Clinical features and long-term prognosis of primary biliary cholangitis in patients with past hepatitis B virus infection / 中华肝脏病杂志

Objective: To investigate the clinical features and long-term prognosis of primary biliary cholangitis (PBC) in patients with past hepatitis B virus (HBV) infection. Methods: 353 cases with PBC who visited the Liver Disease Center of Beijing Friendship Hospital Affiliated to Capital Medical University between January 2000 and January 2018 were retrospectively analyzed and were divided into the past HBV infection group (156 cases) and the no HBV infection group (197 cases). The two groups' baseline clinical features were compared. Ursodeoxycholic acid response rate after one year, GLOBE score, UK-PBC score, and long-term liver transplantation-free survival rate were compared through outpatient and telephone follow-up. Results: PBC with past HBV infection had a significantly reduced female proportion compared to the no HBV infection group (91.9% vs. 79.5%, P = 0.001). However, there were no statistically significant differences in age, biochemical indices, immunological indicators, platelet count, cirrhosis proportion, and others. Ursodeoxycholic acid biochemical response rate was reduced in patients with past HBV infection at the end of one year of treatment, but the difference was not statistically significant (65.8% vs. 78.2%, P = 0.068). In addition, there were no statistically significant differences between the GLOBE score (0.57 vs. 0.59, P = 0.26) and UK-PBC 5-year (2.87% vs. 2.87%, P = 0.38), 10-year (9.29% vs. 8.2%, P = 0.39) and 15-year liver transplantation rates (16.6% vs. 14.73%, P = 0.39). Lastly, the overall 5-year liver transplantation-free survival rate had no statistically significant difference between the two groups of patients (86.4% vs. 87.5%, P = 0.796). Conclusion: Primary biliary cholangitis had no discernible effect in terms of age at onset, biochemical indices, immunological indicators, cirrhosis proportion, ursodeoxycholic acid response rate after one year, GLOBE score, UK-PBC score, or overall liver transplantation-free survival rate in patients with past hepatitis B virus infections.

Liver manifestation of circulatory disorders / 中华肝脏病杂志

The liver is abundant in blood supply and receives 25% of the cardiac output via the hepatic artery and portal vein. Circulatory disorders may cause hepatic injury, resulting in congestive hepatopathy(CH) and ischemic hepatitis(IH). Hepatic congestion arising from increased hepatic venous pressure and decreased cardiac output is the common pathophysiological basis of both CH and IH. In addition, extensive arteriovenous shunts affect portal pressure and cardiac function, leading to alterations of hepatic blood supply. The current review summarizes the pathophysiology, clinical manifestations and therapeutic interventions of the above diseases, in order to provide reference for clinical practice.

Connective tissue diseases and the liver injury / 中华肝脏病杂志

Connective tissue disease (CTD) are closely related to liver abnormality. CTD can affect the liver causing various degrees of liver injury, coexist with other liver diseases, especially autoimmune liver disease (ALD). Medications for CTD can also lead to liver injury or reactivate the hepatitis B virus. CTD patients can also be positive for ALD-related autoantibodies without corresponding manifestation; and vis versa. The diagnosis and differential diagnosis should be made on integrating clinical presentation, laboratory, imaging, and histological studies, not solely relying on autoantibody positivity.

Liver involvement in endocrine diseases / 中华肝脏病杂志

As a secondary endocrine organ, the liver is closely related to the endocrine system. Liver involvement is not uncommon in endocrine diseases, such as hyper/hypothyroidism, diabetes, dysfunction of adrenal and gonadal. It can be manifested in a variety of forms, including hepatocyte injury (elevated transaminase), bile duct injury (cholestasis), hepatocyte steatosis, vascular injury and liver tumor. Direct and indirect liver injury caused by abnormal hormone levels and side effects of drugs for the treatment of endocrine diseases are common pathogenesis. In addition, endocrine diseases can be concomitant with liver diseases, such as autoimmune thyroiditis and autoimmune hepatitis. Systemic diseases can also involve the endocrine system and liver at the same time, such as systemic lupus erythematosus and IgG4 related diseases. For patients with unexplained liver injury, endocrine system diseases should be considered as the differential diagnosis.

Clinical analysis of intrahepatic cholestasis of pregnancy / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To generate a comprehensive clinical profile of intrahepatic cholestasis of pregnancy (ICP) by systematically reviewing ICP cases managed in our hospital.</p><p><b>METHODS</b>The recorded clinical data, including diagnosis, complications, management, and maternal and infant outcomes, of nine ICP cases were collected retrospectively and reviewed systematically.</p><p><b>RESULTS</b>Seven of the nine total ICP patients presented with pruritus. All nine of the ICP patients showed bile acid level beyond the normal range. ICP complications included gestational hypertension (n = 3), diabetes mellitus (DM, n = 1) and impaired glucose tolerance (IGT, n = 1), and pre-eclampsia (n = 1). The infant of one patient with severe ICP showed meconium-stained liquor. All nine of the ICP patients underwent surgical delivery, of which three were delivered preterm (between the 35th and 36th week of gestation). All mothers' total bile acids declined to normal levels after delivery, and all infants survived without complication.</p><p><b>CONCLUSION</b>ICP does not increase the puerpera mortality rate and does not represent a poor prognosis for infants. Bile acid levels in the ICP patients, however, may be related to the extent of premature delivery time. While the standard drug treatment of ursodeoxycholic acid is suitable for most ICP cases, those with insufficient gestational age may benefit from adjuvant corticosteroid therapy to promote fetal lung maturation prior to preterm delivery. Severe ICP cases should be managed by inducing artificial labor or performing Caesarean section.</p>

The clinical profiles of primary biliary cirrhosis with a suboptimal biochemical response to ursodeoxycholic acid / 中华肝脏病杂志

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.

Clinical and pathological features of 27 cases of primary sclerosing cholangitis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To elucidate clinical and pathological features of primary sclerosing cholangitis (PSC) in order to improve clinician's awareness of this rare disease.</p><p><b>METHODS</b>We retrospectively analyzed clinical data and follow-up information of 27 PSC patients who were admitted to Beijing Friendship Hospital from January 1990 to November 2009. The patients were classified into classic PSC and small-duct PSC according to biochemistry and imaging results. After 3 to 6 months of therapy, those patients with serum ALT < or = 1.5, TBil < or = 2 and ALP < or = 2.5 ULN were determined as good responders. The treatment results between the two groups were compared.</p><p><b>RESULTS</b>9 out of 27 cases of PSC were small duct PSC and 18 cases were large bile duct or classic PSC. Male patients (7) were less than females (20) and the average age was 47.6 years. Main clinical symptoms included jaundice (85.2%), pruritis (48.1%),fatigue (68.4 %), abdominal pain (40.7%) and fever (14.8%), main physical sign included hepatomegaly (44.4%), splenomegaly (48.1 %) and ascites (14.8%). Laboratory features included elevated IgG (81.8%), positive ANA (69.6%) and pANCA (52.9%). 22% of these PSC patients had ulcerative colitis or Sjogren's syndrome. A small percentage of patients were responsive to standard therapy, of which small duct PSC had a better response than classic PSC (66.7 % vs 33.3%, P = 0.041).</p><p><b>CONCLUSIONS</b>Ulcerative colitis (22.2%) is not as common as reported by western countries. Small duct PSC has a better treatment response. Searching of effective treatment regimen for large bile duct PSC is warranted in future studies.</p>

An ultrasonic scoring system for assessing the severity of hepatic fibrosis in patients with chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To discuss the diagnostic value of an ultrasonic assessing system for detecting the severity of hepatic fibrosis in patients with chronic hepatitis B (CHB).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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%.</p><p><b>CONCLUSION</b>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.</p>

An analysis of clinical features in HBeAg-negative and HBeAg-positive chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To analyze the frequency and the clinical and virological features of HBeAg-negative and HBeAg-positive chronic hepatitis B.</p><p><b>METHODS</b>Four hundred and seventeen chronic hepatitis B patients, 286 males and 131 females seen in our center were studied. Liver biopsies were taken from 83 patients.</p><p><b>RESULTS</b>The cases with HBeAg-negative chronic hepatitis B were 241 (57.8%), with an average age of 43.7+/-10.8 and a history of 16.8+/-8.5 years. HBeAg-positive chronic hepatitis B cases were 176 (42.2%), with an average age of 36.95+/-11 and a history of 12.3+/-8.0 years. HBeAg-negative patients were significantly older (P < 0.01) in age and had a longer disease history. ALT levels and the percentage of HBV DNA were higher than 10(5) copies/ml in HBeAg-negative patients and were significantly lower than those in the HBeAg-positive patients [(37.66+/-32.93) U/L vs. (82.09+/-107.57) U/L, 38.2% vs. 94.3%, P < 0.01]. Liver biopsies from 47 HBeAg-negative patients showed that the number of cases with inflammation scores of G1, G2, G3 and G4 were 5, 27, 14, 1 and the number of cases with fibrosis scores of S1, S2, S3 and S4 were 10, 12, 5, 20, respectively. In the 36 HBeAg-negative patients the respective number of cases with inflammation scores of G1, G2, G3 and G4 were 5, 14, 15, 2, and with fibrosis scores of S1, S2, S3, S4 were 8, 12, 6, 10. Although histopathological inflammation and fibrosis scores had no statistical difference between HBeAg-negative and positive patients (P > 0.05), 53.2% patients of HBeAg-negative group and 44.5% patients of HBeAg-positive group had a fibrosis score of >or= S3.</p><p><b>CONCLUSION</b>Despite lower serum ALT and HBV DNA, HBeAg-negative chronic hepatitis B still has a significant disease progression. This observation may help to develop better clinical management in HBeAg-negative chronic hepatitis B patients.</p>

Malignant tendency of basophilic liver cells in experimental rat hepatocarcinogenesis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the malignant tendency of liver basophilic cells in rats by examining the liver dynamic pathological changes during the hepatocarcinogenesis induced by diethylnitrosamine (DEN).</p><p><b>METHODS</b>One hundred forty male Sprague-Dawley rats, about 200 g each, were randomly divided into a normal group and a model group. The model group rats were administered 1% DEN intragastrically once a week for 14 weeks. The normal control group rats were given saline instead of DEN. Seven to ten rats of the model group were sacrificed at 2, 3, 5, 8, 10, 12, 14, 18 weeks. The remaining rats were followed to the end of the experiment at 26 weeks. Histopathological changes of the livers were analyzed, and the localization of GST-P and PCNA in the livers were detected in situ by immunohistochemistry.</p><p><b>RESULTS</b>According to the characteristics of the lesions in the model group, histological liver change patterns were categorized into three phases: (1) liver injury phase (2 to 5 weeks) with centrilobular necrosis, a small amount of collagen deposition in the necrotic regions with fibrous septa development and cell proliferation; (2) the cirrhosis phase (8 to 12 weeks) with significant hepatocellular regeneration and collagen deposition. As the regenerative nodules and fibrous septa formed, cirrhosis with uniform sized nodules developed in all the rats at 12 weeks. In the regenerative nodules, significant hepatocellular metamorphosis was seen; (3) In the carcinomatous transformation and nodular remodeling phase (after 14 weeks), two types of cancer, namely hepatocellular carcinoma and cholangiocarcinoma were found. Incidence of the cancer was 62.5% at 18 weeks. Basophilic cell lesions appeared beginning at 10 weeks. Pale bodies were seen in some basophilic cells. Small cell changes appeared starting at 12 weeks. Some of these cells containing droplets like lipid vacuoles, invaded into the surrounding liver tissues. Both basophilic cell lesions and small cell changes were all positive for proliferating cell nuclear antigen (PCNA).</p><p><b>CONCLUSION</b>Development of foci of basophilic small cells, with cells containing lipid vacuoles and pale bodies, and invading into the surrounding liver tissues are the changes highly suggestive of an early hepatocellular carcinoma transformation.</p>

Noninvasive assessment of liver fibrosis in chronic hepatitis B using a predictive model / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To develop a diagnostic model comprising clinical and serum markers for assessing HBV-related liver fibrosis.</p><p><b>METHODS</b>270 chronic hepatitis B patients were randomly allocated to either an estimation group (195 cases) or a validation group (75 cases). Liver biopsies were done and staging of fibrosis was assessed. Twenty-six common clinical and serum markers were analyzed initially in the estimation group to derive a predictive model to discriminate the stages of fibrosis. The model created was then assessed with ROC analysis. It was also applied to the validation group to test its accuracy.</p><p><b>RESULTS</b>Among 13 variables associated with liver fibrosis selected by univariate analysis, age, gamma glutamyltranspeptidase (GGT), hyaluronic acid (HA), and platelet count (PLT) were identified by multivariate logistic regression analysis as independent factors of fibrosis. A fibrosis index constructed from the above four markers was established. In ROC analysis, the AUC was 0.889 for the estimation group and 0.850 for the validation group for discriminating > or =S3 from < or=S2. Using the optimal cutoff score 3.0, the sensitivity of the index was 90.2%, the specificity 76.1%, and the accuracy was 82%. There was a positive linear relationship between the index scores and the fibrosis stages (r = 0.731, P<0.001). The AUC for identifying > or=S2 was 0.873 with sensitivity/specificity of 79%/82%, cutoff score 2.2; The AUC for identifying S4 was 0.872 with sensitivity/specificity of 83%/75%, cutoff score 5.4. There were no significant differences in diagnostic efficacy in the model between the estimation and the validation group (P>0.05).</p><p><b>CONCLUSION</b>A model for assessment of liver fibrosis was established with easily accessible markers. It appears to be sensitive, accurate and reproducible, suggesting it could be used to assist or replace liver biopsy to detect dynamic changes of HBV-related liver fibrosis.</p>

Clinical features of 30 cases of amyloidosis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>Clinical features of 30 cases of amyloidosis, a rare disease in China, were analyzed in order to improve the recognition of the disease here.</p><p><b>METHODS</b>30 cases of biopsy-proven amyloidosis, admitted to Beijing Friendship Hospital from July 1980 to December 2003 were retrospectively reviewed.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

A discussion of standardization for prothrombin time in patients with advanced liver diseases / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To determine which expression mode of prothrombin time (PT) might achieve PT standardization in patients with advanced liver diseases.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

The contrast study of Pre-S1 protein, HBV-DNA and HBeAg in diagnosing viral replication in patients with chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To determine the role of Pre-S1 protein in diagnosing viral replication in patients with chronic hepatitis B.</p><p><b>METHODS</b>104 consecutive patients with chronic hepatitis B were included in the study, liver biopsy were performed in all patients. Serial serum samples were studied with the quantitative determination of HBV-DNA by a quantitative PCR assay, determination of Pre-S1 protein by ELISA.</p><p><b>RESULTS</b>The positive rates of HBV-DNA and Pre-S1 protein in patients with HBsAg HBeAg anti-HBc (+) both were 96.5%. The positive rates of HBV-DNA and Pre-S1 protein in patients with HBsAg anti-HBe anti-HBc (+) were 81.5%, 72.3%, respectively. The positive rates of HBV-DNA and Pre-S1 protein in patients with HBsAg anti-HBc (+) were 87.5%, 75.0%, respectively. It represented some patients with HBeAg (-) anti-HBe (+/-) still had viral replication. HBV-DNA>10(3) copy/ml as positive criteria for diagnosing viral replication, the positive rate of HBeAg, Pre-S1 were 31.5% (28/89), 80.9% (72/89) in patients with HBV-DNA>10(3) copy/ml, respectively. The concordance rates of HBeAg, Pre-S1 with HBV-DNA were 40.0% (42/104), 82.0% (85/104), respectively.</p><p><b>CONCLUSION</b>It showed that Pre-S1 was more sensitive than HBeAg in diagnosing viral replication in patients with chronic hepatitis B.</p>