Concomitant Liver Cirrhosis Research Articles

Leberresektion bei Lebercirrhose

The benefits of liver resection for patients with hepatocellular carcinoma (HCC) and concomitant liver cirrhosis have been questionable due to high rates of postoperative complications. As a result of advance in surgical techniques, along with improved perioperative management and increased knowledge of the pathophysiology of liver cirrhosis, liver resection in cirrhotic patients has become a safer surgical procedure during the 1990s. This article introduces our techniques of parenchymal resection in patients with liver cirrhosis, avoiding inflow occlusion of the hepatic circulation by using a Cavitron Ultrasonic Surgical Aspirator (CUSA) and bipolar cautery that is equipped with a mechanism for channeling water at the point of cauterization. Analysis of survival rates showed that surgical resection was more advantageous than treatment such as percutaneous ethanol injection, although the discovery of multicentric carcinogenesis in livers with hepatitis C viral infection required us to reconsider surgical indications for HCC and concomitant liver cirrhosis.

Primary liver tumors in China

Until now, no large series studies on the clinicopathological features of primary liver tumors (PLTs) in mainland China have been reported. The authors retrospectively investigated 3,160 cases of PLTs surgically resected at Shanghai Oriental Hospital of Hepatobiliary Surgery between January 1982 and January 1996. Most of them are true neoplasms, others are tumor-like lesions. The 3,160 cases of PLTs could be divided into 3 groups of 25 types arising from three germinal layers, of which tumor-like lesions (Group 1) were of 4 types involving 112 cases (3.5%), benign PLTs (Group 2) were of 10 types involving 499 cases (15.8%) and malignant PLTs (Group 3) were of 11 types involving 2,549 cases (80.7%). The most common type of lesion in each group was solitary necrotic nodule, cavernous hemangioma and hepatocellular carcinoma (HCC), accounting for 73.2%, 74.3% and 96.6% of their respective groups. The patients ranged in age from 5 months to 79 years (mean, 45.7 years), but the age distribution and sex ratio varied reciprocally from group to group and from lesion to lesion. For example, the mean age of the patients in Group 1 was 39.1 years of age, whereas in Group 2 and Group 3, it was 45.9 years and 49.6 years, respectively. The sex ratio of men to women was 2.6:1 in Group 1, 1:1.1 in Group 2 and 7.7:1 in Group 3. The rates of serum HBsAg positivity and concomitant liver cirrhosis in the patients with HCC were 74.4% and 72%, respectively, and the concomitant rate of cirrhosis in small HCC (<3 cm in diameter) was as high as 83.3% (P<0.05), demonstrating a close relationship of HCC with HBV infection and liver cirrhosis. HCC amounts to 78.4% of the total 3,160 PLTs in this series, indicating that HCC is the most common malignant tumor of the liver in China.

Detection of a soluble form of the human adhesion receptor lymphocyte function-associated antigen-3 (LFA-3) in patients with chronic liver disease

Background/Aims: Multiple immune functions, such as cytotoxic reactions, B cell differentiation, and monocyte activation, are mediated via the adhesion receptor/ligand pairs CD2/lymphocyte function-associated antigen(LFA)-3 and LFA-1/intercellular adhesion molecule (ICAM)-1. Since soluble forms of LFA-3 (sLFA-3) and ICAM-1 (sICAM-1) can interfere with these functions, we asked whether increased levels of sLFA-3 can be found in patients with different forms of chronic liver disease and/or hepatocellular carcinoma. Methods: sLFA-3 was measured in sera from 84 patients with chronic liver disease (39 with chronic viral liver disease, 30 with autoimmune liver disease, 12 with alcoholic cirrhosis, 3 with other causes of cirrhosis), 24 patients with hepatocellular carcinoma (15 with and 9 without cirrhosis), and 61 normal controls. From 36 of the patients with liver cirrhosis, arterial and hepatic venous serum samples were simultaneously obtained and tested for sLFA-3 and sICAM-1. Results: In comparison to controls, sLFA-3 levels were elevated in patients with liver cirrhosis due to autoimmune liver disease ( p<0.0001) and viral liver disease ( p=0.001), but not in patients with alcoholic cirrhosis. Increased sLFA-3 levels were also found in patients with hepatocellular carcinoma and liver cirrhosis. However sLFA-3 was not significantly elevated in sera from patients with autoimmune liver disease, viral liver disease, and hepatocellular carcinoma without concomitant liver cirrhosis. No difference was found between arterial and hepatic venous serum levels of sLFA-3 and sICAM-1. sLFA-3 levels correlated positively with aspartate transaminase, alkaline phosphatase, bilirubin, sICAM-1, and inversely with albumin and cholinesterase. Conclusions: Taken together, sLFA-3 serum concentrations of patients with liver cirrhosis due to autoimmune liver disease or viral liver disease and of patients with hepatocellular carcinoma and cirrhosis are significantly increased compared to controls. Elevated sLFA-3 and sICAM-1 levels might reflect the generalized inflammation in cirrhosis and by interference with cell-cell interactions sICAM-1 and sLFA-3 may limit the extent of inflammation.

Overexpression of Matrix Metalloproteinase 9 Gene in Hepatocellular Carcinoma With Invasive Potential

The prognosis for hepatocellular carcinoma (HCC) depends mainly on the clinicopathological characteristic regarding invasion and metastasis. In addition, another distinguishing feature of HCC is the high incidence of concomitant liver cirrhosis, in which the extracellular matrix proliferates markedly. Therefore, the present study was designed to investigate the molecules responsible for the invasion potential of HCC by focusing on matrix metalloproteinase (MMP) in particular, MMP–2 and MMP–9 and the corresponding tissue inhibitor of metalloproteinase (TIMP–2 and TIMP–1), because these enzymes participate in the degradation of the extracellular matrix including the basement membrane. Tumorous and adjacent nontumorous liver samples were obtained from 23 HCC patients who underwent a partial hepatectomy. In 16 of the 23 HCC samples, transcripts for MMP–9 were detected in the tumorous tissues, and 15 of 16 of these samples showed stronger expression in the tumorous tissues than in the nontumorous tissues. On the other hand, MMP–2 messenger RNA (mRNA) was detected in 18 of the 23 cases. Eight of these 18 cases showed more intense expression in the tumorous tissues than in the nontumorous tissues, whereas the expression levels were lower in the tumorous tissues than in the nontumorous tissues in 7 of 18 samples. With respect to the correlation between the clinicopathological features and mRNAs expression, it was found that the expression of MMP–9 mRNA in HCC with capsular infiltration was significantly higher than in HCC without capsular infiltration. HCC with capsular infiltration also tended to have a higher ratio of MMP–9 mRNA expression to TIMP–1 mRNA expression. In addition, the expression of MMP–2 mRNA in nontumorous cirrhotic tissues was significantly higher than in nontumorous tissues from patients with chronic hepatitis. Immunohistochemical examinations revealed that MMP–9 immunoreactivity was the most intense in the HCC cells, particularly in those cells in the marginal areas of the tumorous tissues. In conclusion, the present study shows that MMP–9 is closely participated in capsular infiltration in HCC.

Overexpression of matrix metalloproteinase 9 gene in hepatocellular carcinoma with invasive potential

The prognosis for hepatocellular carcinoma (HCC) depends mainly on the clinicopathological characteristic regarding invasion and metastasis. In addition, another distinguishing feature of HCC is the high incidence of concomitant liver cirrhosis, in which the extracellular matrix proliferates markedly. Therefore, the present study was designed to investigate the molecules responsible for the invasion potential of HCC by focusing on matrix metalloproteinase (MMP) in particular, MMP-2 and MMP-9 and the corresponding tissue inhibitor of metalloproteinase (TIMP-2 and TIMP-1), because these enzymes participate in the degradation of the extracellular matrix including the basement membrane. Tumorous and adjacent nontumorous liver samples were obtained from 23 HCC patients who underwent a partial hepatectomy. In 16 of the 23 HCC samples, transcripts for MMP-9 were detected in the tumorous tissues, and 15 of 16 of these samples showed stronger expression in the tumorous tissues than in the nontumorous tissues. On the other hand, MMP-2 messenger RNA (mRNA) was detected in 18 of the 23 cases. Eight of these 18 cases showed more intense expression in the tumorous tissues than in the nontumorous tissues, whereas the expression levels were lower in the tumorous tissues than in the nontumorous tissues in 7 of 18 samples. With respect to the correlation between the clinicopathological features and mRNAs expression, it was found that the expression of MMP-9 mRNA in HCC with capsular infiltration was significantly higher than in HCC without capsular infiltration. HCC with capsular infiltration also tended to have a higher ratio of MMP-9 mRNA expression to TIMP-1 mRNA expression. In addition, the expression of MMP-2 mRNA in nontumorous cirrhotic tissues was significantly higher than in nontumorous tissues from patients with chronic hepatitis. Immunohistochemical examinations revealed that MMP-9 immunoreactivity was the most intense in the HCC cells, particularly in those cells in the marginal areas of the tumorous tissues. In conclusion, the present study shows that MMP-9 is closely participated in capsular infiltration in HCC. (Hepatology 1996 Aug;24(2):316-22)

Effects of alcohol on membrane fluidity of human erythrocyte.

Membrane fluidity in human erythrocytes was measured by a spin label method using an electron spin resonance spectrometer in healthy volunteers after ingestion of alcohol (1.5 ml of whisky/kg body weight). Fluidity in the lipid bilayer closer to the hydrophilic face decreased at 30 min and 90 min, and fluidity in the hydrophobic core decreased at 90 min after ingestion of alcohol. In the same experiment, the level of thiobarbituric acid reactive substances in the serum decreased 30 min after ingestion of alcohol, and the triglyceride level increased and free fatty acid level decreased, and serum superoxide dismutase activity increased 150 min after ingestion. Furthermore, membrane fluidity in human erythrocytes was examined in patients with alcohol dependence syndrome who had not any alcohol for about 26 months. Erythrocyte membrane fluidity of patients with alcohol dependence syndrome was not different from that of healthy controls. However, erythrocyte membrane fluidity of the lipid bilayer closer to the hydrophilic face increased in patients who had concomitant liver cirrhosis compared with those who did not. These results suggest that alcohol affects temporal change of membrane fluidity in human erythrocytes.

CLINICOPATHOLOGICAL STUDIES ON RESECTED CASES OF GIANT HEPATOCELLULAR CARCINOMA

Between January 1985 and June 1992, 208 cases of hepatocellular carcinoma (HCC) were resected in the institute. In this study 22 cases of giant HCC (larger than 10cm in diameter) were clinicopathologically compared to the other 186 cases of HCC (smaller than 10cm). The mean age of 22 patients with giant HCC was 51.0 years old. There were 14 males and 8 females. The frequency of positive HBsAg was higher, while the frequency of concomitant liver cirrhosis was lower than the smaller HCC group. More than 50% of cases showed higher α-fetoprotein above 1000ng/ml. Eighteen cases out of 22 cases underwent more than 2 segment hepatectomy. Portal invasion and intrahepatic metastasis showed significantly higher frequency. The cumulative 3-year survival rate of giant HCCs was 28.4%, versus 61.7% in the smaller HCC group. Three out of 22 cases alived more than 5 years after the operation. These cases were treated by adjuvant chemotherapy, 2 of them received 5-FU via the portal vein and the other was infused adriamycin via the hepatic artery after hepatectomy.

Efficacy and Safety of Omeprazole in the Long-Term Treatment of Peptic Ulcer and Reflux Oesophagitis Resistant to Ranitidine

A total of 143 patients with peptic ulceration of the duodenum, stomach and oesophagus who did not respond to 3 or more months of high-dose treatment with ranitidine, 450 mg or more daily, were treated with oral omeprazole, 40 mg daily. In 94% of the patients, ulcers healed within 2-8 weeks. After healing, 133 patients underwent long-term maintenance treatment with omeprazole, 40 mg daily, for 1-5 years (continuing). During maintenance therapy with omeprazole, no endoscopically verified relapses occurred, and no drug-related adverse effects were seen. There were no significant changes in routine laboratory tests in any patient, including 27 with concomitant liver cirrhosis. Basal serum gastrin levels, which were already elevated by the previous high-dose ranitidine treatment, rose to 4 times normal levels after 4 months of treatment with omeprazole. Thereafter, no further increases in basal serum gastrin levels were observed, even after 5 years of administration. The volume density of argyrophilic cells in the oxyntic mucosa increased during omeprazole treatment, but no dysplasia of the gastric enterochromaffin-like cells was seen. In conclusion, omeprazole was highly effective in healing ranitidine-resistant peptic ulcers, and subsequent maintenance therapy with omeprazole, 40 mg daily, was found to be effective and safe over the period observed.

Omeprazole in the Long-term Management of Patients with Acid-related Diseases Resistant to Ranitidine

A total of 143 patients with peptic ulceration of the duodenum, stomach or oesophagus, who did not respond to 3 or more months high-dose treatment with ranitidine (450 mg or more daily), were admitted to oral treatment with omeprazole, 40 mg/day. In 94.4% of the patients, ulcers healed within 2-6 weeks. After healing of their ulcers, 122 patients were admitted to long-term maintenance treatment with omeprazole, 40 mg/day; 91 patients have been on the drug for 1-5.5 years. During maintenance therapy with omeprazole, 40 mg/day, no relapses (verified by endoscopy) have yet occurred and no drug related adverse effects have been observed. There were no significant changes in routine laboratory tests in any patients, including 27 with concomitant liver cirrhosis. Serum gastrin levels were already elevated approximately 2-fold during the initial high-dose ranitidine treatment and rose a further 2-fold at 2-3 months of omeprazole treatment. Thereafter, no further increase of serum gastrin was observed even after 5.5 years of continuous observation. Volume density of G and D cells in the antral mucosa did not change significantly. The volume density of argyrophilic cells in the oxyntic mucosa was 0.73 +/- 0.1% before the start of omeprazole treatment and 0.85 +/- 0.09% after 17-24 months of continuous treatment with omeprazole (ns). In antrectomized patients the volume density was lower (0.23 +/- 0.04%). No clusters of argyrophilic cells were observed in any of the groups. In a control group of patients with gastrinoma the volume density of these cells was higher (1.3 +/- 0.23%, n = 8).(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatocellular Carcinoma in Saudi Arabia: Evaluation of Prognostic Factors

ABSTRACT The medical records and pathologic materials of 41 Saudi patients (22 males and 19 females) with confirmed diagnosis of hepatocellular carcinoma were reviewed retrospectively. None of the ...

Therapy with omeprazole in patients with peptic ulcerations resistant to extended high-dose ranitidine treatment.

94 patients with peptic ulcerations of duodenum, stomach, and esophagus, who did not respond to 3 or more months high-dose (450 or 600 mg) treatment with ranitidine, were treated orally with 40 mg omeprazole daily. After healing all patients were offered long-term maintenance therapy with the same dose for 5 years. In 75 patients the peptic ulcerations healed within 4 weeks, in 13 patients within 8 weeks, and in 3 patients only after an increase to 60 mg omeprazole daily. In 3 patients the ulcers did not heal. So far 83 patients have entered long-term maintenance therapy. 59 of these patients are on the drug between 1 and 4 years. During maintenance therapy with 40 mg omeprazole no relapses have occurred up to now as demonstrated by endoscopy and no drug-related adverse effects were observed. Routine laboratory tests remained without significant changes in all patients including 18 patients with concomitant liver cirrhosis. Serum gastrin levels were already elevated during the initial high-dose ranitidine treatment (106 +/- 15.4 pg/ml). 4 weeks after the start of omeprazole treatment serum gastrin levels rose to 4 times normal levels (195 +/- 28 pg/ml). Thereafter, no further increase in serum gastrin was observed even up to 4 years of continuous observation. It is therefore concluded that omeprazole is highly effective in healing ranitidine-resistant peptic ulcerations and that omeprazole maintenance therapy with 40 mg omeprazole is safe during the time observed and highly effective in the prevention of ulcer recurrence.

Plasma lecithin: Cholesterol acyltransferase activity in liver disease

The plasma lecithin: cholesterol acyltransferase was determined in patients with various liver diseases and the relationship between this enzyme activity and the other liver function tests were studied including long term observations. Lecithin: cholesterol acyltransferase activity in fulminant hepatitis and liver cirrhosis showed a significant decrease in comparison with normal volunteers. Although the enzyme activity of hepatoma showed significant decrease, they were ascribed to the influence of concomitant liver cirrhosis. The enzyme activity showed insignificant changes in the acute and chronic hepatitis and alcoholic liver disease. Lecithin: cholesterol acyltransferase activity was correlated with the concentration of cholesterolester rather than with the ratio of esters to cholesterol. In addition, it was well correlated with pseudocholine esterase and serum albumin. The lecithin: cholesterol acyltransferase activity in the cases during follow-up period varied in good parallel with cholesterol-esters concentration and pseudocholine esterase in the cases with acute hepatitis; with serum albumin in the cases with liver cirrhosis. Furthermore, it varied inversely with SGPT in the cases with acute hepatitis. In a case with hepatoma, lecithin: cholesterol acyltransferase activity decreased more sharply than the cholesterolesters concentration and serum albumin immediately before death.