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PubMed1977

Adsorption of messenger RNA of Novikoff hepatoma, normal liver, and regenerating liver on complementary DNA-cellulose affinity matrices.

Complementary DNA (cDNA)-oligodeoxythmidylate-celluloses were prepared from cDNA copies of polysomal messenger RNA (mRNA) of Novikoff hepatoma, normal rat liver, and regenerating rat liver. cDNA synthesis with reverse transcriptase was approximately 46% with respect to input mRNA with oligodeoxythymidylate-cellulose primer. The cDNA's of normal liver, regenerating liver, and Novikoff hepatomas were used as affinity matrices for hybridization of different mRNA species. Under the conditions used, degradation of mRNA was not detected. After normalization for homologous hybridization efficiency, 53 and 65% of the Novikoff hepatoma mRNA bound to normal liver and regenerating liver cDNA's. Under these conditions an average of 82% of mRNA of normal liver bound to regenerating liver cDNA, and 92% of regenerating liver mRNA bound to normal liver cDNA. The bound and unbound mRNA's were analyzed by translation in the wheat germ system; 2-D gel analysis of the proteins synthesized in the wheat germ system indicated that the cDNA affinity columns selectively adsorbed some mRNA species.

Animals↗
PubMed1994

Acetaldehyde-modified epitopes in liver biopsy specimens of alcoholic and nonalcoholic patients: localization and association with progression of liver fibrosis.

Acetaldehyde, the first product of ethanol oxidation, has been shown to stimulate collagen gene expression and to form protein-acetaldehyde adducts. Because little is known about these adducts in human liver tissue, we assessed, with an immunohistochemical procedure, the presence and location of acetaldehyde-protein adducts in liver biopsy specimens of alcoholic patients. In addition, we correlated the presence of adducts with the progression or subsequent occurrence of liver fibrosis. The group included 106 patients with high alcohol consumption (> 90 gm ethanol/day for the last 5 yr), 10 nonalcoholic patients with normal livers and 23 patients with other liver diseases. Sixty-four of the 106 alcoholic patients had a second liver biopsy, whose specimen was used to assess the progression of liver fibrosis. Polyclonal antibodies were produced against homologous low-density lipoprotein purified from rabbit serum and modified in vitro in the presence of acetaldehyde. Protein-acetaldehyde adducts could be detected by immunohistochemistry in biopsy specimens of 90 alcoholic patients (85%), in none of the 10 nonalcoholic patients with normal livers and in 65% of the patients with nonalcoholic liver disease. Acetaldehyde-modified epitopes were detected in the intracellular and extracellular compartment. Intracellular protein-acetaldehyde adducts were localized in the cytoplasm of hepatocytes with a more intense staining in zone 3. No correlation existed between the intensity of intracellular staining and the histologically assessed severity of liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗
PubMedDate not supplied

Cytokines and the liver in health and disease. Effects on liver metabolism and fibrogenesis.

The liver is the largest organ in the body providing a large number of essential functions for the organism. It is the center for the metabolism of nutrients and drugs, and plays a key role in the unspecific immune system by harbouring Kupfer cells, the majority of all macrophages. The liver is the main site for the synthesis of many different metabolites and releases most of the plasma proteins. All these functions of the liver must be coordinated and regulated in response to metabolic changes and minor or major injuries. This is accomplished by metabolites, the autonomous nerve system, the endocrine system and by cytokines, which form a complex network of mediator molecules. Cytokines modulate liver metabolism in many ways. Synthesis of acute phase proteins is regulated by cytokines such as IL-1, IL-6, IL-11, leukemia inhibitory factor, TNF, transforming growth factor beta, epidermal growth factor, and ciliary derived neurotropic factor, which interact synergistically with corticosteroids and insulin. Hepatic lipid metabolism and hepatic carbohydrate metabolism are also regulated by cytokines and by classical hormones. Cytokines play an important role in the pathogenesis of liver diseases and liver fibrosis, which is the common morphological reaction after chronic injury of the liver. An uncontrolled production of extracellular matrix and its impaired degradation destroy the architecture of the liver and its function. Fat-storing cells (Ito cells, lipocytes, perisinusoidal cells) are the major source of extracellular matrix in the liver. They are activated to proliferate or to produce extracellular matrix compounds by cytokines like transforming growth factor beta, and platelet derived growth factor (PDGF). Interferon gamma and alpha inhibit this activation. Modulation of fibrogenesis by these cytokines may be helpful for future treatment of liver fibrosis.

Acute-Phase Proteins↗
PubMed1995

[Liver transplantation for alcoholic liver disease. Selective indications].

Alcoholic liver disease represents about 15% of all indications for liver transplantation. Patient selection is difficult, and must be rigorous. Peri-operative risks are evaluated on the same basis as for other chronic liver diseases, with special attention for alcoholic extra-hepatic morbidity and nutritional status. Definite withdrawal from alcohol is mandatory. Predictive factors of long-term abstinence are the absence of psychopathologic state, an adequate social and affective situation, the possibilities of professional reinsertion, and a strong motivation of the patient towards liver transplantation. A six-month period of complete abstinence before registration on a liver transplantation waiting list is not mandatory, although intermittent alcoholic abuse before transplantation should be an exclusion factor. Liver transplantation must be proposed based on the severity of liver failure, as assessed by pronostic scores. It must be rapidly discussed following an acute episode of decompensation, in the absence of a significant improvement despite adequate medical therapy. It must also be discussed for long-term abstinent patients, with an apparently stabilized cirrhosis, but with an important decrease of the functional liver mass. The evaluation of the functional liver mass is based upon the Child-Pugh score, associated with the results of metabolic liver function tests, the measurement of the hepatic volume and the severity of portal hypertension.

Hepatitis, Alcoholic↗
PubMed1993

The alcohol-altered liver membrane antibody and hepatitis C virus infection in the progression of alcoholic liver disease.

Progression of alcoholic liver disease is closely related to drinking habits. However, prognosis of alcoholic liver disease is not determined just by drinking habits, but also by other factors. In this study, the roles of alcohol-altered liver membrane antibody and hepatitis C virus infection were analyzed in alcoholic patients who were followed up for various lengths of time. Serial changes of liver histological appearance were analyzed in 39 patients with alcoholic liver disease who were followed for long periods (49.7 +/- 34.3 mo) and who underwent liver biopsy at least two times. Prognoses of 35 patients with alcoholic cirrhosis who were followed for more than 1 yr were also evaluated. Development of cirrhosis in alcoholic liver disease was significantly higher in the alcohol-altered liver membrane antibody-positive patients than in the patients negative for this antibody. On the other hand, hepatitis C virus markers were not related to development of cirrhosis. However, hepatocellular carcinoma developed more frequently in the hepatitis C virus marker-positive patients. In patients with cirrhosis, the cumulative rates of hepatocellular carcinoma development were significantly higher in the hepatitis C virus marker-positive patients than in the marker-negative patients. Cumulative survival rates in the hepatitis C virus marker-positive patients were significantly lower than rates in the hepatitis C virus marker-negative patients, even in noncancer patients. However, such differences were not observed in the alcohol-altered liver membrane antibody-positive and alcohol-altered liver membrane antibody-negative cirrhotic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohols↗
PubMed1977

[Significance of liver volume for the early survival of patients with liver cirrhosis operated on porta-caval anastomosis: Clinical data and relation to pathophysiological implications (author's transl)].

It is thought that the early outcome of patients with liver cirrhosis after end-to-side porta-caval anastomosis not only depends on their clinical situation but also on the postoperative haemodynamic state of the liver. The postoperative haemodynamics can be estimated if the relation of liver volume and the predicted hepatic arterial perfusion is focused. The maximum of arterial liver perfusion seems to be 1200 ml/min in the absence of a portal liver blood supply. Thus, a postoperative perfusionindex between 0.8-1.2 like in normal subjects seems to be the best situation to prevent postoperative hepatic underperfusion. 25 patients were investigated, in which the clinical situation was classified as recommended by Child, and liver volume was estimated by means of ultrasonography. Those patients having liver volumes between 1000 and 1500 ml providing a postoperative PI between 0.8-12 survived in 100%. The early mortality rate of those, having liver volumes more or less these thresholds died in 69%. It was concluded that hepatomegaly or extreme liver atrophy are situations not to be recommended for classical porta-caval anastomosis. Other procedures are dissussed which "seem to be some good news" by clinical data and by means of experimental results. The techniques discussed consist in procedures preventing the pancreatic venous blood to shunt away from the liver.

Adult↗
PubMed1997

Minimal criteria for placement of adults on the liver transplant waiting list: a report of a national conference organized by the American Society of Transplant Physicians and the American Association for the Study of Liver Diseases.

This report summarizes a recent meeting cosponsored by the American Society of Transplant Physicians and the American Association for the Study of Liver Diseases to formulate minimal criteria by which patients with severe liver disease will be placed on the waiting list for liver transplantation. The participants agreed that only patients in immediate need of liver transplantation should be placed on the waiting list. Patients should not be placed in anticipation of some future need for such therapy. It was agreed that minimal criteria could assist but not replace the clinical judgment of the transplant professionals at individual centers. The criteria will be summarized below for adult patients with acute or chronic liver disease. The most important non-disease-specific criterion for placement on the transplant waiting list was an estimated 90% chance of surviving 1 year. This translated into a Child-Pugh score of > or = 7 for patients with cirrhosis which places the patient in Child-Pugh class B or C. Cirrhotic patients who have experienced gastrointestinal bleeding caused by portal hypertension or a single episode of spontaneous bacterial peritonitis would meet the minimal criteria irrespective of their Child-Pugh score. There were disease-specific criteria also. These include a sole minimal criterion for patients with fulminant hepatic failure regardless of etiology of the onset of stage 2 hepatic encephalopathy. A requirement for 6 months abstinence from alcohol before placement on the transplant waiting list was considered appropriate for most patients with alcoholic liver disease. Exceptional cases could get access to the waiting list through a regional review process. Chronic cholestatic diseases present difficulties because of a different natural history than that of chronic hepatocellular diseases. The use of specific risk scores for primary biliary cirrhosis and primary sclerosing cholangitis will likely replace Childs-Pugh classification as the scoring systems become refined. Minimal criteria for any patient with a primary hepatocellular cancer would admit any patient with a tumor confined to the liver irrespective of size or number of tumors, after careful investigation had failed to show spread to lymph nodes, the portal vein, or distant organs. Unusual or rare indications for liver transplantation, including Budd-Chiari syndrome, Wilson's disease, and other hereditary disorders, were also discussed. Finally, it was agreed that there should be no absolute contraindications to placement of patients on the liver transplant waiting list. These criteria should be open to regular review to accommodate advances in the field.

Adult↗
PubMed1984

[Ultrasound-guided thin-needle biopsy in focal liver diseases. II. Benign focal liver diseases].

Sixty patients with benign focal liver disease underwent sonography-guided percutaneous fine needle biopsy for definitive diagnosis. The benignancy of all lesions was determined accurately by cytohistologic evaluation. All 44 liquid space-occupying lesions (30 hepatic cysts, 9 abscesses, 3 hematomas, 2 serous residual cavities after surgery) could be classified by cytological, biochemical and bacterial examination. The diagnosis of hepatic hemangiomas by fine needle puncture is problematic, because the cytological identification of benign endothelial cells is difficult. The histological examination of tissue cylinders of 4 small echogenic lesions revealed focal fatty change of the liver. Tissue fragments of focal nodular hyperplasias and liver cell adenomas showed histologically typical liver cells arranged in trabecular structure. The additional identification of bile ducts supplies proof of focal nodular hyperplasia and excludes liver cell adenoma. Percutaneous puncture of liver abscesses and cysts afforded effective therapeutic decompression. Eight out of 9 liver abscesses were cured by evacuating fine needle puncture. More than 50% of the liver cysts showed long-term growth shrinkage subsequent to puncture. The histological confirmation of benign and malignant liver tumors by sonographyguided fine needle biopsy is considered a decisive step forward in the diagnostic possibilities of update imaging methods.

Adult↗
PubMed1997

[Auxiliary liver transplantation for acute liver failure after intake of 3,4-methylenedioxymethamphetamine ("Ecstasy")].

HISTORY AND CLINICAL FINDINGS: An 18-year-old patient had for 6 days been suffering from right upper abdominal pain, weight loss, vomiting and yellow discoloration of the skin. For the preceding 8 months he had been regularly taking 1-2 tablets of "ecstasy" (3,4-methylenedioxymethamphetamine--MDMA) per week, the last 8 days before the onset of the described signs. Physical examination was unremarkable, except for pain on pressure over the right upper abdomen and the jaundice. INVESTIGATIONS: The activities of SGOT (756 U/I), SGPT (1450 U/I). gamma GT (164 U/I) and lactate dehydrogenase (539 U/I) as well as total bilirubin level (7.5 mg/dl) were elevated. The synthesising functions of the liver were impaired (thromboplastin time 47%, fibrinogen 116 mg/dl). Abdominal sonography was unremarkable. All virological tests (hepatitis A, B, C and D; Epstein-Barr virus; cytomegalovirus; HIV 1 and 2) were negative. TREATMENT AND COURSE: The suspected diagnosis was acute liver failure after "ecstasy" intake. The cholestasis and the parameters of liver synthesis and hepatocellular functions deteriorated under symptomatic treatment. 15 days after onset of the first symptoms progressive hepatic encephalopathy occurred and required heterotopic auxiliary liver transplantation (piggy-back technique). 5 months later hepatobiliary sequential scintigraphy demonstrated regenerating of the patient's own liver an atrophy of the transplanted liver. Immunosuppression with cyclosporin A and prednisolone was gradually reduced, and the transplant was removed 6 months postoperatively because of an abscess in it. 11 months after the transplantation liver functions is normal and the patient well. CONCLUSION: In young patients with jaundice of unknown origin toxic hepatitis after "ecstasy" intake should be considered. Auxiliary liver transplantation can lead to regeneration during temporary relief of the patient's own liver. After its function has been restored immunosuppression is no longer needed.

Adolescent↗
PubMed2006

Effect of low-molecular-weight heparin on the commitment of bone marrow cells to liver sinusoidal endothelial cells in CCl(4)-induced liver injury.

BACKGROUND/AIMS: Recently liver regeneration by bone marrow transplantation has been proposed as an alternative source of functional liver cells. We investigate commitment of bone marrow cells (BMCs) to liver regeneration and the effect of dalteparin sodium (DS) on regeneration of the damaged liver caused by carbon tetrachloride (CCl(4)) administration in the mice. METHODS: Liver injury was produced in 8-week-old mice by treating with CCl(4) for 4 weeks. Thereafter, mice received a lethal dose of irradiation (10Gy) to whole body, followed by injection of 1x10(7) green fluorescent protein (GFP)-positive BMCs via the tail vein. DS (50IU/kg, intraperitoneally) was administered daily for 28 consecutive days starting at 1 day post-BMC transplantation. Lineage marker analysis of GFP-positive liver cells was performed immunostaining with a CD31 antibody. RESULT: Four weeks after BMC transplantation, GFP-positive cells in the CCl(4)-damaged liver could be detected in the lobule displaying a meshwork architecture extending from the periportal to pericentral regions, a pattern simulating sinusoidal lining. This localization of GFP-positive cells suggested that these cells were closely associated with sinusoidal endothelial cells. By staining the GFP-positive cells for CD31, it was confirmed that the majority of the GFP-positive cells are also positive for CD31. The GFP(+)CD31(+) cells were barely detected in the control group (1.0+/-1.2 per field). In marked contrast, a numerous number of GFP(+)CD31(+) cells were detected in the liver section obtained from the CCl(4)-induced liver damage group (3.8+/-1.3 per field, P<0.05 versus control). The number of GFP(+)CD31(+) cells in CCl(4) plus DS-treated group was further increased to 8.3+/-1.3 per field (P<0.05 versus CCl(4)-induced liver damage group). CONCLUSION: The majority of GFP-positive BMCs was committed to sinusoidal endothelial cells. DS promoted BMC differentiation into sinusoidal endothelial cells in the CCl(4)-damaged liver.

Journal Article↗
PubMed1999

Comparative evaluation of hepatitis C virus infection in serum and liver tissue of patients with chronic liver disease by reverse transcription-polymerase chain reaction.

OBJECTIVE: To undertake a comparative evaluation of diagnostic modalities used in the detection of hepatitis C virus (HCV) infection by serum antibody in ELISA and HCV-RNA in the serum as well as in the liver tissue of the same patients with chronic liver disease by reverse transcription-polymerase chain reaction (RT-PCR). METHODS: Thirty-five subjects comprising 30 cases of cirrhosis of the liver and five cases of chronic hepatitis were included in the study group. The criteria for including the subjects in the study were the availability and quality of serum and liver samples. Serologic ELISA tests for HCV antibody as well as HBsAg and anti-HBc IgG for hepatitis B virus (HBV) were performed on the patient's sera, while RT-PCR was carried out with RNA extracted from both serum and liver biopsies of the patients. Primer sequences selected from the conserved NS5 region of the HCV genome were used in RT-PCR. RESULTS: Of 30 cases of cirrhosis studied, five (16.6%) were anti-HCV antibody positive, while seven (23.3%) were positive for HCV RNA in serum and 10 (33.3%) were positive in liver tissue. One of the anti-HCV antibody-positive patients was negative for HCV RNA in both liver and serum by PCR. All seven patients who showed positivity for HCV RNA in serum were also positive for HCV RNA in the liver. Another three cirrhosis cases (10%) found to be HCV positive in liver tissue were negative for both antibody and HCV RNA in serum. Of the five cases of chronic hepatitis, two (40%) were found to be positive by all three tests. HCV was found to be more prevalent in HBV-infected cases (8/18; 44.5%). However, two of the three cirrhotic patients who showed HCV positivity only in liver PCR tested negative for HBV surface antigen. CONCLUSIONS: RT-PCR detection of HCV RNA in liver tissue is of significant clinical importance and is more reliable than RT-PCR in serum or antibody tests by ELISA. RT-PCR can effectively complement antibody tests for reliable diagnosis, since assessment of HCV positivity by a single test seems to be inadequate. The frequent association of HCV infection with HBV suggests that hepatitis B and C viruses may share similar modes of transmission in India.

Journal Article↗
PubMed1999

Experimental study of bioartificial liver with cultured human liver cells.

AIM:To establish an extracorporeal bioartificial liver support system (EBLSS) using cultured human liver cells and to study its support effect for fulminant hepatic failure (FHF).METHODS:The liver support experiment of EBLSS consisting of aggregates cultured human liver cells, hollow fiber bioreactor, and circulation unit was carried out in dizhepatic dogs.RESULTS:The viability of isolated hepatocytes and nonparenchymal liver cells reached 96%. These cells were successfully cultured as multicellular spheroids with synthetic technique. The typical morphological appearance was retained up to the end of the artificial liver experiment. Compared with the control dogs treated with EBLSS without liver cells, the survival time of artificial liver support dogs was significantly prolonged. The changes of blood pressure, heart rate and ECG were slow. Both serum ammonia and lactate levels were significantly lowered at the 3rd h and 5th h. In addition, a good viability of human liver cells was noted after 5h experiment.CONCLUSION:EBLSS playing a metabolic role of cultured human hepatocytes,is capable of compensating the function of the liver, and could provide effective artificial liver support and therapy for patients with FHF.

Journal Article↗
PubMed2000

An improved model of acute liver failure based on transient ischemia of the liver.

HYPOTHESIS: A reproducible and potentially reversible model of acute liver failure in the pig is feasible based on transient ischemia of the liver. DESIGN: To determine the shortest period of liver ischemia sufficient to cause 100% mortality, ischemia of the liver was induced for different lengths of time, starting with 6 hours. If the pig survived, ischemia time was prolonged for 2 hours in the next animal. In the first group, the common bile duct was not tightened. In the second group, the common bile duct was tightened. SETTING: The Laboratory for Hepatopathophysiology, Catholic University, Leuven, Belgium. PARTICIPANTS: Female stress-negative Belgian Landrace pigs weighing 18 to 22 kg. INTERVENTIONS: During preparatory surgery, all ligaments around the liver and connective tissue around the liver hilum were transected and an end-to-side portacaval shunt was made. Vessel loops were placed around the branches of the hepatic artery and bile duct. Three days later, in fully awake pigs, the loops were tightened. MAIN OUTCOME MEASURES: Mortality. Development of acute liver failure was determined based on neurologic, biochemical, and pathological variables. RESULTS: When occluded for 10 hours, all pigs in group 2 (n = 5) [corrected] died between 12 and 17 hours after the induction of ischemia. All pigs developed typical acute liver failure. Tissue specimens showed 90% necrosis of the liver parenchyma. CONCLUSION: A highly reproducible and potentially reversible model of acute liver failure in the large animal has been established.

Animals↗
PubMedDate not supplied

Analysis of liver disease, nuclear HBcAg, viral replication, and hepatitis B virus DNA in liver and serum of HBeAg Vs. anti-HBe positive carriers of hepatitis B virus.

Nine HBeAg+ and 24 anti-HBe+ subjects with chronic hepatitis B virus (HBV) infection were studied for HBV DNA in the serum by molecular hybridization, for HBcAg in the liver by immunofluorescence, and for histologic evidence of liver disease. All HBeAg+ patients had underlying chronic liver disease (chronic persistent hepatitis, chronic active hepatitis, or cirrhosis with or without hepatocellular carcinoma), and all were found positive for both HBV DNA in the serum and HBcAg in the nucleus of hepatocytes. Of the 24 anti-HBe+ individuals, 18 had various forms of chronic liver disease. Six HBsAg+/anti-HBe+ patients had normal liver histology except for numerous "ground-glass" hepatocytes with abundant cytoplasmic HBsAg. All six were negative for nuclear HBcAg and serum HBV DNA, but three showed HBV DNA which appeared to be integrated into unique sites in host liver DNA by hybridization analysis. In contrast, 14/18 (78%) of HBsAg+/anti-HBe+ patients with chronic liver disease were positive for nuclear HBcAg, serum HBV DNA, or both of these markers of HBV replication. It is suggested that in long-term HBsAg carriers with serum anti-HBe and normal liver histology, viral replication is suppressed or inactive and HBV potential infectivity is presumably very low or absent. However, when viral replication is present in HBsAg+/anti-HBe+ carriers (as demonstrated by serum HBV DNA and/or nuclear HBcAg), active liver disease is often found. In these individuals, active chronic liver disease appears to be related to continued replication and secretion of HBV and may occur in a much higher proportion of HBsAg+/anti-HBe+ carriers than was previously suspected.

Adult↗
PubMed1989

Changes in liver and spleen volume in alcoholic liver fibrosis of man.

Alcoholic liver fibrosis is a relatively common form of alcoholic liver disease in Japan. It is regarded by some investigators as a prodromal stage of alcoholic liver cirrhosis, but little is known about the volumes of the liver and spleen in this disease state. Therefore, liver and spleen volumes were measured by computed tomography in 32 patients with alcoholic liver fibrosis in comparison with 10 healthy volunteers. Patients with alcoholic liver fibrosis were divided into three subgroups (13 of Grade 1, 9 of Grade 2 and 10 of Grade 3) according to the severity of fibrosis. The volume was calculated from the sum of the area measurements of successive transverse sections of the two organs. The liver volume (mean +/- S.D.) in Grade 2 alcoholic liver fibrosis (1,281 +/- 112 cm3) was significantly (p less than 0.01) larger than in healthy volunteers (1,017 +/- 73 cm3) and in Grade 1 (1,090 +/- 157 cm3), and the liver volume in Grade 3 (1,490 +/- 132 cm3) was larger than in Grade 2 (p less than 0.01). The mean volume of hepatocytes estimated by a two-dimensional image analysis system was significantly (p less than 0.05) larger in Grade 3 than in Grade 2, and that in Grade 2 was larger than in Grade 1. The spleen volume in Grade 3 (151 +/- 40 cm3) was significantly (p less than 0.01) larger than in healthy volunteers (86 +/- 26 cm3), Grade 1 (89 +/- 38 cm3) and Grade 2 (68 +/- 19 cm3). The presumed reason for hepatic volume increase would be the ballooning of hepatocytes along with increased fibrotic component.

Humans↗
PubMed2003

Smoking and liver cancer in China: case-control comparison of 36,000 liver cancer deaths vs. 17,000 cirrhosis deaths.

Liver cancer and liver cirrhosis are common causes of death in China, where chronic lifelong hepatitis B infection is a major cause of both diseases. To help determine whether smoking is a cofactor for the development of liver cancer, we ascertained retrospectively the smoking habits of 36,000 adults who had died from liver cancer (cases) and 17,000 who had died from cirrhosis (controls) in 24 Chinese cities and 74 rural counties. Calculations of the smoker vs. nonsmoker risk ratios (RR) for liver cancer mortality were standardised for age and locality. Among adult men (aged 35+) there was a 36% excess risk of death from liver cancer among smokers (smoker vs. nonsmoker standardised risk ratio [RR] =1.36, with 95% confidence interval [CI] 1.29-1.43, 2p<0.00001; attributable fraction 18%). In the general male population this indicates absolute risks of death from liver cancer before age 70 of about 4% in smokers and 3% in nonsmokers (in the absence of other causes). Most liver cancer, however, occurs among the 10-12% of men with haematological evidence of chronic hepatitis B infection, so among them the corresponding risks would be about 33% in smokers and 25% in nonsmokers. The RR was approximately independent of age, was similar in urban and rural areas, was not significantly related to the age when smoking started but was significantly (p<0.001) greater for cigarette smokers than for smokers of other forms of tobacco. Among men who smoked only cigarettes, the RR was significantly (p<0.001 for trend) related to daily consumption, with a greater hazard among those who smoked 20/day (RR 1.50, 95% CI 1.39-1.62) than among those who smoked fewer (mean 10/day: RR=1.32, 95% CI 1.23-1.41). Smoking was also associated with a significant excess of liver cancer death in women (RR 1.17, 95% CI 1.06-1.29, 2p=0.003; attributable fraction 3%), but fewer women (17%) than men (62%) were smokers, and their cigarette consumption per smoker was lower. Among women who smoked only cigarettes, there was a significantly greater hazard among those who smoked at least 20/day (mean 22/day: RR=1.45, 95% CI 1.18-1.79) than among those who smoked fewer (mean 8/day: RR=1.09, 95% CI 0.94-1.25). These associations indicate that tobacco is currently responsible for about 50,000 liver cancer deaths each year in China, chiefly among men with chronic HBV infection.

Adult↗
PubMed1994

Monocyte chemoattractant protein 1 (MCP-1) expression occurs in toxic rat liver injury and human liver disease.

Considerable evidence suggests that monocytes/macrophages play a crucial role in the process of liver injury and repair. Recent investigations have focused on the function of various macrophage-produced cytokines in liver disease. Much is still unknown, however, about the mechanism of macrophage recruitment and activation during liver disease. To further define this process, the gene expression of the monocyte chemoattractant monocyte chemoattractant protein 1 (MCP-1) was examined in animal and human liver disease. MCP-1 mRNA was not found in normal rat liver by Northern blot analysis. After single-dose treatments with the hepatotoxins carbon tetrachloride and galactosamine, MCP-1 mRNA was detectable beginning at 2 and 4 h after treatment, respectively, and was expressed continuously until 60-72 h. During chronic carbon tetrachloride administration, MCP-1 mRNA levels were elevated for the entire 10 weeks of treatment with peak levels of expression occurring early (weeks 1-3) and late (weeks 8-10) in this model. Isolated liver cell fractions from rats treated for 3 weeks with carbon tetrachloride revealed the major cellular source of MCP-1 mRNA to be fat-storing or Ito cells, with some expression occurring in the endothelial cell fraction. Studies of potential inducers of hepatic MCP-1 expression showed that lipopolysaccharide, tumor necrosis factor-alpha, and interleukin-1 alpha and beta treatments all led to MCP-1 expression. Finally, studies of human liver samples revealed MCP-1 gene expression in nondiseased liver and greatly increased levels in livers from patients with fulminant hepatic failure. These data implicate MCP-1 from fat-storing cells as a modulator of the process of liver injury and further support a role for MCP-1 in the pathogenesis of human disease.

Animals↗
PubMed2006

Surgical injuries of postmortem donor livers: incidence and impact on outcome after adult liver transplantation.

The exact frequency and clinical consequences of surgical hepatic injuries during organ procurement are unknown. We analyzed the incidence, risk factors, and clinical outcome of surgical injuries in 241 adult liver grafts. Hepatic injuries were categorized as parenchymal, vascular, or biliary. Outcome variables were bleeding complications, hepatic artery thrombosis (HAT), and graft survival. In 82 livers (34%), 96 injuries were detected. Most injuries were minor, but clinically relevant injuries were detected in 6.6% (16/241) of the livers. Fifty (21%) liver grafts had some degree of parenchymal or capsular injury, 40 (17%) had vascular injury, and 6 (2%) had an injury to the bile duct. Procurement region was the only risk factor significantly associated with surgical injury. The rate of hepatic artery injury was significantly higher in livers with aberrant arterial anatomy. Bleeding complications were found in 18% of patients who received livers with a parenchymal or capsular injury in contrast to 9% without parenchymal injury (P = 0.065). HAT was found in 23% of the patients who received a liver with arterial injury compared to 4% without arterial injury (P = 0.001). Overall graft survival rates were not significantly different for grafts with or without anatomical injury. In conclusion, surgical injuries of donor livers are an underestimated problem in liver transplantation and can be observed in about one-third of all cases. Clinically relevant injuries are detected in 6.6% of all liver grafts. Arterial injuries are associated with an increased risk of HAT.

Adult↗