Differentiation of clinical patterns and survival outcomes of hepatocellular carcinoma on hepatitis B and nonalcoholic fatty liver disease

Abstract

Background: The main etiologies of hepatocellular carcinoma (HCC) were often hepatitis B virus (HBV) or C and alcohol, rarely autoimmune and biliary diseases. Nonalcoholic fatty liver disease (NAFLD) has been an emerging role that could lead to chronic liver disease, nonalcoholic steatohepatitis, cirrhosis, and eventually HCC in recent years. The aim of our study is to investigate and compare the clinical features of HCC in patients with NAFLD and HBV, including age, gender, cirrhosis, liver function tests, largest tumor size, and cancer stage at the time of diagnosis. The survival outcome was compared between the two groups and the significant predictors of mortality were also analyzed in all patients with HCC. Methods: Most patients with HCC were recruited from the database of Cancer Registries in Taipei City Hospital, Ren-Ai Branch, from 2011 to 2017; and the other patients consecutively from the HCC multidisciplinary conference between January 2018 and December 2019. NAFLD was defined as nonviral hepatitis B (negative HBsAg and either positive anti-HBs or negative anti-HBc), nonviral hepatitis C (negative antihepatitis C virus [HCV]), nonalcoholic (alcohol consumption of <30 g/d for men and <20 g/d for women) liver disease, or present or past histological or ultrasonographic evidence of fatty liver. Totally, 23 NAFLD-related and 156 HBV-related HCC patients were enrolled in our study for further analysis. Results: NAFLD-related HCC patients were significantly older (median age: 70.0 [61.0–79.0] years vs. 63.0 [56.0–72.0] years, p = 0.012) and heavier (median body mass index [BMI]: 26.6 [24.2–30] kg/m2 vs. 24.8 [22.0–27.1] kg/m2, p = 0.044) than those with HBV-related HCC. They were also more susceptible to diabetes mellitus (DM), and 60.9% (14 of 23) of them had this comorbidity compared with 29.5% (46 of 156) of those with HBV-related HCC (p = 0.003). Only 34.8% (8 of 23) and 71.2% (111 of 156) of patients with NAFLD- and HBV-related HCC were cirrhotic, respectively (p = 0.001). However, gender, tobacco use, international normalized ratio, albumin, creatinine, and cholesterol levels were not significantly different between the two groups. Tumor characteristics such as the Barcelona clinic liver cancer stage, largest tumor size, tumor number, extrahepatic metastasis, and treatment modalities had no significant difference between such groups. According to the Kaplan–Meier method analysis, the overall survival was not significantly different between these two patient groups (log-rank test, p = 0.101). To evaluate which patient group would lead to poor prognosis, we analyzed the survival of all patients through multivariate Cox proportional hazard regression after controlling other factors that may influence the hazard ratio. The analysis revealed that NAFLD and HBV infection as the cause of HCC are not risk factors of poor prognosis. Conclusion: In conclusion, our study showed NAFLD-related HCC patients were older, heavier, and more had DM than HBV-related. In addition, more NAFLD-related HCC patients were noncirrhotic than HBV-related. The survival rate was similar between NAFLD and HBV-related HCC patients.

Outcomes of Liver Resection for Metabolic Dysfunction-Associated Fatty Liver Disease or Chronic Hepatitis B-Related HCC

“…MAFLD was originally known as NAFLD. In our cohort, the incidence of MAFLD was 12.9% (243/1887)—similar to that found in other series ( 41 , 45 ). However, its incidence was higher in series from Korea (52.3%) ( 46 ) or USA (33.4%) ( 44 ).…”

“…In our study, MAFLD counterparts had the highest overall and recurrence-free survival than CHB/MAFLD or CHB counterparts, which was consistent with the findings that NAFLD-related HCC had better long-term survival outcomes compared to non-NAFLD etiologies after liver resection or radiofrequency ablation (36,38,41,44,45). Our findings was confirmed by propensity score analysis.…”

“…This phenomenon highlights the importance of HCC screening or surveillance programs for MAFLD or NAFLD patients without cirrhosis. However, the proportion of cirrhosis among the MAFLD patients with HCC was significantly lower than CHB or CHB/MAFLD counterparts, which is consistent with the findings that NAFLD patients with HCC had the lowest proportion of cirrhosis than those with any other etiologies including CHB, HCV and alcoholic liver disease in Eastern or Western centers (3,38,39,41,(43)(44)(45)(46). Hence, active HCC surveillance is recommended in MAFLD patients for the early detection of HCC.…”

Association between Pre-Pregnancy Overweightness/Obesity and Pregnancy Outcomes in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis

“…Second, though various criteria for diagnosis of PCOS have been proposed by different societies, including National Institutes of Health (NIH) in 1990, Rotterdam criteria in 2003, and Androgen Excess and PCOS Society (AE-PCOS) in 2006 [ 62 , 63 , 64 ], most of the cohort studies enrolled into this meta-analysis adopted Rotterdam criteria, and only one study conducted in 1992 using ultrasound image as diagnostic method was included [ 40 ]. Third, the definitions of BMI were heterogenous in the literatures [ 65 , 66 , 67 , 68 , 69 , 70 , 71 ]. Generally, studies conducted in western countries used WHO classification for nutritional status, whereas studies in China partly used WHO classification, partly used lower cutoff for overweightness and obesity (i.e., BMI 24 kg/m 2 and 28 kg/m 2 ) compared to the WHO classification.…”

Analysis of Clinical Characteristics of Hepatitis B and Alcohol-Related Liver Cancer

“…DNA methylation can occur simultaneously with histone modifications such as acetylation. HBX acts on histone deacetylases to stimulate epigenetic modifications of tumor-related genes and induce the occurrence of HCC [ 11 ]. HBx can also promote the occurrence of HCC by changing the expression of certain microRNAs.…”