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)

We used phosphorus magnetic resonance spectroscopy (31P-MRS) to assess in vivo the brain bioenergetics of 28 patients with liver cirrhosis. Seven had clinical hepatic encephalopathy (HE), nine hepatocellular carcinoma. 31P-MRS was performed by the DRESS localisation technique on occipital lobes. Brain phosphocreatine was significantly reduced in patients with or without overt HE, and inorganic phosphate was increased in both groups of patients. The cytosolic phosphorylation potential (PP), the relative rate of oxidative metabolism and the regulatory [ADP] were all abnormal. Brain PP was inversely correlated with serum ammonia concentration only in patients without liver cancer. The degree of bioenergetic failure was significantly higher in the presence of overt encephalopathy. We conclude that patients with liver cirrhosis had a derangement of brain energy metabolism, and that 31P-MRS offers a non-invasive method for investigating the underlying mechanisms of HE, with relevant implications in the identification and management of this condition.
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PMID:Abnormal brain energy metabolism shown by in vivo phosphorus magnetic resonance spectroscopy in patients with chronic liver disease. 1237 52

Data on the long-term outcome of nonalcoholic steatohepatitis (NASH)-associated cirrhosis are few, and most reports describe cases of cryptogenic cirrhosis associated with risk factors for NASH but without histologic definition. In this prospective cohort study, we describe the long-term morbidity and mortality of 23 patients with NASH-associated cirrhosis defined by strict clinicopathologic criteria. Outcomes were compared with 46 age- and gender-matched patients with cirrhosis from chronic hepatitis C virus (HCV) infection: 23 untreated and 23 nonresponders to antiviral therapy. During follow-up (mean, 84 months; median, 60 months; range, 5-177 months), 9 of the 23 NASH-associated cirrhosis cases developed liver-related morbidity (8 ascites and/or encephalopathy, 1 variceal bleeding). The probability of complication-free survival was 83%, 77%, and 48% at 1, 3, and 10 years, respectively, and the cumulative probability of overall survival was 95%, 90%, and 84% at 1, 3, and 10 years, respectively. Five deaths were from liver failure, 1 from a non-liver-related cause. By multivariate analysis, bilirubin (P =.02) and platelet (P =.04) were independent predictors of complication-free survival; bilirubin (P =.05) was the only predictor for overall survival. After controlling for these factors, there was no difference in complication-free or overall survival between the NASH-cirrhosis cohort and either group of HCV-cirrhosis. However, 8 cases of liver cancer occurred in the HCV-cirrhosis groups compared with none among NASH cases. In conclusion, liver failure is the main cause of morbidity and mortality in NASH-associated cirrhosis. The prognosis is either similar or less severe than HCV-cirrhosis, except that HCC appears less common.
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PMID:Long-term outcomes of cirrhosis in nonalcoholic steatohepatitis compared with hepatitis C. 1664 56

Several treatments have been proven to be effective for variceal bleeding in patients with cirrhosis. The aim of this multicenter, prospective, cohort study was to assess how these treatments are used in clinical practice and what are the posttherapeutic prognosis and prognostic indicators of upper digestive bleeding in patients with cirrhosis. A training set of 291 and a test set of 174 bleeding cirrhotic patients were included. Treatment was according to the preferences of each center and the follow-up period was 6 weeks. Predictive rules for 5-day failure (uncontrolled bleeding, rebleeding, or death) and 6-week mortality were developed by the logistic model in the training set and validated in the test set. Initial treatment controlled bleeding in 90% of patients, including vasoactive drugs in 27%, endoscopic therapy in 10%, combined (endoscopic and vasoactive) in 45%, balloon tamponade alone in 1%, and none in 17%. The 5-day failure rate was 13%, 6-week rebleeding was 17%, and mortality was 20%. Corresponding findings for variceal versus nonvariceal bleeding were 15% versus 7% (P =.034), 19% versus 10% (P =.019), and 20% versus 15% (P =.22). Active bleeding on endoscopy, hematocrit levels, aminotransferase levels, Child-Pugh class, and portal vein thrombosis were significant predictors of 5-day failure; alcohol-induced etiology, bilirubin, albumin, encephalopathy, and hepatocarcinoma were predictors of 6-week mortality. Prognostic reassessment including blood transfusions improved the predictive accuracy. All the developed prognostic models were superior to the Child-Pugh score. In conclusion, prognosis of digestive bleeding in cirrhosis has much improved over the past 2 decades. Initial treatment stops bleeding in 90% of patients. Accurate predictive rules are provided for early recognition of high-risk patients.
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PMID:Upper digestive bleeding in cirrhosis. Post-therapeutic outcome and prognostic indicators. 1293 86

The incidence of hepatocellular carcinoma (HCC) is increasing in the United States. Several modalities are available for the treatment of HCC, and decisions regarding the optimal choice of therapy are based on tumor burden and severity of liver disease. Classification systems are helpful for prognostic purposes and to guide in the choice of therapy. Surgical resection is a mainstay of therapy for patients with solitary small tumors and preserved liver function (noncirrhotic or Child-Pugh class A cirrhotic patients without portal hypertension). Unfortunately, a minority of patients is eligible for resection, and postoperative recurrence or de novo HCC is common. Liver transplantation offers the best chance of curing HCC in cirrhotic patients. Patients with a solitary tumor less than 5 cm or no more than three tumors each 3 cm or less have a survival rate of 70% with less than 20% recurrence at 5 years. Access to liver transplantation is limited by organ availability, and tumor progression during the waiting period can lead to ineligibility. Ethanol injection and radiofrequency ablation are effective modalities to ablate small tumors (generally <5 cm) in patients who are not candidates for resection or liver transplantation. These modalities can also be used to treat HCC prior to liver transplantation. Transarterial chemoembolization is used to treat patients with multifocal or large HCC who are ineligible for other therapies. Chemotherapeutic agents are infused into the tumor via the hepatic artery along with embolic material in order to induce tumor necrosis. This technique should be used in selective patients with relatively preserved liver function, absence of portal vein thrombosis, or encephalopathy. Limited data exist to support the use of this modality as a primary treatment option for small HCC. Chemotherapeutic or hormonal therapies have a limited role in the management of patients with HCC. Despite mixed outcomes, we routinely use the somatostatin analog octreotide in advanced, multifocal HCC. Emerging therapies should focus on treatment of small tumors and targeted pharmacologic therapy for advanced disease.
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PMID:Treatment of Hepatocellular Carcinoma. 1458 35

The natural history of PBC is characterized by slowly progressive cholestasis with liver damage, development of cirrhosis and its complications, and death, unless the patient undergoes liver transplantation. The disease has at least three clinical presentations, each with a different course and prognosis: the silent and usually less aggressive form, the asymptomatic form, and the symptomatic form. There are no identifiable features that distinguish the asymptomatic population who will remain symptom-free from those patients who will develop symptoms. As expected, the survival is longer in asymptomatic than in symptomatic patients. Overall survival of asymptomatic PBC is shorter than for an age- and gender-matched control population, but the patients remaining asymptomatic had a survival equal to that of the general population. Natural history studies have identified several variables associated with survival, particularly age, bilirubin, albumin, prothrombin time, ascites, encephalopathy, and advanced histological stage. Development of esophageal varices and hepatocellular carcinoma can also affect survival. Serum bilirubin level is, however, the most heavily weighted prognostic variable and can be used as a simplistic prognostic index for patients with PBC. In the last two decades, natural history models have been developed that include clinical, biochemical, and histological variables, the most popular being the Mayo model. It has the advantage ofavoiding histological variables, and therefore can be applicable to a broad spectrum of patients with PBC. The models may also be used to evaluate the efficacy of different new treatments. Prognostic models based on serial measurements of the independent predictors of poor prognosis would lead to a more accurate prediction of survival; however, they probably will not replace clinical outlook.
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PMID:Natural history of primary biliary cirrhosis. 1459 31

Alpha-1-antitrypsin (alpha(1)-antitrypsin) is the archetypal member of the serine proteinase inhibitor or serpin superfamily. The most common severe deficiency variant is the Z allele, which results in the accumulation of mutant protein within hepatocytes. This 'protein overload' causes neonatal hepatitis, cirrhosis and hepatocellular carcinoma. The lack of circulating plasma alpha(1)-antitrypsin results in early-onset panlobular emphysema. The mechanism underlying the deficiency of Z alpha(1)-antitrypsin is due to an aberrant conformational transition within the protein and the formation of chains of polymers that tangle within the secretory pathway of hepatocytes. This mechanism also underlies the plasma deficiency of other members of the serpin superfamily to cause a class of diseases called the serpinopathies. Specifically mutant alleles of antithrombin, C1-inhibitor and alpha(1)-antichymotrypsin have been reported that favour the spontaneous formation of polymers and the retention of protein within hepatocytes. The consequent lack of plasma antithrombin, C1-inhibitor and alpha(1)-antichymotrypsin results in thrombosis, angio-oedema and emphysema, respectively. Moreover, the polymerisation of mutants of neuroserpin results in the retention of polymers within neurones to cause the inclusion body dementia, familial encephalopathy with neuroserpin inclusion bodies or FENIB. We review here the genetic and molecular basis and clinical features of alpha(1)-antitrypsin deficiency, and show how this provides a platform to understand the other serpinopathies.
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PMID:Practical genetics: alpha-1-antitrypsin deficiency and the serpinopathies. 1469 55

Accurate assessment of utilities to calculate quality-adjusted life expectancy for medical interventions is needed in cirrhosis. To date, limited data exist in cirrhotics and are generally physician-assigned. Therefore, our aim was to determine utilities for six clinical scenarios in cirrhosis and to define if differences exist in utilities assigned by physicians versus patients. We administered a questionnaire to 83 physicians and 114 cirrhotics to obtain utilities using the time trade-off method for (1) compensated cirrhosis, (2) decompensated cirrhosis, (3) encephalopathy, (4) spontaneous bacterial peritonitis, (5) variceal bleeding, and (5) hepatocellular carcinoma. On a scale from 0 (death) to 1 (perfect health), mean utilities of physicians and patients were compared using the Student t test. One-way analysis of variance was used to compare the utilities between patients according to Child-Pugh class. Statistical significance was defined as a P value <0.05. The mean age of the physicians was 42 +/- 11, with 52% being male. The mean age of the patients was 52 +/- 9; with 59% male. The mean Child-Pugh score was 8 +/- 2 and HCV was the most common etiology (54%). The mean utilities for physicians and patients were as follows: CC, 0.78 vs. 0.88; DC, 0.55 vs. 0.74; E, 0.38 vs. 0.55; SBP, 0.33 vs. 0.45; VB, 0.27 vs. 0.40; and HCC, 0.19 vs. 0.30. All comparisons were statistically significant. Although physicians and patients assigned similar relative rankings to each health state, physicians assigned utilities were significantly different from those assigned by patients. These results suggest that studies that have used physician-assigned utilities do not accurately reflect patient preferences.
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PMID:Comparison of health-related quality of life preferences between physicians and cirrhotic patients: implications for cost-utility analyses in chronic liver disease. 1513 97

This retrospective pilot study was conducted in a series of 166 patients hospitalized for the first time for management of cirrhosis with or without complications over a two-year period at the University Hospital Center in Brazzaville, Congo. Complications included ascitics, hepatic encephalopathy, gastrointestinal bleeding, and hepatocellular carcinoma. Total care cost was determined by adding up expenditures for the initial examination, each day of hospitalization, adjuvant investigations, and administered medication. The mean per-patient cost was 272345 F CFA (415.79 [symbol: see text]) in cases involving ascites, 195675 F CFA (298.74 [symbol: see text]) in cases involving encephalopathy, 207935 F CFA (317.45 [symbol: see text]) in cases involving hepatocellular carcinoma, 245680 F CFA (375.08 [symbol: see text]) in cases involving gastrointestinal bleeding and 205615 F CFA (313.90 [symbol: see text]) in uncomplicated cases. These data document the high cost of hospital care for cirrhosis and related complications in Congo.
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PMID:[Cost of of hospital management of cirrhoses and its complications at the University Hospital of Brazzaville]. 1522 58

Chronic hepatitis B infection (HBV) is a major health problem worldwide. The prognosis is grave for patients with HBV-related decompensated liver cirrhosis (LC). We evaluated the effectiveness and the determinants of early mortality of lamivudine treatment in patients with HBV-related decompensated LC. Thirty patients with HBV-related decompensated LC and active viral replication were treated with lamivudine 100 mg daily for a median duration of 9 months. Among these patients, five patients died within 3 months. Two patients were lost to follow-up at week 8 and 9. One patient was treated for <6 months. Twenty-two patients were treated over 6 months. Univariate analysis revealed that the total bilirubin (P = 0.008), prothrombin time (P = 0.004), Child-Turcotte-Pugh score (P = 0.005), the model of efd-stage liver disease score (P = 0.004) and stage III hepatic encephalopathy (P = 0.001) were predictive factors of early mortality. Multivariate analysis revealed that the independent factor associated with early mortality was stage III encephalopathy. Among 22 patients, liver function improved markedly after lamivudine therapy. Of the nine hepatitis B e antigen (HBeAg)-positive patients, three had HBeAg seroconversion. Two patients had YMDD mutant and virological breakthrough at 41 and 46 weeks. One of the two had hepatocellular carcinoma and died of hepatic failure at week 125; the other received adefovir and is doing well. Lamivudine appeared to have benefits in viral suppression and significant improvement in liver function in patients with HBV-related decompensated LC. As noted in prior studies, poor baseline liver function is associated with a poor prognosis in Asian patients with decompensated HBV cirrhosis treated with lamivudine.
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PMID:Determinants of early mortality and benefits of lamivudine therapy in patients with hepatitis B virus-related decompensated liver cirrhosis. 1598 9

The cirrhosis prevalence in the whole French population can be estimated between 2000 and 3300 cases/million of individuals. Alcoholism, hepatitis C virus and non alcoholic fatty liver disease are the three most common causes of cirrhosis in France. About 40% of patients with cirrhosis have compensated cirrhosis and are asymptomatic over long period of 1 to 10 years. Decompensation of cirrhosis was considered when a patient first developed one of the mayor complications of the disease (ascites, jaundice, encephalopathy or gastrointestinal haemorrhage). After the first decompensation, the incidence of death is about 10% by year, in the absence of hepatic transplantation. The mortality of patients with cirrhosis and acute varicose bleeding has greatly decreased over the past 2 decades in concurrence with an early and combined use of pharmacological and endoscopic therapy, but hepatocellular carcinoma is the most frequent life threatening complication.
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PMID:[Epidemiology and natural history of cirrhosis]. 1625 93


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