Variceal bleeding is aggravated by portal venous invasion of hepatocellular carcinoma: a matched nested case-control study.

BACKGROUND: We hypothesized that portal vein tumor thrombosis (PVTT) in hepatocellular carcinoma (HCC) increases portal pressure and causes esophageal varices and variceal bleedings. We examined the incidence of high-risk varices and variceal bleeding and determined the indications for variceal screening and prophylaxis. METHODS: This study included 1709 asymptomatic patients without any prior history of variceal hemorrhage or endoscopic prophylaxis who underwent upper endoscopy within 30 days before or after initial anti-HCC treatment. Of these patients, 206 had PVTT, and after 1:2 individual matching, 161 of them were matched with 309 patients without PVTT. High-risk varices were defined as large/medium varices or small varices with red-color signs and variceal bleeding. Bleeding rates from the varices were compared between matched pairs. Risk factors for variceal bleeding in the entire set of patients with PVTT were also explored. RESULTS: In the matched-pair analysis, the proportion of high-risk varices at screening (23.0% vs. 13.3%; P = 0.003) and the cumulative rate of variceal bleeding (4.5% vs. 0.4% at 1 year; P = 0.009) were significantly greater in the PVTT group. Prolonged prothrombin time, lower platelet count, presence of extrahepatic metastasis, and Vp4 PVTT were independent risk factors related to high-risk varices in the total set of 206 patients with PVTT (Adjusted odds ratios [95% CIs], 1.662 [1.151-2.401]; 0.985 [0.978-0.993]; 4.240 [1.783-10.084]; and 3.345 [1.457-7.680], respectively; Ps < 0.05). During a median follow-up of 43.2 months, 10 patients with PVTT experienced variceal bleeding episodes, 9 of whom (90%) had high-risk varices. Presence of high-risk varices and sorafenib use for HCC treatment were significant predictors of variceal bleeding in the complete set of patients with PVTT (Adjusted hazard ratios [95% CIs], 26.432 [3.230-216.289]; and 5.676 [1.273-25.300], respectively; Ps < 0.05). CONCLUSIONS: PVTT in HCC appears to increase the likelihood of high-risk varices and variceal bleeding. In HCC patients with PVTT, endoscopic prevention could be considered, at least in high-risk variceal carriers taking sorafenib.

Hepatocyte-Specific Magnetic Resonance Imaging-Based Assessment of Indeterminate Hepatic Nodules in the Liver Transplant Evaluation of Patients With Cirrhosis.

We aimed to determine the identities in explants of indeterminate hepatic nodules (IDNs) that had been scanned by dynamic magnetic resonance imaging (MRI) to establish clinicoradiological parameters predicting which IDNs were hepatocellular carcinomas (HCCs). This study included 88 patients with cirrhosis who underwent gadoxetic acid-enhanced MRI in pre-liver transplantation (LT) workup followed within 90 days by primary LT. The MRI detected 168 hepatic nodules that were classified into 6 benign tumors, 49 HCCs, and 113 IDNs, in 5, 34, and 72 patients, respectively. We compared these pre-LT radiologic diagnoses and stagings with explant pathology on a per-lesion basis to enable us to identify features of IDNs related to malignancy. Of the 168 nodules seen on MRI, 119 that were classified radiologically as consisting of 1 benign nodule (33.3%), 46 HCCs (93.9%), and 72 IDNs (63.7%) all turned out to be pathological HCCs. Of 32 patients inside Milan and 54 without HCC staged by MRI, 11 progressed beyond the criteria after LT. High serum alpha-fetoprotein level (≥20 ng/mL) was the only per-patient factor significantly associated with malignant IDNs. Per-tumor analysis of the MRI signals revealed that arterial hyperintensity, hepatobiliary hypointensity, T2 -weighted mild-to-moderate intensity, and restricted diffusion-weighted images were significantly correlated with malignant IDN. A model combining these 4 MRI factors with alpha-fetoprotein level had the best performance in predicting the identification of IDNs as HCCs in explanted livers. Over 60% of the IDNs seen on dynamic images of cirrhotic livers proved to be HCCs when explanted livers were examined. It may therefore be possible to identify HCCs with reasonable accuracy by means of their hepatocyte-specific MRI features when patients are being assessed for LT.

Continued value of the serum alpha-fetoprotein test in surveilling at-risk populations for hepatocellular carcinoma.

BACKGROUNDS AND AIMS: Because of the known limitations of ultrasonography (US) alone, we re-evaluated whether complimentary testing for serum alpha-fetoprotein (AFP) is helpful in surveilling for hepatocellular carcinoma (HCC) in high-risk populations. METHODS: We included, from a hospital-based cancer registry, 1,776 asymptomatic adults who were surveilled biannually with the AFP test and US and eventually diagnosed with HCC between 2007 and 2015. Based on the screening results, these patients were divided into three groups: AFP (positive for AFP only; n = 298 [16.8%]), US (positive for US only; n = 978 [55.0%]), and AFP+US (positive for both; n = 500 [28.2%]). We compared the outcomes of the three groups, calculating the survival of the AFP group both as observed survival and as survival corrected for lead-time. RESULTS: In terms of tumor-related factors, the separate AFP and US groups were more likely to have early stage HCC and to receive curative treatments than the combined AFP+US group (Ps<0.05). The AFP group had significantly better overall and cancer-specific survival than the AFP+US group after adjusting for covariates (adjusted hazard ratios [HRs] 0.68 and 0.62, respectively). In analyses correcting for lead-time in the AFP group (doubling time 120 days), the respective adjusted HRs for the AFP group were unchanged (0.74 and 0.67), but they were no longer significant after additional adjustment for tumor stage and curative treatment (0.87 and 0.81). CONCLUSIONS: HCC cases detected by the AFP test without abnormal ultrasonic findings appear to have better survival, possibly as a result of stage migration and the resulting cures. Complementary AFP surveillance, together with US, could be helpful for at-risk patients.

The clinical behavior and survival of patients with hepatocellular carcinoma and a family history of the disease.

PURPOSE: Familial clustering is a common feature of hepatocellular carcinoma (HCC) as well as a risk factor for the disease. We aimed to assess whether such a family history affected prognostic outcomes in patients with HCC diagnosed at different stages of the disease. MATERIALS/METHODS: This hospital registry-based cohort study included 5484 patients initially diagnosed with HCC. Individual family histories of cancer were obtained by interview and reported by trained nurses who constructed three-generation pedigrees. Overall survival data were compared between cases with and without first-degree relatives affected by HCC, with adjustment for other potential predictors. RESULTS: Of 5484 patients, 845 (15.4%) had first-degree relatives with a history of HCC. Family history was associated with longer survival in the entire cohort (adjusted hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.80-0.98, P = .025). A significant trend for reduced risk of death with increasing number of affected family members was also observed (P for trend = 0.018). The stage-stratified analysis showed that the presence of family history was especially associated with a reduced risk of death in the subset of patients with HCC at a (very) early stage (adjusted HR 0.83, 95% CI 0.69-0.99; P = .042). The proportion of cases receiving curative treatment was also higher in early-stage patients with a family history (72.6% vs 63.3%; P < .001). CONCLUSIONS: A first-degree family history of the disease is a prognostic factor for improved survival in patients with HCC, especially in those whose tumors can be cured by radical treatments.

A Prospective Evaluation of the Reliability and Utility of Quality of Life Measures in Patients With Hepatocellular Carcinoma.

OBJECTIVES: Little is known about how quality of life (QOL) can assist clinical decision-making for patients with hepatocellular carcinoma (HCC). This study aimed to investigate the reliability and validity of QOL as well as its prognostic value and utility. MATERIALS AND METHODS: A prospective cohort of 300 HCC patients at various stages was recruited from 2015 to 2017 in Korea. The subjects answered the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30) and QLQ-HCC18 and the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire. Prognostic nomograms including the QOL scales were developed. The prediction performance of the Barcelona Clinic Liver Cancer (BCLC) and the American Joint Committee on Cancer (AJCC) staging systems when they were incorporated with QOL was investigated. RESULTS: The EORTC QLQ-C30 and QLQ-HCC18 subscales showed higher reliability than FACT-Hep subscales. With regard to the validity, both questionnaires discriminated the patients by stages, treatment modalities, and performance status effectively. Multivariable analysis revealed that EORTC role functioning and EORTC appetite loss subscales were statistically associated with overall survival and disease progression. The developed nomograms accurately estimated the 1-year overall survival and disease progression-free rates. Incorporating the EORTC role functioning subscale or Hepatobiliary Cancer Subscale of FACT-Hep with the BCLC and AJCC systems improved the prognostic classification. Incorporating QOL into the AJCC system showed better predictive accuracy than incorporating performance status into it did. CONCLUSIONS: The findings suggest that QOL data can serve as a reliable predictive factor and assist prognostic calculation for HCC patients.