Hepatitis B and alcohol affect survival of hepatocellular carcinoma patients

AIM: In the USA, Hawaii has the highest incidence of hepatocellular carcinoma (HCC) and a diverse population.It is an ideal place to characterize HCC in the context of ethnicity/risk factors.METHODS: A total of 262 cases of HCC (1992-2003) were retrospectively reviewed for demographics, ethnicity, birthplace, viral hepatitis, alcohol use, diabetes, smoking and risk factors for viral hepatitis such as intravenous drug abuse (IVDA), transfusions, tattoos and vertical transmission. Tumor stage, Child's class, Cancer of the Liver Italian Program (CLIP) score, α-fetoprotein level, treatment and survival were recorded.RESULTS: Gender, age, viral hepatitis, alcohol, IVDA, and diabetes differed significantly in Asians, non-Asians and Pacific Islanders. There were also specific differences within Asian subgroups. Alpha-fetoprotein, smoking, transfusions, stage and resectability did not differ between groups. Asians were more likely to have hepatitis B, while non-Asians were more likely to have hepatitis C. Factors that decreased survival included hepatitis B, alcohol, elevated alpha-fetoprotein, CLIP ＞2 and increased Child's class. When Asians were combined with Pacific Islanders, median survival (1.52 years vs 3.54 years), 1- and 3-year survival was significantly worse than those for non-Asians. After Cox regression analysis for hepatitis B and alcohol, there was no difference in survival by ethnicity.CONCLUSION: Various ethnicities have different risk factors for HCC. Hepatitis B, alcohol, and α-fetoprotein are more important factors for survival than ethnicity.

Do we really need a standardized approach to spontaneously ruptured hepatocellular carcinoma?

Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-related death in Asian and African countries due to a high prevalence of chronic hepatitis B infections(1,2).The vast majority of current studies focus on the treatment of HCC itself rather than complications from HCC.A potentially life-threatening complication of HCC is spontaneous rupture,and its prevalence has been reportedly to be 5-15%of all HCC cases(1).This is the third leading cause of HCC-related death after tumor progression and liver failure,and there is a high mortality associated with rupture(3,4).

MELD score and AST-to-platelet ratio index predict long-term survival in patients with a small hepatocellular carcinoma following non-transplant therapies: a pilot study

Aim: Liver transplantation (LT) is the most effective treatment for long-term survival from hepatocellular carcinoma (HCC);however, insufficient donors limit therapy. The authors sought to identify characteristics that predicted long-term survival after non-transplant therapies in patients with small HCC. Methods: In a database of 1,050 HCC patients, the authors identified those with single HCC ≤ 3.0 cm, who underwent hepatic resection (HR, n= 16), radiofrequency ablation (RFA, n = 55), or LT (n = 23) with 5-year follow-up. Overall survival (OS) and odds-ratios (OR) for survival after HR/RFAwere calculated for MELD score, platelet count, creatinine, albumin, AST/platelet ratio index (APRI), international normalized ratio, and bilirubin. Results: LT patients had 3- and 5-year OS of 82.6% and 73.9% compared to HR/RFA patients with 3- and 5-year OS of 40.8% and 33.8%. The strongest predictors of survival after HR/RFA were MELD < 10 [OR 4.43, 95% confidence interval (CI) 1.85-10.58] and APRI ≤ 0.5 (OR 4.25, 95% CI 1.63-11.08). HR/RFA patients with both MELD < 10 and APRI ≤ 0.5 had 3- and 5-year OS of 77.3% and 72.7%. Conclusion: Patients with MELD< 10 and APRI ≤ 0.5 who undergo HR/RFA have survival approaching LT. Perhaps patients who meet these criteria can safely undergo non-transplant therapy and donor livers can be allocated to patients with a greater need.

Clinical and molecular sub-classification ofhepatocellular carcinoma relative to alpha-fetoproteinlevel in an Asia-Pacific island cohort

Aim: Increased serum alpha-fetoprotein (AFP) levels are associated with specific molecular subclasses of hepatocellular carcinoma (HCC), supporting AFP as a predictive or therapeutic biomarker for precision treatment of this disease. Considering recent efforts to validate HCC molecular classification systems across different populations, we applied existing signature-based classification templates to Hawaii cohorts and examined whether associations between HCC molecular sub-class, AFP levels, and clinical features found elsewhere can also be found in Hawaii, a region with a unique demographic and risk factor profile for HCC. Methods: Whole-genome expression profiling was performed on HCC tumors collected from 40 patients following partial hepatectomy. Tumors underwent transcriptome-based categorization into 3 molecular sub-classes (S1, S2, and S3). Patient groups based on molecular sub-class and AFP level were then compared with regards to clinical features and survival. Differences associated with AFP level and other clinical parameters were also examined at the gene signature level by gene set enrichment analysis. Results: Statistically confident (false discovery rate < 0.05) sub-classifications were made in 98% (39/40) of tumors. Patient sub-groups differed significantly with regards to serum AFP level, with significantly lower levels in the S3 sub-group as compared to S1 (P = 0.048) and S2 (P = 0.010). Serum AFP > 400 ng/mL predicted significant tumor enrichment for genes corresponding to MYC target activation, high cell proliferation, poor clinical prognosis, and the S2 sub-class. AFP > 400 ng/mL and non-S3 tumor classification were found to be significant predictors of overall survival. Conclusion: Distinct sub-classes of HCC associated with different molecular features and survival outcomes can be detected with statistical confidence in a Pacific Island cohort. Molecular classification signatures and other predictive markers for HCC that are valid for all patient populations are needed to support multi-center efforts to develop targeted therapies for HCC.

Ten-year survival and recurrence of hepatocellular cancer

Aim:Long-term survival after hepatocellular cancer(HCC)is difficult to achieve likely related to recurrence.This study aimed to identify factors that were predictive of 10-year survival after the diagnosis of HCC.Methods:In a prospectively collected database of 1374 HCC cases(1993-2019),we identified 70 patients who survived over 10 years regardless of treatment.We then identified 164 patients in the entire cohort who either had liver resection or transplant,and died before 10 years.Demographics,tumor characteristics,treatment,recurrence and treatment of recurrence were compared.Results:Of the 10-year survivors,36 underwent transplant,27 had liver resection and 7 patients had only locoregional therapy.Compared to the non-survivors,the 10-year survivors were younger and had fewer comorbidities or recurrence,smaller tumor size,lower AST,ALT,AFP,platelets,neutrophil-to-lymphocyte ratio.Multivariate analysis showed only age and diabetes to be negative predictors.Recurrence occurred in 24 survivors(34.3%)with mean time to recurrence with standard deviation 57.1±42.6 months compared to 80 non-survivors(48.7%)with mean time to recurrence of 15.3±14.8 months.For hepatic resection,10-year survivors had longer time to recurrence compared to non-survivors(median:31.3 months).Conclusion:Long-term survivors mostly occur after resection or transplant,but 10%of our cohort survived 10 years with only locoregional therapy.Underlying health status maybe an important predictor of 10-year survival for ;patients receiving liver resections.Recurrence of HCC occurs in both 10-year survivors and non-survivors,but later recurrence with aggressive treatment of the recurrence may allow for 10-year survival.

Prognostic ability of inflammation-based markers in radioembolization for hepatocellular carcinoma

Aim:Inflammation-based markers,such as the neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR),have recently been used as prognostic indicators in hepatocellular carcinoma(HCC).We aimed to determine whether NLR and PLR may predict response to yttrium-90 transarterial radioembolization(TARE)as primary treatment for HCC.Methods:We performed a retrospective review of a prospectively collected database of HCC cases(1994-2019)and selected patients who received TARE as primary treatment(n=42).Laboratory studies were used to calculate NLR and PLR.Response to TARE was determined using the modified response evaluation criteria in solid tumors(mRECIST).Patients were classified as non-responders(stable or progressive disease)or responders(partial or complete response)to treatment based on mRECIST.Results:Receiver operating characteristic curves identified a pre-treatment NLR cutoff of≥2.83 and a pre-treatment PLR cutoff of≥83 for predicting non-response to treatment.Pre-treatment NLR≥2.83 was the only significant predictor of non-response to TARE in multivariate logistic regression analysis(odds ratio 7.83,P=0.036).On time to progression analysis,both pre-treatment NLR≥2.83 and pre-treatment PLR≥83 were associated with a higher proportion of tumor progression at 6 months post-treatment(43.6%vs.10.0%,P=0.014,log-rank)and(38.6%vs.0%,P=0.010,log-rank),respectively.Conclusion:NLR confers prognostic value and may be superior to PLR in determining response to TARE as primary treatment for HCC.Future studies are necessary to validate these findings in a larger cohort.

Surveillance of hepatocellular cancer—why can’t we do better?

Hepatocellular carcinoma(HCC)has become a priority because of high case fatality and increasing incidence,especially in the United States.Because the best curative therapies are liver resection and transplantation,the Holy Grail of HCC is early identification.Finding smaller tumors allows for surgical intervention with better outcome and also allows time to wait for precious donor livers.