Clinical and pathological features of autoimmune hepatitis: no significant differences between genders / 中华肝脏病杂志

<p><b>UNLABELLED</b>To explore the clinical and pathological features of male and female autoimmune hepatitis (AIH) patients.</p><p><b>METHODS</b>One hundred and sixty-nine AIH patients were enrolled. The clinical and histological data of the male cases were compared with the female ones.</p><p><b>RESULTS</b>There were 23 (13.6%) male patients in our study. The general status, biochemical and immunological test, and histological findings between two groups had no significant difference (P more than 0.05). The IAIHG's revised original scoring system pretreatment scores of male patients (14.4+/-2.3) were lower than that of female ones (16.6+/-2.6, Z= -3.728, P=0.000), whereas the simplified scoring system scores of male patients (7.2+/-0.8) were higher than that of female ones (6.5+/-1.2, Z=-2.372, P=0.018). There were 15 male AIH patients treated with immunosuppressive therapy, then 12 of them reached complete biochemical remission, the other three cases were incomplete response. The complete biochemical remission rate in our male cases was 80%. Median duration of remission was 3 months (95% CI 2.070-3.930 months).</p><p><b>CONCLUSION</b>There are no significant differences in clinical and pathological features of AIH between genders. The diagnosis of AIH should be suspected in male patients with any abnormality in serum aminotransferases levels. Liver biopsy examination is recommended to establish the diagnosis of AIH. The simplified criteria have good diagnostic value for male AIH patients.</p>

Validation of transient elastography (Fibroscan) in assessment of hepatic fibrosis in autoimmune hepatitis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To validate transient elastography (Fibroscan) in assessment of hepatic fibrosis in autoimmune hepatitis (AIH).</p><p><b>METHODS</b>Liver stiffness was assessed using Fibroscan in totally 30 patients with AIH. We compared the results of Fibroscan with the Scheuer fibrosis stage in liver biopsy in each patient.</p><p><b>RESULTS</b>4 patients were shown as liver fibrosis stage S0, 6 as S1, 5 as S2, 11 as S3 and 4 as S4. Failure of the Fibroscan measurement occurred in 1 case (3.3%) because of her increased body mass index (BMI). The stiffness of Fibroscan was significantly correlated with the liver biopsy fibrosis stage (r = 0.801, P less than 0.001). The liver stiffnesses between mild and moderate fibrosis (S0-2) and advanced fibrosis (S3-4) were significantly different (t = -3.937, P = 0.001).</p><p><b>CONCLUSION</b>Transient elastography (Fibroscan) is a promising non-invasive method for detection of fibrosis in patients with autoimmune hepatitis. Its use for the follow up and management of these patients and should be evaluated further.</p>

Clinical and pathological features of primary biliary cirrhotic patients with negative anti-mitochondria antibody / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To explore the clinical and pathological features of primary biliary cirrhosis (PBC) patients with negative anti-mitochondria antibody (AMA).</p><p><b>METHODS</b>Two hundreds and eight PBC patients were enrolled. The clinical and histological data of the negative AMA cases were compared with the AMA/AMA-M2 positive cases.</p><p><b>RESULTS</b>30 out of the 208 cases (14.4%) were AMA negative patients in our study. The general status, biochemical tests and histological findings between the two groups had no significant difference (P > 0.05). The Gamma-globulin, IgG, IgM and IgA levels of AMA/AMA-M2 positive PBC patients were higher than that of the AMA negative cases (P < 0.05). The abnormal rate of cholesterol in AMA negative PBC patients was 65.4% as compared to 50.4% in AMA/AMA-M2 positive cases, no significant difference existed between (P > 0.05). Anti-nuclear antibody (ANA) was observed in 29 (96.7%) AMA negative PBC patients, including 14 (48.3%) with granular pattern, 8 (27.6%) with nuclear membrane pattern, 6 (20.7%) with kinetochore pattern and 1 (3.4%) with homogeneous pattern. AMA negative PBC patients had elevated serum ALP, GGT, IgM and cholesterol levels, and decreased serum AST, IgG and IgA levels as compared with that of autoimmune hepatitis patients (P < 0.05, respectively).</p><p><b>CONCLUSION</b>In cholestatic patients with elevated IgM and cholesterol levels, ANA positive with non-homogeneous pattern, the diagnosis of PBC should be suspected, albeit AMA negative. The clinical, biochemical and histological features of the AMA negative PBC patients were similar to classic PBC patients, but quite different from autoimmune hepatitis.</p>

Clinical features of 107 autoimmune hepatitis patients and 30 of them with AIH-primary biliary cirrhosis overlap syndrome / 中华肝脏病杂志

<p><b>OBJECTIVE</b>In order to provide a reliable basis for the diagnosis and treatment of autoimmune hepatitis (AIH) and its overlap syndrome, we investigated the clinical, immunological characteristics of and the therapeutic methods for AIH and AIH-primary biliary cirrhosis (PBC) overlap syndrome.</p><p><b>METHODS</b>One hundred seven patients (77 with AIH and 30 with AIH-PBC overlap syndrome) were enrolled in the study. Their clinical manifestations, serum liver function tests (LFTs) findings, serum immunoglobulins, liver histopathological changes and their responsiveness to the therapies were investigated.</p><p><b>RESULTS</b>The age distribution of AIH patients showed a single peak during their fifties and their main clinical manifestations were malaise, abdominal distension, anorexia and jaundice. Serum gamma globulin and IgG were significantly higher than their normal levels. 74% of the patients were positive for anti-nuclear antibody (ANA), 32% of the patients were positive for anti-smooth muscle antibody (AMA), and over 50% of the patients suffered from concurrent extrahepatic autoimmune diseases. The main histological changes in the liver biopsies were interface hepatitis (65%), lobular hepatitis and rosette formation of liver cells. Bridging necrosis was observed in severe AIH cases. In the AIH-PBC overlap syndrome patients, the levels of serum ALT, AST, GGT, ALP and incidences of ANA and AMA/AMA-M2 were all significantly higher than those of the AIH group. After treating AIH patients with prednisolone and azathioprine (Aza), complete response was seen in 42 cases (70%), sustained response was seen in 26 cases (43%). Sixteen cases had relapses after the withdrawal of the treatment or prednisolone dosage was reduced lower than 10 mg/d. The cases having normal serum ALT, AST, gamma-globulin and IgG levels after treatment were still responding to the reduced prednisolone dosage of 5-10 mg/d without azathioprine added. After combination with ursodeoxycholic acid (UDCA) treatment, the liver function tests (AST, ALT, TBil) of AIH-PBC overlap syndrome patients also significantly improved compared to those before the treatment (P<0.01).</p><p><b>CONCLUSION</b>AIH and AIH-PBC overlap syndrome are not rare in our clinics. Their diagnoses should be based on the clinical presentations, biochemical and immunological indices and liver histological changes. In AIH cases, once their AST, ALT, gamma-globulin and IgG levels return to normal, the prednisolone dosage can be maintained at 5-10 mg/d and Aza can even be withdrawn. Good improvement for patients with AIH-PBC overlap syndrome can be obtained with UDCA and immunosuppression treatment.</p>

Assessment of the health-related quality of life of patients with minimal hepatic encephalopathy / 中华肝脏病杂志

<p><b>OBJECTIVE</b>The Medical Outcome Study of 36-item Short-Form Health Survey (SF-36) is a well-validated generic questionnaire widely used to assess health-related quality of life (HRQOL), and the Chronic Liver Disease Questionnaire (CLDQ) is a specific HRQOL assessment designed for patients with liver diseases. The aim of our study is to evaluate the HRQOL based on SF-36 and CLDQ (Chinese version) in patients with chronic hepatitis B and liver cirrhosis, especially in the status of minimal hepatic encephalopathy (MHE).</p><p><b>METHODS</b>The SF-36 and CLDQ were answered by 160 healthy volunteers, 20 patients with chronic hepatitis B and 106 patients with cirrhosis. HRQOL scores of the groups with different liver disease severities and with or without MHE were compared. The SF-36 includes one multi-item scale that assesses eight health categories: physical functioning, role-physical, body pain, general health, vitality, social functioning, role-emotion, and mental health. CLDQ assesses 6 categories: abdominal symptoms, fatigue, systemic symptoms, activity, emotional function and worry.</p><p><b>RESULTS</b>Compared with the healthy controls, patients with chronic hepatitis B and liver cirrhosis at baseline had a lower HRQOL on all scales of the SF-36 and CLDQ (P < 0.01 for all). Increased severity of liver cirrhosis (based on the Child-Pugh score but with MHE or without) was associated with a decrease in most components, both in SF-36 and in CLDQ. However, patients with Child-Pugh B and C disease had similar HRQOL scores on both the SF-36 and CLDQ (P > 0.05), except role-physical and vitality on SF-36. There was a significant difference between patients with and without MHE on the SF-36 score (P < 0.01), and no significant difference (P > 0.05) on CLDQ scores except in abdominal symptoms.</p><p><b>CONCLUSION</b>The Chinese version of SF-36 along with CLDQ are valid and reliable methods for testing MHE in patients with liver cirrhosis.</p>

Expression of endotoxin receptors on hepatic stellate cells during their activation / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the role of endotoxin receptor expression in the activation of hepatic stellate cells (HSCs).</p><p><b>METHODS</b>HSCs were isolated from normal rats and the expression of endotoxin receptors on quiet HSCs and in vitro activated HSCs was determined using RT-PCR and immunocytochemical staining methods. A rat model of liver fibrosis and cirrhosis was established. The expressions of CD14 and alpha-SMA in liver tissues were detected by immunohistochemical staining.</p><p><b>RESULTS</b>Freshly isolated HSCs had a low level of CD14 mRNA expression and no expression of TLR4 mRNA was detected. The in vitro activated HSCs had increased expressions of CD14 mRNA and TLR4 mRNA and LPS up-regulated the expression of endotoxin receptors. Immunocytochemical staining showed cytoplasmic and nucleolus staining for CD14 in the cultured HSCs. LPS played a further role on CD14 protein expression. In the development of liver fibrosis, the number of CD14-positive cells in the livers was increased and these cells were distributed along the sinusoids. In the later stage of liver fibrosis, the CD14-positive cells were gathered in the fibrotic septae, which also contained alpha-SMA positive cells.</p><p><b>CONCLUSION</b>The activated HSCs expressed endotoxin receptors. The endotoxin receptors may be involved in the role in which HSCs played in the inflammatory process and liver fibrosis development.</p>

Protective effect of Jiechangning decoction in treating experimental ulcerative colitis in guinea pigs / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the therapeutic effects and mechanism of Jiechangning (JCN) decoction on carrageenan induced experimental ulcerative colitis (UC).</p><p><b>METHODS</b>After sensitizing guinea pigs with carrageenan, we established UC animal models by free drinking water containing 2% acid degraded carrageenan (ADC). JCN decoction was orally administered once a day for 2 weeks after carrageenan treatment. Salicylazosulfapyridine (SASP) and normal saline were given to the other two groups as control. The levels of colon lipid peroxide (LPO), acid phosphatase (ACP) activity and tumor necrosis factor-alpha (TNF-alpha) were measured; colitis activity score (CAS) was carried out for assessment of the degree of tissue inflammation and injury; the colonic pathological changes were examined simultaneously with hematoxylin and eosin (HE) and toluidine blue staining used to evaluate the therapeutic effects of JCN decoction and SASP.</p><p><b>RESULTS</b>Experimental colitis models resembling human UC were successfully induced. The levels of tissue LPO, ACP activity and the content of tissue TNF-alpha were markedly increased in the model group as compared with the normal control group (P < 0.01) and were positively correlated with CAS. JCN decoction could reverse these changes like SASP. HE staining showed that JCN decoction and SASP could reduce CAS and the degree of tissue injury, toluidine blue staining revealed that mucosa and submucosa red metachromasia pellets in JCN group and SASP group were markedly fewer than those in the model group.</p><p><b>CONCLUSION</b>JCN decoction is effective in treating experimental UC, which provides theoretical basis for its clinical application.</p>

Cytokine gene polymorphisms in Chinese patients with type I autoimmune hepatitis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To assess the role of Tumor necrosis factor alpha (TNF-alpha) and interleukin 10 (IL-10) gene polymorphisms in susceptibility to type I autoimmune hepatitis (AIH).</p><p><b>METHODS</b>We detected 2 polymorphisms in TNF-alpha promoter gene at positions -238 and -308 and 3 polymorphic sites in IL-10 gene promoter at positions -1082, -819, -592 by polymerase chain reaction and dot blot with probes in the patients with 32 type I AIH and 48 health controls.</p><p><b>RESULTS</b>Genotypes associated with guanine to adenine substitution at position -308 of TNF-alpha promoter gene occurred more commonly in the patients than in health controls (53.1% vs. 27.1%, RR = 3.05, P < 0.01). There is no significant difference in polymorphisms of TNF-alpha gene at position -238 and 3 polymorphic sites in IL-10 promoter gene between patients and health controls.</p><p><b>CONCLUSION</b>Genotypes associated with guanine to adenine substitution at position -308 of TNF-alpha promoter gene (TNF-308A) may involve in the pathogenesis of type I AIH</p>

Effect of T-cell vaccination in murine experimental autoimmune hepatitis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the effect of T-cell vaccination in murine experimental autoimmune hepatitis (EAH).</p><p><b>METHODS</b>To induce the EAH model, the syngeneic S-100 antigen emulsified in complete Freud's adjuvant was injected intraperitoneally to C57Bl/6 at day 1 and day 7. For T-cell vaccination, splenocytes were removed from animal 2 weeks after induction of EAH and from control animals, and activated in vitro by mitogen stimulation with Concanavalin A (Con A), then inactivated by mitomycin and injected at 5 10(7) cells per animal as T-cell vaccination at 14 and 7 days before first induction of EAH.</p><p><b>RESULTS</b>The histological grade and serum ALT level of the mice who received T-cell vaccination were decrease significantly, compared with that of model group (1.44+/-0.88 vs. 2.33+/-0.87, t=2.24, P<0.05; 63.0U/L+/-23.4U/L vs. 115.0U/L1+/-39.6U/L, t=2.37, P<0.01, respectively); there was no significant change in mice who received irrelevant T-cell vaccination.</p><p><b>CONCLUSION</b>T-cell vaccination with T cells from EAH animals, but not with irrelevant T cells, was able to protect animals from EAH.</p>

Effects of Chinese herbal compound on the expression of hepatocyte cytochrome P450IIE1 in rats with alcoholic fatty liver / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the effect of Chinese herbal compound (CHC) on the expression of hepatocyte cytochrome P450IIE1 in rat model of alcoholic fatty liver (AFL).</p><p><b>METHODS</b>The AFL rats models were established by administering the drinking water with 40%(v/v) ethanol, and the changes of pathology in liver and hepatocyte P450IIE1 expression, as well as the contents of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), vitamin E (VitE) in liver were detected and compared with those in the control group.</p><p><b>RESULTS</b>Fatty degeneration in liver recovered normally in the CHC-treated group. Immunohistochemical and in situ hybridization examination showed that CHC could inhibit the hepatocyte cytochrome P450IIE1 expression markedly, and restore the contents of MDA, SOD, GSH, VitE to nearly normal range.</p><p><b>CONCLUSION</b>CHC can prevent AFL through inhibiting the hepatocyte cytochrome P450IIE1 expression markedly</p>

The application of psychometric measures in diagnosis of minimal hepatic encephalopathy / 中华消化杂志

Objective To establish the normal parameters of psychometric measures such as the number connection tests A(NCT-A)and digit symbol tests(DST)in assessment of minimal hepatic en- cephalopathy(MHE).Methods One hundred and sixty healthy volunteers(aged 25 to 64 years;educa- tional level＞9 years)were divided into＜35 ys,35～44 ys,45～54 ys and 55～64 ys groups.All of the healthy volunteers were assessed with NCT-A and DST to establish the normal value of age-related parameters,which can be used for diagnosis of MHE in patients with liver cirrhosis.Two standard devi- ation of the normal mean was used as a diagnostic criterion for MHE.One hundred and six cirrhotic patients were assessed with these parameters.Results The parameters of NCT-A were(25.1?4.6) sec in＜35 ys group,(32.1?6.8) sec in 35～44 ys group,(38.6?7.1)sec in 45～54 ys group or (49.3?6.3)sec in 55～64 ys group.The scores of DST were 49.9?4.7 in＜35 ys group,44.6?4.8 in 35～44 ys group,38.5?5.0 in 45～54 ys group or 35.4?4.7 in 55～64 ys group.Thirty one out of 106 cirrhotic patients were diagnosed as MHE based on these parameters.Conclusion The NCT- A and DST are psychometric assessments for diagnosis of MHE.Age-based normal paramerters of NCT- A and DST are needed to be established.