血清α-L-岩藻糖苷酶活性在非癌性肝脏损害中的临床意义

目的:观察α-L-岩藻糖苷酶(AFU)活性在慢性肝炎、肝硬化、重型肝炎患者中的临床意义。方法:血清AFU活力测定采用上海海军医学研究所生物技术中心提供的试剂盒。选择临床资料齐全的265例住院病历,按照2000年西安会议修订的诊断标准,慢性肝炎147例,肝硬化72例,重型肝炎46例。结果:在慢性肝炎、肝硬化、重型肝炎三组AFU的活力变化有所不同,肝硬化与重型肝组病情变化和病死率与AFU活性变化关系呈现明显的相关性,AFU升高显著者病情重、预后差。结论:本研究表明在非癌性肝脏损害程度与AFU酶活性有密切关系,AFU酶活性的检测可能成为慢性肝炎、肝硬化。

Masson染色在辅助诊断肝纤维化中应用

目的探讨Masson染色在肝纤维化诊断中的辅助作用。方法 89例慢性肝炎、肝硬化患者的石蜡包埋肝组织标本,连续切片并行HE染色及Masson染色,染色完成后行单盲阅片,根据染色结果分别对HE染色及Masson染色的标本进行G-S分级分期,并作出初步诊断。统计HE染色和Masson染色的染色结果;比较HE染色和Masson染色对慢性肝炎、肝硬化程度划分情况;比较HE染色和Masson染色对慢性肝炎、肝硬化程度划分与临床分度的吻合程度。结果标本染色完成后, HE染色标本胞浆均被染成红色,胞核均被染成紫色,胶原纤维与肝细胞团分界不清楚;Masson染色标本胶原纤维被染成蓝色,包绕红色的肝细胞团,颜色对比明显,分界清楚。HE染色和Masson染色对慢性肝炎、肝硬化程度划分情况比较,差异有统计学意义(P<0.05)。HE染色结果与临床诊断相符78例,不吻合11例;Masson染色结果与临床诊断相符86例,其中3例临床诊断为慢性肝炎-重度,经Masson染色确诊为早期肝硬化;Masson染色对慢性肝炎、肝硬化的吻合程度高于HE染色,差异有统计学意义(P<0.05)。结论 Masson染色能更清楚地显示肝纤维化病变中的胶原纤维,提高早期肝硬化的检出率,具有重要的临床应用价值。

Future prospectives for the management of chronic hepatitis B

Chronic hepatitis B virus infection affects about 400 million people around the globe and causes approximately a million deaths a year. Since the discovery of interferon-α as a therapeutic option the treatment of hepatitis B has evolved fast and management has become increasingly complicated. The amount of viral replication reflected in the viral load （HBV-DNA） plays an important role in the development of cirrhosis and hepatocellular carcinoma. The current treatment modalities for chronic hepatitis B are immunomodulatory （interferons） and antiviral suppressants （nucleoside and nucleotide analogues） all with their own advantages and limitations. An overview of the treatment efficacy for both immunomodulatory as antiviral compounds is provided in order to provide the clinician insight into the factors influencing treatment outcome. With nucleoside or nucleotide analogues suppression of viral replication by 5-7 log10 is feasible, but not all patients respond to therapy. Known factors influencing treatment outcome are viral load, ALT levels and compliance. Many other factors which might influence treatment are scarcely investigated. Identifying the factors associated with response might result in stopping rules, so treatment could be adapted in an early stage to provide adequate treatment and avoid the development of resistance. The efficacy of compounds for the treatment of mutant virus and the cross-resistance is largely unknown. However, genotypic and phenotypic testing as well as small clinical trials provided some data on efficacy in this population. Discontinuation of nucleoside or nucleotide analogues frequently results in viral relapse; however, some patients have a sustained response. Data on the risk factors for relapse are necessary in order to determine when treatment can be discontinued safely. In conclusion： chronic hepatitis B has become a treatable disease; however, much research is needed to tailor therapy to an individual patient, to predict the sustainability of response and determine the best treatment for those failing treatment.

Clinical features and management of autoimmune hepatitis

Autoimmune hepatitis(AIH) is a chronic hepatitis of unknown etiology which can progress to cirrhosis.Its clinical manifestations are highly variable and some-times follow a fluctuating course.Diagnosis is based on characteristic histologic,clinical,biochemical and sero-logical findings.Anti-inflammatory/immunosuppressive treatment frequently induces remission but long-term maintenance therapy is often required.Liver transplan-tation is generally successful in patients with decompen-sated cirrhosis unresponsive to or intolerant of medical therapy.

Assessment of health-related quality of life in Chinese patients with minimal hepatic encephalopathy

AIM:To evaluate the health-related quality of life (HRQOL) based on the Chinese version of SF-36 and Chronic Liver Disease Questionnaire (CLDQ) in subjects with chronic hepatitis B,liver cirrhosis,including patients with minimal hepatic encephalopathy (MHE). METHODS:The SF-36 and CLDQ were administered to 160 healthy volunteers,20 subjects with chronic hepatitis B and 106 patients with cirrhosis (33 cases exhibited MHE). HRQOL scores were compared among the different study groups. The SF-36 includes eight health concepts:physical functioning,role-physical,body pain,general health,vitality,social functioning,role-emotion,and mental health. Six domains of CLDQ were assessed:abdominal symptoms,fatigue,systemic symptoms,activity,emotional function and worry. RESULTS:Compared with healthy controls (96.9 ± 4.5,86.6 ± 18.4,90.1 ± 12.5,89.0 ± 5.7,87.5 ± 4.3,95.8 ± 7.1,88.5 ± 15.9,88.7 ± 5.2 in SF-36 and 6.7 ± 0.5,6.1 ± 0.6,6.3 ± 0.6,6.5 ± 0.5,6.3 ± 0.5,6.8 ± 0.4 in CLDQ),patients with chronic hepatitis B (86.3 ± 11.0,68.8 ± 21.3,78.9 ± 14.4,60.8 ± 10.5,70.8 ± 8.6,76.1 ± 12.6,50.0 ± 22.9,72.2 ± 10.6 and 5.5 ± 1.0,4.5 ± 1.0,5.2 ± 1.1,5.3 ± 0.9,4.8 ± 0.9,4.9 ± 1.0) and cirrhosis (52.8 ± 17.4,32.8 ± 27.9,61.6 ± 18.9,30.2 ± 18.3,47.9 ± 20.1,54.0 ± 19.2,28.9 ± 26.1,51.1 ± 17.8 and 4.7 ± 1.2,3.9 ± 1.2,4.7 ± 1.2,4.7 ± 1.3,4.7 ± 1.0,4.4 ± 1.1) had lower HRQOL on all scales of the SF-36 and CLDQ (P < 0.01 for all). Increasing severity of liver cirrhosis (based on the Child-Pugh score/presence or absence of MHE) was associated with a decrease in most components of SF-36 and CLDQ,especially SF-36.CONCLUSION:The Chinese version of SF-36 along with CLDQ is a valid and reliable method for testing MHE in patients with liver cirrhosis. Cirrhosis and MHE are associated with decreased HRQOL.

Prognostic value of ^(13)C-phenylalanine breath test on predicting survival in patients with chronic liver failure

AIM: To evaluate the prognostic value of percentage of 13C-phenylalanine oxidation (13C-PheOx) obtained by 13C-phenylalanine breath test (13C-PheBT) on the survival of patients with chronic liver failure. METHODS: The hepatic function was determined by standard liver blood tests and the percentage of 13C-PheOx in 118 chronic liver failure patients. The follow-up period was of 64 mo. Survival analysis was performed by the Kaplan-Meier method and variables that were significant (P < 0.10) in univariate analysis and subsequently introduced in a multivariate analysis according to the hazard model proposed by Cox. RESULTS: Forty-one patients died due to progressive liver failure during the follow-up period. The probability of survival at 12, 24, 36, 48 and 64 mo was 0.88, 0.78, 0.66, 0.57 and 0.19, respectively. Multivariate analysis demonstrated that Child-Pugh classes, age, creatinine and the percentage of 13C-PheOx (HR 0.338, 95% CI: 0.150-0.762, P = 0.009) were independent predictors of survival. When Child-Pugh classes were replaced by all the parameters of the score, only albumin, bilirubin, creatinine, age and the percentage of 13C-PheOx (HR 0.449, 95% CI: 0.206-0.979, P = 0.034) were found to be independent predictors of survival.CONCLUSION: Percentage of 13C-PheOx obtained by 13C-PheBT is a strong predictor of survival in patients with chronic liver disease.

Reduced bone mineral density and altered bone turnover markers in patients with non-cirrhotic chronic hepatitis B or C infection

AIM: Previous studies suggest that loss of bone mineral density (BMD) frequently occurs in patients with chronic viral liver disease, presenting with histologically proven liver cirrhosis. However, little is known about the occurrence of bone disease in non-cirrhotic patients with chronic hepatitis B or C. Therefore, it was the aim of this study to evaluate this particular population for BMD and bone turnover markers. METHODS: Biochemical markers of bone turnover and BMD were measured in 43 consecutive patients with HCV (n = 30) or HBV (n = 13) infection without histological evidence for liver cirrhosis. Mean age was 49 years (range 26-77 years). BMD was measured by dual X-ray absorptiometry in the femoral neck (FN) and the lumbar spine (LS) region. In addition, bone metabolism markers were measured. RESULTS: BMD was lowered in 25 (58%) of the patients with chronic hepatitis B or C (FN; 0.76 (0.53-0.99); LS: 0.96 (0.62-1.23) g/cm2). Eight (32%) osteopenic patients were diagnosed with osteoporosis. Bone-specific alkaline phosphatase (P= 0.005) and intact parathyroid hormone (iPTH) (P = 0.001) were significantly elevated in the more advanced stages of fibrosis. Mean T-score value was lower in patients with chronic hepatitis C as compared to patients suffering from chronic hepatitis B; however, the difference was not statistically significant (P= 0.09). CONCLUSION: There was a significantly reduced BMD in non-cirrhotic patients with chronic hepatitis B or C infection. Alterations of bone metabolism already occurred in advanced liver fibrosis without cirrhosis. According to our results, these secondary effects of chronic viral hepatitis should be further investigated.

Prevalence of metabolic syndrome, obesity and diabetes type 2 in cryptogenic cirrhosis

AIM: To evaluate the prevalence of metabolic syndrome (MS), obesity and type 2 diabetes mellitus (T2DM) in a group of Mexican Mestizo patients with cryptogenic cirrhosis (CC) and to compare this group with patients with cirrhosis secondary to other causes (disease controls). METHODS: Patients with CC, diagnosed between January, 1990 and April, 2005, were included in a retrospective study. Patients with cirrhosis caused by chronic hepatitis C, alcohol abuse or autoimmune hepatitis (AIH) served as disease controls. RESULTS: A total of 134 patients with CC were analyzed. Disease controls consisted of 81 patients with chronic hepatitis C, 33 with alcohol abuse and 20 with AIH. The median age of patients with CC was 57 years (range, 16-87); 83 (61.9%) patients were female; 53 (39.6%) were Child A, 65 (48.5%) Child B, and 16 (11.9%) were Child C cirrhosis. The prevalence of MS (29.1% vs 6%; P < 0.001), obesity (16.4% vs 8.2%; P = 0.04) and T2DM (40% vs 22.4%; P = 0.013) was higher in CC patients than in disease controls. There were no differences in sex, age or liver function tests between the two groups. CONCLUSION: The prevalence of MS, obesityand T2DM were higher in patients with CC than in patients with cirrhosis secondary to others causes. Our findings support the hypothesis that non-alcoholic steatohepatitis (NASH) plays an under-recognized role in CC.

Is liver biopsy mandatory in children with chronic hepatitis C?

Liver biopsy is considered the most accurate means to estimate the necroinflammatory activity and the extent of fibrosis. However, histology evaluation is an invasive procedure associated with risk to the patient, risk of sampling error and diagnostic inconsistencies due to inter- and intra-observer error. On the basis of histological studies performed so far, chronic hepatitis C in children appears morphologically benign in the majority of cases. At the Pediatric Liver Unit of our university, a total of 67 children with chronic hepatitis C underwent liver biopsy. Liver biopsy was repeated 5.5 years after the initial histological evaluation in 21 children. On a total number of 88 liver biopsies, micronodular cirrhosis was detected only in one genotype 1b-infected obese child. Since liver histology investigation of a child with chronic hepatitis C has few chances to highlight severe lesions, we question how liver biopsy helps in the management of children with chronic hepatitis C.

Is laparoscopy an advantage in the diagnosis of cirrhosis in chronic hepatitis C virus infection?

AIM:To evaluate the potential of laparoscopy in the diagnosis of cirrhosis and outcome of interferon treatment in HCV-infected patients. METHODS:In this retrospective study,diagnostic laparoscopy with laparoscopic liver biopsy was performed in 72 consecutive patients with chronic HCV infection.The presence or absence of drrhosis was analyzed macroscopically by laparoscopy and microscopically by liver biopsy specimens.Clinical and laboratory data and outcome of interferon-alfa treatment were compared between cirrhotic and noncirrhotic patients. RESULTS:Laparoscopically,cirrhosis was seen in 29.2 % (21/72)and non-cirrhosis in 70.8 %(51/72)of patients. Cirrhotic patients were significantly older with a significant longer duration of HCV infection than noncirrhotic patients. Laboratory parameters(AST,y-GT,y-globulin fraction)were measured significantly higher as well as significantly lower (prothrombin index,platelet count)in cirrhotic patients than in non-cirrhotic patients.Histologically,cirrhosis was confirmed in 11.1%(8/72)and non cirrhosis in 88.9 %(64/72).Patients with macroscopically confirmed cirrhosis(n=21)showed histologically cirrhosis in 38.2 %(8/21)and histologically non- cirrhosis in 61.9 %(13/21).In contrast,patients with macroscopically non-cirrhosis(n=51)showed histologically non cirrhosis in all cases(51/51).Thirty-nine of 72 patients were treated with interferon-alfa,resulting in 35.9 %(14/39) patients with sustained response and 64.1%(25/39)with non response.Non-responders showed significantly more macroscopically cirrhosis than sustained responders.In contrast,there were no significant histological differences between non-responders and sustained responders. CONCLUSION:Diagnostic laparoscopy is more accurate than liver biopsy in recognizing cirrhosis in patients with chronic HCV infection.Liver biopsy is the best way to assess inflammatory grade and fibrotic stage.The invasive marker for staging,prognosis and management,and treatment outcome of chronic HCV-infected patients need further research and dinical thals.Laparoscopy should be performed for recognition of drrhosis if this parameter is found to be of prognostic and therapeutic relevance in patients with chronic HCV infection.

Clinical study of warm needling moxibustion combined with entecavir in the treatment of compensated cirrhosis due to chronic hepatitis B

Objective:To investigate the efficacy and possible mechanism of action of warm needling moxibustion combined with entecavir in the treatment of compensated cirrhosis due to chronic hepatitis B(CHB).Methods:Ninety patients were randomly divided into a control group and an observation group,with 45 patients in each group.The control group was given oral entecavir,and the observation group was given additional warm needling moxibustion.The serum alanine transaminase(ALT),aspartate transaminase(AST),albumin(ALB)levels,portal vein internal diameter,splenic vein internal diameter,spleen thickness,and liver hardness were compared before and after treatment.The serum hyaluronic acid(HA),laminin(LN),procollagen typeⅢ(PCⅢ),typeⅣcollagen(Ⅳ-C),interleukin(IL)-21,and platelet-derived growth factor(PDGF)levels were also measured.Results:After treatment,the serum ALT and AST levels decreased(P<0.05),and the serum ALB levels increased(P<0.05)in both groups.The serum ALT and AST levels were lower in the observation group than in the control group(P<0.05),and the ALB level was higher in the observation group(P<0.05).The portal vein internal diameter,splenic vein internal diameter,spleen thickness,and liver hardness values were reduced in both groups after treatment(P<0.05),and were lower in the observation group than in the control group(P<0.05).The serum HA,LN,PCⅢ,andⅣ-C levels were reduced in both groups(P<0.05),and were lower in the observation group than in the control group(P<0.05).In the control group,the serum IL-21 level decreased(P<0.05),but the serum PDGF level did not change significantly(P>0.05);in the observation group,the serum IL-21 and PDGF levels decreased significantly(P<0.05)and were lower than those in the control group(P<0.05).Conclusion:Warm needling moxibustion combined with entecavir treatment can improve liver function,reduce the inner diameters of the portal vein and splenic vein,spleen thickness,and liver hardness,and improve liver fibrosis indicators in patients with CHB cirrhosis,which may be related to the reduction of serum IL-21 and PDGF levels.