 0.90 and 0.81, respectively. Furthermore, the combined Homogeneity values from left and right lobes over 1300-1540 m s-1improved the AUC to 0.94. The correlation between texture features and steatosis severity was improved by using the images from various beamforming SoSs. The combined Contrast values over 1300-1540 m s-1from left and right lobes demonstrated the highest correlation (r= 0.90) with the MRI PDFF while the combined Homogeneity values over 1300-1540 m s-1from left and right lobes showed the highest correlation with the biopsy grades (r= -0.81).Significance.The diagnostic accuracy of ultrasound texture features in detecting and quantifying hepatic steatosis was improved by combining its values extracted using various beamforming SoSs.
Subject(s)
Non-alcoholic Fatty Liver Disease , Humans , Liver/diagnostic imaging , Liver/pathology , Magnetic Resonance Imaging/methods , Ultrasonography/methods , Biopsy , ProtonsABSTRACT
RATIONALE AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is currently diagnosed by liver biopsy or MRI proton density fat fraction (MRI-PDFF) from left hepatic lobe (LTHL) and/or right hepatic lobe (RTHL). The objective of this study was to compare the diagnostic value of ultrasound attenuation coefficients (ACs) from RTHL and LTHL in detecting hepatic steatosis using biopsy or MRI-PDFF as a reference standard. MATERIALS AND METHODS: Sixty-six patients with suspected NAFLD were imaged with an Aplio i800 ultrasound scanner (Canon Medical Systems, Tustin, CA). Five AC measurements from RTHL and LTHL were averaged separately and together to be compared with the reference standard. RESULTS: Forty-seven patients (71%) were diagnosed with NAFLD. Mean ACs were significantly higher in fatty livers than non-fatty livers (RTHL: 0.73 ± 0.10 vs. 0.63 ± 0.07 dB/cm/MHZ; p < 0.0001, LTHL: 0.78 ± 0.11 vs. 0.63 ± 0.06 dB/cm/MHz; p < 0.0001, RTHL & LTHL: 0.76 ± 0.09 vs. 0.63 ± 0.05 dB/cm/MHz; p < 0.0001). Biopsy steatosis grades (n =31) were better correlated with the mean ACs of RTHL & LTHL (r = 0.72) compared to LTHL (r = 0.67) or RTHL (r = 0.61). Correlation between MRI-PDFF (n = 35) and mean ACs was better for LTHL (r = 0.69) compared to the RTHL & LTHL (r = 0.66) or RTHL (r = 0.45). Higher diagnostic accuracy was shown for the mean ACs of RTHL & LTHL (AUC 0.89, specificity 94%, sensitivity 78%) compared to LTHL (AUC 0.89, specificity 88%, sensitivity 82%) or RTHL (AUC 0.81, specificity 89%, sensitivity 68%). CONCLUSION: Ultrasound ACs from RTHL and LTHL showed comparable diagnostic values in detection of hepatic steatosis with the highest diagnostic accuracy when they were averaged together.
Subject(s)
Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Liver/diagnostic imaging , Liver/pathology , Magnetic Resonance Imaging/methods , Ultrasonography/methods , Adipose Tissue/diagnostic imaging , ProtonsABSTRACT
BACKGROUND: Turmeric is a commonly used herbal product that has been implicated in causing liver injury. The aim of this case series is to describe the clinical, histologic, and human leukocyte antigen (HLA) associations of turmeric-associated liver injury cases enrolled the in US Drug-Induced Liver Injury Network (DILIN). METHODS: All adjudicated cases enrolled in DILIN between 2004 and 2022 in which turmeric was an implicated product were reviewed. Causality was assessed using a 5-point expert opinion score. Available products were analyzed for the presence of turmeric using ultra-high-performance liquid chromatography. Genetic analyses included HLA sequencing. RESULTS: Ten cases of turmeric-associated liver injury were found, all enrolled since 2011, and 6 since 2017. Of the 10 cases, 8 were women, 9 were White, and median age was 56 years (range 35-71). Liver injury was hepatocellular in 9 patients and mixed in 1. Liver biopsies in 4 patients showed acute hepatitis or mixed cholestatic-hepatic injury with eosinophils. Five patients were hospitalized, and 1 patient died of acute liver failure. Chemical analysis confirmed the presence of turmeric in all 7 products tested; 3 also contained piperine (black pepper). HLA typing demonstrated that 7 patients carried HLA-B*35:01, 2 of whom were homozygous, yielding an allele frequency of 0.450 compared with population controls of 0.056-0.069. CONCLUSION: Liver injury due to turmeric appears to be increasing in the United States, perhaps reflecting usage patterns or increased combination with black pepper. Turmeric causes potentially severe liver injury that is typically hepatocellular, with a latency of 1 to 4 months and strong linkage to HLA-B*35:01.
Subject(s)
Chemical and Drug Induced Liver Injury , Hepatitis , Humans , Female , United States , Adult , Middle Aged , Aged , Male , Curcuma/adverse effects , Dyphylline , Chemical and Drug Induced Liver Injury/etiologyABSTRACT
Nonalcoholic Fatty Liver Disease (NAFLD) is a growing global phenomenon, and its damaging effects in terms of cardiovascular disease (CVD) risk are becoming more apparent. NAFLD is estimated to affect around one quarter of the world population and is often comorbid with other metabolic disorders including diabetes mellitus, hypertension, coronary artery disease, and metabolic syndrome. In this review, we examine the current evidence describing the many ways that NAFLD itself increases CVD risk. We also discuss the emerging and complex biochemical relationship between NAFLD and its common comorbid conditions, and how they coalesce to increase CVD risk. With NAFLD's rising prevalence and deleterious effects on the cardiovascular system, a complete understanding of the disease must be undertaken, as well as effective strategies to prevent and treat its common comorbid conditions.
ABSTRACT
BACKGROUND: The purpose of this systematic literature review (SLR) was to evaluate the accuracy of noninvasive diagnostic tools in detecting significant or advanced (F2/F3) fibrosis among patients with nonalcoholic fatty liver (NAFL) in the US healthcare context. METHODS: The SLR was conducted in PubMed and Web of Science, with an additional hand search of public domains and citations, in line with the PRISMA statement. The study included US-based original research on diagnostic test sensitivity, specificity and accuracy. RESULTS: Twenty studies were included in qualitative evidence synthesis. Imaging techniques with the highest diagnostic accuracy in F2/F3 detection and differentiation were magnetic resonance elastography and vibration-controlled transient elastography. The most promising standard blood biomarkers were NAFLD fibrosis score and FIB-4. The novel diagnostic tools showed good overall accuracy, particularly a score composed of body mass index, GGT, 25-OH-vitamin D, and platelet count. The novel approaches in liver fibrosis detection successfully combine imaging techniques and blood biomarkers. CONCLUSIONS: While noninvasive techniques could overcome some limitations of liver biopsy, a tool that would provide a sufficiently sensitive and reliable estimate of changes in fibrosis development and regression is still missing.