Exposure to Agent Orange and Hepatocellular Carcinoma Among US Military Personnel.

Importance: Hepatocellular carcinoma (HCC) and its mortality are on the rise. Viral hepatitis and alcohol are leading risk factors; however, other risk factors among veterans are less defined, including Agent Orange (AO), an herbicide linked to several cancers. Objective: To assess the association of AO exposure and HCC in a national cohort of Vietnam veterans. Design, Setting, and Participants: This retrospective cohort study included Vietnam veterans who served between 1966 and 1975, were male, were older than 18 years at the time of deployment, and had established follow-up in the Veterans Affairs (VA) between 2000 and 2019. Veterans with AO exposure were identified in the disability data via validated clinical surveys. Relevant clinical risk factors for cirrhosis and HCC were collected. Patients were stratified based on cirrhosis status, as defined by consecutive diagnosis found by documented International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision scores or calculated Fibrosis-4 scores. Data were collected from January 1, 2019, to December 31, 2020, and analyzed from December 2020 to October 2023. Main Outcome and Measures: Incident HCC was the primary outcome. AO and HCC association was estimated using a multivariable Cox regression analysis, with death and liver transplant as competing events. Results: Of the 296 505 eligible veterans (222 545 [75.1%] White individuals and 44 342 [15.0%] Black individuals), 170 090 (57%) had AO exposure (mean [SD] age, 21.62 [3.49] years; 131 552 White individuals [83.2%] and 22 767 Black individuals [14.4%]) and 35 877 (12.1%) had cirrhosis. Veterans who were not exposed to AO were more likely to smoke (109 689 of 126 413 [86.8%] vs 146 061 of 170 090 [85.9%]); use alcohol (54 147 of 126 413 [42.8%] vs 71 951 of 170 090 [42.3%]) and have viral hepatitis (47 722 of 126 413 [37.8%] vs 58 942 of 170 090 [34.7%]). In a multivariable competing risk model, AO exposure was not associated with HCC. Among veterans with cirrhosis, self-identification as Hispanic individuals (aHR, 1.51; 95% CI, 1.30-1.75; P <.001) or Black individuals (aHR, 1.18; 95% CI, 1.05-1.32; P = .004), and having a diagnosis of viral hepatitis (aHR, 3.71; 95% CI, 3.26-4.24; P <.001), alcohol-associated liver disease (aHR, 1.32; 95% CI, 1.19-1.46; P <.001), and nonalcoholic fatty liver disease (NAFLD) (aHR, 1.92; 95% CI, 1.72-2.15; P <.001) were associated with HCC. Among veterans without cirrhosis, hypertension (aHR, 1.63; 95% CI, 1.23-2.15; P <.001) and diabetes (aHR, 1.52; 95% CI, 1.13-2.05; P = .005) were also associated with HCC. Early smoking and alcohol use were significant risk factors for HCC. Conclusions and Relevance: In this large nationwide cohort study of Vietnam veterans, AO exposure was not associated with HCC. Smoking, alcohol, viral hepatitis, and NAFLD were the most important clinical risk factors for HCC.

Efficacy and Safety of a Botanical Formula Fuzheng Huayu for Hepatic Fibrosis in Patients with CHC: Results of a Phase 2 Clinical Trial.

Background: Hepatitis C virus (HCV) is a common cause of progressive hepatic fibrosis, cirrhosis, and hepatocellular carcinoma worldwide. Despite the availability of effective direct-acting antivirals, patients often have significant hepatic fibrosis at the time of diagnosis due to delay in diagnosis and comorbidities which promote fibrogenesis. Thus, antifibrotic agents represent an attractive adjunctive therapy. Fuzheng Huayu (FZHY), a traditional Chinese medicine botanical formulation, has been used as an antifibrotic agent in chronic HBV infection. Our aim was to assess FZHY in patients with HCV infection and active viremia. Method: We randomized 118 patients with active viremia from 8 liver centers in the U.S. to receive oral FZHY (n = 59) or placebo (n = 59) for 48 weeks. Efficacy was assessed by histopathologic changes at the end of therapy. A subset of biopsies was further analyzed using qFibrosis to detect subtle changes in fibrosis in different zones of the hepatic lobules. Results: FZHY was well tolerated and safe. Patients with baseline Ishak fibrosis stages F3 and F4 had better response rates to FZHY than patients with baseline F0-F2 (p=0.03). qFibrosis zonal analysis showed significant improvement in fibrosis in all zones in patients with regression of the fibrosis stage. Conclusions: FZHY produced antifibrotic effects in patients with baseline Ishak F3 and F4 fibrosis stages. Reduction in fibrosis severity was zonal and correlated with the severity of inflammation. Based on its tolerability, safety, and efficacy, FZHY should be further investigated as a therapy in chronic liver diseases because of its dual anti-inflammatory and antiibrotic properties. Lay Summary. This is the first US-based, multicenter and placebo-controlled clinical trial that shows statistically significant reduction in fibrosis in patients with active HCV using an antifibrotic botanical formula. This has important implications as there is an immediate need for effective antifibrotic agents in treating many chronic diseases including NASH that lead to scarring of the liver. With artificial intelligence-based methodology, qFibrosis, we may provide a more reliable way to assess the FZHY as a therapy in chronic liver diseases because of its dual anti-inflammatory and antifibrotic properties.

Nonalcoholic fatty liver disease-related hepatocellular carcinoma growth rates and their clinical outcomes.

AIM: Nonalcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC) is projected to become the leading indication for liver transplantation. Previous studies indicate that tumor growth rates (TGR) may predict survival and were helpful in determining HCC surveillance intervals. Therefore, we aimed to determine its usefulness in predicting clinical outcomes and treatments. METHODS: We conducted a retrospective study of hepatitis B, C and NAFLD-HCC cases. TGR was measured using 2-consecutive pre-treatment contrast-enhanced imaging studies ≥ 25 days apart. A multivariate regression model was used to determine predictors of TGR. In addition, the Cox regression model was used to evaluate the relationship between TGR and overall survival. RESULTS: From 2000-2019, the study cohort comprised 38, 60, and 47 HBV, HCV, and NAFLD patients, respectively, with TGRs. NAFLD-HCC tumor size was inversely correlated to the extent of liver disease as measured by Child-Pugh score (7.2 cm in non-cirrhosis; 3.7 cm, 2.6 cm, and 2.1 cm in Child A, B, and C, respectively; P < 0.001). After adjusting for baseline characteristics, the TGR per month was fastest in HBV (9.4%, 95%CI: 6.3%-12.5%) compared to HCV (4.9%, 95%CI: 2.8%-7%) and NAFLD patients (3.6%, 95%CI: 1.6%-6.7%). Predictors of TGR included elevated AFP, low albumin, and smaller tumor size. Fast TGR in viral etiologies had higher mortality [adj. hazard ratio (HR) = 2.6, 95%CI: 1.2-5.7, P = 0.02] than slow TGRs, independent of treatments. Fast TGR in NAFLD had a trend towards higher mortality (HR = 3.6, 95%CI: 0.95-13.3, P = 0.059). CONCLUSION: NAFLD-HCC patients have more indolent growths than viral-related HCC TGRs. The addition of TGR as a biomarker may assist in stratifying treatment options.

Improved survival after treatments of patients with 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. Despite the rise in these disease entities, detailed long-term outcomes of large NAFLD-associated HCC cohorts are lacking. In this report, we compared the overall and recurrence-free survival rates of NAFLD HCC cases to patients with HBV and HCV-associated HCC cases. Distinguishing features of NAFLD-associated HCC patients in the cirrhosis and non-cirrhosis setting were also identified. We conducted a retrospective study of 125 NAFLD, 170 HBV and 159 HCV HCC patients, utilizing clinical, pathological and radiographic data. Multivariate regression models were used to study the overall and recurrence-free survival. The overall survival rates were significantly higher in the NAFLD-HCC cases compared to HBV-HCC (HR = 0.35, 95% CI 0.15-0.80) and HCV-HCC (HR = 0.37, 95% CI 0.17-0.77) cases. The NAFLD-HCC patients had a trend for higher recurrence-free survival rates compared to HBV and HCV-HCC cases. Within the NAFLD group, 18% did not have cirrhosis or advanced fibrosis; Hispanic ethnicity (OR = 12.34, 95% CI 2.59-58.82) and high BMI (OR = 1.19, 95% CI 1.07-1.33) were significantly associated with having cirrhosis. NAFLD-HCC cases were less likely to exhibit elevated serum AFP (p < 0.0001). After treatments, NAFLD-related HCC patients had longer overall but not recurrence-free survival rates compared to patients with viral-associated HCC. Non-Hispanic ethnicity and normal BMI differentiated non-cirrhosis versus cirrhosis NAFLD HCC. Further studies are warranted to identify additional biomarkers to stratify NAFLD patients without cirrhosis who are at risk for HCC.

Late development of hepatocellular carcinoma after viral clearance in patients with chronic hepatitis C: A need for continual surveillance.

OBJECTIVE: Eradication of chronic hepatitis C (CHC) infection decreases the incidence of hepatocellular carcinoma (HCC), but a risk remains. We aimed to investigate HCC development-associated factors in CHC patients with sustained virological response (SVR) after antiviral therapies. METHODS: We compared CHC patients achieving SVR from 1996-2016 who did and did not develop HCC. Their median follow-up period was 8.01 years. RESULTS: Compared with 164 non-HCC SVR patients, 22 who developed HCC were older at SVR (P = 0.032), had a higher incidence of diabetes (P = 0.013) and higher pre-antiviral treatment alpha-fetoprotein (AFP) levels (P = 0.016), more had fibrosis stage 3 and cirrhosis (P = 0.0009) and hepatitis B core antibody (anti-HBc) positivity (P = 0.006). Eight and seven of 22 patients, respectively, developed HCC at 4-10 years and 10 years after SVR. The longest duration from SVR to HCC was 18.7 years. Independent factors associated with HCC development were anti-HBc positivity (hazard ratio [HR] 5.57, P = 0.012), age at SVR (HR 1.08, P = 0.014), higher pre-antiviral treatment AFP levels (HR 1.01, P = 0.01) and Hispanic ethnicity (HR 12.9, P = 0.002). HCC risk was significantly less in genotype 2 patients (HR 0.2, P = 0.02) or in those with higher pre-antiviral treatment albumin levels (HR 0.33, P = 0.04). CONCLUSIONS: The risk for HCC exists in a subset of CHC patients after SVR and may occur up to 18 years after viral clearance. Indefinite HCC surveillance is necessary in SVR patients with other risk factors.

Eradicating hepatitis B virus: The critical role of preventing perinatal transmission.

Prevention of hepatitis B virus (HBV) transmission from infected mothers to their newborns is critical to HBV control and eventual eradication. Mother-to-child perinatal transmission causes the highest chronic carrier rate (>85%) with a high rate of subsequent chronic liver disease and hepatocellular carcinoma. This risk is reduced by 90% with HBV vaccine given along with hepatitis B immune globulin (HBIG) starting at birth. New analyses of our data from US trials of HBIG and HBV vaccine in high-risk infants revealed better efficacy with yeast-recombinant vaccine than plasma-derived vaccine, especially in preventing late onset infections, with evidence that vaccine prevented transmission of maternal HBV infection with the glycine to arginine mutation in surface antigen codon 145 (sG145R). Most late infections with sG145R were in vaccine non-responders, suggesting escape from HBIG rather than from vaccine-induced antibody. Our findings also help explain survey results from Taiwan following universal childhood immunization implemented in the mid-1980s. We conclude that current vaccines will remain effective against surface antigen mutants. Anti-viral drugs in high-risk pregnant women, in combination with newborn HBIG and vaccine, show promise for eliminating residual breakthrough neonatal infections, critical to meeting WHO 2030 goals and for eradicating HBV.

Comparison of Triple-Drug Transcatheter Arterial Chemoembolization (TACE) With Single-Drug TACE Using Doxorubicin-Eluting Beads: Long-Term Survival in 313 Patients.

OBJECTIVE: We compared survival outcomes in 313 patients with unresectable hepatocellular carcinoma (HCC) treated with two different transcatheter arterial chemoembolization (TACE) regimens: triple-drug TACE or single-drug TACE using drug-eluting beads. MATERIALS AND METHODS: In this retrospective study, patient selection criteria were uniform. The triple-drug group (n = 166) underwent TACE using ethiodized oil with doxorubicin, cisplatin, and mitomycin-C with a microsphere embolic. The single-drug group (n = 147) underwent TACE using doxorubicin-eluting beads. Group characteristics were classified and analyzed, and survival was calculated using standard statistical methods. All patients were followed until death. Those undergoing orthotopic liver transplant (OLT) were also followed. RESULTS: There were no significant differences between the two groups in terms of demographics, Child-Pugh class, or Okuda stage. With patients undergoing OLT censored (n = 73), the mean (± standard error) survival in the triple-drug group was 23.49 ± 2.38 months, and the median survival was 16.00 ± 1.51 months. Mean survival in the single-drug bead group was 28.16 ± 2.75 months, and the median survival was 15.00 ± 1.50 months (p = 0.168). With patients undergoing OLT censored, the mean and median survival for the total cohort were 26.25 ± 1.97 and 15.00 ± 1.08 months, respectively. In the entire cohort that did not undergo OLT, patients with Child-Pugh class A disease survived significantly longer than did patients with Child-Pugh class B disease. Elevated α-fetoprotein levels were associated with shorter survival, and patients undergoing TACE with drug-eluting beads had shorter hospital stays. Although a greater percentage annual survival was observed in patients undergoing drug-eluting bead TACE who had Child-Pugh class A, Okuda stage I, and Barcelona Clinic Liver Cancer classes A and B disease starting at 36 months, this suggested survival advantage did not reach statistical significance. CONCLUSION: We found no significant survival difference in patients with unresectable HCC treated with triple-drug TACE compared with single-drug TACE using doxorubicin-eluting beads.

Radiofrequency ablation of hepatocellular carcinoma as bridge therapy to liver transplantation: A 10-year intention-to-treat analysis.

In a long-term (10-year) study of radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) as bridging therapy in patients listed for orthotopic liver transplantation (LT), we evaluated the impact of RFA on waiting list dropout rate, post-LT tumor recurrence, and long-term intention-to-treat, disease-specific survival (DSS). From March 2004 to October 2014, RFA was performed as the initial stand-alone bridge therapy to LT for 121 patients (men/women ratio, 83:38; mean age, 60.0 years) with 156 de novo HCCs (mean size, 2.4 cm). Follow-up period from initial RFA ranged from 1.3 to 128.0 months (median, 42.9 months). We assessed the overall and tumor-specific waiting list dropout rates, post-LT tumor recurrence, and 10-year post-LT and intention-to-treat survival rates. Dropout from the waiting list due to tumor progression occurred in 7.4% of patients. HCC recurrence after LT occurred in 5.6% of patients. The post-LT overall survival (OS) rate at 5 and 10 years was 75.8% and 42.2%, respectively, and the recurrence-free survival (RFS) rate was 71.1% and 39.6%, respectively. Intention-to-treat OS, RFS, and DSS rates for the entire study population at 5 and 10 years were 63.5% and 41.2%, 60.8% and 37.7%, and 89.5% and 89.5%, respectively. CONCLUSION: RFA as a first-line stand-alone bridge therapy to LT achieves excellent long-term overall and tumor-specific survivals, with a low dropout rate from tumor progression despite long wait list times and a sustained low tumor recurrence rate upon post-LT follow-up of up to 10 years. (Hepatology 2017;65:1979-1990).

Long-term survival after surveillance and treatment in patients with chronic viral hepatitis and hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the main cause of mortality in patients with chronic viral hepatitis (CVH). We determined the impact of surveillance and treatments on long-term outcomes in patients with CVH who developed HCC. Between 1984 and 2014, 333 patients with HCC and with hepatitis B or hepatitis C virus infection were evaluated. An adjusted lead time bias interval was added to patients with HCC who presented with HCC (no surveillance), and their survival was compared to patients whose HCC was detected by surveillance. After HCC treatments, survival rates within and beyond 3 years of follow-up were compared. In 175 (53%) patients, HCC was detected through surveillance using alpha-fetoprotein and abdominal ultrasound examinations. Compared to 158 (47%) patients with HCC who had no surveillance, more patients with HCC detected by surveillance received surgical and locoregional treatments (P < 0.0001 to P < 0.001), and their 1-, 3-, and 5-year overall and disease-free survival rates were significantly higher (P < 0.001 for both). During the first 3 years of follow-up, patients with HCC receiving liver transplantation had similar survival rates as those with liver resection or radiofrequency ablation (RFA); however, due to HCC recurrence, survival in resection and RFA patients became significantly less when followed beyond 3 years (P = 0.001 to P = 0.04). Factors associated with mortality included tumors beyond University of California at San Francisco criteria (hazard ratio [HR] 2.02; P < 0.0001), Child-Pugh class B and C (HR, 1.58-2.26; P = 0.043 to P = 0.015, respectively), alpha-fetoprotein per log ng/mL increase (HR, 1.30; P < 0.0001), previous antiviral therapy in hepatitis B virus patients (HR, 0.62; P = 0.032), and treatments other than liver transplantation (HR, 2.38-6.45; P < 0.0001 to P < 0.003). Conclusion. Patients with HCC detected by surveillance had prolonged survival. Due to HCC recurrence, survival rates after liver resection and RFA were lower when followed beyond 3 years after treatments. (Hepatology Communications 2017;1:595-608).

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.

Evaluation of alpha-fetoprotein in detecting hepatocellular carcinoma recurrence after radiofrequency ablation.

BACKGROUND AND AIM: The performance of alpha-fetoprotein (AFP) in the detection of hepatocellular carcinoma (HCC) recurrence after radiofrequency ablation was analyzed. METHODS: One hundred and forty-six solitary HCC lesions treated by radiofrequency ablation were evaluated. Using the AFP cutoff level at ≥ 20 ng/mL, tumors were categorized into AFP or non-AFP-producing HCC. Factors associated with true and false interpretations for cancer recurrence including analysis of elevated alanine aminotransferase (ALT) were evaluated. The performance of AFP using different cutoff levels adjusted for abnormal ALT was compared. RESULTS: Of 146 HCCs, 103 demonstrated no HCC recurrence while 43 had local recurrence. In non-recurrence HCC cases, increased AFP levels (false positive) were associated with concomitant ALT elevations, while those with normal AFP (true negative) had correspondingly normal ALT values (P < 0.001). The AFP false positive rate in cases of elevated ALT was significantly higher than those with normal ALT levels (31.9% vs 5.4%, P = 0.001). Among all positive AFP tests, those with false positive values (non-recurrence) had a significantly lower AFP level than the true positive (recurrence) HCC cases (39.8 ng/mL vs 372 ng/mL, P < 0.001). At the 20 ng/mL cutoff level, the sensitivities of AFP for detecting recurrence in non-AFP-producing HCC and AFP-producing HCC were 12.0%, and 72.2%, respectively. Using a modified AFP criteria of ≥ 100 ng/mL for cases where ALT ≥ 40 U/L, the sensitivity and specificity in AFP-producing tumors increased from 72.2% and 56% to 100% and 85%, respectively. CONCLUSION: Serum AFP is a useful test in the detection of HCC recurrence in AFP-producing HCC. The performance in AFP-producing HCC was significantly improved after adjusting for elevation of serum ALT.

Impact of coffee on liver diseases: a systematic review.

Coffee is one of the most commonly consumed beverages in the world. Its health benefits including improved overall survival have been demonstrated in a variety of disease states. To examine the association of coffee consumption with liver disease, a systematic review of studies on the effects of coffee on liver associated laboratory tests, viral hepatitis, nonalcoholic fatty liver disease (NAFLD), cirrhosis and hepatocellular carcinoma (HCC) was performed. Coffee consumption was associated with improved serum gamma glutamyltransferase, aspartate aminotransferase and alanine aminotransferase values in a dose dependent manner in individuals at risk for liver disease. In chronic liver disease patients who consume coffee, a decreased risk of progression to cirrhosis, a lowered mortality rate in cirrhosis patients, and a lowered rate of HCC development were observed. In chronic hepatitis C patients, coffee was associated with improved virologic responses to antiviral therapy. Moreover, coffee consumption was inversely related to the severity of steatohepatitis in patients with non-alcoholic fatty liver disease. Therefore, in patients with chronic liver disease, daily coffee consumption should be encouraged.

Hepatitis B inactive carriers: clinical course and outcomes.

OBJECTIVE: Hepatitis B virus (HBV) inactive carriers are HBV e antigen (HBeAg)-negative patients with normal alanine aminotransferase (ALT) levels and HBV DNA of ≤ 10000 copies/mL. We aimed to determine the clinical impact of ALT and HBV DNA elevations during the course of HBV infection. METHODS: From January 1989 to January 2012, 146 inactive carriers were prospectively followed every 6-12 months with ALT and HBV DNA measurements and with hepatocellular carcinoma (HCC) surveillance. RESULTS: During the follow-up of 8 ± 6.3 years, 56 of the 146 patients maintained ALT ≤ 40 U/L and HBV DNA ≤ 10000 copies/mL. However, 39 had rises of ALT > 40-80 U/L and 4 had ALT > 80 U/L; all except one reverted to baseline values. Also, during follow up, 69 (47.3%) inactive carriers had increases in HBV DNA of > 10000-999999 copies/mL; 38 of these patients' HBV DNA returned to baseline levels, while the remaining 31 patients maintained elevated HBV DNA values but had corresponding ALT of ≤ 40 U/L. There were four liver-related outcomes: 129 (88.4%) remained "inactive carriers", 13 (8.9%) had loss of hepatitis B surface antigen (HBsAg), one (0.7%) had a spontaneous reactivation to HBeAg-negative chronic hepatitis, and two (1.4%) developed HCC. CONCLUSIONS: Although the prognosis of inactive carrier is favorable, transient ALT and HBV DNA elevations may be observed but have minimal clinical significance. Moreover, continuous HCC surveillance remains necessary since the risk of development still exists.

Complete tumor encapsulation on magnetic resonance imaging: a potentially useful imaging biomarker for better survival in solitary large hepatocellular carcinoma.

The aim of this study was to determine the prognostic value of complete tumor encapsulation as visualized on magnetic resonance imaging (MRI) in patients with a solitary large hepatocellular carcinoma (HCC) beyond the Milan criteria for liver transplantation (LT). Between December 2000 and March 2011, 57 patients who had a solitary HCC exceeding 5 cm in diameter at the time of initial MRI before any treatment were identified. MRI images of the patients were independently reviewed by 2 experienced readers for the presence of complete tumoral encapsulation. The medical records of the patients were reviewed for an outcome analysis. Thirty of the 57 patients had completely encapsulated HCC according to MRI. There was excellent interobserver agreement between the 2 readers for the assessment of complete encapsulation (κ=0.86). Overall survival was significantly longer for patients with completely encapsulated HCC versus patients with incompletely or nonencapsulated tumors (P<0.001), and this included a subanalysis of 33 patients who received locoregional treatment (LRT; P=0.04). The presence of complete encapsulation was a strong predictor for survival in these patients according to both univariate [hazard ratio (HR)=0.24, 95% confidence interval (CI)=0.12-0.52, P<0.001] and multivariate analyses (HR=0.25, 95% CI=0.07-0.85, P=0.03). The rates of down-staging (P<0.001) and eventual LT (P=0.02) after LRT were also significantly higher in the patients with completely encapsulated tumors. In conclusion, complete tumor encapsulation on MRI is a potentially useful predictor for favorable biology in patients with a solitary large HCC. This new imaging biomarker may have a role in treatment selection for patients whose tumors exceed the Milan criteria size limits.

MRI detection of intratumoral fat in hepatocellular carcinoma: potential biomarker for a more favorable prognosis.

OBJECTIVE: The purpose of this study was to determine whether the presence of intratumoral fat in hepatocellular carcinoma (HCC) could serve as an imaging biomarker to predict a favorable prognosis. MATERIALS AND METHODS: After a search of the radiology and pathology databases from January 2002 to December 2010, a cohort of patients with fat-containing HCC imaged by chemical-shift MRI techniques was matched with a cohort of patients with nonfat-containing HCC for TNM stage and type of subsequent treatment. The number and type of tumor progression, time to tumor progression (TTP), and overall survival (OS) were determined for each cohort. RESULTS: There were 46 patients included in each cohort. Tumor progression was more prevalent in the non-fat-containing HCC cohort (30 patients, 65.2%) compared with the fat-containing HCC cohort (16 patients, 34.7%; p = 0.001). Distant metastasis occurred more commonly in the non-fat-containing HCC cohort (10 patient, 21.7%) compared with the fat-containing HCC cohort (two patients, 4.3%; p = 0.039). The median TTP was significantly longer in the fat-containing HCC group (52 months) compared with the non-fat-containing HCC group (27 months; p = 0.037). The significantly longer TTP was primarily observed in the locoregional treatment subgroup (p = 0.028). No statistical significance in OS and subanalysis by treatment was observed (p = 0.63-0.81). CONCLUSION: Fat-containing HCC, imaged on an MRI unit, may predict a more favorable prognosis compared with nonfat-containing HCC.

The management of chronic hepatitis B in Asian Americans.

Hepatitis B virus (HBV) infection is common with major clinical consequences worldwide. In Asian Americans, the HBsAg carrier rate ranges from 7 to 16%; HBV is the most important cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Patients are first diagnosed at different stages of clinical disease, which is categorized by biochemical and virologic tests. Patients at risk for liver complications should be identified and offered antiviral therapy. The two antiviral agents recommended for first-line treatment of chronic hepatitis B (CHB) are entecavir and tenofovir. The primary goal of therapy is sustained suppression of viral replication to achieve clinical remission, reverse fibrosis, and prevent and reduce progression to end-stage liver disease and HCC. Asian patients with chronic hepatitis, either HBeAg-positive or -negative, with HBV DNA levels >10(4) copies/mL (>2,000 IU/mL) and alanine aminotransferase (ALT) values above normal are candidates for antiviral therapy. HBeAg-negative patients with HBV DNA >10(4) copies/mL (>2,000 IU/mL) and normal ALT levels but who have either serum albumin ≤3.5 g/dL or platelet count ≤130,000 mm(3), basal core promoter mutations, or who have first-degree relatives with HCC should be offered treatment. Patients with cirrhosis and detectable HBV DNA must receive antiviral therapy. Considerations for treatment include pregnant women with high viremia, coinfected patients, and those requiring immunosuppressive therapy. In HBsAg-positive patients with risk factors, lifelong surveillance for HCC with alpha-fetoprotein testing and abdominal ultrasound examination at 6-month intervals is required. These recommendations are based on a review of relevant literature and the opinion of a panel of Asian American physicians with expertise in hepatitis B treatment.

Comparative analysis of resection and liver transplantation for intrahepatic and hilar cholangiocarcinoma: a 24-year experience in a single center.

OBJECTIVES: To compare the survival difference between 2 surgical modalities in the treatment of locally advanced intrahepatic and hilar cholangiocarcinoma (CCA) and to identify factors that predict mortality. DESIGN: Retrospective study. SETTING: University transplant center. PATIENTS: Of the 132 patients with a diagnosis of CCA treated from February 1, 1985, through June 30, 2009, 75 had metastatic disease at presentation and were excluded from the study, whereas 57 patients were candidates for surgical therapy. Tumor type was intrahepatic in 37 patients and hilar in 20 patients. Surgical therapy included orthotopic liver transplant (OLT) in 38 patients and combined radical bile duct resection with partial hepatectomy (RR) in 19 patients. RESULTS: Tumors were locally advanced in 35 of 37 patients (95%) with intrahepatic tumors and 16 of 20 patients (80%) with hilar tumors. Adjunctive therapy was used in 35 patients (61%). The 5-year tumor recurrence-free patient survival was significantly higher in the OLT group compared with the RR group (33% vs 0%; P = .05). In the OLT group, neoadjuvant and adjuvant therapies resulted in better patient survival compared with no therapy or adjuvant therapy only (47% vs 20% vs 33%, respectively; P = .03). Multivariate factors predictive of worse survival outcomes included hilar CCA, multifocal tumors, perineural invasion, and RR as the treatment modality compared with OLT. Tumor sizes--5 cm or larger for intrahepatic and 3 cm or larger for hilar CCA--were not predictors of poor outcome. CONCLUSION: Orthotopic liver transplant in combination with neoadjuvant and adjuvant therapies is superior to RR with adjuvant therapy in locally advanced intrahepatic and hilar CCA.