[A noninvasive diagnostic model of liver fibrosis using serum markers in primary biliary cirrhosis].

OBJECTIVE: To verify and assess diagnostic value of noninvasive diagnostic model of liver fibrosis in primary biliary cirrhosis (PBC) based on conventional laboratory markers. METHODS: Seventy-three patients with PBC diagnosed by liver biopsy between January 2003 and June 2011 in Beijing Friendship Hospital, Capital Medical University were recruited in this study. Correlation analysis and logistic regression analysis between the conventional laboratory markers and histology stages were assessed. A liver fibrosis diagnostic model was established based upon aforementioned biomarkers and verified by its sensitivity and specificity for predicting the liver fibrosis. RESULTS: The predictive model (H index) consisting of five conventional laboratory markers, i.e., platelet count, serum cholinesterase, albumin, HDL-C and prothrombin time activity, could predict advanced fibrosis (stages III-IV) with an AUC(ROC) of 0.861. The sensitivity of predicting the absence of advanced fibrosis using H index < -2.20 was 96.6% and the specificity of predicting the presence of advanced fibrosis using H index > 0.41 was 93.2%. CONCLUSION: The established noninvasive diagnostic model consisting of five laboratory markers could accurately distinguish pathological changes of early stage PBC (stages I-II) from advanced stage PBC (stages III-IV).

[The clinical profiles of primary biliary cirrhosis with a suboptimal biochemical response to ursodeoxycholic acid].

To observe the characteristics of primary biliary cirrhosis (PBC) with a suboptimal biochemical response to ursodeoxycholic acid. A total of 38 Chinse PBC patients (5 male patients, 33 female patients, average age 55 years old) with treatment of ursodeoxycholic acid in our hospital from January 1999 to January 2009 were erolled and studied retrospectively. 17 suboptimal biochemical responders mainly presented with liver diseases related symptoms including jaundice (41.1%), fatigue, anorexia (23.5%), edema and abdominal distension (11.7%). 21 good biochemical responders mainly presented with abnormal liver function tests without symptoms. The suboptimal biochemical responders had significantly higher baseline levels of total serum bilirubin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, immunoglobulin G and globulin as compared to the good biochemical responsers. There were no differences in gender, age and the dose of UDCA. PBC patients with liver diseases related symptoms, marked abnormal liver tests and characteristics of autoimmune hepatitis may have a suboptimal biochemical response to ursodeoxycholic acid treatment.

Antiviral therapy for hepatitis B in special populations.

There has been much progress in antiviral therapy for chronic hepatitis B; however, antiviral therapy for hepatitis B in special populations is still very challenging. Here, we review antiviral therapy for hepatitis B in special populations, including children and pregnant patients, patients with hepatitis-B-related cirrhosis, patients with acute hepatitis B and chronic hepatitis B surface antigen carriers who receive immunosuppressive or cytotoxic therapy. Major advances have been made in antiviral therapy for hepatitis B in these special populations because of recent increasing availability of oral nucleoside/nucleotide analogues that are well-tolerated and highly effective; however, the findings are mostly based on small uncontrolled short-term studies. More well-designed clinical studies on antiviral therapy for hepatitis B in these special populations are urgently needed to obtain more evidence-based high-quality data.

Activation of canonical Wnt signaling pathway promotes proliferation and self-renewal of rat hepatic oval cell line WB-F344 in vitro.

AIM: To investigate the effect of activation of canonical Wnt signaling pathway on the proliferation and differentiation of hepatic oval cells in vitro. METHODS: WB-F344 cells were treated with recombinant Wnt3a (20, 40, 80, 160, 200 ng/mL) in serum-free medium for 24 h. Cell proliferation was measured by Brdu incorporation analysis; untreated WB-F344 cells were taken as controls. After treatment with Wnt3a (160 ng/mL) for 24 h, subcellular localization and protein expression of beta-catenin in WB-F344 cells treated and untreated with Wnt3a were examined by immunofluorescence staining and Western blot analysis. CyclinD1 mRNA expression was determined by semi-quantitative reverse-transcript polymerase chain reaction (RT-PCR). The mRNA levels of some phenotypic markers (AFP, CK-19, ALB) and two hepatic nuclear factors (HNF-4, HNF-6) were measured by RT-PCR. Expressions of CK-19 and AFP protein were detected by Western blot analysis. RESULTS: Wnt3a promoted proliferation of WB-F344 cells. Stimulation of WB-F344 cells with recombinant Wnt3a resulted in accumulation of the transcriptional activator beta-catenin, together with its translocation into the nuclei, and up-regulated typical Wnt target gene CyclinD1. After 3 d of Wnt3a treatment in the absence of serum, WB-F344 cells retained their bipotential to express several specific phenotypic markers of hepatocytes and cholangiocytes, such as AFP and CK-19, following activation of the canonical Wnt signaling pathway. CONCLUSION: The canonical Wnt signaling pathway promotes proliferation and self-renewal of rat hepatic oval cells.

Undifferentiated connective tissue diseases-related hepatic injury.

Hepatic injury is rarely associated with undifferentiated connective tissue diseases (UCTD). We report, here, a case of a middle-aged woman with UCTD-related hepatic injury, including its case history, clinical manifestations, laboratory findings, treatment and its short-term effect. The patient was admitted to the hospital with symptoms of fatigue, anorexia, low-grade fever and skin rashes. She had a past history of left knee joint replacement. Laboratory tests showed elevated levels of serum transaminase, IgG and globulin, accelerated erythrocyte sedimentation rate, eosinophilia and a high titer of antinuclear antibodies (1:320). Imaging studies showed interstitial pneumonitis and hydropericardium. Liver biopsy showed the features which were consistent with those of connective tissue diseases-related polyangitis. After treatment with a low-dose of oral prednisone, both symptoms and laboratory findings were significantly improved. UCTD-related hepatic injury should be considered in the differential diagnosis of connective tissue diseases with abnormal liver function tests. Low-dose prednisone may effectively improve both symptoms and laboratory tests.

[Relationship between serum HBV DNA levels and hepatic fibrosis markers in chronic hepatitis B].

OBJECTIVE: To study the relationship between serum HBV DNA levels and hepatic fibrosis markers in chronic hepatitis B. METHODS: One hundred and fifty-seven patients with chronic hepatitis B were included in the study, 49 patients among them were diagnosed as early cirrhosis by liver biopsy. Serum HBV DNA levels were determined using fluorescent quantitative PCR, and serum hepatic fibrosis markers including hyaluronic acid (HA), laminin (LN), amino terminal propeptide of type III precollagen (P III P) and type IV collagen (IV-C) were determined by radioimmunity assay. The relationship between serum HBV DNA levels and hepatic fibrosis markers were analyzed. Serum HBV DNA levels and hepatic fibrosis markers of 49 patients with early cirrhosis were compared with those of 108 non-cirrhotic patients. RESULTS: There was no significant relationship between serum HBV DNA levels and hepatic fibrosis markers in chronic hepatitis B (P>0.05). Patients with early cirrhosis had much higher hepatic fibrosis markers together with lower HBV DNA levels than non-cirrhotic patients (P<0.05). CONCLUSIONS: There were no significant relationship between serum HBV DNA levels and hepatic fibrosis markers in patients with chronic hepatitis B.

[An ultrasonic scoring system for assessing the severity of hepatic fibrosis in patients with chronic hepatitis B].

OBJECTIVE: To discuss the diagnostic value of an ultrasonic assessing system for detecting the severity of hepatic fibrosis in patients with chronic hepatitis B (CHB). METHODS: Ultrasonographic variables were analyzed in 110 CHB patients. An ultrasonic semi-quantitative scoring system using seven ultrasonic morphologic parameters, a Fisher discriminating function and three quantitative ultrasonic parameters was developed. The performance of these methods was also studied and compared. RESULTS: The areas under the curve of the scoring system for different liver fibrosis stages were >or= S2: 0.946, >or= S3: 0.914, and S4: 0.915. The total score was well correlated with the histological stage of fibrosis (r=0.824, P < 0.001). There was a significant difference between the stages of fibrosis. The accuracy of the Fisher discriminating function for identifying three study endpoints was 76.5%, 78.2% and 67.3%. Combining the ultrasonic scoring system and the discriminating function, the specificity was 85%-90% and the accuracy was 77%-84%. CONCLUSION: Our ultrasonic semi-quantitative scoring system is a noninvasive method for quantitating liver fibrosis. If it is used together with a discriminating function, the accuracy of diagnosing liver fibrosis can be significantly increased.

Lamivudine treatment of decompensated hepatitis B virus-related cirrhosis.

BACKGROUND: Patients with decompensated hepatitis B virus (HBV)-related cirrhosis tend to have low or undetectable HBV replication. However, some patients continue to have high levels of HBV replication and effective suppression of HBV replication with antiviral agents may potentially decrease hepatic necroinflammation and improve or stabilize liver function. This review was to understand the efficacy and safety of lamivudine in the treatment of decompensated HBV cirrhosis. DATA SOURCES: An English-language literature search (MEDLINE January 1988-July 2005) was performed, and a total of 52 articles/abstracts relevant to the issue were selected. After review of the selected papers, the meaningful results and conclusions were extracted using scientific criteria. The papers reviewed pertained mainly to the efficacy and safety profiles of lamivudine treatment for decompensated HBV cirrhosis. RESULTS: The ultimate treatment of decompensated HBV cirrhosis is liver transplantation, but lamivudine treatment may lead to rapid suppression of viral replication and improvement of biochemical and clinical parameters, reduced morbidity and hospitalization for complications of liver disease, increased pre-transplant survival as well as reduced need for transplantation. However, viral resistance can develop after prolonged treatment with lamivudine, and breakthrough hepatitis may be fatal in few patients. Adefovir is effective for lamivudine-resistant HBV mutants. CONCLUSIONS: Antiviral therapy with lamivudine for decompensated HBV cirrhosis can be effective. However, some patients may experience a hepatitis flare with the emergence of YMDD mutants resulting in progressive worsening of liver disease, and should be referred for "rescue" therapy with other nucleoside/nucleotide analogues such as adefovir dipivoxil.

[The prognostic value of end-stage liver disease model in liver cirrhosis].

OBJECTIVES: The prognostic ability of the model for end-stage liver disease (MELD) has been validated in many countries, but its abilities remain uncertain in China. Our aim is to evaluate the abilities of MELD in prognosis of liver cirrhosis. METHODS: A cohort of 315 patients with liver cirrhosis were retrospectively studied and followed up at least for one year. MELD score was obtained for each patient according to the modified formula by Kamath P.S.. The area under the receiver operating characteristic (ROC) curve (AUC) was used to compare MELD and Child-Turcotte-Pugh (CTP) score and classification in predicting accuracy. Kaplan-Meier survival analysis was used to compare the mortality in subgroups ranked by the MELD score. RESULTS: The AUC values generated by the ROC curves for the MELD were 0.95, 0.85 and 0.83 respectively in predicting 3, 6 month and 1 year survival, and were all more than 0.80 in predicting longer time survival, whereas the AUC was 0.82, 0.78, 0.74 for CTP score and 0.70, 0.66, 0.61 for CTP classification respectively in predicting 3, 6 month and 1 year survival. The differences of AUCs between the MELD and CTP classification were significant in predicting 6 month and 1, 3 and 4 year survival, but were not significant in predicting other time point survival. The differences of AUCs between the MELD and CTP score were not significant in predicting survival. In the subgroups of patients ranked by MELD score lower than 10, 10 to 20, 20 to 30, and more than 30, the survival rate was significant different (P = 0.000). CONCLUSIONS: MELD is a useful prognosis indicator for the liver cirrhosis. The ability of prognosis by MELD is similar to Child-Turcotte-Pugh classification and score.

Treatment of patients with alcoholic liver disease.

BACKGROUND: The proportion of alcoholic liver disease among all kinds of liver diseases in China is increasing. Recent research has elucidated the mechanisms of alcohol-induced liver injury and offered the prospect of advances in the management of alcoholic liver disease. DATA RESOURCES: Searching MEDLINE (1982-July 2004) for papers on alcoholic liver disease, especially those on the treatment of alcoholic liver disease. RESULTS: Abstinence remains the cornerstone of management of all forms of alcoholic liver disease. Nutritional support therapy is also a basal treatment. Corticosteroids may be benefitial for some severe alcoholic hepatitis. None of other measures including anti-inflammatory agents, antioxidants or colchicine has been shown consistently to improve the course of alcoholic liver damage. Ultimately, liver transplantation remains an option for selected patients with liver failure due to chronic alcoholic liver disease. CONCLUSIONS: Abstinence and nutritional support remain the base management of alcoholic liver disease. Corticosteroid is efficient for some severe alcoholic hepatitis. Anti-inflammatory agents and antioxidants may be of benefit but need further studies. The efficacy of other measures including the use of colchicine and propylthiouracil is controversial. Liver transplantation remains an option for selected patients with liver failure.

[A discussion of standardization for prothrombin time in patients with advanced liver diseases].

OBJECTIVE: To determine which expression mode of prothrombin time (PT) might achieve PT standardization in patients with advanced liver diseases. METHODS: PT was measured with six thromboplastins with different ISI values in 16 severe chronic hepatitis patients, 50 decompensated liver cirrhosis patients and 30 patients on oral anticoagulation therapy. The results were expressed in PT (second), PTA (%), PTR and INR. RESULTS: In chronic hepatitis patients, the means of the six group's PTAs ranged from 24% to 34%, while their upper limits ranged from 47% to 61%. The means of the INRs ranged from 2.55 to 5.13, while their upper limits ranged from 4.65 to 12.77. Through one-way ANOVA of repeated measures, PPTA (0.489) was > PINR (0.120). In patients with liver cirrhosis, the means of the PTA in six groups ranged from 50% to 59%, while their upper limits ranged from 82% to 90%. The means of the INR ranged from 1.40 to 1.80, while their upper limits ranged from 1.97 to 3.69. Through one-way ANOVA of repeated measures, PPTA (0.102) was > PINR (0.01). In patients on oral coagulation therapy, the means of PTA ranged from 26% to 37%, while their upper limits ranged from 39% to 49%. The means of INR ranged from 2.35 to 2.66, while their upper limits ranged from 3.16 to 4.26. Through one-way ANOVA of repeated measures, PPTA (0.01) was less than PINR (0.102). The correlation between the results detected by Neoplastine and by other reagents were analyzed. They correlated well with each other when PTA was used as the expression mode of PT in patients with advanced liver disease. But in patients on oral anticoagulation therapy, when only the INR was used as the expression mode of PT, the correlation was well with each other. CONCLUSION: The use of INR provides inadequate standardization. Only when the PT is expressed in PTA, then it may provide a standardization mode in patients with advanced liver diseases.

[Clinical features of 30 cases of amyloidosis].

OBJECTIVE: Clinical features of 30 cases of amyloidosis, a rare disease in China, were analyzed in order to improve the recognition of the disease here. METHODS: 30 cases of biopsy-proven amyloidosis, admitted to Beijing Friendship Hospital from July 1980 to December 2003 were retrospectively reviewed. RESULTS: 12 of the 30 cases were systemic amyloidosis. Among them 9 were primary amyloidosis, 1 secondary amyloidosis and 2 familial amyloid polyneuropathy. The other 18 cases were localized amyloidosis. Males (17) were more than females (13). In the 12 primary amyloidosis patients, kidney (75.00%), liver (58.33%), peripheral nervous system (58.33%) and heart (50.00%) were most commonly involved. Nonspecific symptoms such as fatigue, weight loss, hepatomegaly, limb numbness, edema and heavy albuminuria were the most common clinical manifestations. Localized amyloidosis involved only one organ, such as skin, alimentary tract and nasopharynx without evidences of a systemic disease. Excision of the localized amyloid deposits was performed in 13 cases. CONCLUSION: Systemic amyloidosis usually involves multiple organs and systems, leading to highly variable clinical manifestations. An increase in the vigilance of the awareness of this disease among clinicians will improve the possibilities for its diagnosis.

Interferon-alfa in the treatment of chronic hepatitis B.

BACKGROUND: Interferon-alfa has been used in the treatment of chronic hepatitis B for more than 20 years and has its own advantages including a definite course of therapy, no production of drug-resistant variants, and sustained efficacy. This review was to understand the role of interferon-alfa therapy in chronic hepatitis B. DATA RESOURCES: An English-language literature search using Medscape and MEDLINE was performed and a total of 48 articles on the treatment of chronic hepatitis with interferon-alfa or pegylated interferon-alfa were selected. RESULTS: Interferon-alfa therapy was associated with a higher HBV DNA inhibition rate and HBeAg loss rate compared with controls, and it may have long-term beneficial effects in terms of HBV clearance, reduction of hepatocellular carcinoma, and prolongation of survival. Pegylated interferon-alfa was more effective than conventional interferon-alfa in the treatment of chronic hepatitis B as well as chronic hepatitis C, and was also associated with greater efficacy than conventional interferon in difficult-to-treat disease. CONCLUSIONS: Interferon-alfa is still regarded as one of the first-line drugs for the treatment of chronic hepatitis B. Pegylated interferon is a more promising therapy than conventional interferon-alfa, especially in patients with refractory chronic hepatitis B.

Clinical evaluation of serum antimitochondrial antibody-negative primary biliary cirrhosis.

BACKGROUND: Primary biliary cirrhosis (PBC) is characterized by frequent presence of antimitochondrial antibodies (AMAs). The sensitivity and specificity of AMA for PBC are both greater than 90%-95%, so the presence of AMA in serum is the major hallmark in PBC. However, it has long been recognized that in 5%-10% of patients the clinical, biochemical and histological features are diagnostic for PBC, but their sera are consistently tested negative for AMA/AMA-M2. This study aimed to evaluate whether the presence of AMA alters the clinical, serological and histological features of the disease. METHODS: Clinical data of 70 patients clinically and/or histologically diagnosed with PBC were reviewed. AMA-negative and AMA-positive patients were compared in terms of clinical, biochemical, immunological and histological features. RESULTS: At presentation, 11 patients were serum AMA/AMA-M2 negative. At the initial visit, AMA-negative and AMA-positive patients were similar in terms of age, sex, clinical manifestations, liver biochemistries and histological findings. The mean level of serum immunoglobulin M (IgM) was significantly lower in AMA-negative PBC patients than in AMA-positive PBC patients (2851+/-1418 mg/L vs 6361+/-4928 mg/L, P=0.033). Serum antinuclear antibodies (ANA) and/or smooth muscle antibodies (SMA) were more frequently positive in the AMA-negative PBC patients than in the AMA-positive patients (81.8% vs 40.7%, P=0.031). CONCLUSION: AMA-negative PBC patients are characterized by relatively lower levels of serum IgM and a higher prevalence of serum ANA/SMA and are not associated with substantial differences in the clinical biochemical and histological spectrum of the disease.