Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cirrhosis, a condition whose diagnosis is dependent on histology, is characterized by a combination of two main lesions, namely fibrosis and regeneration nodules. Alcohol abuse and viral infections are the two most common causes of cirrhosis. Symptoms and laboratory test abnormalities appear when hepatic failure and portal hypertension occur as a result of the cirrhosis. Ascites, gastrointestinal bleeding, encephalopathy, and bacterial infections are the main clinical manifestations. Hepatocellular carcinoma is a common and dreaded complication of cirrhosis. Serum albumin, serum bilirubin, and the prothrombin time are the most useful laboratory parameters. In combination with clinical criteria they allow determination of the Child-Pugh stage, which is largely used to evaluate the severity of cirrhosis, and evaluation of the prognosis. Recently, the early detection of cirrhosis has been shown to benefit from assays of serum markers for fibrosis, most notably hyaluronate. Quantitative tests evaluating the functional liver mass are helpful for monitoring cirrhosis and for selecting patients for liver transplantation, which is the only available treatment for end-stage cirrhosis.
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PMID:[Cirrhosis]. 1060 69

Chronic hepatitis C virus (HCV) infection is associated with a spectrum of liver diseases and a proportion of chronic cases progress through cirrhosis to hepatocellular carcinoma (HCC). The viral and host factors that are important in the clinical and histological progression of HCV infection are unclear. We investigated the effect of moderate (<80 g/day) and heavy (>80 g/day) alcohol intake on the histological and clinical progression of HCV infection and their associated risk of hepatic cancer in a group of Japanese patients. A number of other variables were assessed to evaluate their impact on disease progression. We recruited 120 patients with HCV infection and categorized them into four groups, based on alcohol consumption pattern. All clinical and biochemical profiles were collected from recorded files. Liver biopsies were analysed for the degree of fibrosis, presence of cirrhosis and histological activity of necroinflammation. Hepatic tumours were detected by the follow-up imaging analysis. There was no difference in the age, length of exposure to HCV infection and HCV RNA serum levels in the alcohol and alcohol-free groups. The histological grading of necroinflammation, serum levels of alanine aminotransferase and HCV RNA did not have any correlation with each other in the alcohol and alcohol-free group. There was a 1.5-2. 5-fold greater risk of liver cirrhosis and hepatocellular carcinoma in the alcohol intake group compared to the alcohol-free group. Kruskal-Wallis analysis among four groups demonstrated a significant transition to fibrosis (P < 0.05) for alcoholics with HCV infection. The increased risk of liver cancer in the alcohol group is independent of size and growth of tumours. The clinical manifestations of gastro-oesophageal variceal bleeding, ascites, and encephalopathy were also higher in the alcohol intake group. Alcohol consumption is an important risk factor in the histological and clinical progression of HCV infection and has no relation with HCV replication. Chronic HCV carriers should avoid excessive alcohol intake to reduce the acceleration of liver disease and risk of liver cancer.
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PMID:Effect of alcohol consumption on the progression of hepatitis C virus infection and risk of hepatocellular carcinoma in Japanese patients. 1086 50

We report 5 cases of liver transplantation which showed phlebosclerotic lesions of the distal portal vein on the explant confirming a diagnosis of hepatoportal sclerosis. This lesion was associated with nodular regenerative hyperplasia (2 cases), incomplete septal cirrhosis (4 cases) and tumors (2 cases, 1 adenoma and 1 hepatocellular carcinoma). Indications for transplant were chronic liver failure (1 case), encephalopathy without liver insufficiency (2 cases), an adenoma (1 case), a liver mass (1 case). Three patients out of 5 had a past history of surgical portacaval shunts to treat variceal bleeding non related to cirrhosis, one had a spontaneous portacaval shunt, and 2 had undergone a splenectomy for pancytopenia. The review of liver biopsies (4 cases out of 5) performed during surgery showed distal portal vein phlebosclerotic lesions. The diagnosis of hepatoportal sclerosis associated with complications, which is obvious retrospectively, is seldom made prior to transplantation. Portacaval shunts could play at least a partial role in the progressive deterioration of the liver.
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PMID:[Vascular pathology of the portal vein distal branches: a rare cause of liver transplantation and a protean clinical presentation]. 1096 91

Five cases that were referred to the Division of Transplantation at NYU School of Medicine for consideration for liver transplantation were discussed among a panel of hepatitis B and liver transplant experts. Opinions were obtained on the management at every stage of treatment of patients with the following initial information: Case one: young Asian woman in stage IV hepatic coma; intubated; prothrombin time (PT): 30 s; serum glutamic oxaloacetic transaminase (SGOT): 8,000 IU; total bilirubin: 25 mg/dL; hepatitis B surface antigen (HBsAg) positive. Case two: 70-yr-old woman, native of Greece; decompensated cirrhosis with encephalopathy; Child-Pugh Class C; HBsAg positive; hepatitis B surface antibody (HBsAb) negative; hepatitis B e antigen (HBeAg) positive; hepatitis B e antibody (HBeAb) negative; hepatitis B virus (HBV) DNA titer: 10,000. Case three: Muscular detective working full-time; cirrhosis; Child Pugh Class B; ascites controlled with spironolactone and furosemide; PT: 19s; HBsAg positive; HBsAb negative; HBV DNA titer: 50,000; low platelet count. Case four: 45-yr-old baker; cirrhosis and resectable 4-cm hepatoma; Child-Pugh Class B; PT: 16 s; Blood type O; United Network for Organ Sharing (UNOS) 2B; HBV DNA titer: 3,000. Case five: 40-yr-old Indian man; 300 pounds with massive ascites; Child Pugh Class C; PT: 17 s; HBsAg positive; HBV DNA titer: 22,000; transplanted with intra-operative hypotension; tacrolimus; graft functioning; HBIg 10,000 IU intra-operative and around the clock during the first post-operative week; required huge doses of hepatitis B immune globulin (HBIg) to maintain adequate HBsAb level; daily loss of 5 6 L of ascites fluid; post-operative day 8: anuric, blood urea nitrogen (BUN) 127, creatinine 3, mental status changes.
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PMID:Case studies in orthotopic liver transplantation for hepatitis B: a panel discussion. 1096 64

Chronic liver diseases are potentially evolving clinical situations which, independently by the etiology, could proceed towards progressive liver structural and functional impairments. The only efficient treatment is orthotopic liver transplantation. Chronic liver diseases, and up to 40% of liver cirrhosis, are initially asymptomatic, but cirrhosis is the most frequent cause of death among non-neoplastic digestive diseases. Important elements complicating a decompensated liver cirrhosis are ascites, hepatic encephalopathy, digestive bleeding and jaundice. Acute liver failure (ALF) is the expression of a clinical state, that is common to many conditions sharing severe liver structural and functional impairments. In patients affected by decompensated liver cirrhosis, ALF could be triggered by several factors, while the death is caused by bleeding episodes, hepato-renal syndrome, spontaneous bacterial peritonitis or hepatocarcinoma. In patients affected by chronic liver diseases, the diagnosis of ALF is based on progressively increasing jaundice, encephalopathy and coagulopathy. Recent clinical trials have evaluated the efficacy of extrahepatic liver support systems, either artificial or bio-artificial, in treating episodes of ALF in chronic liver patients. The preliminary results indicate a potential use of such systems in blood detoxification, but they also showed limits in increasing patient survival.
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PMID:[Acute liver failure in chronic hepatic disease. Clinico-therapeutic evaluation]. 1101 9

Chronic portosystemic encephalopathy (CPSE) is uncommon, and its management has yet to be determined. We have been able to control five cases of CPSE using transjugular retrograde obliteration (TJO), and we report our clinical results with this technique. All of the five patients were suffering from cirrhosis and had gastric varices and large gastrorenal shunts. According to Sherlock's classification, the grade of encephalopathy was II in two patients, III in two, and IV in one. According to Child's classification, one had class B and four had class C cirrhosis. TJO was performed using a 6-F angiographic catheter with an occlusive balloon 20 mm in diameter. Absolute ethanol and 5% ethanolamine oleate with iopamidol were used to obliterate the gastrorenal shunt. The gastrorenal shunt was successfully obliterated, and the encephalopathy improved to grade 0 after TJO in all cases. The portal flow volume increased significantly from 542 +/- 189 to 992 +/- 139 mL/min (p < 0.01). The plasma ammonia levels before and after TJO were 189 +/- 40 and 51 +/- 23 microg/dL, and the indocyanine green retention rates at 15 min were 44 +/- 13% and 27 +/- 12%, with both changes being significant (p < 0.01). Minor complications observed were fever of over 38 degrees C and tarry stools due to hemorrhagic gastritis in one patient, which was being controlled conservatively. One patient died of hepatocellular carcinoma 27 months after TJO. The other four patients survived without recurrence of CPSE 17-74 months (44 +/- 24 months) after TJO. We conclude that TJO can be adopted as a safe and effective treatment for CPSE.
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PMID:Transjugular retrograde obliteration for chronic portosystemic encephalopathy. 1102 85

Dengue viruses (DEN) cause a broad spectrum of clinical manifestations including potentially life-threatening conditions such as hemorrhagic shock syndrome and less frequently acute hepatitis with liver failure and encephalopathy. In addition, dengue viruses provide a potential model to understand the initiation of hepatocyte infection by the structurally closely related hepatitis C virus (HCV), because this virus at present cannot be grown in cell culture. Although the initial steps of viral infection are a critical determinant of tissue tropism and therefore pathogenesis, little is known about the molecular basis of binding and endocytic trafficking of DEN or of any other flavivirus. Our studies revealed that binding of radiolabeled DEN to the human hepatoma cell line HuH-7 was strictly pH dependent and substantially inhibitable by the glycosaminoglycan heparin. Ligand-blot analysis, performed as a viral overlay assay, showed two heparan sulfate (HS) containing cell-surface binding proteins resolving at 33 and 37 kd. Based on the sensitivity of unprotected virus and the viral binding site on the cell surface to trypsin, viral internalization was quantified as an increase in trypsin protected virus over time. Virus trafficking to the site of degradation was inhibited by pH dissociation of the clathrin coat and dependent on IP(3)-mediated homotypic endosomal fusion. These findings confirm the hypothesis that binding and internalization of DEN by hepatocytes are mediated primarily by HS containing proteoglycans and suggest that flaviviruses traffic the major clathrin-dependent endocytic pathway during infection.
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PMID:Heparan sulfate proteoglycans initiate dengue virus infection of hepatocytes. 1105 58

The aim of this study was to evaluate the prognostic factors at presentation and survival in Italian patients with hepatocellular carcinoma (HCC). Clinical and demographic data of 176 patients consecutively observed from 1993 to 1997 were evaluated by univariate and multivariate analyses. Overall median survival was 18 months. At univariate analysis, low albumin, high bilirubin, high alkaline phosphatase, high alpha-fetoprotein (AFP); high platelet count, hepatitis B surface antigen (HBsAg)-positivity, the presence of ascites, of encephalopathy, of portal vein thrombosis (PVT), male sex, no treatment, poor differentiation, untreatable tumours and incidental diagnosis were each associated with shorter survival. HBsAg-positive subjects more often presented with untreatable lesions or diffuse tumours (P=0.001 and P=0.007, respectively) and had significantly worse survival (P=0.0057). By multiple regression analysis, low albumin, high bilirubin, abnormal AFP, presence of PVT and of untreatable lesions were independent risk factors for worse survival. Thus, the most important factors influencing survival are the degree of functional impairment of the liver, the presence of hepatitis B viral (HBV) infection, the type of diagnosis and the aggressiveness of the tumour.
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PMID:Prognostic features and survival of hepatocellular carcinoma in Italy: impact of stage of disease. 1116 52

Complications of liver cirrhosis are increasingly frequent in elderly patients due to increased life expectancy and better management of cirrhotic patients. However, the influence of this condition on the evolution of variceal bleeding has not been well established. The aim of the present study was to determine the characteristics of esophagogastric variceal bleeding in elderly patients and the possible influence of advanced age on hemorrhage-related mortality. We analyzed 321 episodes of variceal bleeding in 227 cirrhotic patients. One hundred and thirteen (35.2%) episodes occurred in patients older than 65 years. No differences were found among patients older or younger than this age in terms of bleeding characteristics or Child-Pugh score. Patients older than 65 years more frequently presented serious associated diseases, hepatocellular carcinoma and hepatic encephalopathy during the episode (52.7% vs. 14%, p < 0.001; 19.7% vs. 8.7%, p = 0.01 and 17.4% vs. 10%, p = 0.09 respectively). Although hemorrhage-related mortality was higher in elderly patients (23.2% vs. 13.5%, p = 0.04), only the Child-Pugh score, definitive hemostasis, hepatocellular carcinoma and the development of encephalopathy or bacterial infection were independent predictive factors of mortality. A considerable proportion of the patients with esophagogastric variceal bleeding were older than 65 years. Advanced age does not independently influence mortality due to variceal bleeding.
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PMID:[Predictive factors of the mortality of digestive hemorrhage caused by esophageal varices in elderly patients]. 1124 89

Alpha(1)-antitrypsin functions as a "mousetrap" to inhibit its target proteinase, neutrophil elastase. The common severe Z deficiency variant (Glu(342)-->Lys) destabilizes the mousetrap to allow a sequential protein-protein interaction between the reactive-centre loop of one molecule and beta-sheet A of another. These loop-sheet polymers accumulate within hepatocytes to form inclusion bodies that are associated with juvenile cirrhosis and hepatocellular carcinoma. The lack of circulating protein predisposes the Z alpha(1)-antitrypsin homozygote to emphysema. Loop-sheet polymerization is now recognized to underlie deficiency variants of other members of the serine proteinase inhibitor (serpin) superfamily, i.e. antithrombin, C1 esterase inhibitor and alpha(1)-antichymotrypsin, which are associated with thrombosis, angio-oedema and emphysema respectively. Moreover, we have shown recently that the same process in a neuron-specific protein, neuroserpin, underlies a novel inclusion-body dementia, known as familial encephalopathy with neuroserpin inclusion bodies. Our understanding of the structural basis of polymerization has allowed the development of strategies to prevent the aberrant protein-protein interaction in vitro. This must now be achieved in vivo if we are to treat the associated clinical syndromes.
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PMID:Hypersensitive mousetraps, alpha1-antitrypsin deficiency and dementia. 1202 31


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