Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

At routine determination of serum activities of transaminases (aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) increased levels are frequently found. An algorithm may be used in the analysis of elevated transaminase levels: after elimination of the most frequent causes of hepatitis (alcoholic hepatitis, chronic hepatitis B and C) and some rare conditions (autoimmune hepatitis, alpha 1-antitrypsin deficiency, haemochromatosis and Wilson's disease), the diagnosis will often be nonalcoholic steatohepatitis. Although nonalcoholic steatohepatitis is considered a stable disease, recent literature shows a progression to cirrhosis in 8-17%. So far, no effective therapeutic strategies are available for nonalcoholic steatohepatitis.
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PMID:[Management of asymptomatic elevated serum aminotransferase levels, particularly in nonalcoholic steatohepatitis]. 1032 Dec 58

Two patients with hemophagocytic lymphohistiocytosis who presented with acute liver failure are reported. Both presented with fever, hepatosplenomegaly, markedly elevated liver function tests, abnormal coagulation profiles, and an increase in serum ferritin. Both infants were diagnosed with neonatal hemochromatosis based on a clinical picture of hepatic insufficiency with hyperferritinemia and were referred for liver transplantation. The first patient died of liver failure and septicemia before transplantation. Review of autopsy material revealed a hepatitis-like pattern and extensive infiltration of liver and other organs including bone marrow by histiocytes, some of which were hemophagocytic. The second patient underwent liver transplantation but died 44 days thereafter from progressive hemophagocytic lymphohistiocytosis. Examination of the resected liver demonstrated a hepatitis-like pattern, proliferation of histiocytes, and hemophagocytosis, and the bone marrow revealed hemophagocytic histiocytosis. Hemophagocytosis recurred in the allograft. Hepatic manifestations are common in hemophagocytic lymphohistiocytosis and overt hepatic failure may occur, but initial presentation as fulminant hepatic failure is not well recognized. Elevated serum ferritin can make the distinction from neonatal hemochromatosis and other forms of neonatal liver failure difficult. Hemophagocytic lymphohistiocytosis should be considered in the differential diagnosis of neonatal liver disease, especially when it is accompanied by cytopenias.
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PMID:Hemophagocytic syndrome presenting as acute hepatic failure in two infants: clinical overlap with neonatal hemochromatosis. 1034 80

There is increasing evidence that hepatotoxins, such as alcohol and the hepatitis viruses, act as co-factors in causing hepatic fibrosis and cirrhosis. For example, alcohol aggravates the hepatic damage produced by iron in hereditary haemochromatosis. We present evidence that the reverse is also true, that is, that iron loading of mild to moderate degree due to heterozygosity or homozygosity for the haemochromatosis genetic mutations acts as a significant hepatotoxin aggravating hepatic damage from other causes of liver disease. These include non-alcoholic steatohepatitis, chronic hepatitis C, porphyria cutanea tarda and possibly primary liver cell cancer. However, any additional hepatotoxic effect is due to the hepatic iron concentration and not the mutations in the haemochromatosis genes.
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PMID:The haemochromatosis gene: a co-factor for chronic liver diseases? 1048 24

Even at an early stage, hepatocellular carcinoma (HCC) in patients with cirrhosis is often deemed unresectable because of limited liver reserve. In these circumstances, liver transplantation (LTx) offers some hope for palliation or cure. The results of LTx for selected cirrhotic patients with HCC were analysed. The outcomes were compared with those of patients who underwent LTx for other forms of hepatic malignancy and those who underwent LTx for non-malignant conditions. Four hundred and eighty LTx were performed in 441 patients between January 1986 and December 1998. Twenty-eight LTx recipients (25 males, 3 females) of mean age 51 (14 63) yr had cirrhosis and HCC. Twenty-seven patients had underlying predisposing conditions (11 had hepatitis B, 10 had hepatitis C, 2 had hepatitis B and C, 1 had haemochromatosis, 1 had autoimmune hepatitis, 1 had alcoholic cirrhosis and 1 had alpha-1 antitrypsin deficiency). In 22 patients, HCC was diagnosed pre-LTx, and in 6 patients, the cancers were discovered incidentally. The average tumour size and number were 2.8 (0.4-11.5) cm and 1.3 (1-4), respectively. Two patients with known HCC died during and shortly after the LTx operation. Of the other patients, 3 died; 1 died of HCC recurrence 18 months post-LTx, 1 died of graft failure from recurrent hepatitis C and 1 died of fungal sepsis. Twenty-three (82%) patients survived to 22.5 (0.5-96) months post-LTx without HCC recurrence and with 1- and 3-yr actuarial patient survival rates of 87 and 76%, respectively. Equivalent survival rates of patients who underwent LTx for other malignancies (n = 11) were 82 and 46% (p = NS), and for those who underwent LTx for benign causes (n = 402), they were 77 and 73% (p = NS). All 15 patients with known HCC, who met the selection criteria now in use, survived. LTx can result in prolonged. cancer-free survival in a good proportion of patients with cirrhosis and HCC, particularly when the cancers are incidental, or when diagnosed pre-LTx, conforming to established selection criteria. An active LTx programme for this group of patients is justified.
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PMID:An active liver transplant programme for hepatocellular carcinoma in cirrhotic patients: is it justified? 1061 45

It has been proposed that iron overload may adversely affect liver disease outcome. The recent identification of 2 mutations in the HFE gene related to hereditary haemochromatosis (Cys282Tyr and His63Asp) provided an opportunity to test whether they are associated with hepatic iron accumulation and the activity and severity of liver disease in hepatitis C virus (HCV) infection. We investigated the prevalence of HFE mutations in 135 male patients with chronic HCV hepatitis, and correlated genotype distribution with different parameters of iron status and the activity and severity of liver disease. Of these 135 patients, 6 (4.4%) carried Cys282Tyr and 32 (23.7%) carried His63Asp, frequencies which were similar to those observed in healthy controls. Serum iron levels and transferrin saturation (but not ferritin levels or liver iron content) were significantly higher in carriers than in non-carriers of HFE mutations. No difference was observed in serum ALT, AST and GGT levels between carriers and non-carriers. Finally, scores for necroinflammatory activity and fibrosis in the liver were significantly higher in HFE carriers than in non-carriers. Patients with chronic HCV infection carrying HFE mutations tend to present more evident body iron accumulation and a higher degree of necroinflammatory activity and fibrosis in the liver. HFE gene mutations might be an additional factor to be considered among those implicated in the determination of a worse prognosis of the liver disease in chronic HCV infection.
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PMID:Are haemochromatosis mutations related to the severity of liver disease in hepatitis C virus infection? 1069 80

We performed a case-control study to assess the role of hepatitis B virus (HBV), hepatitis C virus (HCV), GB virus C/hepatitis G virus (HGV), TT virus, alcohol intake, and tobacco smoking as risk factors for hepatocellular carcinoma (HCC) in the presence or absence of cirrhosis. We prospectively recruited 174 patients with a first diagnosis of HCC admitted to the main hospitals in Brescia, North Italy. On the basis of histological, clinical, and radiological criteria, the presence of cirrhosis was established in 142 cases, excluded in 21 cases, and remained undefined in 11 cases. Among the HCC cases without cirrhosis, a histological picture of normal liver was found in a single patient, chronic viral hepatitis was found in 11 patients, alcoholic hepatitis was found in 5 patients, nonspecific reactive hepatitis was found in 3 patients, and hemochromatosis was found in 1 patient. As controls, we also included 610 subjects unaffected by hepatic diseases and admitted to the same hospitals as cases. The odds ratios for having HCC according to positivity for HCV RNA, HBsAg and/or HBV DNA, and alcohol intake > 80 g/day (95% confidence interval) were as follows, in the presence and absence of cirrhosis, respectively: (a) 33.5 (17.7-63.4) and 19.7 (6-64.8) for HCV RNA; (b) 17.6 (9.0-34.4) and 20.3 (5.7-72.6) for HBsAg; and (c) 5.5 (3.1-9.7) and 4.6 (1.5-13.8) for alcohol intake. No association was found with HGV or TT virus infections or tobacco. This study has shown that most HCC cases arising in the area are due to HBV, HCV, or alcohol intake, in both the presence and absence of cirrhosis.
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PMID:Etiology of hepatocellular carcinoma in Italian patients with and without cirrhosis. 1069 84

The gut and the liver are the key organs in nutrient absorption and metabolism. Bile acids, drugs, and toxins undergo extensive enterohepatic circulation. Bile acids play a major role in several hepatic and intestinal diseases. Endotoxins deriving from intestinal Gram-negative bacteria are important in the pathogenesis of liver and systemic diseases. Chronic liver diseases can influence gastrointestinal motility, which together with other factors may contribute to bacterial overgrowth and in patients with ascites to an increased risk of spontaneous bacterial peritonitis. Patients with end-stage liver disease frequently develop portal hypertension leading to varices, gastric vascular ectasia, and portal hypertensive gastroenteropathy. Several liver and biliary abnormalities are observed in patients with inflammatory bowel disease (primary sclerosing cholangitis, autoimmune hepatitis, cholelithiasis). The primary defect in hemochromatosis is located in the intestine, causing an inappropriate increase in iron absorption, and the liver is the site of earliest and heaviest iron deposition. Elevated transaminases are observed in many patients with celiac disease, and steatohepatitis frequently develops in patients with jejunoileal bypass and short bowel syndrome. Furthermore, the liver is the primary organ for metastasis of intestinal cancer. Many viral, bacterial, fungal, and parasitic diseases affect the intestine as well as the liver and the biliary tract.
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PMID:Gut-liver axis. 1085 47

An imbalance between cytoproliferation and apoptosis may be relevant in liver carcinogenesis. The aim of this study was to analyse these parameters in patients with chronic liver damage in relation to the aetiology of the disease. Forty-eight patients were studied: 23 had hepatitis C virus (HCV)- and 11 had hepatitis B virus (HBV)-related chronic hepatitis, seven had alcoholic liver disease, and seven had haemochromatosis. The biopsies were used for routine diagnosis, cytoproliferative indexing (MIB1, Ki67 monoclonal antibody), apoptosis (APO, in situ end labelling) and, in part, liver iron and malondialdehyde determination. Apoptosis was similar in all patient subgroups and correlated with hepatitis grading (P=0.002) and ALT levels (P=0.004); cytoproliferation (MIB1) levels were higher in HCV patients, both as a whole and in the periportal area (P=0.02 and P=0.03). MIB1 correlated with ALT levels (P=0.0001), hepatitis grading (P=0.02) and tissue iron (P=0.04). APO and MIB1 were higher in patients with than in those without cirrhosis (P=0.0006 and P=0.03, respectively). APO correlated with MIB1 (P=0.001), overall but not in HCV patients. The MIB1/APO ratio was significantly higher in HCV patients than in the other groups (P=0.02). In summary, cytoproliferation is more pronounced in chronic HCV-related hepatitis, while APO is not significantly higher than in other types of liver damage, suggesting an imbalance between the two. APO and MIB1 are directly related to the extent of liver damage and, from a biochemical point of view, to tissue iron levels.
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PMID:Imbalance between cytoproliferation and apoptosis in hepatitis C virus related chronic liver disease. 1115 50

Thirty children received 35 liver transplants for fulminant or late-onset liver failure between March 1988 and May 1993. Aetiology included non-A non-B hepatitis in 12, Wilson's disease in 8, drug-induced hepatic failure in 6, hepatitis B in 1, hepatitis A in 1, tyrosinaemia in 1 and congenital haemochromatosis in 1. Three patients were retransplanted, one each for hepatic artery thrombosis, non-A non-B graft reinfection, and chronic rejection. Two of these three patients received a third transplant for chronic rejection and hepatic artery thrombosis. One patient in the retransplant group survived. Overall, graft and patient survival at a mean follow-up of 17 months were 49% and 57%, respectively. Mortality was related to vascular complications in three patients (hepatic venous obstruction, portal vein thrombosis and hepatic artery thrombosis). Two patients died of primary sepsis (cerebral aspergillosis and cytomegalovirus (CMV) pneumonitis in association with graft-versus-host disease). Systemic sepsis and multiorgan failure was documented as a cause of death in four children and sepsis in association with chronic rejection in a further three patients. One child died of respiratory failure 4 weeks after transplantation. Mortality in eight children less than 2 years was 75% and this was significantly greater than for older children (P < 0.003, Mantel Cox). Earlier referral, even in the absence of a definitive diagnosis and particularly in children under 2 years is advisable and may improve survival.
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PMID:Orthotopic liver transplantation for acute hepatic failure in children. 1127 Nov 76

The definable causes of nonalcoholic steatohepatitis (NASH) include jejunoileal bypass surgery (JIB), other causes of rapid and profound weight loss in obese subjects, total parenteral nutrition, drugs, industrial toxins, copper toxicity, and disorders characterized by extreme insulin resistance. However, the etiopathogenesis in most cases of NASH appears multifactorial. Obesity, type 2 diabetes, and hypertriglyceridemia are often associated with hepatic steatosis, and although this does not invariably lead to NASH, the fatty liver is vulnerable to hepatocellular injury initiated by reactive oxygen species (ROS). It is critical to understand not only the triggers for hepatitis (injury and inflammation) in NASH but also how this is perpetuated as chronic liver disease. The present focus is on whether the biochemical processes that generate oxidative stress lead to hepatocyte injury and secondary recruitment of inflammation or whether inflammation is the primary mediator of liver cell injury. Insulin resistance is a reproducible pathogenic factor in NASH. It favors accumulation of free fatty acids in the liver and predisposes to oxidative stress by stimulating microsomal lipid peroxidases and by the direct effects of high insulin levels in decreasing mitochondrial beta-oxidation. CYP2E1 is normally suppressed by insulin but is invariably increased in the livers of patients with NASH. In rodent dietary models of steatohepatitis, CYP2E1 is the catalyst of microsomal lipid peroxidation, while in Cyp 2e1 nullizygous mice, CYP4A proteins are induced and function as alternative microsomal lipid peroxidases. Other studies implicate activation of peroxisome proliferator-activated receptor-alpha (PPAR alpha) as leading to NASH; PPAR alpha is a transcription factor that governs both microsomal (via CYP4A) and peroxisomal (beta-oxidation) pathways of lipid oxidation and ultimately production of ROS. Increased lipid peroxidation is a crucial difference between the livers of rodents with experimental NASH and those of ob/ob genetically obese mice that have uncomplicated steatosis. Administration of endotoxin, through the release of tumor necrosis factor-alpha (TNF-alpha), provokes liver inflammation with hepatocyte injury in the steatotic liver. This may be particularly relevant in JIB and has been suggested as a pathogenic mechanism in primary NASH. It has been proposed that inheriting one or more copies of the hemochromatosis gene, C282Y, promotes fibrotic progression in NASH because of increased hepatic iron deposition, but recent studies have failed to confirm this. The relationship between the severity of hepatitis in NASH and progression to cirrhosis implies that products of the inflammatory infiltrate play a role in fibrogenesis. In summary, NASH can be regarded as the hepatic consequence of the metabolic syndrome (or syndrome X). Attention should now shift from steatosis, a generally benign process that is less evident in the advanced stages of cirrhosis, to the mechanisms for hepatocellular injury, inflammation, and hepatic fibrosis. In particular, the genetic, molecular, and cellular factors that ordain and moderate fibrosis in the context of steatohepatitis will be of greatest relevance to effective therapy and clinical outcome.
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PMID:Etiopathogenesis of nonalcoholic steatohepatitis. 1129 94


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