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

A patient with cirrhosis developed hemoperitoneum, lactic acidosis, and hyperphosphatemia in the absence of shock. At post-mortem examination occult multicentric hepatocellular carcinoma eroding the liver capsule was present. The case emphasizes the central role of the liver in lactic acidosis, indicates that hemoperitoneum may precipitate this complication, and documents the association of lactic acidosis and hyperphosphatemia.
 ...
PMID:Lactic acidosis associated with cirrhosis, hepatoma, hemoperitoneum, and hyperphosphatemia. 301 70

Chronic hepatitis B is a widespread viral illness with the serious sequelae of cirrhosis and hepatocellular carcinoma. Current therapy with interferon is not universally efficacious, and this has led to the evaluation of other antiviral agents. A recent Phase II trial of the nucleoside analogue, fluoroiodoarabinofuranosyluracil (fialuridine, FIAU) was halted because of the sudden development of severe multisystem toxicity characterized by hepatic failure, lactic acidosis, and pancreatitis, which resulted in the deaths of five patients. We systematically evaluated pre- and post-therapy biopsy, explant, and autopsy specimens from the 15 patients involved in this trial to define the hepatic changes of fialuridine toxicity and to determine whether the degree of pre-existing hepatitis contributed to the severity of toxicity. Severe hepatotoxicity from fialuridine was characterized by hepatomegaly with diffuse, predominantly microvesicular steatosis, hepatocellular glycogen depletion, marked bile ductular proliferation, and cholestasis. Ultrastructural examination revealed intracytoplasmic lipid droplets and marked mitochondrial injury. Patients in whom severe toxicity did not develop mainly showed changes caused by the underlying chronic hepatitis B alone. There was a subtle increase in the amount of microvesicular steatosis in two of six patients with mild or no symptoms of toxicity. The microscopic and ultrastructural pattern of injury and systemic symptoms in patients with fialuridine toxicity are consistent with severe mitochondrial and metabolic derangements. Similar hepatic pathologic findings have been reported rarely for other antiviral nucleoside analogues, which suggests that the mechanisms of toxicity might be related.
 ...
PMID:Histopathologic changes associated with fialuridine hepatotoxicity. 907 26

A case is reported in which a large hepatoma presented with rupture and acute severe lactic acidosis. Spontaneous rupture is a rare but recognised mode of presentation of hepatoma. Malignancy has also occasionally been associated with acute lactic acidosis, though the association with hepatoma has not previously been reported.
 ...
PMID:Ruptured hepatoma presenting with peritonitis and acute lactic acidosis. 928 74

Although metformin is widely used for the treatment of non-insulin-dependent diabetes, its mode of action remains unclear. Here we provide evidence that its primary site of action is through a direct inhibition of complex 1 of the respiratory chain. Metformin(50 microM) inhibited mitochondrial oxidation of glutamate+malate in hepatoma cells by 13 and 30% after 24 and 60 h exposure respectively, but succinate oxidation was unaffected. Metformin also caused time-dependent inhibition of complex 1 in isolated mitochondria, whereas in sub-mitochondrial particles inhibition was immediate but required very high metformin concentrations (K(0.5),79 mM). These data are compatible with the slow membrane-potential-driven accumulation of the positively charged drug within the mitochondrial matrix leading to inhibition of complex 1. Metformin inhibition of gluconeogenesis from L-lactate in isolated rat hepatocytes was also time- and concentration-dependent, and accompanied by changes in metabolite levels similar to those induced by other inhibitors of gluconeogenesis acting on complex 1. Freeze-clamped livers from metformin-treated rats exhibited similar changes in metabolite concentrations. We conclude that the drug's pharmacological effects are mediated, at least in part, through a time-dependent, self-limiting inhibition of the respiratory chain that restrains hepatic gluconeogenesis while increasing glucose utilization in peripheral tissues. Lactic acidosis, an occasional side effect, canal so be explained in this way.
 ...
PMID:Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. 1083 93

A 60-year-old male with liver cirrhosis (Child-Pugh class B) underwent laparotomic radio frequency ablation for the treatment of a solitary hepatocellular carcinoma (-4.5 cm in diameter). Severe lactic acidosis (base excess < -12 mEq.l-1, lactate > 150 mg.dl-1) developed during the intraoperative period, when neither his hemodynamics nor arterial oxygenation was significantly impaired. The blood loss was small (-200 g), and the serum hemoglobin level was maintained -10 g.dl-1 during the procedure. There was no evidence for impairment of either peripheral perfusion or renal function. In addition, there was no evidence for development of either splanchnic ischemia or diabetic ketoacidosis. Thus, the acidosis appeared to be caused by significant impairment of liver function possibly resulting from the ablation (total ablation time = -60 min). The core temperature increased rapidly (-1.5 degrees C/60 hr) immediately after the ablation was started, suggesting that a large amount of heat was produced in the ablated area and/or that the vicinity of the ablated area was richly supplied by blood flow. As a result, intact liver cells in the vicinity of the tumor probably suffered from thermal injuries. In conclusion, depending on preoperative liver function, ablated area, and/or blood flow in the vicinity of ablated area, the ablation may become significantly invasive.
 ...
PMID:[Development of severe lactic acidosis during radio frequency ablation conducted for the treatment of hepatocellular carcinomata in a patient with liver cirrhosis]. 1248 57

With highly active antiretroviral therapy (HAART), HIV-infected patients can now live longer and healthier lives, and other comorbid diseases, such as chronic hepatitis C, have emerged as a significant health concern. Coinfection with the hepatitis C virus (HCV) may limit life expectancy because it can lead to serious liver disease including decompensated liver cirrhosis and hepatocellular carcinoma. HCV-induced fibrosis progresses faster in HIV/HCV-coinfected persons, although HAART may be able to decrease this disease acceleration. Combination therapy for HCV with interferon and ribavirin can achieve a sustained viral response, although at a lower rate than in HCV-monoinfected patients. Combination treatment with pegylated interferon and ribavirin will probably emerge as the next HCV therapy of choice for HIV/HCV-coinfected patients. HCV combination therapy is generally safe, but serious adverse reactions, like lactic acidosis, may occur. Cytopenia may present a problem leading to dose reductions, but the role of growth factors is under study. All HIV/HCV-coinfected patients should be evaluated for therapy against the hepatitis C virus. A sustained viral load will probably lead to regression of liver disease, and even interferon-based treatment without viral clearance may slow down progression of liver disease. HIV/HCV-coinfected patients who have progressed to end-stage liver disease have few therapeutic options other than palliative care, since liver transplants are generally unavailable. The mortality post-transplant may be higher than in HCV-monoinfected patients. We are entering an era where safe and effective HCV therapy is being defined for HIV/HCV-coinfected patients, and all eligible patients should be offered treatment.
 ...
PMID:Update on chronic hepatitis C in HIV/HCV-coinfected patients: viral interactions and therapy. 1457 Nov 79

(1) Without treatment, between 15% and 25% of patients with chronic hepatitis B die prematurely, usually of cirrhosis or hepatocellular carcinoma. Two treatments are already available to prevent these complications, namely interferon alfa (2a and 2b), and lamivudine, a nucleotide analogue. (2) Marketing authorization has now been granted in the European Union for another antiviral agent, adefovir dipivoxil, a prodrug of the nucleotide analogue adefovir. (3) Two double-blind placebo-controlled trials in treatment-naive patients with active viral replication showed that adefovir dipivoxil 10 mg/day orally reduced viral load and improved hepatic histology. (4) In lamivudine-resistant patients with active viral replication, the preliminary results of two trials comparing adefovir dipivoxil with continued lamivudine therapy, and data from two non comparative trials (one in HIV-coinfected patients), showed that adefovir dipivoxil reduced viral load by about 4 log after 48 weeks. (5) In clinical trials, creatinine levels rose in 2-5% of patients treated with 10 mg/day adefovir dipivoxil, reflecting renal toxicity. Other possible risks, and especially lactic acidosis, must be monitored closely. (6) In practice, adefovir dipivoxil is currently a third-line option for patients with chronic hepatitis B, when interferon alfa-2 and lamivudine fail or are poorly tolerated.
 ...
PMID:Adefovir dipivoxil: new preparation. A third-line option in chronic hepatitis B. 1505 5

Cirrhosis is a serious complication of viral hepatitis, and its incidence is increasing in HIV patients coinfected with HCV or HBV as they live longer, thanks to effective antiretroviral treatment (Haart). HIV coinfection accelerates the progression of fibrosis in hepatitis. To implement preventive measures, prompt diagnosis of cirrhosis is important, either by liver biopsy or the noninvasive tests for fibrosis now under wide study (FibroTest, FibroScan, etc.). Afterwards, assessment of the severity of cirrhosis and screening for complications are both necessary: testing for liver failure (Child-Pugh and MELD scores), portal hypertension (upper gastrointestinal endoscopy), and hepatocellular carcinoma (ultrasound and alpha fetoprotein assay). Careful consideration of drug prescriptions and possible interactions is essential. Specific treatment for hepatitis B or C virus is possible at this stage of cirrhosis, although more difficult, especially for HCV (results influenced by genotype, additional risk of complications by lactic acidosis or hepatic decompensation). Management of the complications of portal hypertension must be planned, as for those without HIV infection. Treatment of hepatocellular carcinoma is still disappointing, and liver transplantation, although possible in these patients, must be evaluated.
 ...
PMID:[Management of cirrhosis complications in HIV patients coinfected with hepatitis B or C virus]. 1631 17

Glycogen storage disease type Ia (GSD Ia) is a rare metabolic disorder due to hepatic glucose-6-phosphatase deficiency. Although great progress has been made in managing affected patients, severe hypoglycemia, lactic acidosis, hyperlipidemia, hepatic cytolysis, and impaired kidney function are frequent. Liver transplantation is the only radical treatment, for which the main indications are hepatic adenomatosis, hepatocellular carcinoma, or severe hepatic dysfunction. We present the case of a patient with end-stage renal disease without focal hepatic lesions and with moderate hepatic metabolic control, and we explain how combined liver-kidney transplantation (LKT) made it possible to correct the metabolic defects responsible for the impaired glucose homeostasis, liberalize the diet, and give birth to a healthy child after an uneventful pregnancy. Patients with end-stage renal disease that resulted from GSD Ia should be considered for LKT even in the absence of hepatic lesions with the aim of improving their quality of life.
 ...
PMID:Combined liver-kidney transplantation in glycogen storage disease Ia: a case beyond the guidelines. 1745 69

Short-chain quinones are described as potent antioxidants and in the case of idebenone have already been under clinical investigation for the treatment of neuromuscular disorders. Due to their analogy to coenzyme Q10 (CoQ10), a long-chain quinone, they are widely regarded as a substitute for CoQ10. However, apart from their antioxidant function, this provides no clear rationale for their use in disorders with normal CoQ10 levels. Using recombinant NAD(P)H:quinone oxidoreductase (NQO) enzymes, we observed that contrary to CoQ10 short-chain quinones such as idebenone are good substrates for both NQO1 and NQO2. Furthermore, the reduction of short-chain quinones by NQOs enabled an antimycin A-sensitive transfer of electrons from cytosolic NAD(P)H to the mitochondrial respiratory chain in both human hepatoma cells (HepG2) and freshly isolated mouse hepatocytes. Consistent with the substrate selectivity of NQOs, both idebenone and CoQ1, but not CoQ10, partially restored cellular ATP levels under conditions of impaired complex I function. The observed cytosolic-mitochondrial shuttling of idebenone and CoQ1 was also associated with reduced lactate production by cybrid cells from mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) patients. Thus, the observed activities separate the effectiveness of short-chain quinones from the related long-chain CoQ10 and provide the rationale for the use of short-chain quinones such as idebenone for the treatment of mitochondrial disorders.
 ...
PMID:NQO1-dependent redox cycling of idebenone: effects on cellular redox potential and energy levels. 2148 49


1 2 Next >>