Cryoglobulinemia in elderly patients with HCV-related chronic hepatitis

Hepatitis C virus (HCV) infection affects about 3% of the world's population and often leads to chronic liver disease. In some industrialized countries, HCV prevalence increases with age, but the optimal management of older patients has not been accurately defined. HCV infection can also lead to lymphoproliferative disorders, the most common being mixed cryoglobulinemia (MC), and also for this condition that frequently affects elderly patients, the optimal therapeutic strategy is still debated. We report the case of a 77-year-old Caucasian woman with HCV-related chronic hepatitis and cutaneous manifestations consisting of urticaria and pruritus related to MC resistant to antihistamines. The patient underwent a treatment with interferon and ribavirin. Such a treatment led to early biochemical and virological response associated with the resolution of cryoglobulinemia and cutaneous symptoms. After the end of treatment, HCV replication relapsed, but cryoglobulinemia and cutaneous symptoms did not recur. In the absence of definite treatment guidelines in this particular context, our experience suggests that the presence of symptoms related to HCV-infection that deeply affect patient quality of life warrants antiviral therapy even beyond the age limits that currently exclude patients from treatment.     

Prevalence of hepatitis C virus infection in the household contacts of patients with HCV-related chronic liver disease

Summary It is still controversial whether the familial environment plays a role in the diffusion of HCV infection. The aim of this study was to evaluate the prevalence of anti-HCV positivity in the household contacts of patients with HCV-related chronic hepatitis. Nearly all the household contacts of 113 subjects with anti-HCV+ chronic hepatitis (100/113 spouses and 260/290 children) were investigated. Anti-HCV was determined by means of ELISA II and was confirmed by RIBA II. Anti-HCV positivity was found in 27% of the spouses and in 1.9% of the children. Prevalence of anti-HCV positivity in spouses correlated positively with the duration of the marital status. Seventeen/32 (53.1%) of anti-HCV-positive subjects were found to have chronic hepatitis. This study indicates that intrafamilial diffusion of HCV infection is mostly accounted for by horizontal, in particular spouse to spouse, transmission and that spouse to spouse transmission of HCV infection correlates positively with the duration of marital status.

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Prävalenz der Hepatitis-C-Virus-Infektion bei häuslichen Kontaktpersonen von Patienten mit HCV-assoziierter chronischer Lebererkrankung

Zusammenfassung Die Bedeutung der Familie als Faktor für die Ausbreitung der HCV-Infektion wird immer noch kontrovers diskutiert. In der vorliegenden Studie wurde versucht, die Prävalenz anti-HCV-positiver Fälle unter den häuslichen Kontaktpersonen von Patienten mit HCV-assoziierter chronischer Hepatitis zu bestimmen. Nahezu alle Kontaktpersonen von 113 Personen mit anti-HCV-positiver Hepatitis (100/113 Ehegatten, 260/290 Kinder) wurden untersucht. Für die Bestimmung von anti-HCV wurde ELISA-II mit Bestätigung durch RIBA II eingesetzt. 27% der Ehegatten und 1,9% der Kinder erwiesen sich als anti-HCV-positiv. Bei den Gatten korrelierte die Prävalenz der anti-HCV-Positivität mit der Dauer der Ehe. Bei 17/32 (53,1%) der anti-HCV-positiven Personen wurde eine chronische Hepatitis aufgedeckt. Diese Studie gibt Hinweise auf eine vorwiegend horizontale Übertragung der HCV-Infektion zwischen Ehegatten und eine positive Korrelation zwischen Übertragung und Dauer der Ehe.

     

慢性乙型肝炎与非酒精性脂肪性肝病患者内皮功能检测*

目的探讨慢性乙型肝炎（CHB）、非酒精性脂肪性肝病（NAFLD）和CHB合并NAFLD患者内皮功能和脂质代谢的差异。方法在CHB患者32例,NAFLD患者35例和CHB合并NAFLD患者44例,使用Endo-PAT 2000内皮功能检测仪测定外周动脉张力（PAT）,并计算血管反应性充血指数（RHI）;检测空腹血糖（FPG）、丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、甘油三脂（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、载脂蛋白A（apoA）、载脂蛋白B（apoB）、脂蛋白a（LP-A）和游离脂肪酸（FFA）等血液生化指标。结果NAFLD患者RHI（1.95±0.44）显著高于CHB患者[（1.68±0.28）,P<0.05];NAFLD和CHB合并NAFLD患者体质指数【BMI分别为（24.77±3.13） kg/m²和（25.79±2.80） kg/m²]、TG [（1.52±0.70） mmol/L和（1.68±0.89） mmol/L]、TC[（4.32±0.1.32） mmol/L和（4.18±1.18） mmol/L]、LDL-C [（10.72±46.51） mmol/L和（2.71±0.96） mmol/L] apoB [（0.90±0.20）g/L和（0.85±0.28）g/L]均显著高于CHB患者[（22.63±3.14）kg/m²、（0.89±0.26） mmol/L （3.51±0.74） mmol/L（2.23±0.56） mmol/L （0.68±0.15）g/L,P<0.01]。结论CHB与NAFLD患者内皮功能和脂质代谢可能存在差异。     

复方二氯醋酸二异丙胺治疗慢性病毒性肝炎合并酒精性肝损伤的临床疗效观察

观察应用复方二氯醋酸二异丙胺治疗慢性病毒性肝炎合并酒精性肝损伤的临床疗效。选择确诊慢性病毒性肝炎合并酒精性肝损伤58例,随机分成两组。A组（n=30）在常规保肝治疗基础上,加用复方二氯醋酸二异丙胺（0.4-0.8）克溶于生理盐水中静脉滴注,每日一次;B组（n=28）常规保肝治疗,两组均4周为一疗程。两种药物临床总有效率分别为86.7%、64.3%,血清胆红素下降A组较B组明显（P〈0.05）。复方二氯醋酸二异丙胺对改善慢性病毒性肝炎合并酒精性肝损伤症状和降低血清转氨酶有较好的疗效,伴有高胆红素血症患者应用复方二氯醋酸二异丙胺优于常规保肝治疗。     

Platelet indices in chronic alcoholic liver disease patients with thrombocytopenia

AIM: To detect alterations in platelet indices in patients with chronic alcoholic liver disease and thrombocytopenia, and its correlation with other haematological parameters. METHODS: We studied 65 individuals separated in two groups: controls (n = 35) and chronic alcoholic liver disease patients with thrombocytopenia (n = 30). The control group was age and gender matched with patients group. In all, controls and patients, a haematological evaluation was done, including platelets indices. RESULTS: In the patients group we found a low number of erythrocytes, leucocytes and platelet when we compare with controls. The same is true when we compare haemoglobin, hematocrit and absolute count of lymphocyte and neutrophil. The mean globular volume, mean globular haemoglobin and red cell distribution width where significantly higher in patients group. Platelet indices showed a statistical significant increased in platelet distribution width and decreased in platelet crit in the patient group. No differences where found on mean platelet volume between the two groups. Correlation between platelet number and other haematological parameters was found. CONCLUSION: Chronic alcoholic liver disease patients showed a decrease in all haematopoietic cell lines, probably associated with hypersplenism found in those patients. Additionally to the numeric alterations the erythrocyte and platelets showed morphologic alteration revelled by respective indices.     

Fulminant hepatitis in patients with chronic liver disease

The changing epidemiology of hepatitis A virus (HAV) in the UK has led to a decline in natural immunity against the virus. It is estimated that in the UK, HAV is responsible for 10%-20% of cases of liver failure, and an overall mortality rate of 0.1%. It is clear that certain factors predispose patients to more severe HAV disease and increased mortality, although the reasons for this have yet to be elucidated. The age at which infection occurs clearly influences the outcome, with the risk of severe hepatitis increasing sharply after the age of 40 years. Intravenous drug users, homosexual men, individuals with an excessive alcohol intake or patients with chronic liver disease are also at increased risk of severe disease. An analysis of data from King's College Hospital was performed to determine the factors that influence the outcome or clinical course of HAV infection in at-risk patients. Data compiled from 1991 to 1998 revealed 187 cases with confirmed HAV, 45 of whom developed severe hepatitis. Outcomes were varied, eight (17.7%) patients developed acute liver failure and two (4.4%) died.     

IL-10 and IL-12p40 in Egyptian patients with HCV-related chronic liver disease

Hepatitis C virus (HCV) is the leading cause of chronic liver disease worldwide with a prevalence of approximately 14% in Egypt. IL-10 is a cytokine produced by Th2 cells. It down-regulates the proinflammatory response and modulates hepatic fibrogenesis. IL-12 is produced by antigen presenting cells. It promotes Th1 cell response and has many antiviral properties. Data concerning the Th-1/Th-2 balance in chronic hepatitis C (CH-C) are rather conflicting. Using ELISA, we assessed serum IL-10 and IL-12p40 levels in 66 Egyptian patients with HCV-related liver illness (CH-C, cirrhosis, and HCC), and their relationship to disease activity. Our results showed that spontaneous IL-10 was undetectable in patients with CH-C, HCC or controls. Only 5/22 (23%) of patients with cirrhosis showed detectable levels of IL-10. IL-12p40 was elevated in the patient groups compared to controls (p= 0.01, p= 0.01, p= 0.05 in CH-C, cirrhosis and HCC, respectively). The presence of IL-12p40 was associated with HCV level of viremia and serum AST. Serum ALT level was significantly associated with the level of IL-12p40. IL-12p40 was unrelated to liver histology or fibrosis. We concluded that in the Egyptian patients an augmentation of IL-12p40 and a suppression of IL-10 are both found. Whether this pattern is related to HCV genotype 4, or to the presence of schistosomiasis would need to be further investigated.     

Is autoimmune chronic active hepatitis a HCV-related disease?

We evaluated the specificity and clinical relevance of anti-hepatitis C virus antibody positivity in 22 HBsAg-negative patients with autoimmune (anti-nuclear, anti-actin or anti-liver-kidney microsomal antibody positive) chronic active hepatitis. An ELISA anti-HCV test and a recombinant immunoblot assay (RIBA-HCV) were used. Thirteen patients (59%) were anti-HCV positive and five (23%) anti-HCV negative by both ELISA and RIBA-HCV tests. Four patients (18%) were borderline positive by ELISA (OD less than 1.0), and three of them (all with severe disease) were negative by RIBA. Histologic necroinflammation, AST/ALT and gamma-globulins levels were higher and response to prednisolone treatment was better in RIBA anti-HCV-negative than in anti-HCV-positive cases. We confirmed with both RIBA and ELISA tests the high prevalence of anti-HCV already reported by ELISA in anti-nuclear and anti-liver-kidney microsomal antibody positive chronic active hepatitis. False positive for anti-HCV (i.e., a positive ELISA test not confirmed by RIBA) occurred only among patients with severe disease. Since RIBA-negative subjects showed the best response to corticosteroid, they might represent the only subset of cases of 'true' autoimmune chronic active hepatitis.     

The diagnostic value of biomarkers (AshTest) for the prediction of alcoholic steato-hepatitis in patients with chronic alcoholic liver disease

BACKGROUND/AIMS: The aim was to identify a panel of biomarkers (AshTest) for the diagnosis of alcoholic steato-hepatitis (ASH), in patients with chronic alcoholic liver disease. METHODS: Biomarkers were assessed in patients with an alcohol intake>50 g/d, in a training group, and in two validation groups. Diagnosis of ASH (polymorphonuclear infiltrate and hepatocellular necrosis) and its histological severity (four classes: none, mild, moderate and severe) were assessed blindly. RESULTS: Two hundred and twenty-five patients were included, 70 in the training group, 155 in the validation groups, and 299 controls. AshTest was constructed using a combination of the six components of FibroTest-ActiTest plus aspartate aminotransferase. The AshTest area under the ROC curves for moderate-severe ASH was 0.90 in the training group, 0.88 and 0.89 in the validation groups. The median AshTest value was 0.005 in controls, 0.05 in patients without or with mild ASH, 0.64 in moderate, and 0.84 in severe ASH grade 3, (P<0.05 between all groups). At a 0.50 cut-off, the sensitivity of AshTest was 0.80 and the specificity was 0.84. CONCLUSIONS: In heavy drinkers, AshTest is a simple and non-invasive quantitative estimate of alcoholic hepatitis. The use of AshTest may reduce the need for liver biopsy, and therefore allow an earlier treatment of alcoholic hepatitis.     

Clinicopathological analysis of alcoholic liver disease complicating chronic type C hepatitis

Seventy-six chronic alcoholics in Japan were evaluated for histological changes of liver needle biopsies, Chiron C100 antibody (C-100) for hepatitis C virus, as well as clinical and laboratory data. In biopsies, the presence of necroinflammations within the parenchyma, lymphocytic reaction in the portal tracts, or both, might indicate non-A, non-B (NANB) chronic hepatitis. Using these histological criteria, the patients were previously classified into two groups: alcoholic liver disease (ALD) alone and ALD complicating NANB chronic hepatitis. The C100-positive ratio was found to be 12% in the former group and 69% in the latter. Further clinical and laboratory comparison revealed that there were significant differences in gamma-glutamyl transpeptidase, gamma-globulin, and adenosine deaminase levels in the sera between the ALD alone and the ALD complicating NANB chronic hepatitis groups. Since some chronic alcoholics are also affected by chronic type C hepatitis, detailed evaluations of the liver biopsy and C-100 assay are required for the differentiation of these hepatic disorders.     

Turnover of thyrotropin-releasing hormone in patients with chronic renal failure and chronic alcoholic liver disease

Homogenates of liver and kidney tissues are efficient in degrading TRH, but the liver contains only membrane-bound pyroglutamyl aminopeptidase, active in degrading TRH at the extracellular side of cell membranes. In the present study the effect of liver and kidney failure on the degradation of infused TRH was investigated in man. In 7 uremic patients (group I) and 7 patients with chronic alcoholic liver disease (group II) plasma clearance rate, half-time of disappearance (t1/2) and half time of disappearance of TRH in serum in vitro (t1/2p) was determined. The plasma clearance rate, t1/2 and t1/2p were, respectively, 19.8 +/- 6.2 ml.kg-1.min-1, 6.6 +/- 1.5 min and 16.4 +/- 6.2 min in group I versus 28.2 +/- 4.8 ml.kg-1.min-1, 9.3 +/- 2.6 min and 25.3 +/- 15 min (mean +/- SD) in group II. The volume of distribution of TRH was 19.3% of the body weight in group I and 36.5% in group II. The calculated half-time in the extravascular tissue compartment (t1/2) was 5.4 +/- 1.4 min in group I and 9.2 +/- 2.7 min in group II patients (mean +/- SD). TRH metabolism in the uremic patients was almost identical to that previously reported in normal subjects. In the patients with chronic liver disease plasma clearance rate was significantly greater than in normal subjects, indicating an increased TRH-degrading enzyme activity in the tissue compartment. However, owing to the very large expansion of this compartment, the t1/2 and t1/2t were significantly prolonged. Hence, half-time determination of TRH is no reliable indicator of overall TRH degradation in patients with liver disease.     

Early evolution of hepatitis C virus (HCV) quasispecies after liver transplant for HCV-related disease

BACKGROUND: End-stage liver disease as a result of chronic hepatitis C virus (HCV) infection is the main indication for liver transplant (LT), but allografts are systematically infected with HCV soon after transplant. Viral quasispecies are poorly described during the early posttransplant period. METHODS: For 17 patients who received an LT for HCV disease, plasma viral quasispecies evolution was determined by sequence analysis of hypervariable region 1 of the E2 envelope gene before transplant (BT), after 7 days (D7), and after 1 month (M1). T helper (Th)1/Th2 cytokine levels were determined concomitantly. RESULTS: HCV quasispecies showed a significant decrease in amino acid diversity at D7 and M1, compared with BT (P<.05). A correlation was observed between low plasma tumor necrosis factor-alpha levels at D7 and decreased quasispecies amino acid complexity at the same date. Nucleic acid diversity was lower for genotype 1 than for genotype 3 infection (P<.05). The complexity and diversity of amino acids were lower in patients with hepatocellular carcinoma (HCC) BT than in those without HCC (P<.05). Conserved amino acid residues within quasispecies were shared by the whole cohort before and after LT. CONCLUSION: Viral structural and/or host immunological features could favor the emergence of fitter HCV strains after LT.     

Vaccination against hepatitis a in patients with chronic liver disease

Hepatitis A virus (HAV) superinfection is associated with a high risk of liver failure and death in patients with underlying chronic liver disease. HAV vaccination is effective and safe, although the vaccine is less immunogenic in patients with advanced liver disease. Despite recommendations to immunize patients with chronic liver disease, rates of HAV vaccination remain low, thus highlighting the need for public health programs to increase awareness about HAV vaccination.     

Seroepidemiology of hepatitis A in patients with chronic liver disease

Hepatitis A virus (HAV) rarely causes fulminant hepatic failure in the general population. Yet it is a cause of significant morbidity and mortality in patients with chronic liver disease (CLD), in whom routine HAV vaccination is recommended. However, studies of HAV seroprevalence and exposure predictors in populations with CLD are scarce. We have studied a cohort of 473 patients with various causes of CLD between July 2000 and June 2002. Patients were stratified on the basis of age, gender, ethnicity and aetiology of liver disease. The HAV seroprevalence in patients with CLD was compared with that in the general population. We used a logistic regression analysis to identify independent predictors of HAV exposure. Of the 473 patients studied, HAV seroprevalence was available for 454 individuals. HCV, HBV, alcohol, and HCV and alcohol were the causes of CLD in 337, 72, 37 and eight patients, respectively. The overall HAV seroprevalence was 55% in the studied cohort. The age-stratified HAV prevalence for ages 21-30, 31-40, 41-50, 51-60, 61-70 and greater than 70 years was 44, 51, 44, 63, 65 and 64%, respectively. Hispanic ethnicity, Asian ethnicity, alcohol use and ages of 51-70 years were found to be independent predictive variables of prior exposure to HAV. HAV infection in patients with CLD causes considerable morbidity and mortality. We demonstrated that age-stratified seroprevalence of HAV in patients with CLD of various aetiologies is significantly higher than that of the general population, and identified several independent predictors of HAV prior exposure.     

Vaccination against hepatitis b in patients with chronic liver disease

The prevalence of chronic liver disease is increasing, while at the same time, many at-risk populations are witnessing a resurgence of hepatitis B virus (HBV) infection. Thus, more patients are likely to have multiple causes of liver disease, as risk factors often overlap. Such patients may develop either acute viral hepatitis superimposed on pre-existing chronic liver disease or chronic infection with two hepatitis viruses. Patients with chronic HBV and hepatitis C virus coinfection have more severe laboratory abnormalities, more hepatic fibrosis, and greater frequency of cirrhosis, in addition to more complications of cirrhosis and a higher incidence of hepatocellular carcinoma. Acute hepatitis B superimposed on chronic hepatitis C may result in fulminant hepatitis, although this outcome is not as well proven as the increased morbidity of chronic hepatitis B and C coinfection. Both acute and chronic coinfection with HBV can be prevented. Vaccines for hepatitis B are safe in patients with chronic liver disease of a variety of causes and are effective, particularly if used early. Early vaccination against hepatitis B, as well as hepatitis A, should be part of the routine management of chronic liver disease.     

Left ventricular performance in alcoholic patients without chronic liver disease

Left ventricular performance was studied non-invasively in 24 chronic alcoholics without liver disease. Twelve patients who had abstained from drinking for at least one month (group A) and 12 sex and age matched patients who had ceased drinking during the preceding 24 hours (group B) were studied at rest and during 50% submaximal exercise. Cardiac output and stroke volume were measured by first passage and left ventricular ejection fraction by multigated radionuclide cardiography. Twelve healthy sex and age matched controls were also studied. Haemodynamic variables were similar in group A and the controls, except that in group A left ventricular end systolic volume index did not decrease during exercise. In group B the heart rate was increased both at rest and during exercise and plasma noradrenaline concentrations were increased. The stroke volume index did not increase significantly during exercise in group B. In addition, the increase in left ventricular ejection fraction was smaller in group B than in controls. End systolic contraction was reduced in group B patients and diastolic blood pressure was increased. These results suggest that cardiac abnormalities in chronic alcoholics may be reversed after cessation of drinking if no chronic liver disease is present. Recent alcohol consumption increases sympathetic nervous activity, impairs cardiac contractility, and increases afterload during physical stress.