Correlation of MRI liver volume and doppler sonographic portal hemodynamics with histologic findings in patients with chronic hepatitis C

PURPOSE: The purpose of this study was to correlate portal hemodynamics on sonography and liver volume on MRI with histologic findings in asymptomatic patients with chronic hepatitis C. METHODS: Portal blood flow in the left and right portal branches in 20 healthy volunteers and in 26 patients was measured using Doppler sonography during both fasting and postprandial states. Total liver and right-and left-lobe volumes were determined using MRI. The ratio between portal blood flow and liver volume determined the "portal flow index" of the right and left lobes. RESULTS: We observed a statistically significant difference (p < 0.01) between the volunteers and patients in the mean left-lobe volume (352 +/- 81 cm(3) versus 544 +/- 159 cm(3)) and in the mean left portal flow index (1.1 +/- 0.2 ml/minute/cm(3) versus 0.69 +/- 0.2 ml/minute/cm(3)) as measured before the subjects ate. After a meal, the portal blood-flow volume in the right lobe was similar in the 2 groups but in the left lobe was significantly lower in the patients (p = 0.0009). The left postprandial portal flow index was inversely correlated with the grade of liver fibrosis (r = 0.533). CONCLUSIONS: The left-lobe volume (positive predictive value, 83%; negative predictive value, 72%) and left postprandial portal flow index (positive predictive value, 86%; negative predictive value, 88%) are sensitive indicators of chronic hepatitis. The left postprandial portal flow index may be a useful test for differentiating patients with minimal or no fibrosis from patients with mild to severe fibrosis.     

Hepatic arterial resistance after mixed-meal ingestion in healthy subjects and patients with chronic liver disease.

PURPOSE: This study investigated hemodynamic changes in the resistance index of the hepatic artery after mixed-meal ingestion. METHODS: We used color Doppler sonography to measure hemodynamic changes in the right hepatic artery in response to mixed-meal ingestion (225 ml, 69 g, 300 kcal) in 9 healthy subjects, 15 patients with chronic hepatitis with low-grade fibrosis (no bridging), 10 patients with chronic hepatitis with moderate-grade (bridging) fibrosis, and 18 patients with cirrhosis. RESULTS: After mixed-meal ingestion, the mean (+/-standard error) maximum increase in the resistance index of the right hepatic artery in healthy subjects was 31+/-2%. These changes were significantly greater than those in patients with chronic hepatitis with low-grade fibrosis (22+/-2%; p<0.05), patients with chronic hepatitis with moderate-grade fibrosis (11+/-2%; p<0.01), and cirrhotic patients (5+/-2%; p<0.01). Mixed-meal ingestion produced significantly smaller increases in the resistance index in cirrhotic patients than in patients with chronic hepatitis with low-grade fibrosis (p<0.01). A postprandial increase in the resistance index of 15% or less was associated with 100% sensitivity, 72% specificity, and 84% accuracy in distinguishing patients with cirrhosis from patients with chronic hepatitis. CONCLUSIONS: The response of the resistance index after mixed-meal ingestion decreases as the severity of hepatic fibrosis increases. Doppler evaluation of postprandial increases in the resistance index of the right hepatic artery may be useful in differentiating between patients with chronic hepatitis and those with cirrhosis.     

Gastroscopic real-time 13C-urea breath test

BACKGROUND AND STUDY AIMS: Biopsy-based Helicobacter urease testing (HUT) may constitute a hazard in patients with bleeding disorders, those receiving anticoagulant therapy, and those with communicable diseases. In addition, definitive test results may not immediately be available. The aim of this study was to investigate the feasibility of breath testing for H. pylori during gastroscopy (gastroscopic breath testing, GBT) in comparison with the standard HUT in a prospective, randomized, and controlled study. PATIENTS AND METHODS: A total of 119 patients were randomly allocated to undergo H. pylori testing with either HUT (n = 61) or GBT (n = 58) with 75 mg of 13C-labeled urea by endoscopic instillation. Breath samples were continuously analyzed using molecular correlation spectroscopy, displaying real-time results. The procedure time and time until definitive test results were obtained (mean plus or minus standard deviation) were recorded. RESULTS: H. pylori was detected in 10 of 49 patients (20.4 %) with HUT and in 16 of 53 (30.2 %) with GBT. Contraindications to biopsy prevented HUT in 12 of 61 patients. GBT results could not be obtained in one of the 58 patients due to respiratory disease and in four for technical reasons. Slightly less time was required to carry out HUT than GBT (121 +/- 30 s vs. 164 +/- 36 s; P < 0.001). Definitive test results were available within 14.0 +/- 2.2 min using GBT in comparison with 19.6 +/- 9.1 h for HUT ( P < 0.001). GBT prolonged the time spent by the patient in the endoscopy room by only 5.6 min in comparison with HUT (45.1 +/- 8.5 min vs. 39.5 +/- 10.3 min; P < 0.01). CONCLUSIONS: GBT provides immediate, definitive results and allows H. pylori testing in patients in whom biopsies are contraindicated, with only minimal prolongation of the procedure time.     

Proinflammatory cytokines, insulin resistance, and insulin secretion in chronic hepatitis C patients: A case-control study

OBJECTIVE: The purpose of this study was to explore the initial pathogenic mechanisms of diabetes associated with hepatitis C virus (HCV) infection. RESEARCH DESIGN AND METHODS: Insulin resistance, proinflammatory cytokines, and beta-cell function were evaluated in a case-control study. A total of 28 consecutive nondiabetic patients with chronic hepatitis C were included in the study (anti-HCV+). Fourteen patients with chronic hepatitis other than HCV infection served as the control group (anti-HCV-). Both groups were closely matched by the main clinical variables associated with insulin resistance and the degree of liver fibrosis. In addition, there were no differences between groups regarding hepatic insulin extraction measured by calculating the ratio between C-peptide and insulin. Serum levels of proinflammatory cytokines (tumor necrosis factor [TNF]-alpha, soluble TNF receptor [sTNFR] 1, soluble TNFR2, and interleukin-6) were measured by enzyme-linked immunosorbent assay. Insulin resistance (homeostasis model assessment [HOMA] of insulin resistance [HOMA-IR]) and insulin secretion at baseline (HOMA-beta) and after various stimulus (oral glucose tolerance test, standard food intake, and intravenous glucagon) were determined by previously validated mathematic indexes. RESULTS: HOMA-IR was higher in anti-HCV+ than in anti-HCV- patients (4.35 +/- 2.27 vs. 2.58 +/- 1.74; P = 0.01). All the proinflammatory cytokines analyzed were significantly higher in anti-HCV+ patients than in anti-HCV- patients. In addition, sTNFR1 and sTNFR2 were directly correlated to HOMA-IR. HOMA-beta as well as insulin and C-peptide responses after the intravenous glucagon test were significantly higher in anti-HCV+ patients than in anti-HC- patients. CONCLUSIONS: Insulin resistance mediated by proinflammatory cytokines, but not a deficit in insulin secretion, could be the primary pathogenic mechanism involved in the development of diabetes associated with HCV infection.     

Doppler sonography measurement of portal blood flow velocity after glucagon injection in patients with chronic HCV infection

Doppler sonography measurement of portal flow velocity (PFV) after glucagon injection was performed in 45 patients with chronic hepatitis C virus (HCV) infection. Patients were divided into three groups: group 1 = no or mild liver fibrosis; group 2 = moderate to severe liver fibrosis, and group 3 = liver cirrhosis. All patients were examined using a Doppler ultrasound (US) multipurpose equipment and a convex 3.5-MHz probe, 10 min before (baseline), as well as 5 and 10 min after, IV administration of 1 mg of glucagon chloride. No significant differences were found in mean baseline PFV among group 1 (19.4 +/- 2.4 cm/s), group 2 (20.1 +/- 3.6 cm/s) and group 3 (17.5 +/- 3.7 cm/s). Five minutes after glucagon injection, all three groups showed significantly increased values of mean PFV (25.6 +/- 4.8, 23.7 +/- 4.0 and 19.5 +/- 5.0 cm/s, respectively; p < 0.05 vs. baseline). The mean increase of PFV above baseline was significantly higher in group 1 (7.9 +/- 3.7 cm/s) than in group 2 (4.5 +/- 3.9 cm/s) (p < 0.05) or in group 3 (2.7 +/- 2.3 cm/s) (p < 0.05). A significant inverse correlation was found between individual values of fibrosis score and of individual increase of PFV. In patients with chronic HCV infection, Doppler sonography measurement of PFV after glucagon injection could be useful in assessing the severity of liver histological damage.     

Clinical application of breath analysis for dimethyl sulfide following ingestion of DL-methionine.

After overnight-fasting, the concentration of dimethyl sulfide in expired alveolar gas (alv-DMS) was determined serially following ingestion of 2 g of DL-methionine in normal subjects and patients with liver diseases. Alv-DMS rose to a peak in 30 to 90 min, declined markedly within 3 h, and then decreased gradually. Half-disappearance times (T 1/2) (mean +/- S.E. min) in each experimental group were: normal (N = 9) 61.7 +/- 4.7, acute hepatitis (N = 6) 62.5 +/- 6.8, chronic hepatitis (N = 10) 84.0 +/- 13.0, and liver cirrhosis (N = 13) 159.2 +/- 30.4, respectively. Cirrhotics had a T 1/2 significantly longer than that of the other three groups: vs. normal P less than 0.02, vs. acute hepatitis P less than 0.05, and vs. chronic hepatitis P less than 0.05. T 1/2 of alv-DMS following ingestion of DL-methionine seems to be of clinical interest.     

Clinical usefulness of serum tissue inhibitor of metalloproteinases (TIMP)-2 assay in patients with chronic liver disease in comparison with serum TIMP-1

Tissue inhibitors of metalloproteinases (TIMPs) are involved in liver fibrosis through impaired matrix degradation. Previous studies showed that the serum level of TIMP-1 was increased in patients with chronic liver disease, reflecting the liver TIMP-1 level, and that it is useful for assessing liver fibrosis. An enzyme immunoassay for TIMP-2 is now available. In this study, we examined the clinical usefulness of this serum TIMP-2 test for liver fibrosis in patients with chronic liver disease, in comparison with the serum TIMP-1 test. The serum TIMP-2 concentration was 61 +/- 13 ng/ml in healthy controls (n = 32), and 18% higher in the group of chronic active hepatitis (CAH) patients (n = 34), 64% higher in the liver cirrhosis (LC) group (n = 33) and 44% higher in the hepatocellular carcinoma (HCC) group (n = 61), and similar to the control level in the chronic persistent hepatitis (CPH) group (n = 23). In contrast, the serum TIMP-1 concentration was 155 +/- 17 ng/ml in the healthy controls, 18% higher in CPH, 35% in CAH, 63% higher in LC and 92% higher in HCC. The serum TIMP-2 level was related to the histological degrees of both periportal necrosis and liver fibrosis, as well as to the serum TIMP-1 level. However, the relationships for TIMP-2 were weaker compared to those of serum TIMP-1. These results suggest that compared to the serum TIMP-1 level, changes in the serum TIMP-2 level in chronic liver disease are less liver-specific, and the serum TIMP-2 level is less useful in the assessment of liver fibrosis in chronic liver disease.     

Impact of steatosis on long-term histological outcome in chronic hepatitis C after antiviral therapy

BACKGROUND/AIMS: Steatosis is recognized as a cofactor influencing the presence and progression of fibrosis in chronic hepatitis C. It has been reported that antiviral therapy may reduce the progression of fibrosis and leads to regression in chronic hepatitis C patients achieving a sustained virological response (SVR). Whether steatosis might affect the long-term histological outcome of antiviral therapy remains unclear. METHODS: One-hundred and sixty-one consecutive patients (genotype 1, n=76; genotype 2, n=73) receiving interferon-alpha2b and ribavirin were analysed. Ninety patients had paired biopsies with a mean interval of 29.1 +/- 7.1 months. RESULTS: Variables associated with baseline steatosis were higher body mass index (> or = 25, P=0.002) and higher fibrosis stage (> or = 2, P=0.019). Neither the presence nor the severity of steatosis was associated with SVR. Evaluation of paired biopsies showed no different distribution of steatosis evolution between patients with and without SVR (P=0.374). Among patients achieving a SVR, there was a significant difference in fibrosis changes between those with grade 0 or 1 steatosis and with grade 2 or 3 steatosis at post-treatment biopsy (-0.6 +/- 1.2 vs 0.3 +/- 1.3, P=0.041), whereas changes in histological activity index did not differ (-3.7 +/- 2.6 vs -4.0 +/- 2.9, P=0.740). Stepwise logistic regression analysis showed that SVR (odds ratio [OR]: 16.33, P=0.004) and grade 0 or 1 post-treatment steatosis (OR: 12.82, P=0.018) were independently associated with fibrosis regression. CONCLUSIONS: In patients with chronic hepatitis C, steatosis not only correlates with advanced fibrosis at baseline but also affects fibrosis regression after antiviral therapy.     

Connective tissue growth factor in serum as a new candidate test for assessment of hepatic fibrosis

BACKGROUND: No reliable, cost-effective serum test is available for assessment of liver fibrogenesis, the most serious complication of chronic inflammatory liver diseases (CLD). In sera of patients with CLD, we determined the concentration of connective tissue growth factor (CTGF), a secreted downstream mediator of the potent fibrogenic cytokine transforming growth factor beta (TGF-beta). PATIENTS AND METHODS: We studied 83 patients with CLD (17 with chronic hepatitis, 16 with histologically proven fibrosis, and 50 with cirrhosis) and 74 healthy individuals. Serum CTGF was measured by use of a sandwich immunoassay. RESULTS: The mean concentration of CTGF was highest in the fibrosis group (5.2-fold) and in the chronic viral hepatitis group (4.3-fold) but lower in those patients with fully developed cirrhosis. The area under the ROC curve (AUC) of CTGF for fibrosis vs control was 0.955 (95% confidence interval, 0.890-0.987). The CTGF/platelet ratio increased the detection limit for cirrhosis from 84% to 92% and the specificity from 85% to 87.5% (cutoff for CTGF was 364 microg/L, ratio 2.05). CONCLUSION: CTGF in serum is a candidate marker of ongoing fibrogenesis in chronic liver diseases.     

Clinical significance of serum 7S collagen in various liver diseases

Serum type IV collagen fragment (7S collagen domain) was measured in 30 controls and 152 liver disease patients with a radioimmunoassay using a polyclonal antibody to human placenta 7S collagen. The serum concentrations of 7S collagen (mean +/- SD) were 4.2 +/- 0.9 ng/mL in controls, 5.1 +/- 2.0 ng/mL in acute hepatitis, 6.5 +/- 2.5 ng/mL in chronic inactive hepatitis, 9.5 +/- 3.8 ng/mL in chronic active hepatitis, 14.4 +/- 7.5 ng/mL in liver cirrhosis, and 14.4 +/- 6.9 ng/mL in hepatocellular carcinoma. In acute hepatitis, 7S collagen was slightly increased, whereas type III procollagen N-peptide and prolyl hydroxylase were markedly increased. In chronic liver disease, 7S collagen concentrations increased with the severity of the disease, and also reflected the degree of fibrosis. The serum 7S collagen concentrations were significantly correlated with those of type III procollagen N-peptide and prolyl hydroxylase in all subjects. These results suggest that serum 7S collagen concentration is a useful diagnostic aid for determining hepatic collagen metabolism in liver diseases.     

丙型肝炎病毒感染者血清YKL-40水平变化

目的分析丙型肝炎病毒感染者血清YKL-40浓度,探讨丙型肝炎病毒感染者血清YKL-40水平变化与肝功能损害程度的关系。方法收集丙型肝炎病毒感染者107例,分成丙型肝炎病毒携带者、轻度慢性丙型肝炎患者和中度慢性丙型肝炎患者三组。通过酶联免疫吸附法测定丙型肝炎病毒感染者血清YKL-40的水平。结果丙型肝炎病毒携带者、轻度慢性丙型肝炎患者和中度慢性丙型肝炎患者血清YKL-40浓度均值和中值均高于正常对照组(P0.01),且血清YKL-40的水平随丙型肝炎病毒感染者肝功能损害程度的加重而增加。结论血清YKL-40升高是肝纤维化的特征之一,丙型肝炎病毒感染者血清YKL-40水平随肝功能损害程度的加重而增加,这预示随肝功能损害程度加重丙型肝炎病毒感染者出现肝纤维化的可能性增加。     

PKR gene expression and response to pegylated interferon plus ribavirin therapy in chronic hepatitis C

Pegylated interferon (PEG-IFN) alpha combined with ribavirin is the current standard treatment for hepatitis C, but around 50% of patients do not respond for reasons that are not fully understood. To explore the regulation of IFN-inducible protein kinase (PKR), we have measured PKR mRNA levels in peripheral blood mononuclear cells (PBMCs) and in liver biopsies from patients with chronic hepatitis C. PBMCs were also analysed after in vitro incubation with IFN and during antiviral therapy. Non-responders to PEG-IFN plus ribavirin had pre-treatment PKR mRNA levels in PBMCs (0.1+/-0.0074) and in liver (0.102+/-0.051) that were significantly higher than those of responders (PBMCs: 0.023+/-0.014, P=0.0005; liver: 0.034+/-0.020; P=0.0002). On the other hand, PKR mRNA levels in PBMCs were similar in non-responders and in responders after in vitro exposure to IFN (0.434+/-0.301 vs 0.403+/-0.222; P=NS) and during therapy (0.31+/-0.10 vs 0.30+/-0.12; P=NS). These results indicate that in hepatitis C, non-responsiveness to IFN-alpha is associated with pre-treatment up-regulation of the PKR gene, evidence that the infecting hepatitis C virus is able to stimulate endogenous IFN production, being resistant to its antiviral effect. On the other hand, the PKR gene response to exogenous IFN was similar in responders and non-responders, at least in PBMCs, suggesting that variations in its activation are not major determinants of the outcome of antiviral treatment.     

Changes in classic and alternative pathways of bile acid synthesis in chronic liver disease

BACKGROUND: Cholesterol elimination occurs through bile acid synthesis that starts within the liver from 7alpha-hydroxylation or in extrahepatic tissues from 27-hydroxylation. This study was aimed at investigating in vivo these two pathways in patients with chronic liver disease. METHODS: Serum concentrations of 7alpha- and 27-hydroxycholesterol were measured in 54 patients (29 with primary biliary cirrhosis and 25 with chronic hepatitis C) and 18 controls. The rate of oxysterol plasma appearance was calculated after intravenous infusions of deuterated 7alpha- and 27-hydroxycholesterol in patients (n=8) and control subjects (n=8) who gave consent. The expression of sterol 27-hydroxylase was evaluated in macrophages isolated from 20 subjects. RESULTS: In patients with liver disease, the rate of plasma appearance of 7alpha-hydroxycholesterol was significantly reduced (1.44+/-0.96 vs. 2.75+/-1.43 mg/hour, p=0.03), the degree of reduction being related with the severity of the disease (p=0.01) whereas that of 27-hydroxycholesterol was unaffected. The rate of plasma appearance of 27-hydroxycholesterol was significantly related to its serum concentrations (r=0.54, p=0.03) and to its release from cultured macrophages ( r=0.85, p=0.03). CONCLUSIONS: In liver disease 7alpha-hydroxylation of cholesterol seems to be impaired while 27-hydroxylation is unaffected. Serum concentrations of 27-hydroxycholesterol are useful to obtain information on the activity of this alternative pathway.     

Serum hyaluronan as a marker of liver fibrosis in asymptomatic chronic viral hepatitis B.

Increased concentrations of serum hyaluronan, a polysaccharide widely distributed in the extracellular space, have been demonstrated in liver disease of various aetiologies and proposed as a useful marker of liver fibrosis. The aim of the present study was to evaluate the association of serum hyaluronan with the extent of hepatic fibrosis in asymptomatic cases of chronic hepatitis B viral infection. The study was conducted in a consecutive sample of 111 asymptomatic chronic carriers of hepatitis B surface antigen. Liver function tests, alcohol consumption and cigarette smoking were determined and, for 84 subjects, liver biopsy was performed and degrees of inflammation and fibrosis were scored. Hyaluronan was measured using a radiometric assay. Mean serum hyaluronan increased with increasing fibrosis score (from 22.2 +/- 4.8 to 50.6 +/- 12.7 microg/l, p = 0.058) or pathological severity (from 18.8 +/- 5.9 to 50.6 +/- 12.5 microg/l, p = 0.048), even after adjusting for the effect of age. No such correlation was found with portal inflammation. The study showed that, in asymptomatic chronic carriers of hepatitis B, serum hyaluronan concentration correlates with hepatic fibrosis, a known marker of disease prognosis. This finding supports the hypothesis that hyaluronan might be of use in assessing and monitoring time trends in liver disease, substituting for repeated biopsies.     

Logitboost算法在慢性乙型肝炎肝纤维化中的应用研究

目的 将Logitboost算法用于判别分析慢性乙型肝炎肝脏纤维化血清学检测指标,建立一种无创性慢性乙型肝炎纤维化分期诊断模型.方法 226例慢性乙型肝炎患者进行肝活检和肝纤维化血清学指标的检测,血清学指标进行相关系数和Logitboost算法判别分析,并与肝活检结果比对.结果 Logitboost算法在迭代100轮时判别正确率最高,与肝活检的结果相比较,纤维化分期S(0～4) 的诊断符合率分别为92.3%、89.5%、91.5%、96.9%、97.7%.结论 Logitboost算法可以对慢性肝炎肝纤维化进行有效分期.     

Liver contrast enhanced ultrasound perfusion imaging in the evaluation of chronic hepatitis C fibrosis: preliminary results

We wanted to determine whether liver contrast-enhanced ultrasound (CEUS)-derived peak signal intensity (PSI) and peak signal intensity/time (PIT) predict liver fibrosis in chronic hepatitis C (CHC). Forty-nine patients with CHC (METAVIR classification) and 10 control subjects were included in the study. After a bolus of 2.4 mL SonoVue (Bracco Imaging, Milan, Italy) solution was injected into a peripheral vein, the right lobe of the liver containing the right portal vein was scanned in a transverse section. Two-dimensional sonography was performed using the Philips iU22 ultrasound system (Philips Healthcare, Best, the Netherlands). A 1.0-5.0-MHz (C5-1) wideband convex transducer was used, applying the following settings in all cases. Regions of interest were manually drawn over the right liver lobe and over the portal vein (PV). Liver parenchyma PSI (LPpsi) and PIT (LPpit), portal vein PSI (PVpsi) and PIT (PVpit) were automatically calculated. δPSI was defined as the difference between PVpsi and LPpsi. A significant correlation was observed between PA_PSI and fibrosis scores. When patients were stratified according to their LPpsi, a significant difference was achieved only between patients with fibrosis score 0-1 vs. 2-3 and 2 vs. 4. Statistically significant differences between all fibrosis scores, except 0 vs. 1 and 3 vs. 4 were observed when δPSI was used to stratify patients. Overall diagnostic accuracy of LPpsi and δPSI measurement for severe fibrosis by area under the receiving operator characteristic curve analysis was, respectively, 0.87 and 0.88. We suggest that liver CEUS perfusion could have the potential to be used as a complementary tool for the evaluation of liver fibrosis. However, further large-scale studies are required to accurately assess its accuracy in the evaluation of liver fibrosis. (E-mail: aorlacchio@uniroma2.it)     

Prospects for interferon therapy in chronic hepatitis C with normal transaminase levels

AIM: To study effectiveness of recombinant interferon-alpha (Ifna) in patients with chronic hepatitis C with normal transaminases. MATERIAL AND METHODS: 26 patients with positive tests for abHCV and RNA HCV with a normal level of alaninaminotransferase (AlAT) entered the study. 16 patients of the test group received recombinant Ifna three times a week in a dose 3 mln IU. Mean duration of interferon therapy was 7.44 +/- 4.27 months. Control group consisted of 10 patients with natural course of the disease. Biochemical, virusological and morphological examinations were conducted in all the patients. The patients were followed up for 1.5-2 years, on the average. RESULTS: Treatment with recombinant Ifna was well tolerated. A persistent positive virusological response after the treatment was achieved in 25% of the test patients. They exhibited improvement of histological structure of the liver. In control group the dynamics was opposite. CONCLUSION: In patients with chronic hepatitis C with normal transaminases level interferon therapy improves structure of hepatic tissue. Puncture biopsy of the liver is the main method which determines the validity of the treatment and its efficacy.     

Differential expression of matrix metalloproteinases in viral and non-viral chronic liver diseases

BACKGROUND: Fibrosis is a common consequence of chronic liver diseases irrespective of aetiology. Metalloproteinases play an important role in the fibrotic process participating in the balance between collagen synthesis and degradation. We examined whether matrix gelatinases and stromelysins are similarly involved in the development of viral (HCV, HBV) and non-viral (NASH) liver diseases. METHODS: Hepatic mRNA levels of matrix metalloproteinase MMP-2, MMP-9, MMP-10 and MMP-11 isolated from liver biopsies were measured by semi-quantitative RT-PCR. Seventy-three patients were examined in this study: non-diseased controls (10), patients with chronic hepatitis B (14), chronic hepatitis C (33) and non-alcoholic steatohepatitis (16). RESULTS: A significant increase of MMP-9 and MMP-10 expression was found in patients with non-viral (non-alcoholic steatohepatitis) liver disease. Patients with chronic hepatitis B and hepatitis C showed an increase in MMP-2 mRNA expression compared to controls. Moreover, chronic hepatitis B and hepatitis C patients had significantly different mRNA expression patterns. CONCLUSIONS: These findings indicate that matrix metalloproteinases are differentially involved in the fibrotic process of viral and non-viral chronic liver diseases. Differences exist between HBV and HCV chronic hepatitis. Differences between early and late fibrosis indicate that in future studies, careful staging of patients is mandatory for interpretation of results.     

Immune status of patients with different outcomes of acute hepatitis C

AIM: To ascertain parameters of immune response significant for prognosis of the disease outcome in patients with acute hepatitis C (AHC). MATERIAL AND METHODS: Seventy two examinees were divided into three groups: 30 patients of group 1 had AHC; 29 patients of group 2 had chronic hepatitis C (CHC) with the disease history 3-10 years; 13 AHC convalescents who had the disease 3-10 years ago. The control group consisted of 10 healthy subjects. The following parameters of immune status were studied: CD3+, CD4+, CD8+, CD16+, CD20+, HLA-DR+CD3+, CD95+, O-lymphocytes. RESULTS: By clinicobiochemical picture and the results of 12-month follow-up RT-PCR investigations of blood HCV RNA, AHC patients were divided into two groups: in 18 (72%) of 25 patients AHC became chronic, 7 (28%) patients achieved convalescence. The proportion and absolute number of subpopulations of lymphocytes CD8+, CD20+, CD16+ as well as CD4/CD8 in patients with AHC with different outcomes did not differ from the controls. AHC convalescents and patients with AHC transformation into chronic hepatitis had in the acute period of the disease much higher absolute number of subpopulations of the lymphocytes CD3+, CD4+, HLA-DR+CD3+ vs the controls. In patients with chronic hepatitis C with elevated levels of AlAT, 3-10 year follow-up registered significantly higher absolute amount of CD8+, CD3+, CD4+, HLA-DR+CD3+ vs the controls. Only patients with AHC which later became chronic had for 6 months of the disease significantly elevated absolute number of O-lymphocytes vs the controls. CONCLUSION: A high absolute count of O-lymphocytes in AHC patients may indicate probable development of chronic hepatitis C.     

MR体素内不相干运动扩散加权成像评估慢性乙型病毒性肝炎肝纤维化程度的价值研究

目的探讨体素内不相干运动扩散加权成像对慢乙肝肝纤维化程度评估的价值。材料与方法 55例慢乙肝患者根据肝穿病理分为无和轻度肝纤维化组、中度肝纤维化组和重度肝纤维化组,20例健康志愿者为对照组。行磁共振IVIM-DWI等检查。分析对照组与肝纤维化组之间以及肝纤维化各组之间的sADC、D、D*及f值的差异。结果随着肝纤维化程度的加重,肝组织的D、D*及f值均逐渐减低,D值在对照组与肝纤维化组之间有统计学差异。D*及f值在对照组与肝纤维化组之间以及肝纤维化各组之间的差异均有统计学意义。对照组与肝纤维化组的D、D*及f值分别是(0.540±0.031)×10~(-3) mm~2/s和(0.427±0.061)×10~(-3) mm~2/s、(0.380±0.027)×10~(-1) mm~2/s和(0.320±0.052)×10~(-1) mm~2/s、(0.232±0.014)和(0.217±0.011),无和轻度肝纤维化组的D、D*及f值分别是(0.489±0.027)×10~(-3) mm~2/s、(0.349±0.041)×10~(-1) mm~2/s、(0.226±0.010),中度组的分别是(0.398±0.035)×10~(-3) mm~2/s、(0.317±0.040)×10~(-1) mm~2/s、(0.214±0.008),重度组的分别是(0.370±0.048)×10~(-3) mm~2/s、(0.269±0.055)×10~(-1) mm~2/s、(0.206±0.006)。结论磁共振IVIM-DWI参数D、D*及f值可大致反映慢乙肝肝纤维化的严重程度,具有潜在的临床应用价值,尤其可用于早期肝纤维化的无创性评估。