Currently there is no consensus which staging system is best in predicting the survival of patients with hepatocellular carcinoma (HCC). The aims of this study were to identify independent predictors of survival and to compare 7 available prognostic staging systems in patients with HCC. A total of 239 consecutive patients with cirrhosis and HCC seen between January 1, 2000, and December 31, 2003, were included. Demographic, laboratory, and tumor characteristics and performance status were determined at diagnosis and before therapy. Predictors of survival were identified using the Kaplan-Meir test and the Cox model. Sixty-two percent of patients had hepatitis C, 56% had more than 1 tumor nodule, 24% had portal vein thrombosis, and 29% did not receive any cancer treatment. At the time of censorship, 153 (63%) patients had died. The 1-and 3-year survival of the entire cohort was 58% and 29%, respectively. The independent predictors of survival were performance status (P < .0001), MELD score greater than 10 (P ‫؍‬ .001), portal vein thrombosis (P ‫؍‬ .0001), and tumor diameter greater than 4 cm (P ‫؍‬ .001). Treatment of HCC was related to overall survival. The Barcelona Clinic Liver Cancer (BCLC) staging system had the best independent predictive power for survival when compared with the other 6 prognostic systems. In conclusion, performance status, tumor extent, liver function, and treatment were independent predictors of survival mostly in patients with cirrhosis and HCC. The BCLC staging system includes aspects of all of these elements and provided the best prognostic stratification for our cohort of patients with HCC. ( H epatocellular carcinoma (HCC) is the fifth most common tumor worldwide. In the United States, the incidence of HCC has been rising, 1 and it is the tumor with the largest increase in incidence over the last 12 years. 2 Furthermore, the overall survival of patients with HCC has not improved over the last 20 years, with the incidence rate almost equal to the death rate. 3 It is projected that the increase in incidence of HCC will continue over the next 20 years in the United States. 4 Therefore, it is important to understand the factors that predict survival of patients with HCC.

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Measurements of skeletal muscle cross-sectional area, index, and radiation attenuation utilizing clinical computed tomography (CT) scans are used in assessments of sarcopenia, the loss of skeletal muscle mass and function associated with aging. To classify individuals as sarcopenic, sex-specific cutoffs for ‘low’ values are used. Conventionally, cutoffs for skeletal muscle measurements at the level of the third lumbar (L3) vertebra are used, however L3 is not included in several clinical CT protocols. Non-contrast-enhanced CT scans from healthy kidney donor candidates (age 18–40) at Michigan Medicine were utilized. Skeletal muscle area (SMA), index (SMI), and mean attenuation (SMRA) were measured at each vertebral level between the tenth thoracic (T10) and the fifth lumbar (L5) vertebra. Sex-specific means, standard deviations (s.d.), and sarcopenia cutoffs (mean-2 s.d.) at each vertebral level were computed. Associations between vertebral levels were assessed using Pearson correlations and Tukey’s difference test. Classification agreement between different vertebral level cutoffs was assessed using overall accuracy, specificity, and sensitivity. SMA, SMI, and SMRA L3 cutoffs for sarcopenia were 92.2 cm2, 34.4 cm2/m2, and 34.3 HU in females, and 144.3 cm2, 45.4 cm2/m2, and 38.5 HU in males, consistent with previously reported cutoffs. Correlations between all level pairs were statistically significant and high, ranging from 0.65 to 0.95 (SMA), 0.64 to 0.95 (SMI), and 0.63 to 0.95 (SMRA). SMA peaks at L3, supporting its use as the primary site for CT sarcopenia measurements. However, when L3 is not available alternative levels (in order of preference) are L2, L4, L5, L1, T12, T11, and T10. Healthy reference values reported here enable sarcopenia assessment and sex-specific standardization of SMA, SMI, and SMRA in clinical populations, including those whose CT protocols do not include L3.

Endogenous gut-derived bacterial lipopolysaccharides have been implicated as important cofactors in the pathogenesis of liver injury. However, the molecular mechanisms by which lipopolysaccharides exert their effect are not entirely clear. Recent studies have pointed to proinflammatory cytokines such as tumor necrosis factor-alpha as mediators of hepatocyte injury. Within the liver, Kupffer cells are major sources of proinflammatory cytokines that are produced in response to lipopolysaccharides. This review will focus on three important molecular components of the pathway by which lipopolysaccharides activate Kupffer cells: CD14, Toll-like receptor 4, and lipopolysaccharide binding protein. Within the liver, lipopolysaccharides bind to lipopolysaccharide binding protein, which then facilitates its transfer to membrane CD14 on the surface of Kupffer cells. Signaling of lipopolysaccharide through CD14 is mediated by the downstream receptor Toll-like receptor 4 and results in activation of Kupffer cells. The role played by these molecules in liver injury will be examined.

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The incidence of hepatocellular carcinoma (HCC) in the United States is increasing, but the clinical characteristics of American patients with HCC have not been well described. The aims of this study were to determine the etiology of liver disease and short-term outcome among HCC patients presenting to a single center in the United States. One hundred five consecutive patients with HCC were studied; mean age was 59 years, 67% were men, and 76% were non-Hispanic white. The most common etiology of liver disease was hepatitis C (51%) and cryptogenic cirrhosis (29%). Half of the patients with cryptogenic cirrhosis had histologic or clinical features associated with nonalcoholic fatty liver disease (NAFLD).Fifty-three (50%) patients had HCC detected during surveillance (group I), whereas the remaining patients had symptomatic tumors (group 11). Group I patients had smaller tumors (P = .Ol), were more likely to be eligible for surgical treatment (P = .005), and had a better median survival compared with patients in group I1 (P = .OO1). Patients with cryptogenic cirrhosis were less likely to have undergone HCC surveillance and had larger tumors at diagnosis. In conclusion, hepatitis C and cryptogenic liver disease are the most common etiologies of diseases in our patients with HCC. NAFLD accounted for at least 13% of the cases. Patients who underwent surveillance had smaller tumors and were more likely to be candidates for surgical or local ablative therapies. Because of the increasing incidence of NAFLD, further studies are needed to determine the risk of HCC in patients with NAFLD.

Mortality due to hepatocellular carcinoma (HCC) has not improved over the last 20 years. This is in part due to the poor performance of available tumor markers leading to delays in diagnosis. Des-gamma carboxy-prothrombin (DCP) has been reported to be more sensitive and specific for the diagnosis of HCC in Japanese patients compared with ␣-fetoprotein (AFP). We conducted a cross-sectional case control study to evaluate whether DCP is more sensitive and specific than AFP for differentiating HCC from nonmalignant liver disease in a cohort of American patients from a single referral center. Four groups were studied: G1, normal healthy subjects; G2, patients with noncirrhotic chronic hepatitis; G3, patients with compensated cirrhosis; and G4, patients with histologically proven HCC. A total of 207 subjects were enrolled. Both DCP and AFP levels increased progressively from G1 to G4, but DCP values had less overlap among the groups than AFP. ROC curve indicated that a DCP value of 125 mAU/mL yielded the best sensitivity (89%; 95% CI, 77%-95%) and specificity (95%; 95% CI, 82%-96%) for differentiating patients with HCC from those with cirrhosis and chronic hepatitis. The optimal AFP cutoff value was 11 ng/mL and was inferior to the DCP value of 125 mAU/mL, the area under the ROC curves being 0.928 versus 0.810, respectively (P ‫؍‬ .002). In conclusion, DCP was more sensitive and specific than AFP for differentiating HCC from nonmalignant chronic liver disease. Prospective studies to evaluate the role of DCP in early HCC are underway. (HEPATOLOGY 2003;37:1114-1121 T he incidence of hepatocellular carcinoma (HCC) is increasing in the United States. 1 However, patient survival in HCC has improved minimally over the last 2 decades. Between 1981 and 1998, the 5-year survival rate only rose from 2% to 5%. 2 The poor survival rate is in part related to the diagnosis of HCC at advanced stages where effective therapies are lacking. [3][4][5] Surveillance of patients at the highest risk for developing HCC, i.e., patients with cirrhosis, is an important strategy that can potentially decrease the cancer-related mortality rate. Although HCC meets the criteria of a tumor that would benefit from a surveillance program, 6 the poor sensitivity and specificity of currently available tools has prevented widespread implementation of HCC surveillance. For example, ␣-fetoprotein (AFP) has been the serum marker that is most widely used for diagnosis as well as surveillance of HCC. 7,8 However, AFP levels may be normal in up to 40% of patients with HCC, particularly during the early stages (low sensitivity). 9 Furthermore, elevated AFP levels may be seen in patients with cirrhosis or exacerbations of chronic hepatitis (low specificity). 10 Prospective studies evaluating the performance characteristics of AFP for HCC surveillance reported sensitivities of 39% to 64%, specificities of 76% to 91%, and positive predictive values of 9% to 32%. [11][12][13] Abdominal ultrasound is the most common imaging modality used in the surveillance of HCC. T...

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