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.

Hepatic manifestations of hematological diseases / 中华肝脏病杂志

Liver involvement is often observed in hematological disorders, resulting in liver abnormality, including unconjugated hyperbilirubinemia, monoclonal hyperglobulinemia, portal vein, or hepatic vein thrombosis or portal hypertension, hepatosplenomegaly, or iron accumulation in the liver. Here we summarize the major hematological diseases that often affect the liver: hemolytic anemia, defect in coagulation or anti-coagulation factors, myeloproliferative neoplasm, hemophagocytic lymphohistiocytosis, multiple myeloma, leukemia, and lymphoma. We hope this review will help clinicians diagnose and manage the patients with liver involvement by hematological disorders.

Paying attention to other systemic diseases of hepatic manifestations: a return to common sense in clinical practice / 中华肝脏病杂志

Liver have complex functions with a high workload. Various liver diseases are the result of the interaction of diverse genetic and environmental factors. Moreover, other systemic diseases may also affect liver, producing corresponding manifestations, such as abnormal liver function tests, portal vein or hepatic vein thrombosis, portal hypertension, hepatosplenomegaly and liver space-occupying lesions. Therefore, it is extremely important for hepatologists to have an in-depth understanding of other systemic diseases of hepatic manifestations, especially hematologic, connective tissue, endocrine, and circulatory, in order to improve the level of clinical diagnosis and treatment.

Truth-seeking and innovation for the academic excellence / 中华肝脏病杂志

The Chinese Journal of Hepatology has a 2020 core impact factor of 1.807, which position it first among the periodicals of gastroenterology. The China Association for Science and Technology classified it as T1 grade and included in the catalogue of high-level scientific and technological periodicals. Since 2021, it has received the special publishing fund of the Chongqing Municipal Bureau of Press and Publications, the High-quality Scientific and Technological Periodicals Funding Project of Chongqing Association for Science and Technology, and the Industry-university-research Cooperation and Collaborative Education Project of the Ministry of Education of the People's Republic of China and won many awards such as "Sichuan-Chongqing First-class Scientific and Technological Periodical" and "Chongqing High-quality Scientific and Technological Periodical", thereby ensuring the development of both qualitative and quantitative effects. Therefore, in 2022, we will work on attracting high-impact research reports, disseminate the academic results timely, efficiently and accurately, highlight the role of digital communication, and pave the way for the establishment of it as a first-class academic journal.

First line nucleos(t)ide analog monotherapy is more cost-effective than combination strategies in hepatitis B e antigen-positive chronic hepatitis B patients in China / 中华医学杂志(英文版)

BACKGROUND@#Nucleos(t)ide analog (NA) in combination with peginterferon (PegIFN) therapy in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) shows better effectiveness than NA monotherapy in hepatitis B surface antigen loss, termed "functional cure," based on previous published studies. However, it is not known which strategy is more cost-effective on functional cure. The aim of this study was to analyze the cost-effectiveness of first-line monotherapies and combination strategies in HBeAg-positive CHB patients in China from a social perspective.@*METHODS@#A Markov model was developed with functional cure and other five states including CHB, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and death to assess the cost-effectiveness of seven representative treatment strategies. Entecavir (ETV) monotherapy and tenofovir disoproxil fumarate (TDF) monotherapy served as comparators, respectively.@*RESULTS@#In the two base-case analysis, compared with ETV, ETV generated the highest costs with $44,210 and the highest quality-adjusted life-years (QALYs) with 16.78 years. Compared with TDF, treating CHB patients with ETV and NA - PegIFN strategies increased costs by $7639 and $6129, respectively, gaining incremental QALYs by 2.20 years and 1.66 years, respectively. The incremental cost-effectiveness ratios were $3472/QALY and $3692/QALY, respectively, which were less than one-time gross domestic product per capita. One-way sensitivity analysis and probabilistic sensitivity analyses showed the robustness of the results.@*CONCLUSION@#Among seven treatment strategies, first-line NA monotherapy may be more cost-effective than combination strategies in HBeAg-positive CHB patients in China.

First line nucleos(t)ide analog monotherapy is more cost-effective than combination strategies in hepatitis B e antigen-positive chronic hepatitis B patients in China / 中华医学杂志(英文版)

Background@#Nucleos(t)ide analog (NA) in combination with peginterferon (PegIFN) therapy in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) shows better effectiveness than NA monotherapy in hepatitis B surface antigen loss, termed "functional cure," based on previous published studies. However, it is not known which strategy is more cost-effective on functional cure. The aim of this study was to analyze the cost-effectiveness of first-line monotherapies and combination strategies in HBeAg-positive CHB patients in China from a social perspective.@*Methods@#A Markov model was developed with functional cure and other five states including CHB, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and death to assess the cost-effectiveness of seven representative treatment strategies. Entecavir (ETV) monotherapy and tenofovir disoproxil fumarate (TDF) monotherapy served as comparators, respectively.@*Results@#In the two base-case analysis, compared with ETV, ETV generated the highest costs with $44,210 and the highest quality-adjusted life-years (QALYs) with 16.78 years. Compared with TDF, treating CHB patients with ETV and NA - PegIFN strategies increased costs by $7639 and $6129, respectively, gaining incremental QALYs by 2.20 years and 1.66 years, respectively. The incremental cost-effectiveness ratios were $3472/QALY and $3692/QALY, respectively, which were less than one-time gross domestic product per capita. One-way sensitivity analysis and probabilistic sensitivity analyses showed the robustness of the results.@*Conclusion@#Among seven treatment strategies, first-line NA monotherapy may be more cost-effective than combination strategies in HBeAg-positive CHB patients in China.

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>

Serum sodium concentration profile for cirrhotic patients and its effect on the prognostic value of the MELD score / 中华肝脏病杂志

To analyze the characteristics of serum sodium in decompensated cirrhosis and evaluate the prognostic ability of the model for end-stage liver disease (MELD) in Na-containing models. Patients diagnosed with decompensated cirrhosis at our hospital were enrolled for study between June 2005 and October 2010. Patients were classified among three groups, according to serum sodium concentration: less than 125 mmol/L, 125 to 135 mmol/L, and more than 135 mmol/L. Mortality rates among the three groups were compared by Kaplan-Meier survival analysis. In addition, the different serum sodium concentrations were analyzed for correlations between Child-Pugh score and complication incidence rates of portal hypertension. The area under the receiver operating characteristic (ROC) curve (AUC) was used to compare the predictive abilities of MELD, MELD-Na, and the integrated (i) MELD scores for 3-month, 6-month and 1-year mortalities. A total of 467 patients were analyzed, and 50.54% had hyponatremia ( less than 135 mmol/L). Sodium concentration was correlated with mortality, and Kaplan-Meier survival analysis indicated that mortality was significantly higher in each subgroup with lower sodium concentration (all, P = 0.000). Likewise, sodium concentration decreased in conjunction with increased severity of decompensation, as classified by Child-Pugh scoring (sodium: A more than B more than C; mortality: A less than B less than C). With the exception of digestive tract bleeding, complication incidence rates of hepatic encephalopathy, ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome increased when sodium concentration decreased. For predicting 3-month mortality, the AUC scores of MELD were not significantly different from the MELD-Na and iMELD scores (P more than 0.05). For predicting 6-month and 1-year mortality, the AUC scores of MELD-Na and iMELD were significantly higher than those of MELD (P less than 0.05). Hyponatremia is correlated with mortality and complications in decompensated cirrhosis patients. Incorporation of Na into the MELD may enhance it's prognostic ability.

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>

The phenotypic characteristics of human fetal liver progenitors and clonal culture in vitro / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the phenotypic characteristics of human fetal liver cells (FLCs) and to obtain the homogenous hepatic progenitors with cloning.</p><p><b>METHODS</b>Immunofluorescence and flow cytometry were used to determine the phenotypes of the FLCs. The proliferating colonies were isolated using clone ring in different culture conditions. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to determine the mRNA expression after further cultivation.</p><p><b>RESULTS</b>The cultured FLCs showed a non-typical epithelial morphology. The positive rate for hepatic cell specific markers alpha-fetoprotein (AFP), albumin (Alb), cytokeratin 8 (CK8) and CK19 were approximately 28.1%, 84.7%, 55.1% and 9.1% respectively. Furthermore, the FLCs expressed the hematopoietic stem cell markers CD34 and CD45 with percentages of 0.04% and 0.09%. 71.8% and 75.3% of the FLCs were positive for the mesenchymal cell marker CD105 and CD166. Most of the colonies showed an elongated morphology, some with an unregular spreading-out morphology, only a small number of colonies with an epithelial-like morphology. RT-PCR results showed that among the 19 colonies obtained after further cultivation and the percentages of epithelial cell adhesion molecule (EpCAM), AFP, Alb and CK19 were 52.6%, 21.1%, 52.6% and 84.2%, respectively.</p><p><b>CONCLUSIONS</b>The clonal culture system is beneficial to obtain the homogenous hepatic progenitor cells from the heterogeneous culture of FLCs.</p>

The effect of portal hypertension on prognosis in patients with decompensated liver cirrhosis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the effect of portal hypertension on prognosis in patients with decompensated liver cirrhosis.</p><p><b>METHODS</b>The clinical data of decompensated cirrhosis patients in our hospital, between 2003 and 2006, were retrospected and followed up. Model for end-stage liver disease (MELD) score and Child-Turcotte-Pugh (CTP) classification was calculated using the standard formula. Kaplan-Meier survival analysis was used to compare the mortality in subgroups ranked by the syndromes. Cox proportional hazards regression was used to evaluate the effect of the syndromes on prognosis.</p><p><b>RESULTS</b>A cohort of 322 patients was admitted in this study at the end of the follow-up. The mortality of variceal bleeding, hepatic encephalopathy, a large volume ascites, spontaneous bacterial peritonitis, the type I and type II hepatorenal syndrome was 45.9%, 79.4%, 66.7%, 100%, 100% and 84.6% respectively. On the whole, the occurrence of all the syndromes was correlated with CTP classification and MELD score. Kaplan-Meier survival analysis showed that all of these syndromes, except for low to medium volume of ascites, significantly affected the survival rate (P<0.01). In Cox regression analysis, all the syndromes were the independent predictors of prognosis, the regression coefficient values of hepatic encephalopathy, spontaneous bacterial peritonitis, type I and type II hepatorenal syndrome, variceal bleeding and ascites were 0.973, 0.928, 0.935, 0.866, 0.464 and 0.369 respectively.</p><p><b>CONCLUSIONS</b>The portal hypertensive syndromes have significant effect on the prognosis of the patients with decompensated cirrhosis, hepatic encephalopathy is the worst one.</p>

Hepatitis B virus infects hepatic stellate cells and affects their proliferation and expression of collagen type I / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Hepatitis B is at particularly high risk of fibrosis progression. Unfortunately, the mechanism of hepatic fibrogenesis induced by hepatitis B virus (HBV) has not been fully understood to date. The aim of this study was to observe whether HBV can infect hepatic stellate cells (HSCs), and to examine the effects of HBV or HBV S protein (HBs) on the proliferation and collagen type I expression of HSCs.</p><p><b>METHODS</b>The supernatants of HepG2.2.15 cells which contained HBV-DNA or HBs were added to LX-2 cells for 72 hours. Cell survival was determined by MTT assay. HBV particles in LX-2 cells were detected by transmission electron microscopy. The expression of HBs and HBV C protein (HBc) was determined by confocal fluorescence microscopy. The expression levels of HBV-DNA were measured by real-time PCR. The cellular collagen type I mRNA and protein levels were quantified by reverse transcription-PCR and ELISA, respectively.</p><p><b>RESULTS</b>High concentrations of HBV (1.2 x 10(5) - 5.0 x 10(5) copies/ml) or HBs (1.25 - 20 microg/ml) inhibited the proliferation of LX-2 cells, while low concentrations of HBV (1.0 x 10(3) - 6.2 x 10(4) copies/ml) or HBs (0.04 - 0.62 microg/ml) promoted the proliferation. After treating LX-2 cells with HBV for 72 hours, about 42 nm HBV-sized particles and strong expression of HBs and HBc were found in the cytoplasm of LX-2 cells. HBV-DNA in the culture medium of LX-2 cells decreased at 24 hours, rose at 48 hours and thereafter, decreased again at 72 hours. The mRNA and protein expression of cellular collagen type I in LX-2 cells were significantly increased by HBV infection but not by recombinant HBs.</p><p><b>CONCLUSIONS</b>HBV and HBs affect the proliferation of HSCs; HBV can transiently infect and replicate in cultured HSCs and express HBs and HBc in vitro. Furthermore, HBV can significantly increase the expression of collagen type I mRNA and protein in HSCs.</p>

Results of 3 years of continuous entecavir treatment in nucleos(t)ide-naive chronic hepatitis B patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the virological, serological and biochemical outcomes of 3 years of entecavir (ETV) treatment in nucleoside-naive chronic hepatitis B patients.</p><p><b>METHODS</b>This study was divided into two stages: Patients receiving either ETV 0.5 mg/d (n = 258) or lamivudine (LAM) 100 mg/d (n = 261) entered the initial 96-week randomized, double blind, controlled efficacy study. Patients not achieving a consolidated response (HBV DNA less than 0.7 MEq/ml, ALT less than 1.25 times*ULN, and if HBeAg-positive at baseline, loss of HBeAg for >or= 24 weeks), or those experienced viral breakthrough or relapse, entered a 48-week entecavir rollover study.</p><p><b>RESULTS</b>96 weeks after the treatment, 79% of ETV treated and 46% of LAM treated patients had HBV DNA less than 300 copies/ml (P < 0.0001), 96% of ETV treated and 92% of LAM treated patients had normalized ALT (P = 0.06). 21% of ETV treated and 23% of LAM treated patients achieved HBeAg seroconversion. Among the 160 patients received continuous ETV for 144 weeks, 89% had undetectable serum HBV DNA, 86% showed ALT normalization, and 27% achieved HBeAg seroconversion. ETV resistance was rare: only 3 patients showed ETV resistance 96 weeks after the treatment, and additional 2 patients developed ETV resistance during the following 48 weeks, genotyping indicated the ETV resistance was caused by gene mutation. Adverse event rates in ETV-treated patients were similar to those in LAM-treated patients, but fewer ALT flares were observed in ETV-treated patients.</p><p><b>CONCLUSIONS</b>This study demonstrates that ETV treatment results in long-term HBV suppression and ALT normalization in Chinese CHB patients, and is associated with low rate of drug resistance.</p>

Week 24 suppression of HBV in entecavir-treated chronic hepatitis B patients in whom lamivudine treatment failed is associated with efficacy at week 48 / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between the degree of week 24 HBV suppression and week 48 therapeutic response in entecavir-treated chronic hepatitis B patients in whom lamivudine treatment failed, so as to explore a useful predictor for efficacy of enticavir treatment.</p><p><b>METHODS</b>Thirty-three patients with chronic hepatitis B refractory to lamivudine were enrolled to receive treatment with entecavir 1.0 mg once daily. The patients were divided into 4 groups according to serum HBV DNA levels (copies/mL) at week 24: PCR-undetectable (less than 300 copies/ml); QL- less than 3 log10 copies/ml; 3 log10(-4) log10 copies/ml; greater than 4 log10 copies/mL, and the efficacy achieved at week 48 was evaluated.</p><p><b>RESULTS</b>At week 48, mean reductions of serum HBV DNA from baseline was 4.91 log10. HBV DNA became undetectable by PCR assay in 33.3 percent patients and ALT became normal in 75.8%. The lower the HBV DNA level achieved at week 24, the higher the proportion of patients in whom HBV DNA became undetectable by PCR and ALT normalization were acquired at week 48, and viral breakthrough at week 48 also decreased.</p><p><b>CONCLUSION</b>Undetectable HBV DNA by PCR at week 24 in entecavir-treated chronic hepatitis B patients who were refractory to lamivudine, suggests a better efficacy at week 48. The degree of week 24 suppression of HBV may be used as a predictor of long term outcome.</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>

The degree of HBV suppression with 24 week telbivudine- or lamivudine-treatment in hepatitis B patients predicts the efficacy of the treatment at week 52 / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To investigate the possibilities of an association between the degrees of HBV suppression with nucleoside treatments at week 24 and week 52 in hepatitis B patients and to find a useful predictor for treatment efficacy.</p><p><b>METHODS</b>In this phase III, double-blind, multicenter trial, we compared the efficacy of telbivudine treatment with lamivudine treatment in 332 Chinese compensated chronic hepatitis B patients. The patients were randomly assigned to a daily 600 mg telbivudine treatment group or daily 100 mg lamivudine group for 24 weeks. They were then categorized into 4 groups according to their serum HBV DNA levels (copies/ml) at week 24: a PCR-undetectable group (< 300 copies/ml); a QL- < 10(3) copies/ml group; a 10(3)-<10(4) copies/ml group; and a > or = 10(4) copies/ml group. The treatments were continued as they previously had been for another 28 weeks and the patients serum HBV DNA levels were examined again.</p><p><b>RESULTS</b>At week 52, mean reductions of serum HBV DNA were significantly greater in the telbivudine-treated patients than in the lamivudine-treated group (6.2 log10 vs 5.4 log10, t = 3.6, P < 0.01). Viral resistance was twice as common in lamivudine-treated patients compared to those receiving telbivudine. Telbivudine was well-tolerated with an adverse event profile similar to that of lamivudine. The lower the HBV DNA level achieved at week 24, the higher HBV DNA non-detectable by PCR. ALT normalization and HBeAg seroconversion achieved at week 52, and viral resistance at week 48 decreased parallel to the degree of HBV DNA inhibition.</p><p><b>CONCLUSION</b>HBV DNA PCR-undetectable at week 24 in nucleoside-treated hepatitis B patients suggests a better efficacy at week 52 and lower viral resistance at week 48. The degree of suppression of HBV at week 24 may be used as a predictor of 1-year outcome.</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>