Etiology Of Chronic Liver Disease Research Articles

Caroli's disease and orthotopic liver transplantation

Caroli's disease is a rare congenital hepatic disease, characterized by segmental dilatation of the biliary tree. Patients who have recurrent bouts of biliary infection, particularly those with complications related to portal hypertension, may require orthotopic liver transplantation (OLT). Few case reports have described the outcome of OLT in patients with Caroli's disease and to date there is no large series reported in the literature. We retrospectively analyzed the outcome of OLT in patients with Caroli's disease who underwent OLT between 1982 and 2002 at Starzl Transplantation Institute, University of Pittsburgh. Patients were identified and data was collected by computerized search of the electronic database system. All patients had confirmation of diagnosis by histopathology of explanted liver. A total of 33 patients with Caroli's disease were listed for liver transplantation, 3 of whom were excluded, as they were not transplanted. A total of 90% had signs of hepatic decompensation at the time of OLT. Median posttransplantation follow-up was 7.7 yr. Short-term graft and patient survival at 1 month was 83% and 86%, whereas overall long-term graft survival rates at 1, 5, and 10 yr were 73%, 62%, and 53%, respectively, and patient survival rates were 76%, 65%, and 56%, respectively. Long-term outcome in patients who survived the first year after transplantation was significantly better. Their survival rate at 5 and 10 yr was 90% and 78%. On univariable analysis, recipient age, donor male gender, coexistent congenital hepatic fibrosis, and re-OLT were associated with poor patient survival. Eight patients were retransplanted, 3 of whom had primary nonfunction. A total of 13 patients died; the most common cause of death being sepsis and cardiovascular complications. Patients who died of sepsis had cholangitis pre-OLT. In conclusion, OLT is a form of curative and life-saving therapy in patients with Caroli's disease, especially in those with decompensated liver disease. Overall survival is better with liver transplantation and is comparable with the survival of recipients who undergo OLT for other etiologies of chronic liver disease. Survival was poor in patients with congenital hepatic fibrosis (Caroli's syndrome) and in those who had cholangitis at the time OLT.

The pathogenesis of cytokines in preportal fibrosis of human infected with schistosomiasis and viral hepatitis

Cytokines are polypeptides exhibiting a variety of biological activities including metabolic, inflammatory, hematopoietic and immunologic properties.They play an important role in the pathogenesis of various diseases. Inflammation is commonly observed in liver diseases and is frequently complicated by fibrosis and cirrhosis in end-stage disease. The only curative treatment for cirrhotic patients is liver transplantation. Cytokines play a key role in the regulation of immune responses. In viral hepatitis the production of inappropriate cytokine level appears to contribute to viral persistence and to affect response to therapy. The aim of this study is to investigate the level of endogenous IL-1B, IL-6 and IL-10 to determine their relation with liver fibrosis. Forty patients with chronic liver disease and 10 normal adults as control group were studied. Patients in this study were classified into four groups according to etiology of chronic liver disease: Group I (10 patients with bilharzial liver disease),Group II (10 patients with chronic hepatitisC), Group III(10 patients with chronic hepatitisB )and Group IV (10 patients with chronic hepatitis B and C) . All patients with chronic liver disease (n=40) showed highly significant elevation of serum IL-1B, IL-6, IL-10 mean ± SD were (106.4±47.8) (P<0.01) (26.3 ±11.1) (P<0.01) (135.4± 73.9) (P<0.01) respectively when compared to control group. After classifying the patients into 4 groups each group showed highly significant elevation of serum IL-1B, serum IL-6 and serum IL-10 in each group when compared to control group( p < 5051). Regression analysis showed negative significant correlation between serum IL-10 and IL- 1B (r=-0.64, P<0.05), highly negative significant correlation between IL-10 and IL-6 (r=-0.72, P<0.01) in all patients with chronic liver diseases, also there was highly significant positive correlation between serum IL-1B and serum IL-6 (r=0.83, P<0.01). Ten patients with bilharzial liver disease (group I) showed highly negative significant correlation between serum IL-10 and each of serum IL-1B and serum IL-6 (r=-0.9, P<0.01) (r=- 0.8, P<0.01) respectively, and there was highly significant positive correlation between serum IL-1B and serum IL-6 (r=0.96, P<0.01) .There was significant correlation between prothrombin concentration and each of serum IL-10, serum IL-1B and IL-6 (r=0.7, P<0.05), (r=0.68, P<0.05), (r=0.74, P<0.05) respectively. Ten patients with chronic hepatitis C virus (group II) also showed highly negative significant correlation between serum IL-10 and each of serum IL-1B and serum IL-6 (r=-0.9, P<0.01) (r=-0.9, P<0.01) respectively. There was highly significant positive correlation between serum IL-1B and serum IL-6 (r=0.83, P<0.01) and significant correlation between serum IL-1B and serum ALT(r=0.63, P<0.05). As regard (group III) patients with chronic hepatitis B virus there was negative significant correlation between serum IL-10 and IL-1B (r=-0.63, P<0.05), but no significant correlation between serum IL-10 and serum IL-6 and there was highly positive correlation between serum IL-1B and serum IL-6 (r=0.90, P<0.01). Ten patients with chronic hepatitis C&B virus (group VI) showed highly negative significant correlation between serum IL-10 and each of serum IL-1B and serum IL-6 (r=-0.82, P<0.01) (r=-0.80, P<0.01) respectively. There was highly significant positive correlation between serum IL-1B and serum IL-6 (r=0.88, P<0.01) and significant correlation between serum IL-1B and serum ALT(r=0.63, P<0.05), and prothrombin concentration (r=0.67, P<0.05). A significant correlation between the level of serum IL-1B, IL-6, and serum IL-10 and degree of fibrosis was found. The increase in serum level of IL-1B, IL-6 was associated with increase the degree of fibrosis but the mild and moderate fibrosis were associated with higher level of IL-10 while patients with marked degree of fibrosis were associated with lower level of IL-10.

The pathogenesis of cytokines in preportal fibrosis of human infected with schistosomiasis and viral hepatitis

Cytokines are polypeptides exhibiting a variety of biological activities including metabolic, inflammatory, hematopoietic and immunologic properties.They play an important role in the pathogenesis of various diseases. Inflammation is commonly observed in liver diseases and is frequently complicated by fibrosis and cirrhosis in end-stage disease. The only curative treatment for cirrhotic patients is liver transplantation. Cytokines play a key role in the regulation of immune responses. In viral hepatitis the production of inappropriate cytokine level appears to contribute to viral persistence and to affect response to therapy. The aim of this study is to investigate the level of endogenous IL-1B, IL-6 and IL-10 to determine their relation with liver fibrosis. Forty patients with chronic liver disease and 10 normal adults as control group were studied. Patients in this study were classified into four groups according to etiology of chronic liver disease: Group I (10 patients with bilharzial liver disease),Group II (10 patients with chronic hepatitisC), Group III(10 patients with chronic hepatitisB )and Group IV (10 patients with chronic hepatitis B and C) . All patients with chronic liver disease (n=40) showed highly significant elevation of serum IL-1B, IL-6, IL-10 mean ± SD were (106.4±47.8) (P<0.01) (26.3 ±11.1) (P<0.01) (135.4± 73.9) (P<0.01) respectively when compared to control group. After classifying the patients into 4 groups each group showed highly significant elevation of serum IL-1B, serum IL-6 and serum IL-10 in each group when compared to control group( p < 5051). Regression analysis showed negative significant correlation between serum IL-10 and IL- 1B (r=-0.64, P<0.05), highly negative significant correlation between IL-10 and IL-6 (r=-0.72, P<0.01) in all patients with chronic liver diseases, also there was highly significant positive correlation between serum IL-1B and serum IL-6 (r=0.83, P<0.01). Ten patients with bilharzial liver disease (group I) showed highly negative significant correlation between serum IL-10 and each of serum IL-1B and serum IL-6 (r=-0.9, P<0.01) (r=- 0.8, P<0.01) respectively, and there was highly significant positive correlation between serum IL-1B and serum IL-6 (r=0.96, P<0.01) .There was significant correlation between prothrombin concentration and each of serum IL-10, serum IL-1B and IL-6 (r=0.7, P<0.05), (r=0.68, P<0.05), (r=0.74, P<0.05) respectively. Ten patients with chronic hepatitis C virus (group II) also showed highly negative significant correlation between serum IL-10 and each of serum IL-1B and serum IL-6 (r=-0.9, P<0.01) (r=-0.9, P<0.01) respectively. There was highly significant positive correlation between serum IL-1B and serum IL-6 (r=0.83, P<0.01) and significant correlation between serum IL-1B and serum ALT(r=0.63, P<0.05). As regard (group III) patients with chronic hepatitis B virus there was negative significant correlation between serum IL-10 and IL-1B (r=-0.63, P<0.05), but no significant correlation between serum IL-10 and serum IL-6 and there was highly positive correlation between serum IL-1B and serum IL-6 (r=0.90, P<0.01). Ten patients with chronic hepatitis C&B virus (group VI) showed highly negative significant correlation between serum IL-10 and each of serum IL-1B and serum IL-6 (r=-0.82, P<0.01) (r=-0.80, P<0.01) respectively. There was highly significant positive correlation between serum IL-1B and serum IL-6 (r=0.88, P<0.01) and significant correlation between serum IL-1B and serum ALT(r=0.63, P<0.05), and prothrombin concentration (r=0.67, P<0.05). A significant correlation between the level of serum IL-1B, IL-6, and serum IL-10 and degree of fibrosis was found. The increase in serum level of IL-1B, IL-6 was associated with increase the degree of fibrosis but the mild and moderate fibrosis were associated with higher level of IL-10 while patients with marked degree of fibrosis were associated with lower level of IL-10.

THE EFFICACY OF SERUM HYALURONIC ACID LEVEL IN PREDICTION OF HEPATIC HISTOPATHOLOGY

Introduction: Fibrosis associated with chronic liver diseases is an insidious process involving inflammatory responses and alterations in the extracellular matrix (EM). Hyaluronic acid (HA) is a basic component of EM of the liver and it was thought that increased serum levels of HA might indicate hepatic fibrosis as a simple non-invasive marker. Aim: The objective of the current study was to investigate the efficacy of serum HA level to predict the histopathological changes, observed in liver biopsies in children with chronic liver diseases, and to determine the relationships between serum HA level and age, sex, etiology of liver disease, and biochemical parameters. Method: The study group consisted of 34 children with clinical and laboratory findings of chronic liver disease with a mean age of 65.31 ± 64 months. All children underwent liver biopsies for diagnostic purposes. The biopsies were stained by hematoxylin-eosin, reticulin and trichrome staining and evaluated blindly by the same pathologist. The degree of fibrosis on biopsy specimens was graded 0 (no fibrosis) to IV according to the Knodell hepatic activity index. The degree of inflammation and reticulin structure was also graded semi-quantitatively. Simultaneously blood samples were obtained just before the liver biopsy for the measurement of HA levels and biochemical tests. Forty-one healthy children were included into the control group. Results: Histopathological examination of 34 biopsy samples revealed stage I fibrosis in 6 patients, stage II fibrosis in 4 patients, stage III fibrosis in 8 patients, stage IV fibrosis in 1 patients, and no fibrosis was found in remaining 15 patients. The average serum level of HA was 79.25 ± 72.65 ng/ml in the study group, while serum HA level was 5.5 ± 6.4 ng/ml in the control group. The difference was statistically significant (p < 0.0001). The average levels of HA regarding the severity of fibrosis were 56.9, 52.6, 146 ng/ml in grade 0, I-II, III-IV fibrosis, respectively. There was a statistically significant correlation between the degree of fibrosis and the serum HA levels (p < 0.05). When the patients were categorized according to the etiologies of chronic liver disease (hepatitis B, metabolic diseases, biliary pathologies, neonatal hepatitis, autoimmune hepatitis and others) the average serum HA level was higher in patients with biliary pathologies when compared to the other groups (p < 0.01). Since there was a statistically significant difference between serum HA a level of children with chronic liver disease and controls, the reticulin stained liver biopsies were evaluated for condensation and collapse of reticulin fibers, and various degree of collapse in reticulin meshwork was found in all biopsy samples. There was no statistically significant correlation between the levels of HA and degree of inflammatory activity in biopsy samples and the characteristics of study group such as age, sex and liver function tests. Summary: Current study suggests that serum HA level may indicate the presence of chronic liver pathology as a noninvasive marker. Patients with grade III-IV fibrosis had the highest serum HA levels. Although serum HA levels were higher in patients with mild fibrosis when compared to controls, the statistical significance of serum HA level as a noninvasive marker became more prominent in children with moderate to severe fibrosis. Conclusion: Detection of a higher serum HA levels in children with liver fibrosis with respect to healthy controls may indicate that serum HA level may be used as a marker in chronic pathologies of the liver.

Uncertainty in estimating probability of causation in a cross-sectional study: joint effects ofradiation and hepatitis-C virus on chronic liver disease

Exposure to other risk factors is an important consideration in assessing the role played byradiation in producing disease. A cross-sectional study of atomic-bomb survivors suggestedan interaction between whole-body radiation exposure and chronic hepatitis-Cviral (HCV) infection in the etiology of chronic liver disease (chronic hepatitisand cirrhosis), but did not allow determination of the joint-effect mechanism.Different estimates of probability of causation (POC) conditional on HCV statusresulted from additive and multiplicative models. We therefore estimated the riskfor radiation conditional on HCV status using a more general, mixture modelthat does not require choosing between additivity or multiplicativity, or decidingwhether there is interaction, in the face of the large uncertainty. The results supportthe conclusion that POC increases with radiation dose in persons without HCVinfection, but are inconclusive regarding individuals with HCV infection, the lowerconfidence bound on estimated POC for radiation with HCV infection being zeroover the entire dose range. Although the mixture model may not reflect the truejoint-effect mechanism, it avoids restrictive model assumptions that cannot bevalidated using the available data yet have a profound influence on estimatedPOC. These considerations apply more generally, given that the additive andmultiplicative models are often used in POC related work. We therefore consider that anempirical approach may be preferable to assuming a specific mechanistic model forestimating POC in epidemiological studies where the joint-effect mechanism is indoubt.

Analysis of factors contributing to higher erythropoietin levels in patients with chronic liver disease

Background: Dysregulated erythropoietin (EPO) plasma levels may play a role in the pathophysiology of chronic liver disease (CLD) because chronic anaemia is frequently observed in patients with liver cirrhosis. We aimed to identify the factors contributing to EPO regulation in patients with CLD. Methods: Plasma EPO concentrations were correlated with clinical and laboratory parameters in 111 CLD patients and 220 healthy controls. Results: Anaemia, though generally mild, was common in CLD patients, and thrombocytopenia and previous bleeding episodes were observed in two‐thirds of the patients. Plasma EPO levels were significantly elevated in CLD patients (P < 0.001). EPO increased according to Child's stages of cirrhosis, independently of the aetiology of CLD. EPO correlated with haemoglobin (r = −0.498, P < 0.001). Additionally, EPO independently correlated with markers of liver dysfunction, e.g. prothrombin time, albumin concentration or cholinesterase activity, and platelet count. EPO was also significantly elevated in patients with a current bleeding tendency and with prior gastrointestinal haemorrhages. EPO levels were increased in patients with impaired pulmonary function, e.g. decreased diffusion capacity, vital capacity or hyperventilation. Interestingly, plasma interleukin‐6 (IL‐6) concentrations positively correlated with EPO (r = 0.277, P = 0.003), suggesting a possible mechanism of EPO upregulation in patients with CLD through IL‐6 dependent pathways, e.g. binding of STAT transcription factors in the putative EPO promoter region. Conclusions: EPO is upregulated in patients with chronic liver diseases in response to anaemia, bleeding complications, impaired pulmonary function, thrombocytopenia and liver dysfunction. IL‐6 dependent pathways could be involved in mediating elevated EPO levels in CLD patients.

Role of hepatitis C infection in chronic liver disease in Egypt.

Hepatitis C virus (HCV) is considered the most common etiology of chronic liver disease (CLD) in Egypt, where prevalence of antibodies to HCV (anti-HCV) is approximately 10-fold greater than in the United States and Europe. Reported are results that show the role of HCV in both overt and occult CLD, the risk factors for CLD and for HCV infection, and the relative importance of chronic HCV, hepatitis B, or both in causing hepatic morbidity. Case patients included 237 new outpatients at the National Liver Institute. Controls comprised 212 sex- and age-matched neighbors without liver disease. Case patients were more likely than controls to report a history of blood transfusions, schistosomiasis, or parenteral therapy for schistosomiasis; to have anti-HCV, HCV RNA, hepatitis B surface antigen, and serum alanine aminotransferase (ALT) elevations; and to have abdominal ultrasound findings of cirrhosis, portal hypertension, and splenomegaly. Anti-HCV-positive case patients were more likely than anti-HCV-negative patients to be male, older, and farmers: to have received a blood transfusion or parenteral therapy for schistosomiasis; to have ALT elevations; and to have ultrasound findings of cirrhosis, portal hypertension, and spleen enlargement. Anti-HCV-positive controls were more likely than anti-HCV-negative controls to have received parenteral therapy for schistosomiasis. These data support the belief that HCV is the predominant cause of CLD in Egypt and suggest there is a large underlying reservoir of HCV-caused liver disease.

Seroprevalence of hepatitis C virus infection and its association with natural infection of hepatitis B virus among preschool children in Taiwan.

Taiwan is a hyperendemic area of hepatitis B virus (HBV) infection where chronic hepatitis B is the most important cause of liver cirrhosis and hepatoma. Since, diagnostic kit for detecting hepatitis C virus (HCV) infection has been developed, HCV was found to be another important etiology of chronic liver disease. In order to study the seroprevalence of HCV infection among preschool children after mass hepatitis B vaccination program in Taiwan, a community-based survey was carried out in 54 kindergartens in 10 urban areas, 10 rural areas, and two aboriginal areas randomly selected through stratified sampling. Serum specimens of 2538 preschool children were screened for the HCV antibodies (anti-HCV) by a commercially available third-generation microparticle enzyme immunoassay and for HBV markers by radioimmunoassay methods. The multivariate-adjusted odd ratios (ORm) with their 95% confidence intervals (CI) were estimated through the multiple logistic regression analysis. A total of 58 children were anti-HCV seropositive, giving a prevalence of 2.3%. The prevalence of anti-HCV was 1.0% (5 of 484) among aboriginal children, a significantly decreased seroprevalence compared with those among other ethnic groups after multivariate adjustment. Boys had a higher anti-HCV seroprevalence, but not statistically significantly different from girls (ORm: 1.6; 95% CI: 0.9-2.8; p = 0.08). The seroprevalence of the age group of 3-4 years was lower than that of the age group of 5-6 years (ORm: 2.2; 95% CI: 1.1-4.2; p = 0.02). After multivariate adjustment, preschool children with natural HBV infection had a higher anti-HCV seroprevalence, but not statistically significantly different from those without natural HBV-infection (ORm: 2.6; 95% CI: 0.9-7.4; p = 0.08 for HBV-infected vs. uninfected). HCV infection varies with gender, residential area, and natural HBV infection. HCV and HBV might share common transmission routes in Taiwan.

Plasma levels of interleukin-18 and interleukin-18 binding protein are elevated in patients with chronic liver disease.

Interleukin 18 (IL-18) is a recently described proinflammatory cytokine. In mouse models it has been shown to play a key role in the development of liver injury. IL-18 binding protein (IL-18BP) is a naturally occurring antagonist of IL-18. In this study we investigated whether IL-18/IL-18BP levels are altered in patients with chronic liver disease (CLD). We measured IL-18 and IL-18BP plasma levels in 153 patients with CLD and 41 healthy controls by a specific ELISA. Plasma levels of IL-18 were significantly higher in CLD patients than in healthy controls. Cirrhotics had higher levels than noncirrhotics. IL-18 levels increased with disease progression. IL-18BP plasma levels paralled the increase of IL-18 with disease progression, except in stage Child C cirrhosis. IL-18 and IL-18BP levels were elevated independent of the etiology of CLD. IL-18 and IL-18BP correlated with laboratory parameters of inflammation and liver injury. Plasma levels of IL-18 and its antagonist, IL-18BP, are elevated in CLD and correlate with severity of disease. IL-18BP may not be sufficient to counteract the overwhelming proinflammatory response in end stage liver disease.

Study Of The Relation Between Helicobacter Pylori Infection And Gastric Interleukin (8) In Patients With Chronic Liver Disease

Helicobacter pylori (H pylori) is a gram negative spirally shaped bacterium. It is known to be the most common important cause of gastritis, peptic ulcer, non ulcer dyspepsia and gastric carcinoma. The frequency and importance of gastric mucosal lesion in patients with chronic liver disease (CLD) have been increasingly recognized in recent years. IL-8 a potent leukocyte chemo–attractant cytokine produced by H pylori. It promotes polymorphnuclear leucocytes (PMNs) and mononuclear cells (MNCs) accumulation in gastric mucosa.This work aimed to clarify the relation between H pylori and IL-8 production in various chronic liver disease (CLD) lesions. Eighty patients were included in this study, 50 with CLD and 30 dyspeptic patients without CLD. Gastric mucosal biopsies were examined histopathologically for H pylori, cellular infiltration and associated pathology, together with culture of H pylori and assessment of IL-8 level in gastric tissue supernatant. 30/50 (60%) CLD patients,10/15 (66.6%) patients with non gastric dyspepsia, and 14/15 (93.3%) patients with gastric dyspepsia were positive for H pylori. There was no relationship between the prevalence of H pylori and the aetiology of CLD. No significant difference was observed in CLD patients’ group as regard to H pylori and Child grading, degree of varices, gastric or liver histopathology. Statistical difference in H pylori prevalence between patients with CLD and those with gastric dyspepsia was significant. IL-8 showed significant increase in H pylori positive vs H pylori negative patients. Positive correlation was found between H pylori density and tissue IL-8 and cellular infiltration. In conclusion the liver status does not play a role in the prevalence of H pylori infection, further studies to investigate the relation between virulent H pylori and IL-8 are needed.

Hepatocellular Carcinoma in Southern Germany: Epidemiological and Clinicopathological Characteristics and Risk Factors

The aetiology of chronic liver disease leading to hepatocellular carcinoma (HCC) and the clinical characteristics of patients with HCC vary considerably internationally and intranationally. This study analyses the characteristics of HCC patients in southern Germany, a low endemic area of HCC. Methods: The files of 118 consecutive patients with HCC observed in a single tertiary care hospital between 1994 and 2000 have been reviewed. Epidemiological and clinicopathological characteristics such as age at presentation, ethanol consumption, serological hepatitis virus markers, and fibrosis were studied. Additionally, serum levels of α-fetoprotein (AFP) were analysed at the time of diagnosis in 77 patients. Results: The male:female ratio was 4:1 and the mean age at presentation was 61.8 years. Alcohol abuse (49.2%) and chronic hepatitis C infection (17.8%) were the most frequent risk factors. Histologically proven liver cirrhosis in the surrounding non-tumorous tissue was present in only 59.0% of cases. AFP levels were elevated in 78% of cases, but only 34% reached >500 ng/ml, a value considered to be significant for the diagnosis of HCC. AFP levels correlated with the stage of fibrosis. Summary and Conclusions: The sensitivity of AFP serum levels as a tumour marker is poor but might help to detect at least a minority of cases. As in other populations within Europe, chronic alcohol abuse is frequently associated with HCC in southern Germany, confirming that alcohol is still the most important risk factor for hepatocarcinogenesis in areas with low hepatitis virus prevalence. Considering the poor prognosis of HCC, prevention is of pivotal importance, particularly for patients with chronic liver disease and other risk factors for the development of HCC.

Hepatocellular carcinoma in Austria: aetiological and clinical characteristics at presentation

The aetiology of chronic liver disease leading to hepatocellular carcinoma (HCC) and the clinical characteristics at the time of presentation vary considerably among different parts of the world and over time. The number of patients seen at our institution has increased as compared to a period 20 years earlier. We investigated baseline characteristics of patients with hepatocellular carcinoma such as cirrhosis, hepatitis virus markers, age at presentation and stage of the tumour in an area with low prevalence of viral hepatitis. All 245 patients seen at the Department of Gastroenterology and Hepatology at the University of Vienna, Austria, from July 1991 to March 1998 were included in this retrospective study, and 19 different clinical characteristics were studied. The median age at detection of HCC was 63.3 years, and alcoholic liver disease (35.1%) and hepatitis C virus (HCV) infection (36.7%) were the most frequent underlying diseases. Both chronic alcoholism and HCV infection as risk factors were present in 6.9% of the patients. Liver cirrhosis was present in 86.5%. At the time of diagnosis, 43.5% had multi-nodular tumours. Of the remaining patients with a single nodule, only 10% had HCC < or =2 cm. Most of our patients presented at a late stage of the disease (TNM stage 3 29.4%, TNM stage 4 69.7%; Okuda stage 2 65.7%, Okuda stage 3 18.0%). Due to the late stage of the disease at the time of presentation, 145 patients (59.2%) received palliative care only, 24 (9.8%) underwent liver resection, 38 (15.5%) liver transplantation and 38 (15.5%) chemotherapy. In this large single-centre series of HCC, the dominant contribution of HCV infection and chronic alcohol abuse as the underlying aetiology is documented. Diagnosis is usually made very late as reflected in the high proportion of patients in TNM stages 3 and 4 or Okuda stages 2 and 3. This resulted in a high percentage of patients who received palliative care only and very few who were eligible for treatment modalities with curative potential such as resection and liver transplantation.

Accuracy and significance of computed tomographic scan assessment of hepatic volume in patients undergoing liver transplantation.

A small liver volume is considered to be a poor prognostic factor in cirrhosis, often indicative of advanced liver disease. Radiologic assessment of liver volume before liver transplant is routinely performed in many transplant centers. We sought to assess the accuracy and significance of computed tomographic (CT) scanning in hepatic volumetric analysis by correlating CT-derived estimation of liver volume with that of corresponding liver explants. A chart review of all patients aged 17 years or older undergoing liver transplant at Mount Sinai Medical Center between 1989 and 1995 was performed. Each patient underwent conventional CT scanning with measurement of liver volume (CTLV). Recipient liver volume (RLV) was defined as weight of liver explant after all attached ligaments, portal structures, and gallbladder were dissected free. Expected liver volume was calculated pretransplant based on age, gender, height, and weight. Patients were categorized into three groups based on etiology of liver disease: (1) hepatocellular (e.g., viral hepatitis, alcohol-related), (2) cholestatic (e.g., primary biliary cirrhosis), and (3) cryptogenic. The ratio of CTLV to RLV was used as a measure of the accuracy of CT volumetric analysis. A total of 579 patients was studied (group 1=376, group 2=139, group 3=64). All three groups were statistically similar with regard to age, prothrombin time and total bilirubin. Median CT liver volume was 1308 ml (range: 338-3847), 1651 ml (range: 641-3861), and 1210 ml (range: 348-2575) in groups 1-3, respectively; median ratio of CTLV to RLV was 1.02 (range: 0.50-2.31), 1.05 (range: 0.52-2.22), and 1.05 (range: 0.50-1.56) for groups 1-3, respectively. When RLV was small, it tended to be overestimated by CTLV. In contrast, when RLV was large, it was often underestimated. Clinical features such as history of esophageal variceal bleed, encephalopathy or ascites, and laboratory data did not influence accuracy of CT volumetric analysis. CT-derived estimation of liver volume appears to correlate closely with actual weight of liver explant regardless of the etiology of chronic liver disease. With extremes in CT volumetric analysis, actual liver volume tends to be under- or overestimated. For patients with end-stage liver disease, both CT-derived and actual liver volume are greater in cholestatic than in hepatocellular disorders.

Chronic liver disease in central Harlem: the role of alcohol and viral hepatitis.

For reasons not yet determined, chronic liver disease (CLD) has been a leading cause of excess morbidity and mortality in central Harlem. We conducted a case series and case-control analysis of demographic, clinical, epidemiological, and alcohol-intake-related information from patients with CLD and age- and sex-matched hospitalized control patients. Patients' sera were tested for markers of viral hepatitis. The presumed etiology of CLD among case-patients was as follows: both alcohol abuse and hepatitis C virus (HCV) infection, 24 persons (46% of case-patients); alcohol abuse alone, 15 (29%); HCV infection alone, 6 (12%); both alcohol abuse and chronic hepatitis B virus (HBV) infection, 3 (6%); and 1 each (2%) from: 1) schistosomiasis, 2) sarcoidosis, 3) unknown causes, and 4) alcohol abuse, chronic HBV, and HCV combined. In the case-control analysis, patients who had both alcoholism and either HBV (odds ratio [OR]: 6.3; 95% CI: 0. 5-334) or HCV (OR: 2.9; 95% CI: 1.3-6.2) were at increased risk for CLD, whereas patients who had only one of these three factors were not at increased risk for CLD. Patients who tested positive for the hepatitis G virus (HGV) did not have a significantly increased risk of CLD, and neither severity of CLD nor mortality was greater among these patients. Most patients in central Harlem who had CLD had liver damage from a combination of alcohol abuse and chronic viral hepatitis. Alcohol and hepatitis viruses appear to be synergistically hepatotoxic; this synergy appears to explain both the high rate of CLD in central Harlem and the recent reductions in this rate. Persons at risk for chronic HBV and HCV infection should be counseled about their increased risk of CLD if they consume excessive alcohol. Morbidity and mortality from liver disease could be decreased further by a reduction in alcohol consumption among persons who have chronic HBV and HCV infection, avoidance of needle sharing, and hepatitis B vaccination.

Morbidity and Mortality Due to Liver Disease in Children Undergoing Allogeneic Bone Marrow Transplantation: A 10-Year Prospective Study

AbstractWe have conducted a long-term prospective study of children undergoing bone marrow transplantation (BMT) to assess morbidity and mortality for liver disease. One hundred eleven consecutive children were enrolled between June 1985 and June 1995 and were followed-up for a median of 5.5 years after BMT. Before transplant 48/111 children (43%) had abnormal alanine aminotransferase (ALT), none were HBsAg+ and 4/111 were anti-HCV+. After BMT 4/111 patients (3.6%) died of liver failure. No relationship was found between pretransplant hepatitis B (HBV) or C (HCV) infection or elevated transaminases and development of severe liver damage. Eighty-two out of one hundred and eleven patients (74%) had abnormalities of ALT after BMT, transient (n = 54) or persistent (n = 28). None developed clinical signs or symptoms of end stage liver disease or of cirrhosis during follow-up. No significant difference in prevalence of liver disease, was found between children with normal or abnormal ALT at BMT (relative risk [RR] = 1.04). HCV infection could be implicated in the etiology of chronic liver disease in 14/28 patients; 2 other patients were found infected by HBV alone (1 case) or combined with HCV (1 case). In the remaining 12 the etiology of chronic liver disease could not be defined. Posttransplant hepatitis B occurred in 4/111 children (3.6%), including a recipient from a donor who had been previously vaccinated against HBV, while no patient who had been vaccinated developed hepatitis B. The rate of posttransplant seroconversion to anti-HCV was 15%.

A prognostic model for the outcome of liver transplantation in patients with cholestatic liver disease.

We studied the outcome of 436 patients with primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC) who underwent orthotopic liver transplant (OLT) at three major liver transplant centers. Univariate predictors of outcome included age, Karnofsky score, Child's class, Mayo risk score, United Network for Organ Sharing (UNOS) status, nutritional status, serum albumin, serum bilirubin, international normalized ratio, and the presence of ascites, encephalopathy, renal failure (serum creatinine > 2 mg/dL), and edema refractory to diuretics. Using these predictors, we developed a four variable mathematical prognostic model to help the liver transplant physician predict the following: 1) the amount of intraoperative blood loss; 2) the number of days in the intensive care unit (ICU); and 3) severe complications after surgery. The model uses age, renal failure, Child's class, and United Network for Organ Sharing status. This study is the first to model the outcome of liver transplant in patients with a specific etiology of chronic liver disease (PBC or PSC). The model may be used to help select patients for OLT and to plan the timing of their transplantation.

Platelet autoantibodies in patients with chronic liver disease.

The thrombocytopenia in chronic liver disease (CLD) has been attributed mainly to hypersplenism, although other factors such as reduced mean life span with increased platelet turnover have also been demonstrated. Immunological abnormalities have been described in the pathogenesis and progression of CLD. In this sense, many studies have reported elevated levels of platelet associated IgG (PAIgG) in patients with CLD, and it has been suggested that PAIgG could represent true antiplatelet antibody. In this study we used a glycoprotein (GP)-specific immunoassay (MACE) to determine whether PAIgG or circulating antiplatelet antibodies, reacted against the GPIIb/IIIa or GPIb/IX complexes, in patients with CLD. Thirty-six patients with CLD of diverse etiology were studied (20 female, mean age 53 years, range 38-75 years). 23 out of 36 patients (64%) had anti-GP antibodies in MACE. Particularly, 12 had anti-GPIb, 4 anti-GPIIb/IIIa, and 7 had both types of autoantibodies. The existence of these anti-GP antibodies was not related with the blood platelet count or etiology of CLD. These data show that in patients with CLD of diverse origin, there is a high prevalence of autoantibodies reacting specifically with platelet membrane GP, which constitutes the first evidence of the specific nature of platelet-bound IgG in CLD. These findings suggest that in patients with CLD, an immune mechanism may participate in inducing or aggravating the thrombocytopenia.

Antipyrine clearance and Metabolite Excretion in Saudi Patients with Non-Alcoholic Chronic Liver Disease

In this report, we examined the hepatic microsomal enzyme activity in 34 Saudi patients with chronic liver disease (CLD) and in 21 healthy Saudi subjects by measuring antipyrine clearance (APCI) and the fraction (%) of antipyrine (AP) dose excreted in urine unchanged (fAP) and in the form of its main metabolites: 3-hydroxymethylantipyrine (fHMAP), norantipyrine(fNORAP), and 4-hydroxyantipyrine (f4OHAP). While APCI, fHMAP, fNORAP, f4OHAP were significantly reduced in patients with CLD, fAP was significantly higher in these patients. Correlation was observed between serum albumin and APCI, fHMAP, fNORAP, or f4OHAP and between each two of the last three variables. We conclude that Saudis with CLD have uniform rather than selective reduction of hepatic microsomal enzyme activity and that serum albumin is a sensitive indicator of this activity.

Anti-HCV seroconversion in multitransfused and immunocompromised patients. A long-term longitudinal study.

In a series of 6 multitransfused, immunocompromised patients, the diagnosis of posttransfusion hepatitis C was based upon the analysis of long-term follow-up serum samples. The HCV RNA was detected by a nested PCR assay using primers located in the 5' noncoding region (5'NCR), and anti-HCV antibodies were assayed with third-generation tests. The interval between the first rise in alanine aminotransferase and seroconversion varied from less than 5 months to more than 38 months. Five out of 6 patients seroconverted after 14 months or later. In most cases, the anti-NS3 and anti-NS4 antibodies appeared first. In such patients, the etiology of chronic liver disease may thus be overlooked for 1 or more years, a definitive diagnosis requiring the detection of HCV RNA.

Anti-HCV Seroconversion in Multitransfused and Immunocompromised Patients

In a series of 6 multitransfused, immunocompromised patients, the diagnosis of posttransfusion hepatitis C was based upon the analysis of long-term follow-up serum samples. The HCV RNA was detected by a nested PCR assay using primers located in the 5' noncoding region (5'NCR), and anti-HCV antibodies were assayed with third-generation tests. The interval between the first rise in alanine aminotransferase and seroconversion varied from less than 5 months to more than 38 months. Five out of 6 patients seroconverted after 14 months or later. In most cases, the anti-NS3 and anti-NS4 antibodies appeared first. In such patients, the etiology of chronic liver disease may thus be overlooked for 1 or more years, a definitive diagnosis requiring the detection of HCV RNA.