A Longitudinal Analysis of Mortality Related to Chronic Viral Hepatitis and Hepatocellular Carcinoma in the United States.

(1) Background: Hepatocellular carcinoma (HCC) contributes to the significant burden of cancer mortality in the United States (US). Despite highly efficacious antivirals, chronic viral hepatitis (CVH) remains an important cause of HCC. With advancements in therapeutic modalities, along with the aging of the population, we aimed to assess the contribution of CVH in HCC-related mortality in the US between 1999-2020. (2) Methods: We queried all deaths related to CVH and HCC in the multiple-causes-of-death files from the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER) database between 1999-2020. Using the direct method of standardization, we adjusted all mortality information for age and compared the age-adjusted mortality rates (AAMRs) across demographic populations and by percentile rankings of social vulnerability. Temporal shifts in mortality were quantified using log-linear regression models. (3) Results: A total of 35,030 deaths were identified between 1999-2020. The overall crude mortality increased from 0.27 in 1999 to 8.32 in 2016, followed by a slight reduction to 7.04 in 2020. The cumulative AAMR during the study period was 4.43 (95% CI, 4.39-4.48). Males (AAMR 7.70) had higher mortality rates compared to females (AAMR 1.44). Mortality was higher among Hispanic populations (AAMR 6.72) compared to non-Hispanic populations (AAMR 4.18). Higher mortality was observed in US counties categorized as the most socially vulnerable (AAMR 5.20) compared to counties that are the least socially vulnerable (AAMR 2.53), with social vulnerability accounting for 2.67 excess deaths per 1,000,000 person-years. (4) Conclusions: Our epidemiological analysis revealed an overall increase in CVH-related HCC mortality between 1999-2008, followed by a stagnation period until 2020. CVH-related HCC mortality disproportionately affected males, Hispanic populations, and Black/African American populations, Western US regions, and socially vulnerable counties. These insights can help aid in the development of strategies to target vulnerable patients, focus on preventive efforts, and allocate resources to decrease HCC-related mortality.

The chances of hepatic resection curing hepatocellular carcinoma.

BACKGROUND & AIMS: The popular sense of the word "cure" implies that a patient treated for a specific disease will return to have the same life expectancy as if he/she had never had the disease. In analytic terms, it translates into the concept of statistical cure which occurs when a group of patients returns to having similar mortality to a reference population. The aim of this study was to assess the probability of being cured from hepatocellular carcinoma (HCC) by hepatic resection. METHODS: Data from 2,523 patients undergoing resection for HCC were used to fit statistical cure models, to compare disease-free survival (DFS) after surgery to the survival expected for patients with chronic hepatitis and/or cirrhosis and the general population, matched by sex, age, race/ethnicity and year of diagnosis. RESULTS: The probability of resection enabling patients with HCC to achieve the same life expectancy as those with chronic hepatitis and/or cirrhosis was 26.3%. The conditional probability of achieving this result was time-dependent, requiring about 8.9 years to be accomplished with 95% certainty. Considering the general population as a reference, the cure fraction decreased to 17.1%. Uncured patients had a median DFS of 1.5 years. In multivariable analysis, patient's age and the risk of early HCC recurrence (within 2 years) were independent determinants of the chance of cure (p <0.001). The chances of being cured ranged between 36.0% for individuals at low risk of early recurrence to approximately 3.6% for those at high risk. CONCLUSION: Estimates of the chance of being cured of HCC by resection showed that cure is achievable, and its likelihood increases with the passing of recurrence-free time. The data presented herein can be used to inform decision making and to provide patients with accurate information. LAY SUMMARY: Data from 2,523 patients who underwent resection for hepatocellular carcinoma were used to estimate the probability that resection would enable treated patients to achieve the same life expectancy as patients with chronic hepatitis and/or cirrhosis, and the general population. Herein, the cure model suggests that in patients with hepatocellular carcinoma, resection can enable patients to achieve the same life expectancy as those with chronic liver disease in 26.3% of cases and as the general population in 17.1% of cases.

Multiparametric magnetic resonance imaging predicts clinical outcomes in patients with chronic liver disease.

BACKGROUND & AIMS: Multiparametric magnetic resonance (MR) imaging has been demonstrated to quantify hepatic fibrosis, iron, and steatosis. The aim of this study was to determine if MR can be used to predict negative clinical outcomes in liver disease patients. METHODS: Patients with chronic liver disease (n=112) were recruited for MR imaging and data on the development of liver related clinical events were collected by medical records review. The median follow-up was 27months. MR data were analysed blinded for the Liver Inflammation and Fibrosis score (LIF; <1, 1-1.99, 2-2.99, and ⩾3 representing normal, mild, moderate, and severe liver disease, respectively), T2∗ for liver iron content and proportion of liver fat. Baseline liver biopsy was performed in 102 patients. RESULTS: Liver disease aetiologies included non-alcoholic fatty liver disease (35%) and chronic viral hepatitis (30%). Histologically, fibrosis was mild in 54 (48%), moderate in 17 (15%), and severe in 31 (28%) patients. Overall mortality was 5%. Ten patients (11%) developed at least one liver related clinical event. The negative predictive value of LIF<2 was 100%. Two patients with LIF 2-2.99 and eight with LIF⩾3 had a clinical event. Patients with LIF⩾3 had a higher cumulative risk for developing clinical events, compared to those with LIF<1 (p=0.02) and LIF 1-1.99 (p=0.03). Cox regression analysis including all 3 variables (fat, iron, LIF) resulted in an enhanced LIF predictive value. CONCLUSIONS: Non-invasive standardised multiparametric MR technology may be used to predict clinical outcomes in patients with chronic liver disease.

A mutation in the hepatitis E virus RNA polymerase promotes its replication and associates with ribavirin treatment failure in organ transplant recipients.

We analyzed blood samples collected from 15 patients with chronic hepatitis E who were recipients of solid-organ transplants. All patients cleared the hepatitis E virus (HEV) except for 2 (nonresponders); 1 patient died. A G1634R mutation in viral polymerase was detected in the HEV RNA of the nonresponders; this mutation did not provide the virus with resistance to ribavirin in vitro. However, the mutant form of a subgenomic replicon of genotype 3 HEV replicated more efficiently in vitro than HEV without this mutation, and the same was true for infectious virus, including in competition assays. Similar results were obtained for genotype 1 HEV. The G1634R mutation therefore appears to increase the replicative capacity of HEV in the human liver and hence reduce the efficacy of ribavirin.

Response after treatment for advanced hepatitis C--a mortality abstract.

This article presents an analysis of a recently published study of the survival experience among a group of patients treated for hepatitis C with advanced hepatic fibrosis/cirrhosis, divided into groups based on whether or not sustained virological response was achieved. The purpose is to evaluate the magnitude of excess mortality relative to a comparison population. The potential errors inherent in generating mock age/sex distributions from limited published data are also highlighted.

[Prognostic value of procalcitonin, endotoxin and common inflammatory markers combining MELD score in patients with chronic severe hepatitis].

OBJECTIVE: To evaluate the mid-term prognostic value of procalcitonin (PCT), endotoxin and common inflammatory markers combining the model for end-stage liver disease (MELD) score in patients with chronic severe hepatitis. METHODS: A total of 124 chronic severe hepatitis patients were enrolled, who were hospitalized in the Department of Infectious Diseases, Xiangya Hospital, Central South University from May 2011 to December 2011. Indexes of inflammation, liver and kidney function tests and MELD were determined within 24 h after the admission, and blood samples were collected for measurement of endotoxin , procalcitonin (PCT), and C-reactin protein (CRP). The outcome was confirmed after discharge follow-up at the end of the 3rd month. According to the outcome, the 124 patients were divided into a survival group (n=58) and a death group(n=66). RESULTS: 1) Of the 124 patients, 66 died and 58 survived, with statistical difference in age, MELD score, white blood cell (WBC), polymorphonuclear (PMN), CRP and PCT by single factor analysis between the 2 groups(P<0.05). Binary logistic regression analysis indicated that age, MELD scores and PCT were highly correlated with the outcome (OR=1.07, 1.42 and 1.02 respectively, P<0.05), which could be used to predict the 3 month mid-term mortality of chronic severe hepatitis. 2)There was significant correlation between the MELD scores and the mid-term mortality. Age was positively correlated with the MELD score, and Pearson's correlation coefficient was 0.21 (P<0.05). PCT was also positively correlated with the MELD, and Spearman's correlation coefficient was 0.54 (P<0.01). 3)According to the receiver operation characteristic (ROC) curve analysis , the area under the curve (AUC) of MELD score and PCT were 0.91 and 0.77 respectively, higher than those of other indexes (P<0.01). When the MELD score was up to 30.09 or higher, the predicted mortality risk among these tested patients was the highest(82.26%). The mortality risk predicted by PCT combining MELD score and PCT alone was lower than by MELD score alone (75.00%), but the specificity of MELD score combining PCT was 100%, and the positive prediction value was 1.00. CONCLUSION: Endotoxin and common inflammatory markers (WBC, PMN, and CRP) are not reliable indicators to predict the prognosis in patients with chronic-severe hepatitis. MELD score is significantly correlated with the outcome of mid-term chronic severe hepatitis, PCT and age are both positively correlated with the MELD score. PCT and age combining MELD score can be used to predict the 3 month mid-term mortality of chronic severe hepatitis. MELD score has better prognostic value than PCT. MELD score combining PCT can improve the specificity of prediction.

Cyclooxygenase-2 and vascular endothelial growth factor in chronic hepatitis, cirrhosis and hepatocellular carcinoma.

BACKGROUND/AIMS: Cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) are up-regulated in hepatocellular carcinoma (HCC). To investigate the levels of COX-2 and VEGF expression in chronic hepatitis (CH), cirrhosis, and HCC. METHODS: The immunohistochemical expressions of COX-2 and VEGF were evaluated in tissues from patients with CH (n=95), cirrhosis (n=38), low-grade HCC (LG-HCC; n=6), and high-grade HCC (HG-HCC; n=29). RESULTS: The COX-2 expression scores in CH, cirrhosis, LG-HCC, and HG-HCC were 3.3±1.9 (mean±SD), 4.2±1.7, 5.5±1.0, and 3.4±2.4, respectively (CH vs. cirrhosis, P=0.016; CH vs. LG-HCC, P=0.008; LG-HCC vs. HG-HCC, P=0.004), and the corresponding VEGF expression scores were 0.9±0.8, 1.5±0.7, 1.8±0.9, and 1.6±1.1 (CH vs. cirrhosis, P<0.001; CH vs. LG-HCC, P=0.011; LG-HCC vs. HG-HCC, P=0.075). Both factors were correlated with the fibrosis stage in CH and cirrhosis (COX-2: r=0.427, P<0.001; VEGF: r=0.491, P<0.001). There was a significant correlation between COX-2 and VEGF in all of the tissue samples (r=0.648, P<0.001), and between high COX-2 and VEGF expression scores and survival (COX-2: P=0.001; VEGF: P<0.001). CONCLUSIONS: The expressions of both COX-2 and VEGF are significantly higher in cirrhosis and LG-HCC than in CH. High COX-2 and high VEGF expressions are associated with a high survival rate.

Quantitation of plasma circulating DNA using quantitative PCR for the detection of hepatocellular carcinoma.

Circulating DNA is a potential biomarker for tumor diagnosis and prognosis. This study was aimed to quantify the circulating DNA in plasma from patients with hepatocellular carcinoma (HCC) using quantitative PCR and evaluate its potential clinical value. Blood samples were collected from 72 patients with HCC, 37 with liver cirrhosis or chronic hepatitis and 41 healthy volunteers. Plasma DNA was extracted and quantified by a real-time quantitative PCR method. The diagnostic and prognostic value of plasma DNA analysis for HCC was evaluated. DNA levels in the HCC plasma (median: 173 ng/mL) were significantly higher than those in the healthy controls (9 ng/mL) or control benign patients (46 ng/mL) (P < 0.001). The area under the receiver-operation characteristic (ROC) curve (AUC) assessing plasma DNA was 0.949 for healthy controls and 0.874 for control patients. Plasma DNA detection could discriminate HCC from normal controls with 90.2% sensitivity and 90.3% specificity at the cut-off value of 18.2 ng/mL. Combined ROC analyses using plasma DNA and serum AFP revealed an elevated AUC of 0.974 with 95.1% sensitivity and 94.4% specificity in discriminating HCC from normal controls. The plasma DNA levels were positively associated with tumor size (P = 0.012), and were significantly elevated in HCC patients with intrahepatic spreading or vascular invasion (P = 0.035). The overall survival time of patients with high plasma DNA levels showed a shortened tread when compared with that of patients with low plasma DNA concentrations (P = 0.071). Plasma DNA may be a valuable noninvasive tool for the detecting and predicting the metastasis potential of HCC; and the prognostic value of plasma DNA needed further investigation.

Clinical significance of Staphylococcus aureus infection in patients with chronic liver diseases.

BACKGROUND: Staphylococcus aureus increasingly is recognized as an important pathogen in patients with chronic liver diseases. The purpose of this study was to evaluate clinical features and the outcome of S. aureus infections in patients with chronic liver diseases. METHODS: From the database of a surveillance study for S. aureus infections, the data regarding S. aureus infections in patients with chronic liver diseases were analysed and compared with those in patients with other diseases. RESULTS: We identified 298 patients who had chronic liver diseases; 151 (50.7%) patients had cirrhosis, 76 (25.5%) had chronic hepatitis and the remaining 71 (23.8%) had other diseases. The most common type of S. aureus infection in patients with chronic liver diseases was primary bacteraemia (n=68, 22.8%) and 92 (30.9%) patients had concomitant bacteraemia. When compared with other disease group, bacteraemia and bone infection were more frequent in the liver disease group (P<0.05). The 30-day mortality rate of the liver disease group was significantly higher than that of the other disease group (29.4 vs. 16.7%, P<0.001). A multivariate analysis showed that chronic liver disease was a significant factor associated with mortality, along with old age, immunosuppressive treatment, intubated state, indwelling urinary catheter, pneumonia and concomitant bacteraemia. CONCLUSIONS: Bacteraemia was the most common type of S. aureus infection in patients with underlying liver diseases, predicting higher mortality rates. The mortality rate of patients with liver diseases was significantly higher than that of patients with other diseases when S. aureus infection developed.

Prognostic factors for chronic severe hepatitis and construction of a prognostic model.

BACKGROUND: Chronic severe hepatitis is a serious illness with a high mortality rate. Discussion of prognostic judgment criteria for chronic severe hepatitis is of great value in clinical guidance. This study was designed to investigate the clinical and laboratory indices affecting the prognosis of chronic severe hepatitis and construct a prognostic model. METHODS: The clinical and laboratory indices of 213 patients with chronic severe hepatitis within 24 hours after diagnosis were analyzed retrospectively. Death or survival was limited to within 3 months after diagnosis. RESULTS: The mortality of all patients was 47.42%. Compared with the survival group, the age, basis of hepatocirrhosis, infection, degree of hepatic encephalopathy (HE) and the levels of total bilirubin (TBil), total cholesterol (CHO), cholinesterase (CHE), blood urea nitrogen (BUN), blood creatinine (Cr), blood sodium ion (Na), peripheral blood leukocytes (WBC), alpha-fetoprotein (AFP), international normalized ratio (INR) of blood coagulation and prothrombin time (PT) were significantly different in the group who died, but the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB) and hemoglobin (HGB) were not different between the two groups. At the same time, a regression model, Logit (P) =1.573XAge+1.338XHE-1.608XCHO+0.011XCr-0.109XNa+1.298XINR+11.057, was constructed by logistic regression analysis and the prognostic value of the model was higher than that of the MELD score. CONCLUSIONS: Multivariate analysis excels univariate analysis in the prognosis of chronic severe hepatitis, and the regression model is of significant value in the prognosis of this disease.

[Clinical value of Child-Turcotte-Pugh and model for end-stage liver disease score to predict the prognosis of chronic severe hepatitis].

OBJECTIVE: To compare the clinical value in predicting the prognosis of chronic severe hepatitis between the Child-Turcotte-Pugh (CTP) score and the model for end-stage liver disease (MELD) score. METHODS: Fifty-five cases with chronic severe hepatitis were scored by CTP and MELD score systems based on their biochemical and coagulation parameters, and related signs within 24 hours after their admission. The termination date of observation was the 90th day after their admission. The actual survival time were recorded. The comparison scores of CTP/MELD were conducted respectively and compared between the survival group and death group, among different clinical stages of chronic severe hepatitis. The correlation of CTP/MELD score with the clinical stages was analyzed respectively. The survival time, mortality and survival rate were compared respectively among the groups classified by CTP/MELD score according to Kaplan-Meier (K-M) survival curve. RESULTS: The CTP score and the MELD score in death group were higher than those in survival group (both P<0.01). The CTP and MELD scores in the advanced stage group were also higher than those in the early and middle stage (both P<0.01). The correlation of the MELD score with the stage was higher (r(s) =0.689,P<0.01) than that of the CTP score (r(s)=0.428, P<0.01). The survival time of patients with CTP<12 scores, was longer than with CTP>or=12 scores, and their survival rate was also higher(both P<0.01). When the MELD score lowered, survival time was longer, and survival rate was higher. The survival time, mortality and survival rate showed significant difference among the groups classified by MELD score (or=40 points, all P<0.01). CONCLUSION: The parameters employed in MELD score system are more OBJECTIVE: and easy to achieve, the score range for patients classification is wider and more practical, and the correlation with the clinical stage is higher than CTP score system, suggesting the MELD score system is better in predicting the prognosis of patients with chronic severe hepatitis than the CTP score system.

[An evaluation of the prognosis of patients with chronic severe hepatitis using a model for end-stage liver disease].

OBJECTIVE: To investigate the prognosis evaluation and treatment strategy of chronic severe hepatitis (CSH) patients using a model of end-stage liver disease (MELD). METHODS: The MELD scores of 135 CSH patients on the day of their admittance to our hospital and the DeltaMELD scores after two-weeks of medical treatment were retrospectively analyzed. They were also compared with the scores of the three-month mortality rate of the patients. RESULTS: The mean MELD score calculated on the first day of the patients who died after their admission to the hospital was 37.00+/-6.50, while that of the living group was 25.80+/-5.20. The difference was highly significant (chi(2)=72.00, P < 0.01). MELD score after two-weeks medical treatment of the patients who died was 1.57+/-0.89, while that of the living group was -0.99+/-0.73; the difference was also highly significant (chi(2)=56.35, P < 0.01). The area under the ROC curve of MELD score (c-statistic) was 0.90, while the c-statistic for DeltaMELD score was 0.76. On the first day of their admission, when the MELD score was < 25, the three-month mortality rate was 2%; when it was 25 or= 35, the three-month mortality rate was 81%; the differences between these groups were all highly significant (P less than 0.01). When MELD scores were above zero, the three-month mortality was 51%, and when DeltaMELD scores were less than or equal to zero, the three-month mortality rate was 13%. All the differences were highly significant (P < 0.01). CONCLUSION: A high MELD score and a high Delta MELD score herald high three-month mortality rates in patients with CSH. MELD is quite usable in assessing the prognosis in patients suffering CSH. The choice of treatment for the CSH patients could be made by integrating the MELD score calculated on the first day of being admitted to a hospital and the Delta MELD score after their medical treatment.

Long-term results of liver transplant in patients with chronic viral hepatitis-related liver disease in Singapore.

INTRODUCTION: Liver disease from chronic hepatitis B (CHB) and C (CHC) constitutes 57 percent of adult liver transplant in Singapore. Their long-term results post-transplant may be affected by recurrence of the viral illness. This study aims to evaluate the long-term results and survival in patients transplanted for CHB- and CHC-related liver disease. METHODS: Patients transplanted for CHB- and CHC-related disease from 1990 until March 2004, which included decompensated cirrhosis and hepatocellular carcinoma (HCC), were reviewed and analysed. RESULTS: 25 patients were transplanted for CHB-related liver disease, with mean follow-up of 153 +/- 25 weeks. Two- and four-year survival rates were 75 percent and 69 percent, respectively. Hepatitis B recurrence from YMDD mutants occurred in five patients, and four were treated successfully with adefovir dipivoxil, with resolution in transaminases and/or improvement in histology. One patient became non-compliant with follow-up and medications, and died 173 weeks post-transplant from reactivation of the wild-type hepatitis B virus. Nine patients were transplanted for CHC-related liver disease, with mean follow-up of 188 +/- 40 weeks, and two- and four-year survival rates of 89 percent and 76 percent, respectively. Two patients developed hepatitis C recurrence and were treated with interferon and ribavarin. One responded with sustained response but the other remained viraemic and died of HCC recurrence two years post-transplant. CONCLUSION: Long-term results from CHB- and CHC-related liver diseases were satisfactory and comparable to major transplant centres in the USA and Europe. Recurrence of viral hepatitis post-transplant is controllable with current antiviral therapy.

Clinical implications of measurement of serum nuclear matrix protein levels in patients with liver disease.

BACKGROUND/AIMS: Serum aminotransferase, a sensitive marker of hepatocellular damage, often poorly correlates with the severity of damage. Serum nuclear matrix protein (NMP), a structural protein released from dead cell nuclei, is investigated as a candidate marker of organ damage in liver disease. METHODOLOGY: Serum NMP and aminotransferase levels of 134 patients with various liver diseases and 26 healthy individuals were examined. RESULTS: Patients with chronic viral hepatitis showed slightly higher NMP levels (17.8 U/mL; 95% CI 15.0-20.5 U/mL) than those of healthy individuals (6.05 U/mL; 95% CI 4.82-7.27 U/mL). Their NMP values had no correlation with aminotransferase levels. NMP levels were similar irrespective of liver disease progression, whereas aminotransferase values decreased in parallel with progression. Patients with autoimmune hepatitis or primary biliary cirrhosis who were under an appropriate treatment as well as individuals with fatty liver showed no elevation of serum NMP levels. Patients with acute viral hepatitis showed very high NMP levels (38.8 U/mL; 95%CI 27.6-50.0 U/mL) that correlated with serum aminotransferase levels in their sera. CONCLUSIONS: In chronic liver diseases, the serum NMP level elevates to various degrees independent from the degree of aminotransferase elevation. Serum NMP, putatively representing the number of dead cells, is a candidate as an indicator of organ damage severity in liver disease.

[Application of Model for end-stage liver disease to predict the prognosis of and curative effect for chronic severe hepatitis].

OBJECTIVE: To compare the capability in predicting the prognosis of chronic severe hepatitis among 3 prediction systems: Model for end-stage liver disease (MELD), Child-Turcotte-Pugh (CTP) system, and King's College Hospital (KCP) system, and to explore the capability of MELD in predicting the curative effect of artificial liver. METHODS: Scoring was made among 66 patients of chronic severe liver diseases with the underlying disease of hepatitis B, 11 in early stage, 14 in middle stage, 15 in late stage, and 26 unclassified, by MELD, CTP, and KCP systems. The accuracy of each system was evaluated by ROC curve, the differences between the systems was analyzed by Kaplan-Meier survival curve. RESULTS: The MELD score of the patients at admission predicted the mortality within 3 months with the c-statistic of 0.894, higher than those of the CTP and KCP systems (0.703 and 0.89 respectively). The MELD scores of the patients in the early stage was 24 +/- 4, significantly lower than those in the middle and late stages (31.11 +/- 2.90 and 41.38 +/- 9.98 respectively, all P < 0.01). The MELD score was positively correlated with the stage of disease (r = 0.737, P < 0.01). The mortally was 10.7% for the patients with an admission MELD score < or = 30, was 47% for the patients with an admission MELD score of 31 approximately 39, and was 60% the patients with an admission MELD score of > or = 40. CONCLUSION: The predictive capability of MELD system is better than the KCP and CTP systems. Artificial liver support treatment is the best choice e for the patients with an admission MELD score of 31-39. An admission MELD score > 40 is the indication for liver transplantation.

Clinical significance of abnormal lipoprotein patterns in liver diseases.

We analyzed lipids in liver diseases by agarose gel electrophoresis, and differential staining and simultaneous analysis of the cholesterol (Chol) and triglyceride (TG) fractions. Liver diseases were classified into chronic hepatitis (CH), liver cirrhosis (LC), hepatocellular carcinoma (HCC), and metastatic liver cancer, and each fraction was compared among these diseases. Atypical patterns that were unclassifiable according to the WHO classification of hyperlipidemia phenotypes were classified, and their clinical importance was evaluated. With progression of the pathologic conditions of CH, LC, and HCC, the T-Chol level, each Chol fraction, and the TG fraction decreased while the LDL-TG fraction increased. Metastatic liver cancer showed a lower HDL-fraction level but higher levels of the other parameters than HCC. When the subjects were classified into survivors and patients who died, the HDL fraction level in HCC and metastatic liver cancer, and the LDL level in LC and metastatic liver cancer differed between survivors and patients who died. Phenotypes of hyperlipidemia also differed among diseases, and atypical patterns were frequently observed in patients who died. There were 6 atypical patterns, of which 4 (slow alpha HDL, abnormal LDL, Lp-X, and Lp-Y) were associated with liver diseases. Slow alpha HDL appeared during slight bile stagnation and was accompanied by increases in the apo E level and the HDL particle size. Abnormal LDL appeared with severe liver dysfunction; a TG peak appeared at the position of LDL, and the HDL and VLDL fractions were negligible. Lp-X was a Chol-rich band, occurring on the cathode side of LDL in the presence of marked bile stagnation such as that in obstructive jaundice, and was accompanied by appearance of abnormal LDL. Lp-Y was similar to Lp-X in terms of mobility and associated diseases but contained Chol and TG. Abnormal LDL, Lp-X, and Lp-Y were often observed in patients with poor outcomes. Lipid analysis in liver diseases by this method showed results reflecting the pathologic conditions and may be clinically useful.

An evaluation of long-term outcomes after liver transplantation for cryptogenic cirrhosis.

Patients with cryptogenic cirrhosis (CC) comprise a significant proportion of liver transplant recipients. Poor outcome after transplantation has been reported by some centers, with fibrosis occurring in a significant proportion of patients. Outcome of 46 patients with CC who underwent transplantation between 1989 and 1999 at King's College Hospital London were compared with time-matched recipients who underwent transplantation for hepatitis C virus (HCV) cirrhosis (n = 58) and patients with alcohol-related cirrhosis (AC, n = 53) during the same time period. Mean follow-up was 46 +/- 37 months for CC patients, 41 +/- 31 months for AC patients, and 49 +/- 31 months for HCV patients. No protocol liver biopsy specimens were obtained, and biopsies were performed only for investigation of biochemical abnormalities. Acute cellular rejection occurred in 30% of CC, 26% of AC, and 37% of HCV patients (P = NS). Overall patient and graft survival at 1 year was 85% and 80% for CC patients, 87% and 81% for AC patients, and 91% and 82% for patients with HCV (P = NS). Five-year patient and graft survival was 81% and 77% for CC patients, 60% and 48% for AC patients, and 79% and 57% for HCV patients (Log rank; P =.369). Twenty-two percent of CC patients had inflammation on last evaluable liver biopsy, compared with 25% of patients who underwent transplantation for AC and 68% of patients who underwent transplantation for HCV. No patient who underwent transplantation for CC had histologic evidence of cirrhosis on last evaluable biopsy, compared with 2% of patients who underwent transplantation for AC and 16% of patients who underwent transplantation for HCV (Chi-squared = 13.053, P =.0015). These results suggest that CC is a favorable indication for OLT and that although a proportion of patients develop inflammation in the liver allograft, this does not result in significant graft dysfunction or loss.

Clinical assessment of hepatic functional reserve using 99mTc DTPA galactosyl human serum albumin SPECT to prognosticate chronic hepatic diseases--validation of the use of SPECT and a new indicator.

RATIONALE: It is generally known that scintigraphy of 99mTc diethylenetriamine pentaacetic acid-galactosyl human serum albumin (99mTc-GSA) is useful for assessing hepatic functional reserve. For hepatic functional indicators, the index of the calculated planar image has been used in previous studies. However, there have been few reports that suggest that the indicators calculated from static SPECT data would be useful for the assessment of hepatic function. The aims of this study were to establish a simple method for assessing hepatic functional reserve using the liver SPECT of 99mTc-GSA and to apply this method for rich stratification in patients with chronic hepatic diseases. METHODS: A liver phantom (a 50% concentration of 99mTc solution) was used to compare the planar and SPECT methods. According to the definition of the new indicator, the liver SPECT of 99mTc-GSA was divided by a syringe SPECT of 99mTc-GSA and was called the liver uptake ratio (LUR). We correlated the LUR and the liver uptake ratio calculated according to the blood-sampling method. 99mTc-GSA SPECT was performed in 137 patients with hepatic diseases, including chronic hepatic diseases, and 20 healthy volunteers. The LUR was correlated between the formed subtypes for all subjects. RESULTS: The acquired phantom-count ratio calculated by the SPECT method was more accurate than that acquired by the planar method. A good correlation was obtained between the LUR and the blood-sampling method (r = 0.971). The LUR was significantly lower in subjects with severe cirrhosis than in healthy subjects or those with chronic hepatitis and mild cirrhosis, and it was significantly lower in subjects with chronic hepatitis and mild cirrhosis than in healthy subjects. The LUR was significantly correlated with other hepatic function tests. Based on LUR, the chronic hepatic diseases were divided into two groups: Group A, with LURs 30% and higher, and Group B, with LURs below 30%. An LUR of 30% marked the 25th percentile of the mild-cirrhosis group. The cumulative survival rates were lower in Group B than in Group A. CONCLUSION: The SPECT method was superior to the planar method for assessing LURs. LUR was a suitable indicator of 99mTc-GSA clearance from the blood pool and of binding to the asialo-glycoprotein receptor. LUR is a simple and clinically useful indicator for the assessment of hepatic functional reserve in chronic hepatic diseases.

[Single factor study of prognosis from 520 cases with chronic severe hepatitis].

OBJECTIVE: To further understand chronic severe hepatitis (CSH) and to improve the level of diagnosis and treatment and to explore the methods to reduce the fatality rate of CSH through analysing the factors related to prognosis of CSH. METHODS: The factors related to prognosis from 520 cases with CSH were analyzed by SPASS and STATA software. RESULTS: 1. The fatality rate in cases with age > or = 40 years was higher than that in cases with age <40 years (P<0.001), there was no significant difference (P>0.05) in sex and pathogenic basis of CSH; 2. The fatality rate rose in cases with WBC > or = 10.0 x 10(9) per liter or platelet <100 x 10(9) per liter; 3. The fatality rate increased gradually with the ratio of aspartic aminotransferase to alanine aminotransferase (AST/ALT) and serum total bilirubin (TBil), appearance of deviation of TBil and ALT, decrease in prothrombin activity (PTA), total cholesterol (TC), cholinesterase and albumin (Alb) (P<0.001). 4. The fatality rate increased with appearance of complications such as ascites, electrolyte disturbance, spontaneous peritonitis and so on (P<0.001). CONCLUSIONS: The important factors related to prognosis were age, > or = 40 years, WBC 10.0 x 10(9) per liter or platelet <100 x 10(9) per liter; the ratio of AST/ALT, TBil, Tc, cholinesterase, Alb and complication, to monitor dynamically laboratory indexes such as TBil, PTA, Tc, cholinesterase and so on and to prevent and cure various complications are important measures to reduce the fatality rate of CSH.