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PubMed1999

Surgery in the patient with liver disease.

Patients with liver disease often undergo surgery. With the increasing prevalence of liver disease and improved survival due to newer medications and treatments, a growing number of patients with liver disease will require preoperative assessment. Because of the multiple physiological roles of the liver, hepatic dysfunction places these patients at an increased risk of perioperative morbidity and mortality. The precise risks associated with specific liver diseases are poorly understood but are greater with increased impairment of hepatic function. Identifying preexisting problems that could be optimally and appropriately managed before surgery (e.g., coagulation status, intravascular volume, renal function, electrolytes, cardiovascular status, and nutrition) may reduce these risks and decrease mortality in patients with liver disease undergoing surgery.

Anesthesia, General↗
PubMed2006

Diagnostic evaluation of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is a diagnostic consideration among patients with asymptomatic elevated aminotransaminases, patients with radiologic findings of hepatic fatty infiltration, or occasionally in the patient with "cryptogenic" cirrhosis. The diagnosis of NAFLD requires evidence of fatty infiltration of the liver in the absence of excessive alcohol ingestion. Clinical evaluation should examine for metabolic risk factors (central obesity, glucose intolerance, hypertension, hypertriglyceridemia, and low HDL cholesterol), which are suggestive but not specific for the diagnosis of NAFLD. Secondary causes of NAFLD, such as medications and intestinal bypass surgery, should be excluded as management of these conditions may differ. Confirmation of hepatic steatosis can usually be done by imaging studies, although occasionally liver biopsy is required. Among suspected NAFLD patients with chronically elevated aminotransaminases, clinical evaluation and serological testing should be performed to exclude other causes of chronic liver disease. Liver biopsy is required to stage fibrosis and distinguish between nonalcoholic steatohepatitis and steatosis. This is valuable for providing prognosis, excluding other liver disease, monitoring response to therapy or evaluating disease progression over time. Clinical features, particularly diabetes, obesity, and older age, can aid in stratifying patients at risk for advanced fibrosis but are not sufficiently accurate to replace liver biopsy.

Biopsy↗
PubMed2006

The usefulness of bone marrow aspiration in the diagnosis of Niemann-Pick disease type C in infantile liver disease.

BACKGROUND: Niemann-Pick disease type C (NPC) is a fatal, autosomal recessive lysosomal storage disease which may present in infancy with cholestatic jaundice and/or hepatosplenomegaly. In cholestatic patients with splenomegaly, a bone marrow aspirate has been advocated as a relatively accessible tissue to demonstrate storage phenomena. Typically in patients with NPC, macrophages with abnormal cholesterol storage, so called foam cells, can be detected in the bone marrow. AIM: To review our experience of bone marrow aspiration in children with NPC presenting with infantile liver disease. METHODS: A retrospective analysis of 11 consecutive children (8 males) from Birmingham Children's Hospital with NPC presenting with infantile liver disease was undertaken. The diagnosis of NPC was confirmed in all cases by demonstrating undetectable or low rates of cholesterol esterification and positive filipin staining for free cholesterol in cultured fibroblasts. RESULTS: The median age at presentation was 1.5 months (range 0.5-10). Bone marrow aspirates showed storage cells in only 7/11 cases. Bone marrow aspirates which had storage cells were undertaken at a median age of 11 months while those with no storage cells were undertaken at median age 2.3 months. The overall sensitivity of bone marrow aspirates for detecting storage cells in children presenting with infantile liver disease was 64%; however, for children who had bone marrow aspirates in the first year of life it was only 57%. CONCLUSIONS: The sensitivity of bone marrow aspirate for the diagnosis of NPC disease in patients presenting with infantile liver disease was lower than previously reported. Where NPC is suspected clinically, definitive investigations should be undertaken promptly. There is a need to develop sensitive screening methods for NPC in children presenting with infantile liver disease.

Age Factors↗
PubMed2006

[Antioxidant therapy in chronic liver diseases].

In chronic liver diseases with inflammatory reactions (chronic viral hepatitis, alcoholic liver disease, non-alcoholic steatohepatitis, autoimmune hepatitis, chemicals and drug induced hepatitis, Wilson disease, haemochromatosis) the oxidative stress, the cell alteration induced by free radicals is an important part of the pathogeneis beside the aetiological factors. In this paper the development of free radicals and their physiological role are demonstrated. The factors, which are influenced by the free radicals and antioxidants, as well as the pathological effects caused by oxidative stress in biological systems are discussed in details. The authors demonstrate the free radical processes as key factors in alcoholic liver diseases and non-acoholic steatohepatitis, furthermore the possible treatment modalities in the inhibition of these alterations. Also the free radical processes in chronic viral hepatitis and autoimmune hepatitis are discussed as well. The oxidative stress is able to enhance the progression of chronic inflammatory liver disease independently from the aetiological factor or with it together. That is why the antioxidant drugs could be applied also in the treatment of chronic liver diseases beside the therapy based on the aetiological factors.

Antioxidants↗
PubMed2001

In situ detection of oxidative DNA damage, 8-hydroxydeoxyguanosine, in chronic human liver disease.

BACKGROUND/AIMS: 8-Hydroxydeoxyguanosine (8-OHdG) is a promutagenic DNA lesion produced by oxygen radicals and is recognized as a useful marker in estimating DNA damage induced by oxidative stress. METHODS: Hepatic expression of 8-OHdG was immunohistochemically investigated in control and diseased human livers. RESULTS: While no positive immunolabeling for 8-OHdG was observed in control livers, 8-OHdG was widely evident in diseased livers. Nuclear expression of 8-OHdG in the hepatocytes and bile duct cells were found in various forms of chronic hepatitis. 8-OHdG-positive hepatocytes were especially abundant in the periportal area with piecemeal necrosis and prominent cell infiltration. The number of positive hepatocytes significantly increased with the progression of severity of chronic hepatitis activity (r(s)=0.68, P<0.05). In alcoholic liver disease, nuclear expression of 8-OHdG was detected in the hepatocytes in the area of alcoholic hepatitis. Regarding primary biliary cirrhosis, 8-OHdG was preferentially detected in the nuclei of injured bile ducts (11 of 12 cases, 91.7%) and occasionally (2 of 12 cases, 16.7%) in the nuclei of hepatocytes around the bile duct lesions. CONCLUSIONS: These results indicate that oxidative DNA damage is common in various forms of chronic liver disease suggesting a possible link between chronic inflammation and hepatocarcinogenesis.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1993

Clinical value of the determination of fasting glycocholic acid serum levels in patients with liver diseases. A comparison with standard liver tests.

Fasting serum levels of glycocholic acid were measured in 142 patients with benign diffuse liver diseases. A total of 63.4% of the whole group of patients, 86.6% of the cirrhotic patients and 31.7% of the noncirrhotic patients had increased serum levels of glycocholic acid. There were significant correlations with blood liver tests associated with liver disease severity such as prothrombin activity and albumin. There were highly significant differences in glycocholic acid levels according to the histological severity of the liver disease, especially when patients with cirrhosis or chronic active hepatitis were compared to the remaining patients and controls. However, discriminant analysis showed that prothrombin activity and albumin were better than glycocholic acid in predicting the histological severity of liver disease. Glycocholic acid serum levels were relatively independent of cholestasis and cytolysis and appeared to be more linked to liver dysfunction. In conclusion, fasting glycocholic acid measurement can be useful in the evaluation and follow-up of liver diseases as a marker of histological severity, and used in addition to other liver tests.

Adolescent↗
PubMed2003

Respective roles of porto-septal fibrosis and centrilobular fibrosis in alcoholic liver disease.

In alcoholic liver disease, fibrosis classically begins around the centrilobular veins, while portal tract fibrosis is described as inconstant and septal fibrosis is a late event. The aim of this study was to compare the roles of centrilobular fibrosis (CLF) and portal tract/septal fibrosis (PTF) especially in alcoholic chronic liver disease. One hundred and sixty patients with alcoholic chronic liver disease and 83 controls with viral chronic hepatitis were included. The PTF score, derived from the Metavir score, CLF and the area of fibrosis, assessed by image analysis, were evaluated on liver biopsies in addition to blood markers of fibrosis. The correlation between the PTF score and the area of fibrosis was higher in alcoholic liver disease (r = 0.87, p < 10(-4)) than in viral chronic hepatitis (r = 0.66, p < 10(-4)). The PTF score correlated with the CLF score (r = 0.92, p < 10(-4)), serum hyaluronate (r = 0.76, p < 10(-4)), and the prothrombin index (r = -0.77, p < 10(-4)). Multiple regression analyses showed that the area of fibrosis was explained only by the PTF score and not by the CLF score. PTF appears more frequent than CLF in alcoholic chronic liver disease, suggesting that PTF may precede CLF. PTF is more responsible for the amount of fibrosis than CLF. The results of this study also validate the use of the Metavir fibrosis score in alcoholic chronic liver disease.

Biomarkers↗
PubMed1993

Hepatic cytosolic oestrogen receptors in patients with liver disease.

Patients with liver disease present many of the features of 'feminized' hepatic metabolism. Oestrogens exert their effects through interaction with specific cellular high-affinity receptors (ER). We measured hepatic ER in 102 needle biopsies from patients with chronic alcoholic and non-alcoholic liver disease using an enzyme immunoassay. Fifteen patients with no or minimal changes in liver histology served as controls. The hepatic ER concentrations were significantly (P = 0.05) lower in the 44 men (median 13 fmol mg-1 protein, interquartile range 7-17 fmol mg-1 protein) compared to the 58 women (median 15 fmol mg-1 protein, interquartile range 10-21 fmol mg-1 protein). Patients with alcoholic liver disease (n = 63) had significantly (P < 0.05) lower ER concentrations than controls (n = 15) (median 13 fmol mg-1 protein, interquartile range 7-17 fmol mg-1 protein vs. median 16 fmol mg-1 protein, interquartile range 10-26 fmol mg-1 protein), and compared with patients with non-alcoholic liver disease (n = 24) (P < 0.05, median 20 fmol mg-1 protein, interquartile range 11-24 fmol mg-1 protein). ER concentrations were significantly lower (P < 0.05) in patients with alcoholic liver disease and alcoholic hepatitis (n = 21) compared to those without alcoholic hepatitis (n = 42) (medians 10 vs. 14 fmol mg-1 protein, interquartile ranges 6-15 fmol mg-1 protein vs. 9-18 fmol mg-1 protein), while ER concentrations did not differ significantly (P > 0.05) between actively drinking (median 13 fmol mg-1 protein, interquartile range 7-17 fmol mg-1 protein) and abstaining alcoholic patients (median 13 fmol mg-1 protein. interquartile range 7-18 fmol mg-1 protein). In summary, the small but significant variation in hepatic ER concentrations reflects variation in liver function rather than an effect of ethanol.

Adult↗
PubMed2004

Abnormally high resistive index of central retinal artery by ultrasound color Doppler in patients with viral chronic liver disease: correlation with worsening liver staging.

Retrobulbar-ocular circulation provides an opportunity to assess the terminal circulation of the arterial cerebral tree. To evaluate whether retrobulbar circulation in patients with chronic liver disease is affected by adaptive mechanisms, we assessed by echo color Doppler, 1. The resistive-index of the central retinal artery, a terminal branch of the ophthalmic artery, and 2. the potential interrelationships with both liver staging and the most important splanchnic Doppler-parameters used to assess portal hypertension. The resistance index (RI) of the central retinal artery was obtained and compared with other classical Doppler parameters known to be affected by portal hypertension. The RI of the central retinal artery (CRA) was higher in cirrhotic patients than in controls or subjects with chronic hepatitis; it correlated with all the Doppler parameters of portal hypertension considered, with plasma renin-activity, and norepinephrine concentrations. Similarly to renal and splanchnic hemodynamics, retinal arterial circulation assessed by duplex Doppler seems to be affected by the histology of liver disease and by the overactivity of vasoconstrictor systems.

Adult↗
PubMed1997

The contraceptive choice for a Wilson's disease patient with chronic liver disease.

Preserved fertility status is frequently encountered in patients with Wilson's disease, and contraceptive counseling may, therefore, be a relevant issue. Yet, several contraceptive methods can adversely influence the hepatic function, and the efficacy of others may be affected by the liver disease. We describe a patient with Wilson's disease manifested by cirrhosis, portal hypertension, and bleeding esophageal varices who underwent termination of pregnancy at 9 weeks' gestation. Following the procedure, contraceptive advice was sought in order to postpone conception until portal hypertension was controlled and hepatic function improved. Intramuscular depot medroxyprogesterone acetate was administered and tolerated well by the patient. A detailed discussion of the contraceptive options for patients with chronic liver disease, in general, and Wilson's disease, in particular, follows the case report.

Abortion, Induced↗
PubMed2002

Nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) encompasses a broad clinicopathologic spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), which may advance to cirrhosis and end-stage liver disease. Steatosis alone does not appear to be progressive. The prevalence of NAFLD averages 20% and that of NASH, 2% to 3%, making these conditions the most common liver diseases in the United States. NAFLD is associated with insulin resistance, which may be evident clinically with obesity, type 2 diabetes mellitus, and hypertriglyceridemia. The pathogenesis of NAFLD consists of hepatic fat accumulation and oxidative stress with formation of free radicals. The clinical diagnosis is based on the presence of the insulin resistance syndrome and exclusion of alcohol abuse as well as viral, autoimmune, genetic, and drug-induced liver diseases. Liver biopsy is essential for diagnosis but may not be necessary for clinical management. Treatment is aimed at correcting the risk factors for NAFLD and using potentially hepatoprotective agents. Ursodeoxycholic acid and betaine appear particularly promising in early trials.

Biopsy, Needle↗