Incidence and Risk Factors for Hepatocellular Carcinoma in Cirrhosis: The Multicenter Hepatocellular Carcinoma Early Detection Strategy (HEDS) Study.

BACKGROUND & AIMS: Worldwide, hepatocellular carcinoma (HCC) is a common malignancy. We aimed to prospectively determine the incidence and risk factors of HCC in a U.S. METHODS: The multicenter Hepatocellular Carcinoma Early Detection Strategy study of the National Institutes of Health prospectively enrolled patients with cirrhosis who underwent standard surveillance for HCC. Demographics, medical and family history, etiology of liver disease, and clinical features were evaluated for associations with HCC. RESULTS: Between April 10, 2013 and December 31, 2021, 1723 patients were enrolled and confirmed eligible. During median follow-up of 2.2 years (range, 0-8.7 years), there were 109 incident cases of HCC for an incidence rate of 2.4 per 100 person-years: 88 (81%) patients with very early/early Barcelona Clinic Liver Cancer stage (0, A), 20 (18%) intermediate stage (B), and 1 (1%) unknown stage. Risk factor analyses were restricted to 1325 patients, including 95 incident HCC, with at least 6 months of follow-up. The majority were men (53.2%), obese or severely obese (median body mass index, 30.2 kg/m2), and white (86.3%); 42.0% had history of hepatitis C virus infection, 20.7% had alcoholic liver disease, and 24.9% had nonalcoholic fatty liver disease. Fourteen risk factors for HCC were significant (P < .05) in univariate analyses, and a multivariate subset was selected using stepwise logistic regression. The multivariate subset contained gender (P < .001; male; odds ratio [OR], 2.47; 95% confidence interval [CI], 1.54-4.07), years with cirrhosis (P = .004; OR, 1.06; 95% CI, 1.02-1.1), family history of liver cancer (P = .02; yes; OR, 2.69; 95% CI, 1.11-5.86), age (per 5 years; P = .02; OR, 1.17; 95% CI, 1.03-1.33), obesity (P = .02; yes; OR, 1.7; 95% CI, 1.08-2.73), aspartate aminotransferase (log(1+AST); P = .06; OR, 1.54; 95% CI, 0.97-2.42), alpha-fetoprotein (log(1+AFP); P = .07; OR, 1.32; 95% CI, 0.97-1.77), and albumin (P = .10; OR, 0.7; 95% CI, 0.46-1.07). CONCLUSIONS: Thus far, this is the largest prospective and geographically diverse study of a U.S. cohort of patients with cirrhosis that validates known risk factors for HCC (gender, age, obesity, years with cirrhosis, family history of liver cancer, baseline AFP, albumin, and AST). The incidence of HCC was 2.4% per 100 person-years.

Outcomes of kidney, liver, and simultaneous liver and kidney transplants from hepatitis c infected donors to hepatitis c naïve recipients: A large single center experience.

BACKGROUND: With the introduction of direct-acting antiviral therapies (DAAs), the non-use rate of hepatitis C virus (HCV)-positive donor organs (D+) has decreased significantly. We present the donor, recipient, and transplant allograft characteristics, along with recipient outcomes, in one of the largest cohorts of HCV-D+ transplants into HCV-naïve recipients (R-). METHODS: Charts of HCV D+/R- kidney (KT), liver (LT), and simultaneous liver-kidney (SLKT) transplant recipients between January 2019 and July 2022 were reviewed. Primary outcomes of interest included waitlist times and 1-year graft failure. Secondary outcomes included hospital and intensive care unit length of stay, post-transplant complications, effectiveness of DAA therapy, and characteristics of patients who relapsed from initial DAA therapy. RESULTS: Fifty-five HCV D+/R- transplants at our center [42 KT (26 nucleic acid testing positive [NAT+], 16 NAT-), 12 LT (eight NAT+, four NAT-), and one SLKT (NAT+)] had a median waitlist time of 69 days for KT, 87 days for LT, and 15 days for SLKT. There were no graft failures at 1 year. All viremic recipients were treated with a 12-week course of DAAs, of which 100% achieved end of treatment response (EOTR)-85.7% (n = 30) achieved sustained virologic response (SVR) and 14.3% relapsed (n = 5; four KT, one LT). All relapsed recipients were retreated and achieved SVR. The most common post-transplantation complications include BK virus infection (n = 9) for KT and non-allograft infections (n = 4) for LT. CONCLUSIONS: Our study has demonstrated no graft failures or recipient deaths at 1 year, and despite a 14.3% relapse rate, we achieved 100% SVR. Complications rates of D+/R- appeared comparable to national D-/R- complication rates. Further studies comparing D+/R- to D-/R- outcomes are needed.

Sofosbuvir and ribavirin prevent recurrence of HCV infection after liver transplantation: an open-label study.

BACKGROUND & AIMS: Patients with detectable hepatitis C virus (HCV) RNA at the time of liver transplantation universally experience recurrent HCV infection. Antiviral treatment before transplantation can prevent HCV recurrence, but existing interferon-based regimens are poorly tolerated and are either ineffective or contraindicated in most patients. We performed a trial to determine whether sofosbuvir and ribavirin treatment before liver transplantation could prevent HCV recurrence afterward. METHODS: In a phase 2, open-label study, 61 patients with HCV of any genotype and cirrhosis (Child-Turcotte-Pugh score, ≤7) who were on waitlists for liver transplantation for hepatocellular carcinoma, received up to 48 weeks of sofosbuvir (400 mg) and ribavirin before liver transplantation. The primary end point was the proportion of patients with HCV-RNA levels less than 25 IU/mL at 12 weeks after transplantation among patients with this HCV-RNA level at their last measurement before transplantation. RESULTS: Sixty-one patients received sofosbuvir and ribavirin, and 46 received transplanted livers. The per-protocol efficacy population consisted of 43 patients who had HCV-RNA level less than 25 IU/mL at the time of transplantation. Of these 43 patients, 30 (70%) had a post-transplantation virologic response at 12 weeks, 10 (23%) had recurrent infection, and 3 (7%) died (2 from nonfunction of the primary graft and 1 from complications of hepatic artery thrombosis). Of all 61 patients given sofosbuvir and ribavirin, 49% had a post-transplantation virologic response. Recurrence was related inversely to the number of consecutive days of undetectable HCV RNA before transplantation. The most frequently reported adverse events were fatigue (in 38% of patients), headache (23%), and anemia (21%). CONCLUSIONS: Administration of sofosbuvir and ribavirin before liver transplantation can prevent post-transplant HCV recurrence. ClinicalTrials.gov: NCT01559844.

Early treatment with terlipressin in patients with hepatorenal syndrome yields improved clinical outcomes in North American studies.

Hepatorenal syndrome type 1 (HRS-1) is a serious complication of advanced cirrhosis and a potentially reversible form of acute kidney injury that is associated with rapidly deteriorating kidney function. Liver transplantation remains the only curative treatment for decompensated cirrhosis. However, terlipressin, a vasopressin analog, successfully reverses HRS-1, and may improve patient survival while awaiting liver transplantation. Patients with higher baseline serum creatinine have a reduced response to treatment with terlipressin. These post hoc analyses examined pooled data from 352 patients with HRS-1 treated with terlipressin in 3 North American-centric, Phase III, placebo-controlled clinical studies (i.e. OT-0401, REVERSE, and CONFIRM)-across 3 serum creatinine subgroups (i.e. <3, ≥3-<5, and ≥5 mg/dL)-to further delineate their correlation with HRS reversal, renal replacement therapy-free survival, and overall survival. Serum creatinine was significantly associated with HRS reversal in univariate and multivariate logistic regression analyses (P<0.001). The incidence of HRS reversal inversely correlated with serum creatinine subgroup (<3 mg/dL, 49.2%; ≥3-<5 mg/dL, 28.0%; ≥5 mg/dL, 9.1%). At Day 30 follow-up, renal replacement therapy-free survival was significantly higher for patients with HRS-1 in the lower serum creatinine subgroups than in the higher subgroup (<5 vs. >5 mg/dL; p=0.01). Terlipressin-treated patients with HRS-1, with a lower baseline serum creatinine level, had a higher overall survival (p<0.001) and higher transplant-free survival at Day 90 (p=0.04). Patients with HRS-1 and lower serum creatinine levels who were treated with terlipressin had higher HRS reversal and survival outcomes, highlighting the significant need to identify and treat patients with HRS-1 early when they often have lower serum creatinine levels, and likely a greater response to terlipressin.

High-dose ursodeoxycholic acid is associated with the development of colorectal neoplasia in patients with ulcerative colitis and primary sclerosing cholangitis.

OBJECTIVES: Some studies have suggested that ursodeoxycholic acid (UDCA) may have a chemopreventive effect on the development of colorectal neoplasia in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). We examined the effects of high-dose (28-30 mg/kg/day) UDCA on the development of colorectal neoplasia in patients with UC and PSC. METHODS: Patients with UC and PSC enrolled in a prior, multicenter randomized placebo-controlled trial of high-dose UDCA were evaluated for the development of colorectal neoplasia. Patients with UC and PSC who received UDCA were compared with those who received placebo. We reviewed the pathology and colonoscopy reports for the development of low-grade or high-grade dysplasia or colorectal cancer. RESULTS: Fifty-six subjects were followed for a total of 235 patient years. Baseline characteristics (including duration of PSC and UC, medications, patient age, family history of colorectal cancer, and smoking status) were similar for both the groups. Patients who received high-dose UDCA had a significantly higher risk of developing colorectal neoplasia (dysplasia and cancer) during the study compared with those who received placebo (hazard ratio: 4.44, 95% confidence interval: 1.30-20.10, P=0.02). CONCLUSIONS: Long-term use of high-dose UDCA is associated with an increased risk of colorectal neoplasia in patients with UC and PSC.

Bile acid changes after high-dose ursodeoxycholic acid treatment in primary sclerosing cholangitis: Relation to disease progression.

UNLABELLED: High-dose (28-30 mg/kg/day) ursodeoxycholic acid (UDCA) treatment improves serum liver tests in patients with primary sclerosing cholangitis (PSC) but does not improve survival and is associated with increased rates of serious adverse events. The mechanism for the latter undesired effect remains unclear. High-dose UDCA could result in the production of hepatotoxic bile acids, such as lithocholic acid (LCA), because of limited small bowel absorption of UDCA and conversion of UDCA by bacteria in the colon. We determined the serum bile acid composition in 56 patients with PSC previously enrolled in a randomized, double-blind controlled trial of high-dose UDCA versus placebo. Samples for analysis were obtained at the baseline and at the end of treatment. The mean changes in the UDCA level (16.86 versus 0.05 micromol/L) and total bile acid level (17.21 versus -0.55 micromol/L) were significantly higher in the UDCA group (n = 29) versus the placebo group (n = 27) when pretreatment levels were compared (P < 0.0001). LCA was also markedly increased (0.22 versus 0.01 micromol/L) in the UDCA group compared to the placebo group (P = 0.001). No significant changes were detected for cholic acid, deoxycholic acid, or chenodeoxycholic acid. Patients (n = 9) in the UDCA group who reached clinical endpoints of disease progression (the development of cirrhosis, varices, liver transplantation, or death) tended to have greater increases in their posttreatment total bile acid levels (34.99 versus 9.21 micromol/L, P < 0.08) in comparison with those who did not. CONCLUSION: High-dose UDCA treatment in PSC patients results in marked UDCA enrichment and significant expansion of the total serum bile acid pool, including LCA.

The predictors of the presence of varices in patients with primary sclerosing cholangitis.

UNLABELLED: The predictors for developing varices in patients with primary sclerosing cholangitis (PSC) have not been well studied prospectively. We sought to define the predictors for the presence of varices at baseline and for newly developing varices in patients with PSC. We used prospectively collected data from a multicenter randomized trial of high dose ursodeoxycholic acid for PSC. All 150 patients enrolled were reviewed for predictors of varices and we excluded 26 patients who had esophageal varices at baseline so that predictors of newly developing varices could be determined. Clinical examination, blood tests, and upper endoscopy were done before randomization, at 2 years and after 5 years. Liver biopsy was performed at entry and at 5 years. The median age (interquartile range) of patients was 45.9 years (35.8, 54.9). In a multivariable logistic regression, a higher Mayo risk score (> or =0.87) or a higher aspartate/alanine aminotransferase (AST/ALT) ratio (> or =1.12) were significantly associated with the presence of varices at initial endoscopy (odds ratio = 1.9 and 3.9). By the end of the study, 25 patients had new varices (20.2%). In a Cox model, after adjustment for baseline variables lower platelet count and higher total bilirubin at 2 years were significantly associated with the presence of new varices. The platelet count of 205 (x 10(9)/L) and the total bilirubin level of 1.7 mg/dL were the best cutoff values for the detection of new varices. CONCLUSION: A higher Mayo risk score and higher AST/ALT ratio were significantly associated with the presence of varices at initial endoscopy. Lower platelet count and higher total bilirubin at 2 years were significantly associated with an increased risk of developing new varices in patients with PSC.

Accuracy of virtual chromoendoscopy in differentiating gastric antral vascular ectasia from portal hypertensive gastropathy: A proof of concept study.

BACKGROUND: Accurate detection of gastric antral vascular ectasia (GAVE) is critical for proper management of cirrhosis-related gastrointestinal bleeding. However, endoscopic diagnosis of GAVE can be challenging when GAVE overlaps with severe portal hypertensive gastropathy (PHG). AIM: To determine the added diagnostic value of virtual chromoendoscopy to high definition white light for real-time endoscopic diagnosis of GAVE and PHG. METHODS: We developed an I-scan virtual chromoendoscopy criteria for diagnosis of GAVE and PHG. We tested our criteria in a cross-sectional cohort of cirrhotic adults with GAVE and PHG when high-definition white light endoscopy (HDWLE) diagnosis was in doubt. We then compared the accuracy of I-scan vs HDWLE alone to histology. RESULTS: Twenty-three patients were included in this study (65.2% Caucasians and 60.9% males). Chronic hepatitis C was the predominant cause of cirrhosis (43.5%) and seven adults (30.4%) had confirmed GAVE on histology. I-scan had higher sensitivity (100% vs 85.7%) and specificity (75% vs 62.5%) in diagnosing GAVE compared to HDWLE. This translates into a higher, albeit not statistically significant, accuracy of I-scan in detecting GAVE compared to HDWLE alone (82% vs 70%). I-scan was less likely to lead to an accurate diagnosis of GAVE in patients on dialysis (P < 0.05) and in patients with elevated creatinine (P < 0.05). I-scan had similar accuracy to HDWLE in detecting PHG. CONCLUSION: This pilot work supports that virtual chromoendoscopy may obviate the need for biopsies when the presence of GAVE is in doubt. Larger studies are needed to assess the impact of virtual chromoendoscopy on success of endoscopic therapy for GAVE.

Evaluation of Serum-Derived Bovine Immunoglobulin Protein Isolate in Subjects With Decompensated Cirrhosis With Ascites.

Background Bacterial translocation plays a pivotal role in the natural course of cirrhosis and its complications. Serum-derived bovine immunoglobulin (SBI) is an oral medical food that has been shown to both reduce inflammation in the intestines and neutralize bacteria. It represents a unique intervention that has not been studied in this population. Methodology We conducted a prospective open-label trial with an eight-week treatment phase of SBI. Individuals were assessed using lactulose breath testing, serum markers for enterocyte damage and bacterial translocation, and the Chronic Liver Disease Questionnaire (CLDQ) prior to and after completion of the treatment phase. Results We evaluated nine patients with a diagnosis of decompensated cirrhosis with ascites. Subjects had a mean Model for End-Stage Liver Disease (MELD) score of 11.6 ± 3.0 and were not taking lactulose or antibiotics. All subjects tolerated SBI well with no significant adverse events or changes to any of the six domains of the CLDQ. Laboratory tests including liver tests and MELD score remained stable over the course of treatment. There were no significant changes in the rates of small intestinal bacterial overgrowth (55.6% vs 55.6%, p = 1.00) or serum levels of lipopolysaccharide-binding protein, intestinal fatty acid-binding protein, or soluble CD14 (p-values 0.883, 0.765, and 0.748, respectively) when comparing values prior to and immediately after treatment. Conclusions No adverse events or significant changes to the quality of life were detected while on treatment. There were no statistically significant differences in our outcomes when comparing individuals before and after treatment in this small prospective proof-of-concept pilot study. Further prospective randomized studies could be beneficial.

Alpha-fetoprotein, des-gamma carboxyprothrombin, and lectin-bound alpha-fetoprotein in early hepatocellular carcinoma.

BACKGROUND & AIMS: Alpha-fetoprotein (AFP) is widely used as a surveillance test for hepatocellular carcinoma (HCC) among patients with cirrhosis. Des-gamma carboxy-prothrombin (DCP) and lectin-bound AFP (AFP-L3%) are potential surveillance tests for HCC. The aims of this study were to determine performance of DCP and AFP-L3% for the diagnosis of early HCC; whether they complement AFP; and what factors affect DCP, AFP-L3%, or AFP levels. METHODS: We conducted a large phase 2 biomarker case-control study in 7 academic medical centers in the United States. Controls were patients with compensated cirrhosis and cases were patients with HCC. AFP, DCP, and AFP-L3% levels were measured blinded to clinical data in a central reference laboratory. RESULTS: A total of 836 patients were enrolled: 417 (50%) were cirrhosis controls and 419 (50%) were HCC cases, of which 208 (49.6%) had early stage HCC (n = 77 very early, n = 131 early). AFP had the best area under the receiver operating characteristic curve (0.80, 95% confidence interval [CI]: 0.77-0.84), followed by DCP (0.72, 95% CI: 0.68-0.77) and AFP-L3% (0.66, 95% CI: 0.62-0.70) for early stage HCC. The optimal AFP cutoff value was 10.9 ng/mL leading to a sensitivity of 66%. When only those with very early HCC were evaluated, the area under the receiver operating characteristic curve for AFP was 0.78 (95% CI: 0.72-0.85) leading to a sensitivity of 65% at the same cutoff. CONCLUSIONS: AFP was more sensitive than DCP and AFP-L3% for the diagnosis of early and very early stage HCC at a new cutoff of 10.9 ng/mL.

High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis.

UNLABELLED: Previous controlled trials are inconclusive regarding the efficacy of ursodeoxycholic acid (UDCA) for treating primary sclerosing cholangitis (PSC). One hundred fifty adult patients with PSC were enrolled in a long-term, randomized, double-blind controlled trial of high-dose UDCA (28-30 mg/kg/day) versus placebo. Liver biopsy and cholangiography were performed before randomization and after 5 years. The primary outcome measures were development of cirrhosis, varices, cholangiocarcinoma, liver transplantation, or death. The study was terminated after 6 years due to futility. At enrollment, the UDCA (n = 76) and placebo (n = 74) groups were similar with respect to sex, age, duration of disease, serum aspartate aminotransferase and alkaline phosphatase levels, liver histology, and Mayo risk score. During therapy, aspartate aminotransferase and alkaline phosphatase levels decreased more in the UDCA group than the placebo group (P < 0.01), but improvements in liver tests were not associated with decreased endpoints. By the end of the study, 30 patients in the UDCA group (39%) versus 19 patients in the placebo group (26%) had reached one of the pre-established clinical endpoints. After adjustment for baseline stratification characteristics, the risk of a primary endpoint was 2.3 times greater for patients on UDCA than for those on placebo (P < 0.01) and 2.1 times greater for death, transplantation, or minimal listing criteria (P = 0.038). Serious adverse events were more common in the UDCA group than the placebo group (63% versus 37% [P < 0.01]). CONCLUSION: Long-term, high-dose UDCA therapy is associated with improvement in serum liver tests in PSC but does not improve survival and was associated with higher rates of serious adverse events.

Yes-associated protein-1 may serve as a diagnostic marker and therapeutic target for residual/recurrent hepatocellular carcinoma post-transarterial chemoembolization☆.

BACKGROUND AND AIM: The transcriptional co-activator Yes-associated protein-1 (YAP1) has been implicated as an oncogene and is overexpressed in different kinds of human cancers, especially hepatocellular carcinoma (HCC). However, the role of YAP1 has not been reported in residual/recurrent HCC after transarterial chemoembolization (TACE). Our aim is to determine whether YAP1 is overexpressed in the residual/recurrent HCC after TACE. METHODS: A total of 105 tumor tissues from 71 patients including 30 cases of primary HCC without prior treatment, 35 cases of residual/recurrent HCC post TACE, and 6 cases of hepatoblastoma were included in the immunohistochemical study. YAP1 immunoreactivity was blindly scored as 0, 1+, 2+ or 3+ in density and percentages of positive cells. RESULTS: About 33.3% (10/30) of primary HCC without prior treatment showed 2+ of YAP1 immunoreactivity. While 82.8% (29/35) of residual/recurrent HCCs after TACE treatment displayed 2-3+ of YAP1 immunoreactivity, which was significantly higher compared to primary HCC without prior treatment (P = 0.0002). YAP1 immunoreactivity was moderately to strongly positive (2-3+) in 100% of the hepatoblastoma, particularly in the embryonal components (3+ in 100% cases). CONCLUSIONS: YAP1 is significantly upregulated in the residual/recurrent HCCs post TACE treatment, suggesting that YAP1 may serve as a sensitive diagnostic marker and a treatment target for residual/recurrent HCC post TACE.

Treating hepatocellular carcinoma without liver transplantation.

Hepatocellular carcinoma, a significant health problem throughout the world, generally occurs in the setting of cirrhosis. Choice of treatment depends on the size and location of the tumor and hepatic reserve. Liver transplantation provides the best chance for long-term survival and can be performed regardless of hepatic reserve, but it requires small tumor sizes and is available to only a few patients. All other treatments require adequate hepatic reserve. Surgical resection, percutaneous ethanol injection, and radiofrequency ablation are effective treatments for patients with good hepatic reserve and small tumors isolated to the liver. For larger and multinodular tumors, chemoembolization is the best choice. With metastasis, portal vein invasion, or large bilobar disease and intact hepatic function, modest improvements in survival have occurred with the use of sorafenib, a recently approved targeted chemotherapy agent. Patients with poor hepatic function or low performance status should receive only supportive care.

Chronic viral hepatitis.

Chronic liver disease is the tenth leading cause of death in the United States. The economic burden of liver disease is approximately 1% of the total national health care expenditure. Chronic hepatitis C is the most common cause of chronic liver disease in the United States, and chronic hepatitis B is the leading cause of liver disease worldwide. This article provides a brief overview of the evaluation and treatment of chronic hepatitis B and C infection.

Rationale and design of the Hepatocellular carcinoma Early Detection Strategy study: A multi-center longitudinal initiative of the National Cancer Institute's Early Detection Research Network.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignancy with a steadily rising incidence and associated morbidity and mortality. Cirrhosis of the liver is presently the leading risk factor for developing HCC. Abdominal imaging, with or without alpha-fetoprotein (AFP) testing, every 6 months is the current surveillance strategy for patients at risk. The available biomarkers for detecting this cancer at an early stage have inadequate sensitivity and specificity. METHODS: The Hepatocellular carcinoma Early Detection Strategy (HEDS) study, a multi-center initiative of the National Cancer Institutes' (NCI) Early Detection Research Network (EDRN), launched an effort to establish what has become the nation's largest comprehensive biorepository and database on patients at high risk of developing HCC. The cohort has been developed in seven clinical centers across the USA. Subjects are enrolled for a five-year period involving data and specimen collection every six months in accordance with standard surveillance for HCC. Extensive clinical data are collected and specimens are stored at a central repository. RESULTS: The database and biorepository contain longitudinally collected clinical data and serum and plasma samples from 1482 participants with cirrhosis and without evidence of HCC at baseline. Fifty-six percent are male, 85% Caucasian, 30% have a history of chronic HCV and 71% have compensated cirrhosis. CONCLUSIONS: The HEDS cohort provides opportunities for the continued study of the incidence and course of HCC in a comprehensively followed population of patients at high risk for this malignancy. Further, the EDRN biorepository provides a distinct opportunity for the development of novel biomarkers. Trial registry URL: https://edrn.nci.nih.gov/protocols/316-hepatocellular-carcinoma-early-detection-strategy.

GALAD Score for Hepatocellular Carcinoma Detection in Comparison with Liver Ultrasound and Proposal of GALADUS Score.

BACKGROUND: The GALAD score is a serum biomarker-based model that predicts the probability of having hepatocellular carcinoma (HCC) in patients with chronic liver disease. We aimed to assess the performance of the GALAD score in comparison with liver ultrasound for detection of HCC. METHODS: A single-center cohort of 111 HCC patients and 180 controls with cirrhosis or chronic hepatitis B and a multicenter cohort of 233 early HCC and 412 cirrhosis patients from the Early Detection Research Network (EDRN) phase II HCC Study were analyzed. RESULTS: The area under the ROC curve (AUC) of the GALAD score for HCC detection was 0.95 [95% confidence interval (CI), 0.93-97], which was higher than the AUC of ultrasound (0.82, P <0.01). At a cutoff of -0.76, the GALAD score had a sensitivity of 91% and a specificity of 85% for HCC detection. The AUC of the GALAD score for early-stage HCC detection remained high at 0.92 (95% CI, 0.88-0.96; cutoff -1.18, sensitivity 92%, specificity 79%). The AUC of the GALAD score for HCC detection was 0.88 (95% CI, 0.85-0.91) in the EDRN cohort. The combination of GALAD and ultrasound (GALADUS score) further improved the performance of the GALAD score in the single-center cohort, achieving an AUC of 0.98 (95% CI, 0.96-0.99; cutoff -0.18, sensitivity 95%, specificity 91%). CONCLUSIONS: The performance of the GALAD score was superior to ultrasound for HCC detection. The GALADUS score further enhanced the performance of the GALAD score. IMPACT: The GALAD score was validated in the United States.

Imaging of liver disease: comparison between quadruple-phase multidetector computed tomography and magnetic resonance imaging.

BACKGROUND AND AIM: To compare quadruple-phase multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) for the assessment of focal and diffuse liver disease. METHODS: Quadruple-phase contrast-enhanced MDCT and MRI of 37 consecutive patients were retrospectively reviewed by two readers (R1 and R2). In patients with focal liver lesions, the gold standard was histopathology (n = 17) and/or long-term (>6 months) follow-up imaging (n = 27) or transarterial chemoembolization (n = 1). Diffuse liver disease was confirmed by histopathology in all patients, when present. RESULTS: Both readers identified 60 focal liver lesions on MDCT and 56 focal liver lesions on MRI. Gold standard diagnoses revealed 48 focal liver lesions in 25 patients. Diagnosis of malignant liver lesions revealed a sensitivity of 88% (R1) and 91% (R2) for MRI; 63% (R1) and 66% (R2) for MDCT; and a specificity of 75% (R1) and 79% (R2) for MRI; 50% (R1) and 64% (R2) for MDCT. MRI was superior to MDCT for the diagnosis of malignant focal liver lesions, when the mean areas under the alternative free-response receiver operating characteristic curves (A(Z)) were compared (MRI = 0.93 vs CT = 0.69), (P < 0.00001). Thirty-three patients had histopathologically confirmed diffuse liver disease. Overall diagnosis of diffuse liver disease revealed a sensitivity of 88% (R1) and 92% (R2) for MRI; 75% (R1) and 74% (R2) for MDCT; and a specificity of 100% for both modalities by both readers. CONCLUSIONS: MRI is superior for the assessment of malignant focal liver lesions and diffuse liver disease compared to quadruple-phase MDCT, and can be considered as primary diagnostic imaging modality for liver imaging.

Diagnostic and therapeutic approach to hepatocellular carcinoma in the USA.

It is now apparent that hepatocellular carcinoma is occurring with increasing frequency in the USA. This mirrors a trend that occurred in Japan approximately 10 years earlier. Although the approach to diagnosis and treatment are similar in Japan and the USA, there are some differences. Thus, imaging is the primary modality of diagnosis and computed tomography and magnetic resonance imaging are favored over ultrasound. Liver transplantation is an important modality oftherapy, which is associated with excellent survival and, with the introduction of the Model for End-Stage Liver Disease (MELD) system, there has been a sharp rise in liver transplants performed for hepatocellular carcinoma since 2002.

Correction to: Hepatocellular Carcinoma with Bone Metastases: Incidence, Prognostic Significance, and Management-Single-Center Experience.

The original version of this article unfortunately contained a mistake in the Author group section. Author first names and family names were interchanged.

Hepatocellular Carcinoma with Bone Metastases: Incidence, Prognostic Significance, and Management-Single-Center Experience.

BACKGROUND: Hepatocellular carcinoma (HCC) represents one of the most common causes of cancer-related deaths worldwide, with rising incidence in the USA. Bone metastases with HCC, in particular, have an extremely poor prognosis. We present prevalence, treatment, and survival of patients with bone and more specifically spinal metastases from HCC. METHODS: A retrospective analysis was done at a single tertiary care institution of patients with bone metastases from HCC between January 2005 and December 2015. RESULTS: Among 1017 patients with HCC, 20 were found to have bone metastases of which 11 had spinal metastases. Seventeen (85%) were male, with median age of 58 years at time of HCC diagnosis. Systemic chemotherapy and sorafenib were used in 12 (60%) patients, and 12 (60%) received radiation therapy. Among patients who did not receive therapy, median survival was 76 days. Median survival after diagnosis of metastasis in patients on sorafenib and radiation were 106 and 100 days, respectively. CONCLUSION: Bone metastases in HCC are very rare and aggressive. Due to its rarity, optimal treatment strategies are not well defined. Early diagnosis is important for optimal therapy and improved survival.