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Choice of therapy in early hepatocellular carcinoma (HCC) is controversial, and no broad consensus exists as to how patient and tumor characteristics should be used to guide choice of therapy. We have previously reported on decision making in early HCC by liver surgeons. In the present study, we quantified the impact of clinical factors on choice of therapy for early HCC by gastroenterologists and hepatologists. Physicians who treat HCC were invited to complete a web-based survey including ten case scenarios that systematically varied across seven clinical factors. Choice of therapy—liver transplantation (LT), liver resection (LR), radiofrequency ablation or intra-arterial therapy—was analyzed using multinomial logistic regression models. Tumor number and size, type of resection required, biological Model for End-Stage Liver Disease (MELD) score, and platelet count had the largest effects on choice of therapy. For example, LR was more likely to be recommended over LT for patients with small solitary tumors versus multiple tumors [relative risk ratio (RRR) 3.63], those who would require a minor versus major LR (RRR 3.39), those with lower biological MELD score (6 vs. 10; RRR 1.95), and those with a higher platelet count (150,000/μL vs. 70,000/μL; RRR 2.77). In contrast, serum α-fetoprotein level and etiology of cirrhosis were not associated with choice of therapy. No physician-related factors studied had an impact on choice of therapy. The clinical factors weighed most heavily by gastroenterologists and hepatologists are quite similar to those considered important by surgeons. There was good consensus among gastroenterologists and hepatologists as to the factors used to choose therapy.

Effects of chronic cadmium exposure on liver disease and liver-related mortality are unknown. We evaluated the association of creatinine-corrected urinary cadmium levels with hepatic necroinflammation, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), liver-related mortality, and liver cancer mortality in the US general population.We analyzed the relationship of individuals in the top quartile for urinary cadmium measured in 12,732 adults who participated in the Third National Health and Nutrition Examination Survey in 1988-1994 (NHANES III), and hepatic necroinflammation, NAFLD, and NASH. Associations between cadmium, liver-related mortality, and liver cancer mortality were evaluated in the NHANES III mortality follow-up study.The cutoffs for highest quartile of urinary cadmium per gram of urinary creatinine were 0.65 and 0.83 μg/g for men and women, respectively (P 0.001). After multivariate adjustment for other factors including smoking, the odds ratios [95 % confidence intervals (CI)] for hepatic necroinflammation, NAFLD, and NASH associated with being in the top quartile of cadmium levels by gender, were 2.21 (95 % CI, 1.64-3.00), 1.30 (95 % CI, 1.01-1.68) and 1.95 (95 % CI, 1.11-3.41) for men and 1.26 (95 % CI, 1.01-1.57), 1.11 (95 % CI, 0.88-1.41) and 1.34 (95 % CI, 0.72-2.50) for women, respectively. The hazard ratios for liver-related mortality and liver cancer mortality for both genders were 3.42 (95 % CI, 1.12-10.47) and 1.25 (95 % CI, 0.37-4.27).Environmental cadmium exposure was associated with hepatic necroinflammation, NAFLD, and NASH in men, and hepatic necroinflammation in women. Individuals in the top quartile of creatinine-corrected urinary cadmium had over a threefold increased risk of liver disease mortality but not in liver cancer related mortality.

Higher prevalence of nonalcoholic fatty liver disease (NAFLD) in men and postmenopausal women than in premenopausal women has suggested a potential role of sex hormones in the pathogenesis of the disease. We sought to evaluate the association between oral contraceptive pills (OCP) and NAFLD and to determine whether adiposity mediates any effect.We included 4338 women aged 20-60 years who were enrolled in the Third National Health and Nutrition Examination Survey from 1988 to 1994 in a population-based cross-sectional study. We defined NAFLD as moderate-severe steatosis on ultrasonography in women without excessive alcohol use or other identifiable causes. OCP use was based on self-report and was categorized as never, former or current use.The overall weighted prevalence of NAFLD was 11.6 % but lower in current (6.7 %) than in former (12.0 %) or never users (15.6 %, P = 0.016). In the multivariable model, current OCP users experienced a 50 % lower odds of NAFLD than never users (adjusted odds ratio 0.50; 95 % confidence interval 0.26, 0.98) after adjusting for age, race/ethnicity, smoking status, history of diabetes or hypertension and education. Further adjustment for body mass index or waist circumference significantly attenuated the OCP-NAFLD relationship.In this large US-representative population, OCP use was associated with reduced odds of NAFLD. However, this association could be mediated or confounded by adiposity. Prospective studies are needed to further clarify the causal role of sex hormone.

The drop-off risk for patients awaiting liver transplantation for hepatocellular carcinoma (HCC) is 22%. Transplant liver availability is expected to worsen, resulting in longer waiting times and increased drop-off rates. Our aim was to determine whether chemoembolization can decrease this risk.Eighty-seven consecutive HCC patients listed for liver transplant (Milan criteria) underwent statistical comparability adjustments using the propensity score (Wilcoxon, Fisher's, and chi-square tests). Forty-three nonchemoembolization patients and 22 chemoembolization patients were comparable for Child-Pugh and Model for End-Stage Liver Disease scores, tumor size and number, alpha fetoprotein (AFP) levels, and cause of cirrhosis. We calculated the risk of dropping off the transplant list by assigning a transplant time to those who dropped off (equal probability with patients who were on the list longer than the patient in question). The significance level was obtained by calculating the simulation distribution of the difference compared with the permutations of chemoembolization versus nonchemoembolization assignment of the patients. Kaplan-Meier estimators (log-rank test) were used to determine survival rates.Median follow-up was 187 ± 110 weeks (range 38 to 435, date of diagnosis). The chemoembolization group had an 80% drop-off risk decrease (15% nonchemoembolization versus 3% chemoembolization, p = 0.04). Although survival was better for the chemoembolization group, it did not reach statistical significance. Two-year survival for the nonchemoembolization and chemoembolization group was 57.3% ± 7.1% and 76.0% ± 7.9%, respectively (p = 0.078).Chemoembolization appears to result in a significant decrease in the risk of dropping off liver transplant list for patients with HCC and results in a tendency toward longer survival.

Despite advances in hepatitis C therapy and better knowledge of viral/host factors related to disease progression, the hepatitis C virus remains the leading cause of chronic liver disease, causing progression to end-stage liver disease (ESLD) as well as the development of hepatocellular carcinoma. Because hepatitis C virus acquisition is linked to an addictive behavior (ie, injection drug use), any perceived dependence has been a major reason for treatment denial as well as exclusion from clinical trials. Of special interest are two such dependences: drinking alcohol and smoking marijuana (cannabis). We review the available evidence for the effects of alcohol and cannabis on liver disease progression in chronic hepatitis C, and conclude with recommendations regarding the use of these two substances in the setting of chronic hepatitis C.

Obesity increases the risk for liver disease, including liver cancer. The mechanisms for this association are not well understood. At the very least, obesity might function as a comorbidity factor, accentuating processes (such as microsomal enzyme induction or pro-inflammatory cytokine production) that mediate liver damage caused by alcohol, hepatotoxic drugs, or certain viral infections. However, a growing body of evidence suggests that obesity-related insulin resistance plays a fundamental role in the initiation and progression of liver damage and liver cancer by altering the viability of liver cells. Efforts to delineate the molecular mechanisms that mediate insulin’s actions on cellular apoptosis and proliferation are increasing, and should help us design more effective therapies to prevent and treat obesity-related liver diseases.