Background: Endotoxin plays an important role in the initiation and aggravation of alcoholic liver disease. In this study, we evaluated plasma endotoxin levels and serum concentrations of cytokines and lipopolysaccharide binding protein (LBP) during the acute and recovery phase of patients with alcoholic hepatitis; we also explored the prognostic factors associated with a fatal outcome.Methods: Fourteen patients, consisting of eight patients with alcoholic hepatitis (AH), five cirrhotics with superimposed AH (LC+AH), and one patient with severe alcoholic hepatitis (SAH), were studied. Among these, two with LC+AH died of hepatic failure.Results: Plasma endotoxin levels in the acute phase were higher in patients with AH (184.4 ± 159.4 pg/ml) and LC+AH (206.9 ± 174.9 pg/ml) than in healthy subjects (10.4 ± 5.5 pg/ml, p < 0.001). In particular, in one patient with SAH and one of two nonsurvivors, plasma endotoxin levels were markedly high relative to the other cases. In most survivors, plasma endotoxin levels decreased in the recovery phase, whereas they further increased at the terminal stage in one of two nonsurvivors. Serum interleukin (IL)‐6 and IL‐8 levels in the acute phase were significantly higher in patients with AH and LC+AH as compared with healthy subjects. These levels were especially high in nonsurvivors and in one patient with SAH. IL‐10 increased in two nonsurvivors, one patient with SAH, and one with LC+AH. In the recovery phase, these cytokine levels in survivors tended to decrease, but in nonsurvivors, IL‐6 remained high, and IL‐8 and IL‐10 further increased. Tumor necrosis factor‐α levels were below the detection limit throughout the course in all patients. Serum lipopolysaccharide binding protein (LBP) generally was elevated in the acute phase and decreased in the recovery phase in all survivors, but in one of the nonsurvivors, LBP was elevated markedly at the terminal stage. In the acute phase, plasma endotoxin levels were correlated positively with white blood cell counts, neutrophil counts, and serum IL‐8. IL‐8 was correlated positively with neutrophil counts and negatively with serum Cholinesterase, hepaplastin test, and serum albumin levels. IL‐6 was correlated positively with white blood cell and neutrophil counts, C‐reactive protein, and serum total bilirubin and negatively with hepaplastin test and serum total protein levels. Serum LBP was correlated positively with white blood cell and neutrophil counts.Conclusions: Endotoxemia and related elevation of IL‐8 may play an important role in the activation and migration of neutrophils in patients with alcoholic hepatitis. Marked elevation of inflammatory cytokines, IL‐6 and IL‐8, are related to severity and poor prognosis of alcoholic hepatitis. Serum LBP may serve as an index of inflammatory reaction in alcoholics.

Our present study demonstrated that in NASH, the enhanced oxidative stress may be associated with hepatic inflammation and the degree of fat infiltration in the liver. However, simple steatosis and NASH were both exposed to oxidative stress, while NASH alone was associated with mitochondrial abnormality. These findings indicate that mitochondrial abnormality may play a role in the onset and progression of NASH in correlation with oxidative stress.

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Background: The pathogenesis of alcoholic hepatitis (AH) remains unclear and the prognosis of severe alcoholic hepatitis (SAH) is very poor. Deficiency of von Willebrand factor (VWF)‐cleaving protease (VWF‐CP/ADAMTS13) results in an increase of the plasma unusually large VWF multimer and leads to platelet clumping, which causes microcirculatory disturbance and finally multiorgan failure. The aim of this study was to explore the potential role of ADAMTS13 on the development of liver disturbance and multiorgan failure in AH.Methods: The activity of plasma ADAMTS13 and its clinical correlation were determined in 14 patients with AH, 4 with SAH (Maddrey score, mean 62), and 10 with alcoholic liver cirrhosis (LC).Results: The activity of the plasma ADAMTS13 significantly decreased in patients with AH (mean 59%, p < 0.001), SAH (17%, p < 0.001) and LC (76%, p < 0.02) as compared with the healthy subjects (102%, n = 60). The activity was markedly lower in SAH than in AH (p < 0.02) and LC (p < 0.02). In three nonsurvivors with SAH who had multiorgan failure, it was extremely low (4.5%, 5.0%, and 16.0%, respectively), but in a survivor with SAH it remained mild decrease (44%). In AH, the protease activity increased at the recovery stage (42%→ 75%, p < 0.05). In the univariate analysis, the activity correlated with 10 clinical variables including functional liver capacity, inflammation signs, renal function, and platelet count in patients with AH and SAH. Among these, multivariate analysis showed that serum total bilirubin and C‐reactive protein independently correlated with the protease activity.Conclusion: The activity of plasma ADAMTS13 markedly decreased in SAH in addition to AH. The activity was closely related to hyperbilirubinemia and inflammation signs, and was extremely low in nonsurvivors with SAH and multiorgan failure. The marked decrease of plasma ADAMTS13 may, in part, contribute to not only the progression of liver disturbance in AH, but also the development of multiorgan failure in SAH through microcirculatory disturbance.

NASH was characterized with over-nutrition and visceral fat type obesity as compared with ALD. The visceral fat accumulation was associated with hepatic inflammation and insulin resistance in NASH, but not in ALD. The difference in the nutritional status between NASH and ALD is not only reflected in the clinical features but also may closely associate with the mechanisms of hepatocellular damage in these diseases.

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CC more frequently presents with the clinical features suggestive of non-alcoholic steatohepatitis compared with controls even in the region where obesity is not prevalent. The lower occurrence of hepatocellular carcinoma and higher survival rate may indicate an indolent clinical course in CC as compared with viral cirrhosis.

Liver disease associated with rheumatoid diseases was the leading cause of liver disturbance in these patients and was characterized by mild and transient liver disturbance, whereas progressive liver diseases were often associated with hepatotropic virus, mainly HCV, or autoimmune liver diseases. Liver histology is indispensable for differentiating AIH from liver disease associated with rheumatoid diseases.