Characteristics, aetiologies and trends of hepatocellular carcinoma in patients without cirrhosis: a United States multicentre study

Abstract

Summary Background Limited data exist on the burden and features of non‐cirrhotic hepatocellular carcinoma (HCC) in the United States. Aim To evaluate characteristics, aetiologies, trends and outcomes of non‐cirrhotic HCC from 2000 to 2014 at five large US centres Methods Patient, tumour and liver disease aetiology data were collected. The presence of underlying cirrhosis was assessed based on published criteria. Results Of 5144 eligible patients with HCC, 11.7% had no underlying cirrhosis. Non‐cirrhotic patients were older (64.1 vs 61.2 years), more frequently females (33.9% vs 20.8%) and less frequently black (8.3% vs 12.4%) (P < .001 for all). Among non‐cirrhotic patients, non‐alcoholic fatty liver disease (NAFLD) was the most common liver disease (26.3%), followed by hepatitis C virus (HCV) (12.1%) and hepatitis B virus (HBV) (10%) infections. As of 2014, there was increased percentage of cirrhotic HCC and a decline in non‐cirrhotic HCC mainly due to significant annual increases in cirrhotic HCC due to HCV (0.96% [P < .0001]) and NAFLD (0.66% [P = .003]). Patients with non‐cirrhotic HCC had larger tumours (8.9 vs 5.3 cm), were less frequently within Milan criteria (15% vs 39%), more frequently underwent resection (43.6% vs 8%) (P < .001 for all) and had better overall survival than cirrhotic HCC patients (median 1.8 vs 1.3 years, P = .004). Conclusions Nearly 12% of HCCs occurred in patients without underlying cirrhosis. NAFLD was the most common liver disease in these patients. During the study, the frequency of non‐cirrhotic HCC decreased, whereas that of cirrhotic HCC increased. Although non‐cirrhotic patients presented with more advanced HCC, their survival was better.

Prognosis after resection of single large hepatocellular carcinoma: Results from an Asian high-volume liver surgery center

“…in Taiwan) is HBV. The leading etiologies of chronic liver disease in HCCs in western countries are HCV, alcohol use disorder, and non-alcoholic fatty liver disease (NAFLD) [17]. Significant proportions of patients with non-cirrhotic liver were noted in the study by Tsilimigras et al (62.4%) [7] and in our study (58.2%).…”

Nonalcoholic fatty liver disease progression rates to cirrhosis and progression of cirrhosis to decompensation and mortality: a real world analysis of Medicare data

“…Consistent with findings from other claims‐based analyses of real‐world diagnosis patterns, 9 the majority (93%) of cirrhotic patients in our analysis were first diagnosed with decompensated cirrhosis. In addition, more than 50% of hepatocellular carcinoma patients were diagnosed without a previous diagnosis of cirrhosis, which may be attributed to the under‐coding of cirrhosis as well as emerging evidence that NAFLD is the most common etiology of liver disease in noncirrhotic hepatocellular carcinoma cases in the United States 12 . These results highlight the challenges faced by clinicians of establishing the presence of NAFLD/NASH and cirrhosis in clinical practice, with the majority of patients with early NAFLD/NASH experiencing nonspecific symptoms, which may not be identified in routine clinical practice, while patients with later stage disease have clear clinical manifestations of the disease 13‐16 …”

Molecular links between non-alcoholic fatty liver disease and hepatocellular carcinoma

“…NAFLD is the most common cause of HCC across the globe [16][17][18][19][20][21][22][23][24][25][26][27][28] . Although the progression of NAFLD to HCC involves NASH and cirrhosis, the direct development of HCC from benign steatosis or non-cirrhotic NASH has also been reported [29,30] . The increased prevalence of the underlying liver disease in the general population has led to an increase of 9% in the annual rates of incidence of NAFLD-associated HCC [31] .…”