Faculty Bibliography
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63
Frequency and Pathological Characteristics of Drug-Induced Liver Injury in a Tertiary Medical Center
Drug-induced liver injury (DILI) accounts for approximately 10% of acute hepatitis cases. DILI can arise as idiosyncratic or intrinsic injury from hundreds of drugs, herbals, and nutritional supplements and is essential to recognize as one of the differential diagnoses of hepatitis in a liver biopsy. The purpose of this study is to investigate the frequency and pathological characteristics of DILI related to the variety of hepatotoxic agents. We searched our pathology database for all patients with hepatitis diagnosed on liver biopsy from January 2012 to May 2016, and selected patients with a diagnosis of DILI. Electronic medical records were reviewed for patient medication list, history of herbal medicine or supplement use, and pre-biopsy liver function test (LFT) results. Clinical and pathologic correlation was used to determine the causative or related agents for DILI. We then assessed histopathologic features of liver injury and categorized biopsy findings as primarily bile duct injury, lobular/portal hepatitis, or mixed changes. 604 total liver biopsies for hepatitis or liver injury were identified, of which 70 cases (11.6%) carried the diagnosis of DILI confirmed by clinical correlation. The most common etiologies associated with DILI were supplements and herbal products (31.4%), antimicrobials (14.3%), chemotherapeutics (11.4%), antilipidemics (7.1%) and immunomodulatory agents (7.1%). LFT results positively correlated with histological findings. Nutritional/herbal supplements have emerged as one of the major hepatotoxicity agents. DILI can manifest as predominantly hepatitis, bile duct injury or combination. Histological pattern recognition in the liver biopsy may help identify specific hepatotoxic agents causing DILI.
PMID: 28873351
ISSN: 1532-8392
CID: 2688712
Proceedings (Baylor University. Medical Center). 2017:30(3):262-264.DOI: 10.1080/08998280.2017.11929610
Imaging and clinical predictors of spontaneous bacterial peritonitis diagnosed by ultrasound-guided paracentesis
Spontaneous bacterial peritonitis (SBP) is a potentially life-threatening complication of ascites diagnosed by paracentesis. We determined predictors of SBP to facilitate patient selection. The 301 paracenteses performed in 119 patients (51 women, 68 men) from July to November 2015 were retrospectively reviewed. Presentation, lab data, depth of the deepest ascites pocket on ultrasound, total volume of ascites removed, absolute neutrophil count, and complications were studied. Of 301 paracenteses, 16 (5%) diagnosed SBP. On univariate analysis, SBP was associated negatively with history of cirrhosis and positively with history of cancer, abdominal pain, greater depth of the fluid pocket, prior SBP, and leukocytosis. Multivariate analysis using these variables to predict SBP was significant (P < 0.0001); only depth of the largest fluid pocket (P = 0.008) and complaint of abdominal pain (P = 0.006) were independent predictors. Receiver-operator curve analysis showed that a 5-cm cutoff of pocket depth yielded 100% sensitivity and 32% specificity. Two (0.1%) hemorrhagic complications occurred, one causing death and one necessitating laparotomy. In conclusion, deeper ascites pockets and abdominal pain are independent predictors of SBP. When the largest ascites pocket is <5 cm, the probability of SBP is nearly negligible. Given the potential for hemorrhagic complications, findings may help triage patients for paracentesis.
PMCID:5468008
PMID: 28670052
ISSN: 0899-8280
CID: 2616812
Obesity conveys poor outcome in patients with hepatocellular carcinoma treated by transarterial chemoembolization
PURPOSE: The purpose of this retrospective study was to evaluate the impact of obesity on radiologic outcomes in patients with hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE). MATERIALS AND METHODS: A total of 100 TACE procedures performed in 57 patients (42 men, 15 women) with a mean age of 62 years+/-8.4 (SD) (range: 39-83 years) were retrospectively reviewed. The 1-2-month follow-up computed tomography or magnetic resonance imaging examinations was assessed for new or residual disease and radiologic response using mRECIST criteria. Patients were categorized into two groups according to body mass index (BMI). Patients with BMI<25kg/m2 were further referred as to low BMI patients and those with BMI>/=25kg/m2 as high BMI patients. Outcomes were compared between the two groups. RESULTS: Low and high BMI patients were similar in regard to age, gender, HCC etiology and stage, and pre-procedure disease burden. TACE for high BMI, compared to low BMI, patients resulted in lower complete response (39% vs. 66%) and higher progressive disease (21% vs. 5%) rates (P=0.04), and higher rates of residual disease (63% vs. 39%, P=0.02) and new lesions in untreated liver (39% vs. 18%, P=0.04) on 1-2-month follow-up imaging. CONCLUSIONS: High BMI is associated with significantly more residual disease, new lesions, and progressive disease in patients with HCC treated by TACE.
PMID: 27372418
ISSN: 2211-5684
CID: 2388212
Lower Observed Hepatocellular Carcinoma Incidence in Chronic Hepatitis B Patients Treated With Entecavir: Results of the ENUMERATE Study
OBJECTIVES: Data from the United States are lacking regarding the impact of entecavir (ETV) on the risk of hepatocellular carcinoma (HCC). Our aim is to determine whether treatment with ETV is associated with a reduced HCC risk by calculating the expected HCC incidence based on the Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B (REACH-B) model and comparing it with the observed HCC incidence. METHODS: The incidence of HCC in US patients treated with ETV between 2005 and 2013 in a retrospective cohort was obtained. The predicted HCC incidence was calculated using the REACH-B model. The standardized incidence ratios (SIRs) were calculated as a ratio of observed over predicted HCC cases. RESULTS: Of 841 patients, 646 (65% male, 84% Asian, median age 47 years, 36% hepatitis B e antigen positive, 9.4% with cirrhosis) met the inclusion criteria. Over a median follow-up of 4 years, 17 (2.6%) cases of HCC were diagnosed, including 8 out of 61 (13.1%) patients with cirrhosis and 9 out of 585 (1.5%) without cirrhosis. Compared with those without HCC, the 17 patients with HCC were older at 53 years vs. 47 years and more likely to have cirrhosis at 47.1% vs. 8.4%. Among patients without cirrhosis, the observed HCC incidence was significantly lower than predicted by the fourth year (SIR, 0.37; 95% confidence interval: 0.166-0.82). A sensitivity analysis that comprised all patients, including those with cirrhosis, showed that at the maximum follow-up time of 8.2 years, a significantly lower than predicted HCC incidence was noted with an SIR of 0.56 (95% confidence interval: 0.35-0.905). CONCLUSIONS: Based on the REACH-B model, long-term ETV therapy was associated with a lower than predicted HCC incidence. However, the risk of HCC persisted, and careful HCC surveillance remains warranted despite the anti-viral treatment.Am J Gastroenterol advance online publication, 21 June 2016; doi:10.1038/ajg.2016.257.
PMID: 27325221
ISSN: 1572-0241
CID: 2159082
Galactosylated Liposomes for Targeted Co-Delivery of Doxorubicin/Vimentin siRNA to Hepatocellular Carcinoma
The combination of therapeutic nucleic acids and chemotherapeutic drugs has shown great promise for cancer therapy. In this study, asialoglycoprotein receptors (ASGPR) targeting-ligand-based liposomes were tested to determine whether they can co-deliver vimentin siRNA and doxorubicin to hepatocellular carcinoma (HCC) selectively. To achieve this goal, we developed an ASGPR receptor targeted co-delivery system called gal-doxorubicin/vimentin siRNA liposome (Gal-DOX/siRNA-L). The Gal-DOX/siRNA-L was created via electrostatic interaction of galactose linked-cationic liposomal doxorubicin (Gal-DOX-L) on vimentin siRNA. Previous studies have shown that Gal-DOX/siRNA-L inhibited tumor growth by combined effect of DOX and vimentin siRNA than single delivery of either DOX or vimentin siRNA. These Gal-DOX/siRNA-Ls showed stronger affinity to human hepatocellular carcinoma cells (Huh7) than other cells (lung epithelial carcinoma, A549). These liposomes also have demonstrated that novel hepatic drug/gene delivery systems composed of cationic lipid (DMKE: O,O'-dimyristyl-N-lysyl glutamate), cholesterol, galactosylated ceramide, POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine), and PEG2000-DSPE (distearoyl phosphatidyl ethanolamine) at 2:1:1:1:0.2 (moral ratios) can be used as an effective drug/gene carrier specifically targeting the liver in vivo. These results suggest that Gal-DOX-siRNA-L could effectively target tumor cells, enhance transfection efficacy and subsequently achieve the co-delivery of DOX and siRNA, demonstrating great potential for synergistic anti-tumor therapy.
PMCID:5224624
PMID: 28335269
ISSN: 2079-4991
CID: 2508172
Serum Tumor Markers Provide Refined Prognostication in Selecting Liver Transplantation Candidate for Hepatocellular Carcinoma Patients Beyond the Milan Criteria
OBJECTIVE: To develop and validate a model to predict tumor recurrence after living donor liver transplantation (LDLT) (MoRAL) for hepatocellular carcinoma (HCC) beyond the Milan criteria (MC). BACKGROUND: Some subgroups of HCC exceeding the MC experience substantial benefit from LDLT. METHODS: This multicenter study included a total of 566 consecutive patients who underwent LDLT in Korea: the beyond-MC cohort (n = 205, the derivation [n = 92] and validation [n = 113] sets) and the within-MC cohort (n = 361). The primary endpoint was time-to-recurrence. RESULTS: Using multivariate Cox proportional hazard model, we derived the MoRAL score using serum levels of protein induced by vitamin K absence-II and alpha-fetoprotein, which provided a good discriminant function on time-to-recurrence (concordance index = 0.88). Concordance index was maintained similarly on both internal and external validations (mean 0.87 and 0.84, respectively). At cut off of 314.8 (75th percentile value), a low MoRAL score ( 314.8, HR = 5.29, P < 0.001) and overall survivals (HR = 2.59, P = 0.001) in the beyond-MC cohort. The 5-year recurrence-free and overall survival rates of beyond-MC patients with a low MoRAL score were as high as 66.3% and 82.6%, respectively. The within-MC patients with a high MoRAL score showed a higher risk of recurrence than beyond-MC patients with a low MoRAL score (HR = 2.56, P = 0.035). The MoRAL score was significantly correlated with explant histology. CONCLUSIONS: This new model using protein induced by vitamin K absence-II and alpha-fetoprotein provides refined prognostication. Among beyond-MC HCC patients, those with a MoRAL score
PMID: 26779979
ISSN: 1528-1140
CID: 1922032
Clinical and pathologic features of nutritional and herbal supplements induced liver injury [Meeting Abstract]
Background: Certain nutritional and herbal supplements may have potential hepatotoxic effects. With increasing use of these supplements in the general population, supplements-induced liver injury (SILI) has become a common problem clinically. However, there is not much data about the clinical and pathologic features of SILI, and pathological characteristics of SILI have not been defined. Design: All liver biopsy cases with diagnoses of hepatitis or liver injury were reviewed from our pathology database from 2014-2015. The cases of SILI were confirmed by pathological and clinical correlation. Pre-biopsy liver function tests (LFTs) were collected from the electronic medical record system. The H&E and Trichrome stain slides were re-assessed for pathologic changes. The morphologic patterns of liver injury, including bile duct injury, portal inflammation, interface hepatitis, lobular inflammation, fibrosis, presence of granulomas, and plasma cell and eosinophil infiltrates were recorded and analyzed. Results: Total 17 cases of SILI were identified from 323 liver biopsy cases of hepatitis and liver injury. Two of 17 patients with SILI developed acute fulminant hepatic failure and succumbed to the illness. The hepatotoxic nutritional/herbal supplements identified included boswellic acid, carnosyn beta-alanine, whey protein, maca extract, rhodiola, holy basil, creatine, and some unspecified tea and anti-itching supplements. Histologically, the major pattern of liver injury was combined bile duct damage and hepatitis, and the majority of cases showed significant cholestasis. Fibrosis ranged from mild portal fibrosis to cirrhosis. No granulomas were identified. Plasma cells were rare to minimal in all cases, while eosinophils ranged from none up to 12 per high power field. Serologically, the mean values of alanine transaminase, aspartate transaminase, alkaline phosphatase, and total bilirubin were 625 U/L, 447 U/L, 241 U/L, and 12 mg/d, respectively. Conclusions: Nutritional and herbal supplements have become a common cause of drug induced liver injury that may be under recognized. Histologically, the pattern of SILI in this study is the combination of bile duct and hepatocytic damage, ranging from mild disease to fulminant hepatitis. Significant elevation of LFTs, in combination with mixed pattern of liver injury should trigger the consideration of SILI
EMBASE:72178664
ISSN: 0023-6837
CID: 1947412
Frequency and Pathological Characteristics of Drug-Induced Liver Injury in a Tertiary Medical Center [Meeting Abstract]
ISI:000370302503127
ISSN: 1530-0285
CID: 2019592
Clinical and Pathologic Features of Nutritional and Herbal Supplements Induced Liver Injury [Meeting Abstract]
ISI:000370302503102
ISSN: 1530-0285
CID: 2019582
Frequency and Pathological Characteristics of Drug-Induced Liver Injury in a Tertiary Medical Center [Meeting Abstract]
ISI:000369270702392
ISSN: 1530-0307
CID: 1955182
