Survival, liver failure, and hepatocellular carcinoma in obesity-related cryptogenic cirrhosis

Abstract

Despite the rising incidence of obesity and diabetes, there is little emphasis on morbidity and mortality from obesity-related cirrhosis, usually considered a rare and asymptomatic condition. Our aim was to assess survival and the occurrence of hepatocellular carcinoma and complications of hepatic insufficiency in obesity-related cryptogenic cirrhosis compared with cirrhosis of other origins. We analyzed retrospectively 27 overweight patients with cryptogenic cirrhosis (CC-O), 10 lean patients with cryptogenic cirrhosis (CC-L) and 391 patients with hepatitis C virus-related cirrhosis (C-HCV). In CC-O patients, cirrhosis was detected later in life than in C-HCV and CC-L patients. Severe liver disease was as frequent in CC-O as in C-HCV patients as indicated by the proportion of Child B or C or of episodes of hepatic decompensation. Survival of CC-O patients was lower than that of untreated, ageand sex-matched C-HCV controls (P < .02 at 30 months), with a higher mortality of Child B or C patients. Hepatocellular carcinoma was detected in 8 of 27 (27%) CC-O patients versus 21% of matched C-HCV controls with a similar age cumulated incidence, suggesting a comparable carcinogenic potential. In conclusion, obesity-related cirrhosis should now be recognized as a distinct entity that can cause severe liver disease and death. Increased awareness of and better diagnostic strategies for nonalcoholic steatohepatitis in overweight patients are urgently needed.

Steatosis: Co-factor in other liver diseases

“…71 In a study of patients with hepatic malignancy complicating cirrhosis, Bugianesi et al 72 found that obesity and diabetes were more frequent in those whose cirrhosis was cryptogenic, supporting the hypothesis of underlying NASH. Ratziu et al 73 found that cryptogenic cirrhotics with a history of overweight were significantly more likely to develop HCC (8/27, 30%) compared with those who were lean (0/10), and the frequency was similar to HCC in matched controls with HCV cirrhosis (21%, P ϭ not significant).…”

Southern Europe as an example of interaction between various environmental factors: a systematic review of the epidemiologic evidence

“…A small study of 42 patients with NASH followed up for 21 years found one patient who developed cirrhosis and then HCC (Powell et al, 1990). Two cohort studies of patients with NASH-related cirrhosis have been published recently, from France (Ratziu et al, 2002) and Australia (Hui et al, 2003). In the French study, which was retrospective, none of 10 patients with cryptogenic cirrhosis and without comorbidities (e.g.…”

“…In the French study, which was retrospective, none of 10 patients with cryptogenic cirrhosis and without comorbidities (e.g. NAFLD, NASH, obesity and/ or diabetes) developed HCC during a mean follow-up of 3.5 years, whereas three of 22 subjects with obesity-related cryptogenic cirrhosis developed HCC during a mean follow-up of 1.8 years (incidence of 0.8 per 100 person-years, recalculated from the original paper) (Ratziu et al, 2002). In the Australian study, which was prospective, none of 23 cases with NASHassociated cirrhosis, defined by strict clinicopathologic criteria, developed HCC during a mean follow-up of 5 years.…”

Hepatocyte-specific Bid depletion reduces tumor development by suppressing inflammation-related compensatory proliferation

“…NAFLD has been recognized, as one of the key drivers for the increase in the number of cases of HCC. 8,9 NAFLD, a spectrum of disorders related to the abnormal accumulation of fat in the liver, affects approximately 20-30% of the adult population in the United States and many other westernized countries and is closely associated with obesity, insulin resistance and type 2 diabetes. 10 Growing epidemiological evidence link NAFLD to the increase in HCC rates.…”