Degree Of Liver Function Impairment Research Articles

Clinical value of AEF in the post-processing technique of liver perfusion-like phase III enhanced CT scan in evaluating the degree of liver function impairment in patients with Hepatitis-B cirrhosis.

Objectives:To investigate the value of CT arterial enhancement fraction (AEF) in the post-processing technique of liver perfusion-like phase III enhanced CT scan in evaluating the degree of liver function impairment in patients with hepatitis B cirrhosis.Methods:The study included 85 patients with hepatitis B cirrhosis admitted to the Department of Radiology, The Affiliated Huai’an Hospital of Xuzhou Medical University from May 2018 to October 2020 were selected as the experimental group, and 71 patients with liver fibrosis during the same period were selected as the control group. All patients underwent routine liver CT phase III perfusion scan, and hepatic AEF (hAEF) and liver/spleen ratio (H/S) were compared between the two groups to analyze the differential value of hAEF and H/S for liver fibrosis and hepatitis B cirrhosis. Patients were divided into the mild group (Grade-A) and the severe group (Grade-B and C) according to Child-Pugh grading. hAEF and H/S values of the two groups were compared, and the evaluation value of AEF on the degree of impairment of hepatitis B cirrhosis was analyzed.Results:hAEF and H/S values of the experimental group were greater than those of the control group (P<0.05), and the AUCs of hAEF and H/S values for distinguishing hepatitis B and cirrhosis were 0.727 (95%CI: 0.650-0.795) and 0.791 (95%CI: 0.718-0.852), respectively. Moreover, hAEF and H/S values of the severe group were greater than those of the mild group (P<0.05), and the AUCs of hAEF and H/S values in evaluating the degree of liver function impairment were 0.746 (95%CI: 0.627-0.834) and 0.770 (95%CI: 0.705-0.928), respectively.Conclusions:AEF boasts the value of differentiating liver fibrosis and cirrhosis, and of evaluating the degree of liver function impairment in patients with hepatitis B cirrhosis.

Overexpression of cytotoxic proteins correlates with liver function impairment in patients with drug reaction with eosinophilia and systemic symptoms (DRESS).

Drug reaction with eosinophilia and systemic symptoms (DRESS) is characterised by skin rash and multivisceral involvement. The liver is the organ most frequently affected and the degree of liver function impairment often correlates with the mortality rate of DRESS. We aimed to examine the expression of cytotoxic proteins, including soluble Fas ligand (sFasL), TNF-α, granulysin, perforin, and granzyme B in the sera and skin lesions of patients with DRESS and evaluate their clinical significance. Our cohort consisted of 21 patients with DRESS and control groups including 39 patients with Stevens-Johnson syndrome/toxic epidermal necrolysis, 21 patients with maculopapular eruption, and 29 normal controls. Concentrations of cytotoxic proteins in the sera were measured using enzyme-linked immunosorbent assays. Tissue samples were also obtained from typical skin lesions, and immunohistochemical staining was conducted to assess the local expression of cytotoxic proteins. We found that sFasL and granzyme B were significantly overexpressed in the sera of DRESS patients compared to normal controls. Furthermore, the levels of sFasL, perforin, and granzyme B significantly correlated with the serum level of liver enzymes in DRESS patients. Immunohistochemical examination also showed overexpressed cytotoxic proteins in cutaneous DRESS lesions. Cytotoxic proteins may play a vital role in the pathogenesis of DRESS, and serum sFasL, perforin, and granzyme B may also be involved in liver function impairment in DRESS patients.

Hepatocellular carcinoma: Therapeutic strategy in 2017

Hepatocellular carcinoma (HCC) is the most frequent primary neoplasm of the liver and it is the most relevant cause of death among patients with chronic liver disease. Prognosis assessment is a critical step in the management of HCC patients. Any attempt to assess the prognosis should consider not only information regarding tumor stage but also data about the degree of liver function impairment and the presence of cancer-related symptoms. In addition, any system aimed to be clinically successful should optimally attempt to link prognostic prediction and treatment indication. The Barcelona Clinic Liver Cancer staging system is the most accepted staging system. It has been externally validated, takes into account the most relevant prognostic parameters, and suggests the treatment approach based on the best scientific evidence. This article summarizes the most updated treatment strategy of HCC and future perspectives.

Assessment of respiratory muscle performance, functional capacity, fatigue, and quality of life in liver transplant candidates

Purpose: This study aimed at assessment of respiratory muscle performance (RMP), functional capacity (FC), feeling of fatigue, and quality of life (QOL) in liver transplant candidates and to correlate these variables with each other and with the Model for End-Stage Liver Disease (MELD). Methods: A prospective study carried out from January/2008 to June/2009 including 130 liver transplant candidates on waiting–list at the São Paulo Health Transplant System, followed at the Unit of Liver Transplantation - Unicamp with cirrhosis of any etiology, independent of gender, age, and degree of liver function impairment as classified by the MELD score. Respiratory muscle performance was determined by respiratory muscle strength (RMS - PIMAX and PEMAX), vital capacity (VC), and FC measured during six-minute walk tests (6MWT). Fatigue was evaluated using the Fatigue Severity Scale (FSS), and QOL was assessed using the SF-36 questionnaire. Results: Expressed as the mean SD and percentage of the predicted value: MELD=16+4, VC=4.0+0.9L - (97%+16%), PIMAX=77+28cmH2O -(71+25%), PEMAX=76+26cmH2O (76+26%), 6MWT=453.9+81.2m (73+13%), FSS=34+17, and compromised QOL, particularly in physical (48+41) and emotional (57+41) aspects, vitality (58+26) and general state (58+24). Predicted VC was negatively correlated with MELD (p=0.0034) and positively correlated with RMS and 6MWT (p=0.0217). Greater distances in the 6MWT were associated with a higher RMS and QOL and less fatigue. Greater FSS scores resulted in lower QOL scores. Conclusion: A decrease in VC was related to the severity of liver disease and a decrease in RMS and FC, which, in turn, correlated with greater fatigue and lower QOL.

Macrovascular Malignant Portal Vein Thrombosis in Cirrhotic Patients with HCC

1.1. Background: The presence of macrovascular malignant portal vein thrombosis (MMPVT) in patients with HCC is one of the most significant prognostic factors. Without treatment, the survival is less than 3 months [1]. Standard treatment regimens have not been established in these patients. 1.2. Aims: Our aim was to explore the prevalence and degrees of MMPVT in cirrhotic patients with HCC. Also, we aimed at determination of a correlation between the degree of MMPVT and both the tumour burden and the degree of liver function impairement. 1.3. Methods: The diagnosis of HCC in cirrhotic patients was based on the EASL guidelines. On contrast-enhanced CT scans, MMPVT was identified by the presence of a low-attenuation intra-luminal filling defect. Intrathrombus vascularity, observed in the arterial phase of imaging studies after the administration of contrast, has been reported to be a sign that is specific for MMPVT on CT [3]. MMPVT was graded into 4 grades according to Nonami grading [3]. Child-Turcotte-Puph (CTP) score was calculated for every patient and AFP was measured. Neutrophil- lymphocyte ratio (NLR) was calculated by dividing the neutrophil count by the lymphocyte count, provided that there was no ongoing infection. 1.4. Results: In 247 consecutive cirrhotic HCC patients (88.9% males, 11.1% females), the mean age was 58.87±7.42 years. MMPVT was detected in 63 patients (57 male, 6 females) representing 26% of all HCC cases. G1 MMPVT was present in 4 patients (6.3%), G2 in 19 patients (30.1%), G3 in 4 patients (6.3%) and G4 in 36 patients (57.1%). In HCC cases with MMPVT the tumor was multifocal or diffuse in 53 patients (82.5%) and unifocal in 11 patients (17.5%).The serum AFP level, CTP score and NLR were significantly higher in presence of MMPVT (P =.022,.005 and<.0005 respectively).The tumor size was significantly larger in presence of MMPVT(P<.0005).There was a significant positive correlation between the grade of MMPVT and CTP score (r = 0.205- p<0. 001), serum AFP level (r = o.423 –p< 0. 0001) and tumor size (r =o.275 - p< 0. 0001).The cut-off serum AFP value above which HCC patients had high risk of having MMPVT was 373.5 ngm/ml with sensitivity of 74.1% and specificity of 77.9% and area under the curve(AUC) of 77.6%.The cut-off tumor size above which HCC patients had high risk of having MMPVT is 5.9 cm with sensitivity of 64.5% and specificity of 72.1% and AUC of 70.5%. 1.5. Conclusion: MMPVT of different degrees was present in 26% of cirrhotic HCC cases. It is associated with tumor burden, aggressiveness and degree of liver function impairment.

Pharmacokinetic drug interactions in liver disease: An update.

Inhibition and induction of drug-metabolizing enzymes are the most frequent and dangerous drug-drug interactions. They are an important cause of serious adverse events that have often resulted in early termination of drug development or withdrawal of drugs from the market. Management of such interactions by dose adjustment in clinical practice is extremely difficult because of the wide interindividual variability in their magnitude. This review examines the genetic, physiological, and environmental factors responsible for this variability, focusing on an important but so far neglected cause of variability, liver functional status. Clinical studies have shown that liver disease causes a reduction in the magnitude of interactions due to enzyme inhibition, which is proportional to the degree of liver function impairment. The effect of liver dysfunction varies quantitatively according to the nature, reversible or irreversible, of the inhibitory interaction. The magnitude of reversible inhibition is more drastically reduced and virtually vanishes in patients with advanced hepatocellular insufficiency. Two mechanisms, in order of importance, are responsible for this reduction: decreased hepatic uptake of the inhibitory drug and reduced enzyme expression. The extent of irreversible inhibitory interactions is only partially reduced, as it is only influenced by the decreased expression of the inhibited enzyme. Thus, for appropriate clinical management of inhibitory drug interactions, both the liver functional status and the mechanism of inhibition must be taken into consideration. Although the inducibility of drug-metabolizing enzymes in liver disease has long been studied, very conflicting results have been obtained, mainly because of methodological differences. Taken together, the results of early animal and human studies indicated that enzyme induction is substantially preserved in compensated liver cirrhosis, whereas no definitive conclusion as to whether it is significantly reduced in the decompensated state of cirrhosis was provided. Since ethical constraints virtually preclude the possibility of performing methodologically rigorous investigations in patients with severe liver dysfunction, studies have recently been performed in animals rigorously stratified according to the severity of liver insufficiency. The results of these studies confirmed that enzyme induction is virtually unaffected in compensated cirrhosis and indicated that the susceptibility of enzyme induction to severe liver dysfunction depends on the type of nuclear receptor involved and also varies among enzyme isoforms under the transcriptional control of the same nuclear receptor. These findings make it clear that no general conclusion can be reached from the study of any particular enzyme and partly explain the conflicting results obtained by previous studies. Since no general guidelines can be provided for the management of drug interactions resulting from enzyme induction, both the effects and the plasma concentration of the induced drug should be strictly monitored. The findings discussed in this review have important methodological implications as they indicate that, contrary to current guidelines, the magnitude of metabolic drug-drug interactions in patients with liver disease cannot be inferred from studies in healthy subjects.

Treatment of intermediate-stage hepatocellular carcinoma.

Hepatocellular carcinoma (HCC)-closely associated with liver cirrhosis and, in fact, the main cause of death in patients with such disease-is now recognized as one of the most-prevalent and lethal neoplasms worldwide. Prognosis and allocation of the multiple available treatment options for patients with HCC are influenced not only by tumour stage, but also by the degree of liver-function impairment. Therefore, accurate assessment and classification of disease is important for patient management. According to the Barcelona Clinic Liver Cancer (BCLC) algorithm, intermediate-stage HCC is defined as extensive multifocal disease without vascular invasion in patients with preserved liver function and absence of cancer-related symptoms; in this context, transarterial chemoembolization (TACE) is considered the standard treatment. The use of drug-eluting beads has enabled standardization of this procedure, resulting in higher reproducibility and tolerability of the treatment. Nevertheless, not all patients with intermediate-stage HCC are good candidates for TACE and, for such patients in whom TACE is not appropriate or has failed, other treatments can be considered, including sorafenib. Radioembolization is a promising alternative that deserves further prospective studies. Herein, we review the current approaches used to accurately stratify patients with intermediate-stage HCC and subsequently allocate the most-appropriate treatments. The key developments in therapeutic strategies are also discussed.

Oral health and liver function in children and adolescents with cirrhosis of the liver.

IntroductionPeople with cirrhosis of the liver are predisposed to developing oral lesions. The occurrence and type of lesion depend on the degree of liver function impairment and its type, and on the severity and duration of systemic diseases. In children, the age at which the early symptoms of liver disease are experienced is also of great importance.AimTo assess the prevalence of oral pathological lesions in children and adolescents with cirrhosis of the liver, and their correlation with the degree of liver function impairment.Material and methodsClinical and laboratory results of liver function tests (Model of End-Stage Liver Disease/Score of Paediatric End-Stage Liver Disease, Child-Pugh score) were assessed in 35 patients with cirrhosis of the liver. The average age of the patients was 10.7 ±4.74 years. All patients also had their oral cavities examined (mucosa, gingiva – GI, hygiene – PLI, teeth – dmft/dmfs and DMFt/DMFs, DDE Index and Candida spp. presence) and this was then correlated to the degree of liver function impairment.ResultsAccording to the Child-Pugh scale, 16 patients were class A and 19 were class B/C. Jaundice during the first 3 years of life occurred in 9 patients. Mucosal lesions were found in 26 out of 35 patients (74%), including 10 out of 16 (63%) in Child-Pugh group A, and 16 out of 19 (84%) in group B/C (NS – non significant). Oral candidiasis occurred more often in class B/C than in class A (47.4% vs. 12.5%; p < 0.05). The GI index (Gingival Index) and PLI index (Dental Plaque Index) did not differ between the groups (A vs. B/C) but correlated in the whole group (R = 0.58) as well as in subgroups A (R = 0.65) and B/C (R = 0.59). Dmft/dmfs and DMFt/DMFs indexes did not differ between groups A and B/C, and neither did the DMFt/DMFs in patients with/without enamel defects.ConclusionsOral mucosal lesions are commonly found in children with cirrhosis of the liver. Advanced liver disease promotes oral candidiasis. Severity of gingivitis correlates with the presence of dental plaque.

Antiangiogenic treatment in hepatocellular carcinoma: the balance of efficacy and safety.

Hepatocellular carcinoma (HCC) is a severe complication of advanced liver disease with a worldwide incidence of more than 600,000 patients per year. Liver function, clinical performance status, and tumor size are considered in the Barcelona Clinic Liver Cancer (BCLC) system. While curative treatment options are available for early stages, most patients present with intermediate- or advanced-stage HCC, burdened with a poor prognosis, substantially influenced by the degree of liver-function impairment. Hypervascularization is a major characteristic of HCC, and antiangiogenic treatments are the basis of treatment in noncurative stages, including interventional and pharmacological treatments. Currently, the tyrosine-kinase inhibitor sorafenib is still the only approved drug for HCC. Further improvements in survival in patients with intermediate- and advanced-stage HCC may be anticipated by both multimodal approaches, such as combination of interventional and systemic treatments, and new systemic treatment options. Until now, the Phase III development of other tyrosine-kinase inhibitors in patients with advanced HCC has failed due to minor efficacy and/or increased toxicity compared to sorafenib. However, promising Phase II data have been reported with MET inhibitors in this hard-to-treat population. This review gives a critical overview of antiangiogenic drugs and strategies in intermediate- and advanced-stage HCC, with a special focus on safety.

Can long term therapy with oral nucleos(t)ide analogs influence the prognosis of chronic hepatitis B‐related complications?

1 the majority of whom acquire infection at birth or in early childhood. 2 It is estimated that 50% of male and 14% of female carriers will die from CHB-related com- plications such as hepatocellular carcinoma (HCC) or cirrhosis. 3 Since the global introduction of routine vaccination against hepa- titis B virus (HBV) in newborns in countries where the incidence of HBV-related complications are high, such as in theAsia-Pacific region, there has been a significant and gratifying decline in rates of CHB and HCC. 3,4 In the last decade, we have developed a better appreciation of the natural history of CHB—it appears that the progression to cirrhosis and HCC in these patients is associated with persistently high serum HBV DNA levels over time. The other major risk predictors of progression to HCC and cirrhosis include age, male gender, hepatitis B e antigen (HBeAg) status, serum alanine ami- notransferase (ALT) levels and HBV genotype. 5 Two recent land- mark clinical trials in Asia (Taiwan) clearly demonstrate the dramatic improvement in survival, reduced risk of HCC and advanced fibrosis/cirrhosis with the use of antiviral therapy. 5,6 Where treatment options are concerned, we have come a long way in the last decade—complete suppression, or elimination of HBV is now eminently feasible and well-tolerated, and should be the key management goal in the treatment of CHB. The major strides in therapy lie in the introduction of newer oral nucleos(t)ide agents with higher genetic barrier to drug resistance. 7

Analysis of 6381 hepatocellular carcinoma patients in southern Taiwan: prognostic features, treatment outcome, and survival

This hospital-based analysis was conducted to identify prognostic factors of hepatocellular carcinoma (HCC) in a hepatitis B virus endemic area. A total of 6381 HCC cases, diagnosed from 1986 to 2002, were enrolled, and 2890 (42.3%) of them were not treated. Survival rates were analyzed by correlation with the national mortality databank. Missing data and correlations among prognostic factors were considered in the analysis. The overall 1-year, 3-year, 5-year, and 7-year survival rates were 44.3%, 24.9%, 17.1%, and 13%, respectively. Multivariate analysis revealed that the independent factors influencing survival were the initial treatment modality, degree of liver function impairment, hepatitis B surface antigen positivity, tumor status, and alpha-fetoprotein. Besides these well-known prognostic factors, high alanine aminotransferase (ALT) levels and a high aspartate aminotransferase (AST)/ALT ratio were identified as independent poor prognostic factors. This study, which considered untreated cases, missing data, and correlations between variables and official survival data sets, provides a large-scale comprehensive survival analysis. According to our results, high ALT and high AST/ALT were independent poor prognostic factors. Therefore, viral activity should be controlled in HCC patients, and patients with elevated AST/ALT ratios should be carefully monitored.

Lethal hepatic injury by combined treatment of radiation plus chemotherapy in rats with thioacetamide-induced liver cirrhosis

Purpose To assess lethal hepatic injury by combined treatment of radiation (RT) plus chemotherapy in a rat model with thioacetamide (TAA)-induced liver cirrhosis. Methods and materials Male Wistar rats were treated with 0.3 g/L TAA in drinking water. The development of liver cirrhosis was histologically confirmed, and the degree of liver function impairment was assessed by indocyanine green retention test (ICG R15). The established cirrhotic rats were given one of the following treatments: partial liver radiotherapy (25 Gy on about one-third of the whole liver), 5-fluorouracil (5-FU) chemotherapy (50 mg/kg), and combined treatment of partial RT plus 5-FU. The treated rats were closely followed until either death or 30 weeks after the treatment, and the postmortem liver sampling was examined for lethal hepatic injury by the treatments. Results The rats developed overt liver cirrhosis after 30 weeks of TAA treatment. At that time, the mean ICG R15 level in the TAA-treated rats (TAA-rats) was 14.1% ± 0.7% compared to 4.6% ± 0.7% in the control ( p < 0.05). The 30-week survival rates in the control and TAA-rats were 100% (5/5) and 75% (6/8), respectively, after partial liver RT ( p = 0.72). In the 5-FU chemotherapy group, the survival in TAA-rats was only one-half of that in the controls (100% vs. 50%, p = 0.06). Poor survival in TAA-rats was shown also in the combined group of partial RT plus 5-FU (87.5% vs. 16.7%, p = 0.06). The rats that died before the last observation time showed advanced cirrhosis with areas of lobular collapse, in contrast to the moderate cirrhotic features in those that survived. Conclusion In a rat cirrhosis model with mildly impaired liver function, combined treatment of partial RT plus 5-FU resulted in significantly high incidence of lethal liver injury. The results in this study show that a combined treatment of RT plus chemotherapy in cirrhotic patients should be applied with extreme caution.

Review article: natural history and prognostic prediction of patients with hepatocellular carcinoma.

The knowledge of the natural history of patients with hepatocellular carcinoma is important to estimate the prognosis at diagnosis and indicate the best therapy. Prognosis is related to tumour stage at diagnosis, degree of liver function impairment induced either by the tumour itself or by the underlying cirrhosis, general physical condition of the patients, and potential impact of therapy. Prognostic estimation should take into account all four aspects. Treatment is very relevant to be considered in patients with early stage tumours since surgical resection, transplantation or percutaneous ablation provide a high rate of complete responses and thus, improve survival. This might be as high as 50-75% at 5 years. Patients diagnosed at an intermediate/advanced stage will receive palliative treatment and prospective studies have recently redefined the outcome predictors of this stratum. Asymptomatic patients in whom the tumour has not invaded vessels or disseminated may reach a 50% survival at 3 years, while those with adverse predictors do not reach this time point. These data have to be taken into account not only in the conventional clinical practice, but also in the design and evaluation of prospective investigations that should be properly powered to reach an informative sample size. To achieve both aims, within the Barcelona Clinic Liver Cancer Group we have developed a staging system that combines prognosis prediction with decision making, thus becoming a useful tool both for practice and research.

Nutritional assessment in various stages of liver cirrhosis

OBJECTIVES: The aims of this study were to determine the prevalence of protein-calorie malnutrition, characteristics, and clinical importance of nutrition disorders in patients with liver cirrhosis according to severity of disease.METHODS: Nutrition assessments such as subjective global assessment, anthropometric and biochemical measurements, immunocompentency, thiamin and riboflavin status in 60 patients with cirrhosis (33 male and 27 female) were recorded between June 1999 and December 1999 at an outpatient clinic at Ramathibodi Hospital, Bangkok, Thailand. The origin of liver disease was alcohol related in 50% of patients. Child-Pugh criteria were used to establish the severity of liver disease.RESULTS: In terms of energy malnutrition, 13.3% of patients had ideal body weights below 90% and 11.7% had body mass indexes below 18.5 kg/m2. Protein malnutrition (low albumin) and immunoincompetence (abnormal response to skin tests) were found much more frequently (45% and 22%) than energy malnutrition. Patients with alcoholic cirrhosis had ascites (P < 0.05) and hepatic encephalopathy (P < 0.001) more frequently and less triceps skinfold thickness than those with non-alcoholic cirrhosis. Subjective global assessment and serum proteins correlated with the degree of liver-function impairment, but immunologic tests correlated inversely in cirrhosis patients. Mean values for creatinine-height index, hemoglobin, cholesterol, and complement C4 showed significant decreases in severe liver failure (Child-Pugh class C) only in patients with alcoholic cirrhosis (P < 0.05). Malnutrition was correlated with the clinical severity of liver disease.CONCLUSIONS: The study showed that protein-energy malnutrition is a common complication of liver cirrhosis. Nutritional disorders appeared to be related to the degree of liver injury and the etiology of nutritional disorders. Nutritional disorders were more severe with alcoholic cirrhosis than with non-alcoholic cirrhosis.

Relationship of blood trace elements to liver damage, nutritional status, and oxidative stress in chronic nonalcoholic liver disease.

Trace elements are involved in chronic liver diseases because these elements may have a direct hepatic toxicity or may be decreased as a consequence of the impaired liver function, particularly in patients with alcoholic cirrhosis and/or malnutrition. In this study, we determined plasma and erythrocytes trace elements in 50 inpatients with nonalcoholic chronic liver disease (11 with biopsy-proven chronic hepatitis, 39 with cirrhosis [16 in stage A according to Child-Pugh criteria, 23 Child B+C]), and in a control group of 10 healthy subjects by the proton induced x-ray emission method. The relationship between trace element concentration and the extent of liver damage, the nutritional status (by anthropometric evaluations), and various blood markers of oxidative stress--reduced glutathione, total lipoperoxides and malonyldialdehyde--was investigated. We found that cirrhotics had a significant decrease of Fe, Zn, Se, and GSH levels in the plasma and of GSH and Se in the erythrocytes with respect to the control and chronic hepatitis groups. GSH levels were related to the degree of liver damage; a significant direct correlation was observed among Se, Zn, and GSH plasma values and between GSH and Se in the erythrocytes. The trace element decrease was, on the contrary, independent of the degree of liver function impairment and only partially affected by the nutritional status. Data indicate that liver cirrhosis, even if not alcohol related, induces a decrease of Se and Zn and that, in these patients, an oxidative stress is present, as documented by the significant correlation between Se and GSH. The plasma Br level was higher in cirrhotics with respect to the control and chronic hepatitis groups.

Nonsurgical treatment of hepatocellular carcinoma.

1. Outcome from nonsurgical treatment is directly related to stage of hepatocellular cancer (HCC) and degree of liver function impairment. 2. Ablative percutaneous procedures, such as alcohol injection or radiofrequency thermal therapy, are most effective in the destruction of solitary tumors of 3 cm or less. 3. In most cases, nonsurgical treatments are not curative, but may slow tumor progression and can provide palliation. 4. Arterial embolization or chemoembolization has an antitumor effect, but it has not been shown to affect patient outcome. 5. Radiation therapy, chemotherapy, hormonal manipulation, and interferon have not been consistently effective in HCC. 6. Ablative procedures, embolization, and systemic chemotherapy should be avoided in patients with advanced cirrhosis.

Radiotherapy for Hepatocellular Carcinoma

To retrospectively evaluate the effectiveness of radiotherapy with or without transarterial embolization (TAE) and/or percutaneous ethanol injection (PEI) in patients with hepatocellular carcinoma who were ineligible for surgery. From October 1984 to November 1997, 62 patients underwent radiotherapy receiving 50 to 70 Gy in 25 to 35 treatments with or without transarterial embolization and/or percutaneous ethanol injection and were followed for a median period of 8.6 months (1.5 to 92 months). Overall median survival rates were 9.5 months. Significant prognostic factors were the extent of pretreatment liver function impairment, radiation field size and the existence of tumor thrombosis. Six-month and 1-year local control rates were 67 and 54%, respectively. Seven of the 8 patients who suffered from hepatic failure had poor pretreatment liver functions. Radiotherapy with or without transarterial embolization and/or percutaneous ethanol injection appears effective in controlling hepatocellular carcinoma and prolonged survival. Individualized treatment strategies are presented depending on the tumor presentation and the degree of liver function impairment.

Parallel Reduction of Plasma Levels of High and Low Molecular Weight Kininogen in Patients with Cirrhosis

Little is known about the regulation of high-molecular-weight-kininogen (HK) and low-molecular-weight-kininogen (LK) or the relationship of each to the degree of liver function impairment in patients with cirrhosis. In this study, we evaluated HK and LK quantitatively by a recently described particle concentration fluorescence immunoassay (PCFIA) and qualitatively by SDS PAGE and immunoblotting analyses in plasma from 33 patients with cirrhosis presenting various degrees of impairment of liver function. Thirty-three healthy subjects served as normal controls. Patients with cirrhosis had significantly lower plasma levels of HK (median 49 microg/ml [range 22-99 microg/ml]) and LK (58 microg/ml [15-100 microg/ml]) than normal subjects (HK 83 microg/ml [65-115 microg/ml]; LK 80 microg/ml [45-120 microg/ml]) (p<0.0001). The plasma concentrations of HK and LK were directly related to plasma levels of cholinesterase (P<0.0001) and albumin (P<0.0001 and P<0.001) and inversely to the Child-Pugh score (P<0.0001) and to prothrombin time ratio (P<0.0001) (reflecting the clinical and laboratory abnormalities in liver disease). Similar to normal individuals, in patients with cirrhosis, plasma HK and LK levels paralleled one another, suggesting that a coordinate regulation of those proteins persists in liver disease. SDS PAGE and immunoblotting analyses of kininogens in cirrhotic plasma showed a pattern similar to that observed in normal controls for LK (a single band at 66 kDa) with some lower molecular weight forms noted in cirrhotic plasma. A slight increase of cleavage of HK (a major band at 130 kDa and a faint but increased band at 107 kDa) was evident. The increased cleavage of HK was confirmed by the lower cleaved kininogen index (CKI), as compared to normal controls. These data suggest a defect in hepatic synthesis as well as increased destructive cleavage of both kininogens in plasma from patients with cirrhosis. The decrease of important regulatory proteins like kininogens may contribute to the imbalance in coagulation and fibrinolytic systems, which frequently occurs in cirrhotic patients.

Malnutrition in alcoholic and virus-related cirrhosis

The study aimed to define the prevalence, characteristics, and clinical importance of nutritional disorders in patients with liver cirrhosis. Nutritional status was evaluated in 120 hospitalized patients--77 with alcoholic and 43 with virus-related cirrhosis--by anthropometric, visceral, and immunologic measurements. Energy malnutrition, defined as triceps skinfold thickness (TSF) and/or midarm muscle circumference (MAMC) below the 5th percentile of standard values, was found in 34% of the study population. Patients below the 5th percentile for MAMC and/or TSF showed significantly lower survival rates at e, 6, 12, and 24 mo compared with patients above the 5th percentile. Protein malnutrition (low albumin, transthyretin, transferrin, and retinol-binding-protein concentrations) and immunoincompetence (abnormal response to skin tests) were much more frequent (81% and 59%) than energy malnutrition (34%). Serum proteins correlated with the degree of liver function impairment, but not with immunologic tests. The prevalence, characteristics, and severity of protein-energy malnutrition were comparable in alcoholic and viral cirrhosis. Malnutrition was correlated with the clinical severity of the liver disease. The study shows that protein-energy malnutrition is a common complication of liver cirrhosis. Nutritional disorders appear to be related to the degree of liver injury rather than to its etiology. Compared with other methods, which have important limitations in liver disease, anthropometry is currently the most reliable method for nutritional assessment in clinical practice and may be valuable for predicting survival in cirrhotic patients.

Pharmacokinetic of lansoprazole in cirrhotics with different degree of liver function derangement

• PHARMACOKINETIC OF LANSOPRAZOLE IN CIRRHOTICS WITH DIFFERENT DEGREE OF LIVER FUNCTION DERANGEMENT S. SIRINGO, L. BOLONDI, L. GRAMANTIER1, G. GERMANO, M. MIGLIOLI~ L. BARBARA. ]STITUTO DI CLINICA MEDICA [ . UNIVERSITA DI BOLOGNA ITALY Lansoprazole is a proton pump inhibitor that inhibits gastric acid secretion and whom t1⁄2 in healthy volunteer is 1.4 hr. (Eur. J. Pharmaeol. 1993;45:367). Lansoprazole is metabolized in the liver and its pharmacokinetic might be altered in cirrhotic patients. This, in turn may require dosages adjustment according to the severity of cirrhosis. Aim of the present study was to assess the 48 hr. pharmacokinetic of LANSOPRAZOLE in relation to the degree of liver function impairment in patients with liver cirrhosis. We studied 25 cirrhotic patients: 84% male, mean age 57.2 years. The severity of liver function impairment was assessed according to the Child-Campbell's criteria: 14 patients were in A class and 11 in B/C class. Lansoprazole (Takeda ®) was given as a single 30 mg oral dosage. Blood sample were taken before drug administration (time 0) and 1, 2, 3, 6, 9, 12, 24, 48 hr. after Lansoprazole. Urine were collected at time 0 and at 12 hr. intervals after Lansoprazolel Lansoprazole and metabolites AGI908, AG1813, AG1777 were measured in plasma and Lansoprazole and metabolites AG1908, AGt909, AG 1907, were measured in urine, respectively, by HPLC with UV detection. The table reports the Lansoprazol e pharmacokinetic parameters.