OBJECTIVETo investigate the expression of the lysosomal enzyme acid sphingomyelinase (ASMase) in alcohol-induced hepatic fibrosis using a rat model.

METHODSThe model of liver fibrosis was induced by administration of alcohol and high fat diet using 20 rats. Six rats given no alcohol and normal diet served as the control group. Real-time PCR, western blotting, and immunohistochemistry were used to evaluate fibrosis-related changes in the mRNA and protein expressions of ASMase.

RESULTSThe fibrotic liver tissues of the model rats showed significantly higher expression levels of ASMase than the non-fibrotic liver tissues of the control rats (P less than 0.05).

CONCLUSIONExpression of ASMase is increased in the fibrotic liver tissue of an alcohol-induced hepatic fibrosis rat model, suggesting that this lysosomal enzyme may contribute to development of this disease condition.

Animals ; Liver ; enzymology ; Liver Cirrhosis, Alcoholic ; enzymology ; Liver Cirrhosis, Experimental ; enzymology ; Male ; Rats ; Rats, Sprague-Dawley ; Sphingomyelin Phosphodiesterase ; metabolism

With recent developments, biologic therapies has shown superior efficacy for rheumatic diseases compared with preexisting pharmacologic therapies, which are associated with high costs, non-response in certain patient groups, and severe adverse effects such as infections limiting their wide-spread use and revealing a need for the development of novel treatments. Since discovering the role of bile acid receptors in regulating inflammation, clinical trials evaluating the use of bile acid receptor agonists as a means to potentially treat various inflammatory disorders, such as alcoholic hepatitis, non-alcoholic steatohepatitis, primary biliary cirrhosis, primary sclerosing cholangitis have been ongoing. This review summarizes the results of studies on the anti-inflammatory effects and mechanisms of bile acid receptors and the results of previous to date looking at the use of bile acid receptor agonists in animal models of inflammatory disorders and clinical trials. Furthermore, we present the potentials of the bile acid receptor agonists in the treatment of inflammatory rheumatic diseases, including rheumatoid arthritis.
Arthritis, Rheumatoid ; Bile* ; Biological Therapy ; Cholangitis, Sclerosing ; Fatty Liver ; Hepatitis, Alcoholic ; Humans ; Inflammation ; Liver Cirrhosis, Biliary ; Models, Animal ; Rheumatic Diseases

PURPOSE: Living donor liver transplantation (LDLT) has several difficulties in biliary reconstruction of the small and thin bile duct, the short stump, and multiple openings. METHODS: 76 cases of LDLT performed in Asan Medical Center from Jan. 1999 to Feb. 2000 were reviewed retrospectively. RESULTS: The causative diseases in this group were hepatitis B associated cirrhosis 47, hepatoma 16, fulminent hepatic failure 6, secondary biliary cirrhosis 3, alcoholic cirrhosis 2, hepatitis C associated cirrhosis 1, and Wilson's disease 1cases. Right lobe graft was done in 54 cases, and a left lobe graft was done in 22. All bile duct reconstructions were done as Roux-en-Y hepaticojejunostomy, single anastomosis in 59, a double anastomosis in 15, and a triple anastomosis in 2cases. Biliary leakage occurred in 7 cases (10.4%), and percutaneous drainage subsequently being done. Post leakage bile duct stricture occurred in 2 cases (2.6%). Delayed bile duct stricture occurred in 3 cases. All stricture cases were treated with PTBD and repeated balloon dilatation. There was no difference between the right and left lobe graft in terms of bile leakage. However, stricture, occurred only in the right lobe graft. Bile duct stricture occurred more frequently in the multiple bile ducts (5% in single duct, 13.3% in double ducts, but there's no significance). CONCLUSION: The prevalence of biliary complication of LDLT was about 10%. In addition, there were more complicationsin the right lobe and multiple bile duct openings. Therefore, careful design and delicate hepatic parenchymal dissection is important to obtain a single duct and safe cut surface of the graft. To avoid severe complications such as an intrahepatic abscess or stone, early diagnosis and treatment of biliary complications is essential.
Abscess ; Bile ; Bile Ducts ; Carcinoma, Hepatocellular ; Chungcheongnam-do ; Constriction, Pathologic ; Dilatation ; Drainage ; Early Diagnosis ; Fibrosis ; Hepatitis B ; Hepatitis C ; Hepatolenticular Degeneration ; Humans ; Liver Cirrhosis, Alcoholic ; Liver Cirrhosis, Biliary ; Liver Failure ; Liver Transplantation ; Liver* ; Living Donors* ; Prevalence ; Retrospective Studies ; Transplants

No abstract available.
Liver Cirrhosis, Biliary

Humans ; Liver Cirrhosis, Biliary

Cirrhosis is the result of chronic liver disease due to a variety of causes. It is deemed to be cryptogenic when the leading cause cannot be identified despite extensive laboratory, radiological and pathological investigations. The prevalence of cryptogenic cirrhosis diagnosis has been dramatically reduced in recent years due to the advanced achievement in diagnostic medicine, whereby it is attributed to only about less than 5% of cirrhosis cases. Here, we present a case of a 16-year-old boy with nonsignificant family history, was not taking any regular medication, and presented with progressive intermittent jaundice for a few years due to liver cirrhosis. Although an extensive investigation has been done, the etiology of the cirrhotic liver was still unknown. He had no features to support nonalcoholic steatohepatitis. He was in Child’s Grade B and prophylactically treated with a regular dose of propranolol to prevent portal hypertension complication while waiting for a liver transplant. This case report served the objective of showing that despite the advances in medical diagnostic techniques, cryptogenic cirrhosis is still used as a diagnosis in cases of chronic liver disease of unknown etiology.
Non-alcoholic Fatty Liver Disease ; Cirrhosis, Cryptogenic

Macroenzymes are high molecular weight complexes formed in the serum by self-polymerization or by association with other proteins. Macroenzymes are filtered with difficulty by normal renal glomeruli. Clinically, it is important to detect macroenzymes, because they frequently interfere with the interpretation of serum enzyme results, and as a result they can cause diagnostic and therapeutic errors. Macroamylasemia and macrolipasemia have been found to occur in apparently healthy humans, as well as in a variety of disease states, including liver disease, diabetes, cancer, malabsorption, and autoimmune disorders. We report a patient with alcoholic liver cirrhosis and macroamylasemia and macrolipasemia, the latter two of which were discovered using a screening test.
Alcoholics ; Humans ; Hyperamylasemia ; Liver Cirrhosis ; Liver Cirrhosis, Alcoholic ; Liver Diseases ; Mass Screening ; Molecular Weight ; Proteins

Bile canalicular antibody (BCA) was first reported in 1969. Many studies of BCA were performed in the 1970s and 1980s and revealed that BCA has a highly positive rate in chronic active hepatitis and primary biliary cirrhosis (PBC). These studies suggested that BCA can be useful in the diagnosis of these liver diseases. However, BCA is almost negative in patients with alcoholic hepatitis. We report a case of BCA in a 50-yr-old woman with a history of heavy alcohol consumption. The patient's serum levels of aspartate transaminase and alanine transaminase were increased, leading to a diagnosis of alcoholic hepatitis. The patient was evaluated for liver disease. Anti-mitochondria antibody, anti-smooth muscle antibody, and anti-liver kidney microsomal antibody tests were conducted, yielding negative results. However, during this testing process, the patient's serum was incidentally found to be positive for BCA at a titer of 1:160. This is the first case report of BCA in Korea.
Alanine Transaminase ; Alcohol Drinking ; Alcoholics* ; Aspartate Aminotransferases ; Bile* ; Diagnosis ; Female ; Hepatitis, Alcoholic* ; Hepatitis, Chronic ; Humans ; Kidney ; Korea ; Liver Cirrhosis, Biliary ; Liver Diseases

BACKGROUND: We summarize our experience in the pathological diagnosis of late complications of liver transplantation (LT) to better understand the causes of late allograft dysfunction in a population mostly composed of patients with hepatitis B virus (HBV) infection. METHODS: We reviewed 361 post-transplant liver biopsies from 174 patients who underwent LT and first presented with liver function abnormalities 3 months post-procedure. The underlying diseases included HBV-associated liver disease (77%), toxic or alcoholic liver disease (10.3%), hepatitis C virus (HCV)-associated liver disease (8.6%), primary biliary cirrhosis (1.2%), primary sclerosing cholangitis (1.2%), and metabolic disease (1.7%). RESULTS: The three most common late complications were acute rejection (32.5%), recurrent disease (19.1%), and biliary complication (17.1%). Patients who underwent LT for HBV infection or for drug- or alcohol-related liver disease had a lower incidence of recurring disease than those who underwent transplantation for HCV infection. During post-transplantation months 3-12, acute rejection was the most common cause of allograft dysfunction and recurring disease was the leading cause for allograft dysfunction (p=0.039). The two primary causes of late allograft dysfunction have overlapping histological features, although acute rejection more frequently showed bile duct damage and vascular endothelialitis than recurring HBV infection, and recurring HBV infection had more frequent lobular activity and piecemeal necrosis. CONCLUSIONS: The causes of late liver allograft dysfunction are closely associated with the original liver diseases and the period after LT. Careful attention is required for differential diagnosis between acute rejection and recurrent HBV.
Bile Ducts ; Biopsy ; Cholangitis, Sclerosing ; Diagnosis, Differential ; Hepacivirus ; Hepatitis B virus ; Humans ; Incidence ; Liver ; Liver Cirrhosis, Biliary ; Liver Diseases ; Liver Diseases, Alcoholic ; Liver Transplantation ; Metabolic Diseases ; Rejection (Psychology) ; Transplantation, Homologous ; Transplants

OBJECTIVETo explore the differential characteristics of the AMA-M2 autoantibody in patients with primary biliary cirrhosis (PBC) and non-PBC patients.

METHODSPatients with abnormal liver function at the Capital Medical University affiliated to Beijing You-an Hospital were enrolled in this study between January 2011 and December 2013. Serum levels of ANA, AMA and AMA-M2 were detected by indirect fluorescence assay and enzyme-linked immunosorbent assay. The patients' clinical data was obtained for retrospective analysis. Statistical analyses were performed using the SPSS 16.0 software. Enumeration data have been presented as numbers and percentages, and were analyzed using the chi-square test and one-way ANOVA test.

RESULTSOf the 5315 patients with abnormal liver function, 15.3% (811/5315) were AMA-M2 positive patients; among those 811 patients, 78.4% (636) had PBC, 4.4% (36) had PBC overlapping with autoimmune hepatitis (AIH), 4.4% (36) had drug-induced liver injury, 6.5% (53) had hepatitis B, 3.3% (27) had hepatitis C, 0.6% (5) had hepatitis E, 0.9% (7) had alcoholic liver disease, 0.5% (4) had non-alcoholic fatty liver, 0.8% (6) had primary hepatic carcinoma, and 0.1% (1) had infectious mononucleosis. Serum AMA-M2 level was significantly higher in the PBC patients (vs. other groups, P less than 0.001) with the exception of the patients with PBC/AIH overlap syndrome. Among the 811 patients with AMA-M2 positivity, 88.5% (718) showed AMA positivity and 91.1% (739) showed ANA positivity. Serum alanine transferase (ALT) and aspartate transferase (AST) levels were significantly higher in the drag-induced liver injury patients (527.74+/-684.65 U/L, 490.60+/-716.89 U/L) and the hepatitis E patients (1015.94 ± 165.55 U/L, 665.4 ± 297.14 U/L) than in the PBC patients (96.02 ± 115.56 U/L, 94.82 ± 83.32 U/L) (ALT: F =8.041, P < 0.001, P < 0.001; AST: F =8.066, P < 0.001, P < 0.001). Serum alkaline phosphatase (ALP; 265.16 ± 179.08 U/L) and glutamyl transferase (GGT; 332.02 ± 279.29 U/L) were significantly higher in the PBC patients than in the hepatitis B patients (135.35 ± 123.17 U/L, 140.27 ± 229.24 U/L) and the hepatitis C patients (85.65 ± 27.77 U/L, 92.70 ± 125.72 U/L) (ALP: F=3.911, P =0.01, P=0.001; GGT: F=4.081, P <0.001, P < 0.001). The serum IgM level was significantly higher in the PBC patients (4.60 ± 2.67 g/L) than in the patients with drug-induced liver injury (1.76 ± 1.15 g/L), hepatitis B (2.02 ± 1.41 g/L), hepatitis C (1.48 ± 0.92 g/L), hepatitis E (1.40 ± 0.68 g/L), alcoholic liver disease (1.57 ± 1.07 g/L), non-alcoholic fatty liver (1.05 ± 0.72 g/L), and primary hepatic carcinoma (2.64 ± 2.26 g/L) (F=16.83, P < 0.001, P < 0.001, Probability value < 0.001, Probability value < 0.05, Probability value < 0.01, Probability value < 0.05 respectively).

CONCLUSIONAlthough detection of serum AMA-M2 is an important feature of PBC diagnostic testing,there is a high ratio of serum AMA-M2 detected in patients with drug-induced liver injury, hepatitis B, C and E, alcoholic liver disease, non-alcoholic fatty liver,and primary hepatic carcinoma. The AMA-M2 positive non-PBC patients still require close observation to watch for future development of PBC.

Autoantibodies ; Beijing ; Carcinoma, Hepatocellular ; Chemical and Drug Induced Liver Injury ; Enzyme-Linked Immunosorbent Assay ; Hepatitis B ; Hepatitis C ; Hepatitis, Autoimmune ; Humans ; Liver Cirrhosis, Biliary ; Liver Diseases, Alcoholic ; Liver Function Tests ; Liver Neoplasms ; Retrospective Studies