Studies on serum immunoreactive prolyl 4-hydroxylase in liver diseases--its elevation both in hepatocellular damage and cholestatic diseases

The concentration of serum immunoreactive prolyl 4-hydroxylase (S-IRPH) was determined in patients with various liver diseases by the radioimmunoassay developed previously. S-IRPH values were elevated in acute hepatitis (p less than 0.01), hepatocellular carcinoma (p less than 0.05), metastatic liver neoplasm (p less than 0.01) and cholestatic diseases (p less than 0.001), but no significant elevation was seen in chronic hepatitis or liver cirrhosis. The mean value of S-IRPH was highest in cholestatic diseases, and next highest in acute hepatitis. In addition to acute hepatitis, S-IRPH was increased in other conditions of hepatocellular damage such as exacerbation of chronic hepatitis or immediately after transcatheter arterial embolization of hepatocellular carcinoma. In cases of hepatocellular damage S-IRPH varied concurrent with cytoplasmic enzyme (AST, ALT and LDH) levels and in cases of cholestatic diseases with biliary enzyme (Al-P and gamma GTP) levels. These properties appear to be unique among serum enzymes. The characteristics of S-IRPH were considered to be related to its unique subcellular localization within the cell, ie the membrane of rough endoplasmic reticulum.     

Serum hyaluronate and type III procollagen aminoterminal propeptide concentration in chronic liver disease. Relationship to cirrhosis and disease activity

To analyse the relationship between the presence of liver cirrhosis and hepatic inflammation and the serum concentrations of the aminoterminal propeptide of procollagen type III (P-III-NP) and of hyaluronic acid (HA) in chronic liver disease, we measured P-III-NP and HA concentrations in paired serum samples from 133 patients with various chronic liver diseases, from 22 patients with acute hepatitis and from 50 healthy age-matched controls. In 24 (of the 133) patients with autoimmune chronic liver disease, follow-up determination was performed during therapeutic treatment with immunosuppressive drugs. Compared with controls P-III-NP concentrations (medians) were significantly elevated in 65% of patients with chronic active hepatitis (P = 0.00097) and in 79% of patients with active liver cirrhosis (P = 0.0126) but not in patients with chronic persistent hepatitis (P = 0.06). Serum concentrations (medians) of HA were increased (P = 0.0058) in 32% of patients with chronic active hepatitis and in 91% of patients with active cirrhosis (P less than 6 x 10(-7)). The difference of HA serum concentrations but not that of P-III-NP serum concentrations in patients with chronic active hepatitis and in patients with active cirrhosis was statistically significant. HA and P-III-NP serum concentrations were significantly elevated in 22 patients with acute hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lysosomal enzyme activities in normals and in patients with chronic liver diseases

The maximal activities of liver lysosomal enzymes (acid phosphatase and cathepsin D) were found to be increased in patients with chronic active hepatitis, cirrhosis and primary hepatocellular carcinoma. The ratio between maximal and basal activity (an expression of the degree of retention of the enzymes to lysosome) of acid phosphatase was significantly decreased in patients with chronic active hepatitis and cirrhosis whereas that of cathepsin D did not show any significant changes between normal and various liver disorders. Serum levels of both the enzymes were elevated significantly in patients with cirrhosis and primary hepatocellular carcinoma.     

Guidelines for serological testing in the diagnosis of acute hepatitis A and B

This study was performed to determine whether elevation of serum transaminases can be used to eliminate unnecessary serological tests to diagnose acute hepatitis A (HAV) and acute hepatitis B (HBV). Serum samples of 1226 patients were tested for HBsAg, anti-HBc (IgM), and anti-HAV (IgM). Acute hepatitis was diagnosed in 113 (9.2%) patients; 75 were serologically positive for HAV, 36 for HBV, and 2 patients for both HAV and HBV. Serum transaminase levels were elevated in 104 of 107 (97.2%) of seropositive patients in whom the results of biochemical tests were available. A review of the medical records of seropositive patients with normal transaminases revealed that each of the three HAV patients had a remote history of hepatitis. None of the seropositive patients with a recent history of acute viral hepatitis had normal transaminase levels. During this period, serological tests were ordered in 266 of 1054 (25.2%) seronegative patients with normal serum transaminases. We conclude that serum transaminase levels can be reliably used to screen sera for acute HAV and HBV infection.     

Transaminase levels in ventilated children with respiratory syncytial virus bronchiolitis

Objectives To compare disease severity as judged by duration of ventilation, inotrope use and mortality in children ventilated for respiratory syncytial virus (RSV)-positive lower respiratory tract infection (LRTI) with and without elevated transaminase levels and to determine the aetiology of elevated transaminase levels in this patient group.Design Prospective observational study.Setting Twenty-two-bed Paediatric Intensive Care Unit.Patients Forty-eight ventilated children with RSV-positive LRTI.Measurements and results Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured daily. In patients with elevated transaminase levels infection with the following viruses was investigated: hepatitis A, B and C viruses, cytomegalovirus, Epstein Barr virus, adenovirus, influenza virus, and parainfluenza viruses (types I, II, and III). Elevated transaminase levels were detected in 22 (46%) patients. The duration of mechanical ventilation (geometric mean; 95% CI) was significantly (P<0.05) longer in the group with elevated transaminase levels: 10.6 (9.4; 11.7) days versus 3.5 (2.8; 4.2) days. This difference remained significant in patients without congenital heart disease. Inotrope use was more common and all deaths occurred in the group with elevated transaminase levels (P<0.05). All patients who died and all but two patients with inotrope requirements had underlying congenital heart disease. One patient with elevated transaminase levels had a simultaneous infection with influenza A virus.Conclusions RSV disease in ventilated children was more severe if transaminase levels were elevated. Transaminase level elevation was due to hepatitis in the majority of patients. In patients with congenital heart disease we also detected myocardial involvement.     

Epstein Barr virus hepatitis: case series and review

Epstein Barr virus (EBV) infection causes asymptomatic liver-associated enzyme abnormalities in 80 to 90% of cases which are often unrecognized. Patients with acute EBV infections may also develop cholestatic hepatitis with associated jaundice and hepatitis with moderate elevations in the transaminase levels. Other gastrointestinal complications associated with EBV may include splenic rupture, liver failure due to acute and/or chronic EBV infection, and perhaps, autoimmune hepatitis and hepatocellular carcinoma. This article presents a case series of EBV infections with clinically significant hepatitis and reviews the literature on the gastrointestinal complications of EBV.     

复合磷酸酯酶片联合苦参素胶囊治疗慢性乙型肝炎疗效观察

目的探讨复合磷酸酯酶片联合苦参素胶囊治疗慢性乙型病毒性肝炎的临床治疗作用。方法将89例乙肝患者随机分为2组,实验组应用复合磷酸酯酶片及苦参素胶囊,对照组单纯服用苦参素胶囊,检测治疗后2组谷丙转氨酶（AIJT）、谷草转氨酶（AST）、谷胺酰转肽酶（γ-GT）、总胆红素（TBil）及HBV—DNA。结果90d后联合药物组ALT、AST、γ一GT、TBil及HBV．DNA改善明显,与对照组相比,具有统计学差异,P〈0．05,且联合用药组及对照组均未发现明显不良反应。结论复合磷酸酯酶片联合苦参素胶囊在临床上治疗慢性乙型肝炎具有良好疗效。     

Serum chemistry templates of disease in liver, pancreas, and gallbladder.

On routine hospital admission, 23,714 patients received a 28-test serum metabolic profile. The 33 most common diseases (4,132 patients) of liver, pancreas, and gallbladder (LPG) had unique chemical templates averaging 15 significant serum deviations. Each LPG disease differed from all others by elevations of both leucine-aminopeptidase (LAP) and alkaline phosphatase (AP) levels. LAP level was low or normal and serum glutamic oxaloacetic transaminase (SGOT) and AP levels were elevated in 43 non-LPG diseases. Patients with acute and chronic pancreatitis had elevated amylase levels. The four nonmalignant diseases of the gallbladder were associated with normal levels of amylase and lactic dehydrogenase (LDH); except for silent cholelithiasis, each showed elevated total bilirubin (BIL) levels. Patients with solitary or scattered lesions of the liver had normal bilirubin levels (2,115 patients), and those with diffuse interstitial or parencymal disease had elevated BIL levels. Cancer patients had elevated LDH and alpha1 globulin (A1G) levels, but low albumin levels. The importance of comprehensive liver profiles in the treatment of psychoses is emphasized by significant liver damage in a number of these patients. A1G was normal and LDH was elevated in patients having mononucleosis, hepatitis, lupus erythematosus, alcoholism, and alcoholic cirrhosis.     

The effects of diseases of the liver, thyroid, and kidneys on the transport of vitamin A in human plasma

The effects of diseases of the liver, the thyroid, and the kidneys on the retinol-binding protein (RBP)-prealbumin (PA) system responsible for the transport of vitamin A in plasma were examined, using a radial gel diffusion immunoassay for PA and the previously described radioimmunoassay for RBP. Measurements were made on plasma samples from 118 normal subjects, 31 patients with cirrhosis, 5 with chronic active hepatitis, 27 with acute viral hepatitis, 14 patients with hyperthyroidism, 7 with hypothyroidism, and 26 patients with chronic renal disease of varying etiologies. In the patients with liver disease, the levels of vitamin A, RBP, and PA were all markedly decreased and were highly significantly correlated over a wide range of concentrations. Serial samples were available in 19 patients with acute hepatitis; as the disease improved the plasma concentrations of vitamin A, RBP, and PA all increased. In patients with acute hepatitis RBP concentrations correlated negatively with the levels of plasma bilirubin, glutamic-oxaloacetic transaminase, and alkaline phosphatase. In the hyperthyroid patients both RBP and PA concentrations were significantly lower than normal; in hypothyroidism, neither protein showed levels significantly different from normal. In both hyper- and hypothyroidism and in liver disease, the molar ratios of RBP:PA and of RBP:vitamin A were not significantly different from normal.Patients with chronic renal disease had marked abnormalities in the plasma concentrations of RBP and vitamin A and in the molar ratios examined. In renal disease the levels of both RBP and vitamin A were greatly elevated, while the PA levels remained normal. The molar ratios of RBP:PA and of RBP:vitamin A were both markedly elevated. In many patients RBP was present in molar excess as compared with PA. The presence of a relatively large proportion of free RBP, not complexed to PA, in some patients with chronic renal disease was confirmed by gel filtration. The free RBP, present in molar excess, was capable of forming a complex with additional purified PA added to the plasma. The kidneys appear to play an important role in the normal metabolism of RBP.     

Comparison of the nucleic acid-based crosslinking hybridization assay and the branched DNA signal amplification assay in the quantitative measurement of serum hepatitis B virus DNA

Quantitative measurement of hepatitis B virus (HBV) DNA has become important in the clinical diagnosis of patients with chronic hepatitis B, especially in patients with hepatitis B e antigen (HBeAg)-negative precore mutant and in patients who received treatment with interferon or antiviral agents. Two different hybridization assays for quantitative measurement of HBV DNA: Naxcor crosslinking assays and Chiron branched DNA signal amplification (bDNA) assay, were applied to 158 serum samples which were positive for HBV DNA by polymerase chain reaction. Among 158 serum samples, 135 samples (85.4%) were positive by the crosslinking assay and 129 samples (81.6%) were positive by the bDNA assay in the quantification of serum HBV DNA (P > 0.05). Serum HBV DNA levels obtained from both assays showed a good linear correlation (r = 0.91, P < 0.001). The sensitivity of both assays in HBeAg-positive samples was 90.5%, significantly higher than in HBeAg-negative samples (69.6% for the crosslinking assay and 56.5% for the bDNA assay, P < 0.05). In HBeAg-negative patients with elevated serum alanine transaminase levels, the so-called precore HBV mutant, the detection sensitivity for HBV DNA was better in the crosslinking assay (83%) than in the bDNA assay (61%). The crosslinking assay was less time consuming than the bDNA assay in performing the measurement of serum HBV DNA (6 hours vs. 20 hours). In conclusion, Naxcor crosslinking hybridization assay was equally as sensitive as Chiron bDNA assay in the quantitative measurement of serum HBV DNA. Less time-consuming procedures and better sensitivity in the detection of HBeAg-negative samples with elevated serum alanine transaminase levels may favor the clinical use of the crosslinking assay.     

Impaired function of dendritic cells circulating in patients infected with hepatitis C virus who have persistently normal alanine aminotransferase levels

Hepatitis C virus (HCV) induces chronic liver disease in hosts which can eventually progresses to liver cirrhosis and hepatocellular carcinoma. However, progression of liver disease is slower in patients with persistently normal levels of alanine aminotransferase (ALT) than in those with active hepatitis. Although distinct immune responses against HCV have been proposed in asymptomatic infection, the role of circulating dendritic cells (DC) in the pathogenesis of these patients remains obscure. To address this issue, we compared the number and function of myeloid DC (MDC) and plasmacytoid DC (PDC) between uninfected individuals and HCV-infected patients with or without elevated ALT levels. Numbers of DC and DC progenitors were significantly lower in patients with chronic active hepatitis than in control subjects. However, no differences were found in the number of DC between normal controls and HCV-infected patients with persistently normal ALT levels. MDC from patients with active hepatitis were less able to polarize naive CD4 T cells into the Th1 phenotype, while their MDC and PDC primed more CD4 T cells producing IL-10 than those from normal controls. Such dysfunction of DC was also observed in patients with persistently normal ALT levels. In conclusion, circulating DC decrease in number predominantly in HCV-infected patients with active hepatitis, and the function of DC is impaired even in those with normal ALT levels.     

Non A-G chronic hepatitis in Japan]

It is clear that certain patients with viral hepatitis are also seronegative for types A, B, C, D, and E. Although hepatitis G virus was discovered recently, this virus has been reported to be non-contributing or only slightly conductive to liver dysfunction. In this article, epidemiological studies regarding patients seronegative for types A to G chronic hepatitis in Japan are reported. Among 1089 patients with chronic liver disease, twenty-five patients (1.8%; 14 chronic hepatitis, 4 cirrhosis, 2 hepatocellular carcinoma) were diagnosed as non A-G hepatitis (negative for HbsAg, HCV-Ab, and HGV RNA). Only 3 of 25 these patients had histories of blood transfusion. The levels of transaminase in the patients with chronic non-A to G hepatitis (without hepatocellular carcinoma) was as the same as those in patients with chronic hepatitis type B and C. Our results indicated a low prevalence of non-A to G chronic hepatitis, yet a few cases were progressive to cirrhosis or HCC, and this may be due to another unknown agents for non-A to G hepatitis.     

紫外线照射充氧自血回输对慢性乙型肝炎患者肝功能及血清可溶性细胞间粘附分子-1水平的影响

目的探讨紫外线照射充氧自血回输(UBIO)对慢性乙型肝炎患者肝功能及血清可溶性细胞间粘附分子-1(sICAM-1)含量的影响及其意义。方法168例慢性乙型肝炎患者分为UBIO治疗组86例和对照组82例,观察两组的疗效和血清sICAM-1的含量变化。结果两组患者治疗后血清SB、ALT、AST均有不同程度下降,但UBIO治疗组下降更明显,与对照治疗组比较,差异有显著性(t＝2.576,2.763,2.746,P＜0.05);SB、ALT和AST复常率UBIO治疗组分别为82.6％,55.8％和46.5％,对照治疗组分别为39.0％,30.5％和18.3％。两组SB、ALT和AST复常率比较,差异均有非常显著性(t＝33.54,10.95,15.18,P＜0.01)。UBIO组血清sICAM-1水平比治疗前明显下降(t＝3.175,P＜0.01),但对照治疗组血清sICAM-1治疗前后无显著性差异(t＝0.661,P＞0.05)。结论UBIO治疗可能会下调肝内sICAM-1的表达,促进肝功能的恢复。     

Clinical features and prognostic implications of severe corticosteroid-treated cryptogenic chronic active hepatitis

To assess the nature and prognosis of severe chronic active hepatitis of unknown cause, we compared 26 patients who had been fully screened for etiologic factors with 112 patients who had autoimmune chronic active hepatitis after similar durations of corticosteroid therapy (17(+)/- 2 versus 23 (+)/- 2 months), and follow-up versus 103 +/- 7 months). Patients with cryptogenic disease could not be distinguished from those with autoimmune disease on the basis of age, sex distribution, duration of illness, immunoglobulin levels, frequency of concurrent immunologic disorders, or histologic findings. Serum gamma-globulin levels were higher (3.4 +/- 0.1 versus 2.5 +/- 0.2 g/dl, P = 0.007) and albumin levels were lower (2.9 +/- 0.1 versus 3.3 +/- 0.1 g/dl, P = 0.003) in patients with autoimmune disease than in those with cryptogenic disease, but individual findings did not differentiate the patients. Remission (69 versus 75%), treatment failure (23 versus 13%), relapse after drug withdrawal (67 versus 68%), progression to cirrhosis (57 versus 36%), and death from hepatic failure (12 versus 11%) occurred as commonly in patients with cryptogenic as in those with autoimmune disease. Patients with different constellations of immunoserologic findings were similar clinically. We conclude that patients with severe chronic active hepatitis who have been fully screened for etiologic factors cannot be distinguished from patients with autoimmune disease of comparable severity. These two groups of patients have a similar prognosis after corticosteroid therapy, and such treatment should be considered in these highly selected patients.     

自身免疫性肝炎与系统性红斑狼疮肝损的异质性

目的 :研究自身免疫性肝炎 (AutoimmuneHepatitis ,AIH)的临床表现 ,肝活检病理以及与系统性红斑狼疮 (SLE)肝损害的异同。方法 :回顾性总结 15例AIH及 2 0例SLE肝损害患者的临床及肝活检病理。结果 :AIH表现为丙氨酸转氨酶(ALT)、天冬氨酸转氨酶 (AST)异常 ,高球蛋白、高γ球蛋白血症 ,存在多种自身抗体 ,伴发自身免疫性疾病 ,病理以慢性肝炎为特点 ;SLE肝损常表现在初发患者一过性ALT、AST、球蛋白、球蛋白升高 ,病理为非特异性肝损。球蛋白、γ球蛋白、免疫球蛋白G(IgG)在AIH中极显著高于SLE的肝损 (P <0 .0 0 1) ,抗双链DNA抗体 (ds-DNA)在SLE肝损病人极显著高于AIH(P <0 .0 0 1)。结论 :AIH肝病损严重 ,肝外病变多样 ,有多系统损害倾向 ,是完全有别于SLE肝损的独立疾病     

微量脂微球载体前列腺素E1静注治疗慢性重度乙型肝炎疗效观察

目的：观察并比较微量脂微球载体前列腺素Ｅ４（ＬｉｐｏＰＧＥ４）为丹参注射液治疗慢性重度乙型病毒性肝炎的疗效。方法：慢性重度乙肝４０例２组，每组各２０例。ＰＧＥ４组（男性１５例，女性５例，女性５例；年龄３６±９岁）用脂微球载体前列腺素Ｅ４１０ｕｇ加入生理盐水１０ｍｌ中静推，ｑｄ×２０天；复方丹参组（男性１６例，女性４例，女性４例；年龄３９±７岁）用复方丹参注射液１６ｍｌ加入５％ＧＳ３００ｍｌ中静谪，     

多项指标联合检测对乙型肝炎后肝硬化诊断治疗中的观察分析

目的探讨肝纤维化四项与天门冬氨酸氨基转移酶(AST)/丙氨酸氨基转移酶(ALT)比值、乙型肝炎病毒(HBV)DNA指标联合检测对乙型肝炎(简称乙肝)后肝硬化诊断治疗的临床应用价值。方法选择2009年5月至2011年5月在该院消化内科收治的130例乙肝后肝硬化患者,同时选择80例单纯慢性乙肝为对照组,检测其血清透明质酸(HA)、Ⅲ型前胶原蛋白(PⅢNP)、Ⅳ型胶原蛋白(Ⅳ-Col)、层黏连蛋白(LN)、AST/ALT比值及乙肝DNA(HBV-DNA)指标水平。结果 (1)乙肝后肝硬化血清中HA、Ⅳ-Col、PⅢNP、LN明显高于单纯慢性乙肝组(P<0.01)。(2)肝纤维化四项指标在乙肝后肝硬化血清中HBV DNA>106copy/mL组中除LN外,其他指标水平明显高于乙肝后肝硬化血清中HBV DNA在103～105copy/mL组和HBV DNA<103copy/mL组的水平,差异有统计学意义(P<0.01);在HBV DNA 103～105copy/mL和HBV DNA<103copy/mL两组间肝纤维化四项指标升高水平差异无统计学意义(P>0.05)。(3)肝纤维化四项指标水平在AST/ALT>2、12时为(785.2±216.4)μg/L,各组间差异有统计学意义(P<0.05);Ⅳ-Col升高水平在AST/ALT>2[(598.2±158.6)μg/L]和AST/ALT<1[(438.7±146.1)μg/L]组间差异统计学意义(P<0.05);PⅢNP和LN升高的水平在各组间差异无统计学意义(P>0.05)。结论联合检测肝纤维化四项与AST/ALT比值、HBV DNA有利于临床对乙肝后肝硬化患者病程的监测,同时为临床对乙肝后肝硬化患者的抗病毒和抗纤维化治疗及疗效的判定提供实验室依据。     

Frequency and significance of antibody to hepatitis C virus in severe corticosteroid-treated autoimmune chronic active hepatitis.

To determine the frequency and significance of antibody to hepatitis C virus (anti-HCV) in severe autoimmune chronic active hepatitis, we tested sera from 85 cortico-steroid-treated patients by an enzyme immunoassay. Seropositive patients were assessed for specific antibodies to hepatitis C virus-encoded antigens by recombinant immunoblot assay. The findings in patients with and without anti-HCV were contrasted, and the frequency of seropositivity was compared with that in patients who had other types of chronic liver disease and in normal adults. Only 5 of the 85 patients with autoimmune hepatitis (6%) were seropositive for anti-HCV, and only 2 of these patients were reactive by recombinant immunoblot assay. The frequency of seropositivity in autoimmune hepatitis was not significantly different from that in hepatitis B surface antigen-positive (9%) and cryptogenic (18%) disease, but it was significantly less than that in posttransfusion chronic active hepatitis (6% versus 75%; P less than 0.001). Two patients became seronegative after corticosteroid therapy; both had been nonreactive by recombinant immunoblot assay. Four of the seropositive patients entered remission during corticosteroid therapy, including three whose sera were nonreactive to virus-encoded antigens. We conclude that anti-HCV occurs infrequently in corticosteroid-treated severe autoimmune hepatitis and that antibodies detected by enzyme immunoassay may be nonreactive to hepatitis C virus-encoded antigens. Seropositive patients who are nonreactive by immunoblot assay may still respond to corticosteroid therapy and become seronegative during treatment.     

甘草酸二铵脂质复合物肠溶胶囊口服治疗慢性乙型肝炎的临床观察

目的观察甘草酸二铵脂质复合物肠溶胶囊（商品名：天晴甘平），治疗慢性乙型肝炎的疗效。方法治疗组40例，服用甘草酸二铵脂质复合物肠溶胶囊（江苏正大天晴药业生产），3次／d，每次150mg；对照组40例，服用甘利欣胶囊（江苏正大天晴药业生产），3次／d，每次150mg。两组均服用8周。结果治疗8周后，治疗组ALT：复常38例，好转2例，AST：复常36例，好转4例。对照组ALT复常8例，好转30例，另有2例ALT反复升高。AsT复常8例，好转30例，另有2例ALT反复升高。治疗组ALT复常率明显高于对照组（P〈0．05），治疗组AST复常率明显高于对照组（P〈0．05）。结论甘草酸二铵脂质复合物因其降酶疗效高，不良反应小，使用方便等特点，为肝病患者提供了有效、方便的口服治疗药物。