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OBJECTIVES Acute insults from viruses, infections, or alcohol are established causes of decompensation leading to acute-on-chronic liver failure (ACLF). Information regarding drugs as triggers of ACLF is lacking. We examined data regarding drugs producing ACLF and analyzed clinical features, laboratory characteristics, outcome, and predictors of mortality in patients with drug-induced ACLF. METHODS We identified drugs as precipitants of ACLF among prospective cohort of patients with ACLF from the Asian Pacific Association of Study of Liver (APASL) ACLF Research Consortium (AARC) database. Drugs were considered precipitants after exclusion of known causes together with a temporal association between exposure and decompensation. Outcome was defined as death from decompensation. RESULTS Of the 3,132 patients with ACLF, drugs were implicated as a cause in 329 (10.5%, mean age 47 years, 65% men) and other nondrug causes in 2,803 (89.5%) (group B). Complementary and alternative medications (71.7%) were the commonest insult, followed by combination antituberculosis therapy drugs (27.3%). Alcoholic liver disease (28.6%), cryptogenic liver disease (25.5%), and non-alcoholic steatohepatitis (NASH) (16.7%) were common causes of underlying liver diseases. Patients with drug-induced ACLF had jaundice (100%), ascites (88%), encephalopathy (46.5%), high Model for End-Stage Liver Disease (MELD) (30.2), and Child-Turcotte-Pugh score (12.1). The overall 90-day mortality was higher in drug-induced (46.5%) than in non-drug-induced ACLF (38.8%) (P = 0.007). The Cox regression model identified arterial lactate (P < 0.001) and total bilirubin (P = 0.008) as predictors of mortality. DISCUSSION Drugs are important identifiable causes of ACLF in Asia-Pacific countries, predominantly from complementary and alternative medications, followed by antituberculosis drugs. Encephalopathy, bilirubin, blood urea, lactate, and international normalized ratio (INR) predict mortality in drug-induced ACLF.

Objective We aimed to estimate the optimal cut-off values of liver stiffness measurement (LSM) for diagnosing and staging fibrosis in non-obese and obese patients with nonalcoholic fatty liver disease (NAFLD). Methods NAFLD patients diagnosed by liver biopsy according to the Nonalcoholic Steatohepatitis Clinical Research Network scoring system were enrolled in this study. Non-obesity was defined as a body mass index (BMI) less than 25 kg/m2 . LSM was performed by experienced physicians within 2 weeks before or after liver biopsy. Results A total of 158 patients were included. Average BMI of the non-obese (n = 68) and obese (n = 90) groups was 23.2 ± 1.6 and 27.9 ± 2.5 kg/m2 , respectively. After adjusted for age, fibrosis stage, steatosis grade and type 2 diabetes mellitus, the obese group had a LSM of 3.522 kPa higher than the non-obese patients (P = 0.003). LSM values of the non-obese patients had a lower trend when stratified by fibrosis stage, especially in cirrhosis (F4; P = 0.021). Applying separate cut-off values for patients with NAFLD in individual fibrosis stage, 5.8 vs 7.5 kPa (≥ F1), 7.6 vs 8.5 kPa (≥ F2), 9.1 vs 11.2 kPa (≥ F3), and 12.5 vs 14.3 kPa (F4), improved their diagnostic odds ratios compared with overall cut-off values. In the non-obese NAFLD group, using a separate cut-off avoided underestimating 9.1% of patients with cirrhosis. Conclusions Non-obese NAFLD group had lower LSM than the obese group. Different cut-off values should be used to measure liver fibrosis stage in non-obese and obese NAFLD patients.

Objective Since July 1, 2011 antiviral therapy for hepatitis B virus infection has been listed as a reimbursable expense for medical insurance in Beijing. This study aimed to assess the impact of this program on liver-related death for patients with chronic hepatitis B (CHB). Methods Profiles of patients with CHB discharged between January 2008 and December 2015 were retrieved from the Beijing hospital discharge database. Liver-related deaths in these patients occurring between January 2008 and December 2017 were retrieved by linking them to the death certification database. Liver-related mortality (number of deaths divided by the observed person-years) before and after this program was launched was calculated and compared. A Poisson regression was performed to assess the strength of association (risk ratio [RR]) between the reimbursement program and liver-related mortality. Results Information on 35 943 discharged patients (17 114 patients with non-cirrhotic and 18 829 with compensated cirrhotic CHB) was retrieved. Altogether 3 832 liver-related deaths during the 190 695 person-years were observed. After the reimbursement program was launched, liver-related mortality per 100 person-years dropped from 0.38% to 0.16% for patients with non-cirrhotic CHB, and from 4.03% to 3.39% for those with compensated cirrhosis. The program was associated with a lower risk of developing liver-related death for patients with non-cirrhotic CHB (RR 0.40, 95% confidence interval [CI] 0.30-0.52) and those with compensated cirrhosis (RR 0.84, 95% CI 0.78-0.89). Conclusion Coverage of antiviral therapy by basic medical insurance reduced the risk of developing liver-related death for patients with non-cirrhotic and with compensated cirrhotic CHB.

BACKGROUND AND AIM Although treatment with direct-acting antivirals has dramatically improved morbidity and mortality attributable to chronic hepatitis C virus infection, universal access to these medicines has been slow in the Asia-Pacific region and Russia. This study evaluated efficacy and safety of elbasvir/grazoprevir in participants with hepatitis C virus infection from Asia-Pacific countries and Russia (C-CORAL). METHODS C-CORAL was a phase 3, randomized, placebo-controlled study (NCT02251990). Treatment-naive, HIV-negative, cirrhotic and non-cirrhotic participants with chronic hepatitis C genotype 1, 4, or 6 infection were randomized to elbasvir 50 mg/grazoprevir 100 mg once daily for 12 weeks (immediate-treatment group) or placebo followed by deferred treatment with elbasvir/grazoprevir (deferred-treatment group). The primary efficacy outcome was sustained virologic response at 12 weeks, and the primary safety outcome was a comparison between the immediate-treatment group and placebo phase of the deferred-treatment group. RESULTS A total of 489 participants were randomized (immediate-treatment group, n = 366; deferred-treatment group, n = 123). Sustained virologic response at 12 weeks in the combined immediate/deferred-treatment groups was 94.4% (459/486; 95% confidence interval = 92.4-96.5%). Sustained virologic response at 12 weeks was 98.2% in participants with genotype 1b, 91.9% with genotype 1a, and 66.7% with genotype 6 infection. Similar rates of adverse events and drug-related adverse events were seen in the immediate-treatment group versus placebo phase of the deferred-treatment group (51.0% vs 50.4% and 21.4% vs 21.1%). CONCLUSIONS Elbasvir/grazoprevir for 12 weeks represents an effective and well-tolerated treatment option for treatment-naive people with genotype 1 infection from Asia-Pacific countries and Russia.

Non-alcoholic steatohepatitis (NASH) is a serious form of non-alcoholic fatty liver disease (NAFLD) that can progress to advanced fibrosis, cirrhosis, and hepatocellular carcinoma. Differentiating between non-alcoholic fatty liver (NAFL) and NASH/advanced fibrosis is an important step in the management of NAFLD. Metabolic syndrome (MS) and its components are important risk factors for NAFLD, and NASH is thought to be the hepatic injury of MS. The prevalence of NASH among NAFLD patients with MS is thought to be high. In China, NAFLD is a relatively new public health concern, and the current prevalence of NASH among Chinese liver biopsy-proven NAFLD patients with and without MS is not known. This multicenter, cross-sectional study will investigate the prevalence of NASH in approximately 480 Chinese NAFLD patients. Patients will be eligible for enrollment if they have biopsy-proven NAFLD and if their liver biopsies are available for rereading. For our analysis, patients will be stratified according to the presence/absence of MS, and the prevalence of NASH in the subgroups will be compared. Other possible tests that could indicate a risk of NASH, including transient elastography, ultrasonography, cytokeratin-18, liver function tests, and others, will be studied in an effort to derive a practical, noninvasive predictive model for NASH. Patients with NAFL who have MS may also have a very high risk of developing NASH. The present study will inform about the risk of NASH in Chinese liver biopsy-proven NAFLD patients with and without MS. This study registered at http://www.chictr.org.cn (registration number: ChiCTR-OOC-16007902). Sanofi (China) Investment Co., Ltd.

AIM To assess daclatasvir plus asunaprevir (DUAL) in treatment-naïve patients from mainland China, Russia and South Korea with hepatitis C virus (HCV) genotype 1b infection. METHODS Patients were randomly assigned (3:1) to receive 24 wk of treatment with DUAL (daclatasvir 60 mg once daily and asunaprevir 100 mg twice daily) beginning on day 1 of the treatment period (immediate treatment arm) or following 12 wk of matching placebo (placebo-deferred treatment arm). The primary endpoint was a comparison of sustained virologic response at posttreatment week 12 (SVR12) compared with the historical SVR rate for peg-interferon plus ribavirin (70%) among patients in the immediate treatment arm. The first 12 wk of the study were blinded. Safety was assessed in DUAL-treated patients compared with placebo patients during the first 12 wk (double-blind phase), and during 24 wk of DUAL in both arms combined. RESULTS In total, 207 patients were randomly assigned to immediate (n = 155) or placebo-deferred (n = 52) treatment. Most patients were Asian (86%), female (59%) and aged < 65 years (90%). Among them, 13% had cirrhosis, 32% had IL28B non-CC genotypes and 53% had baseline HCV RNA levels of ≥ 6 million IU/mL. Among patients in the immediate treatment arm, SVR12 was achieved by 92% (95% confidence interval: 87.2-96.0), which was significantly higher than the historical comparator rate (70%). SVR12 was largely unaffected by cirrhosis (89%), age ≥ 65 years (92%), male sex (90%), baseline HCV RNA ≥ 6 million (89%) or IL28B non-CC genotypes (96%), although SVR12 was higher among patients without (96%) than among those with (53%) baseline NS5A resistance-associated polymorphisms (at L31 or Y93H). During the double-blind phase, aminotransferase elevations were more common among placebo recipients than among patients receiving DUAL. During 24 wk of DUAL therapy (combined arms), the most common adverse events (≥ 10%) were elevated alanine aminotransferase and upper respiratory tract infection; emergent grade 3-4 laboratory abnormalities were infrequently observed, and all grade 3-4 aminotransferase abnormalities (alanine aminotransferase, n = 9; aspartate transaminase, n = 6) reversed within 8-11 d. Two patients discontinued DUAL treatment; one due to aminotransferase elevations, nausea, and jaundice and the other due to a fatal adverse event unrelated to treatment. There were no treatment-related deaths. CONCLUSION DUAL was well-tolerated during this phase 3 study, and SVR12 with DUAL treatment (92%) exceeded the historical SVR rate for peg-interferon plus ribavirin of 70%.

Systemic inflammatory response syndrome (SIRS) is an early marker of sepsis and ongoing inflammation and has been reported in large proportion of acute-on-chronic liver failure (ACLF) patients. Whether sepsis is the cause or the result of liver failure is unclear and is vital to know. To address this, the study investigated the course and outcome of ACLF patients without SIRS/sepsis.Consecutive ACLF patients were monitored for the development of SIRS/sepsis and associated complications and followed till 90 days, liver transplant or death.Of 561 patients, 201 (35.8%) had no SIRS and 360 (64.2%) had SIRS with or without infection. New onset SIRS and sepsis developed in 74.6% and 8% respectively in a median of 7 (range 4-15) days, at a rate of 11% per day. The cumulative incidence of new SIRS was 29%, 92.8%, and 100% by days 4, 7, and 15. Liver failure, that is, bilirubin 12 mg/dL (odds ratio [OR] = 2.5 [95% confidence interval {CI} = 1.05-6.19], P = 0.04) at days 0 and 4, and renal failure at day 4 (OR = 6.74 [95%CI = 1.50-13.29], P = 0.01), independently predicted new onset SIRS. Absence of SIRS in the first week was associated with reduced incidence of organ failure (20% vs 39.4%, P = 0.003), as was the 28-day (17.6% vs 36%, P = 0.02) and 90-day (27.5% vs 51%,P = 0.002) mortality. The 90-day mortality was 61.6% in the total cohort and that for those having no SIRS and SIRS at presentation were 42.8% and 65%, respectively (P 0.001).Liver failure predicts the development of SIRS. New onset SIRS in the first week is an important determinant of early sepsis, organ failure, and survival. Prompt interventions in this 'golden window' before development of sepsis may improve the outcome of ACLF.

Background: Gastric bezoar is a collection of indigestible material in the stomach. It is a relatively rare disease. In this case report, it is shown that Traditional Chinese Medicine (TCM) was effective in treating a patient with gastric bezoar. Subject and setting: A 47-year-old female patient who had undergone Billroth II gastrectomy for gastric cancer had been experiencing abdominal pain and distension for 1 month. She underwent gastroscopic examination at our outpatient department; the gastroscopy showed a bezoar (7×4×2 cm in size) in her remnant stomach. Treatment using a Chinese herbal decoction was suggested. Results: The gastric bezoar dissolved after 2 weeks of regular therapy with San Jie Pai Shi decoction. No complications or adverse effects were noted during the TCM treatment. Conclusions: This case showed that TCM was an effective and alternative treatment option for patients with gastric bezoar.

To verify and assess diagnostic value of noninvasive diagnostic model of liver fibrosis in primary biliary cirrhosis (PBC) based on conventional laboratory markers.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.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 index0.41 was 93.2%.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).

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.

To evaluate the clinical and histological features of patients with abnormal liver tests of unknown etiology, and then to investigate the diagnosis and differential diagnosis.Patients with abnormal liver function test hospitalized and had liver biopsies during 2008 - 2009 constituted this retrospective study cohort. After excluding those patients diagnosed with hepatotropic viral hepatitis, space occupying lesions of the liver, alcoholic liver disease and obstruction of bile duct caused by stone or malignancy and AMA/AMA-M(2) positive of primary biliary cirrhosis (PBC), the clinical and histological characteristics were evaluated.Out of the 180 patients who underwent liver biopsy, 88 patients were included in the present analysis. The final diagnosis involved 15 categories of diseases, with drug-induced liver injury (DILI) [34.09% (30/88)], autoimmune liver diseases [22.73% (20/88)], and nonalcoholic fatty liver disease (NAFLD) [12.50% (11/88)] being the most common causes, following by genetic and other rare diseases.DILI, autoimmune liver disease and NAFLD were the most common causes of abnormal liver tests in these non-viral liver diseases. Some rare diseases such as hereditary metabolic liver disease also represent a considerable proportion in patients with abnormal liver function test.

To elucidate clinical and pathological features of primary sclerosing cholangitis (PSC) in order to improve clinician's awareness of this rare disease.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 ALTor = 1.5, TBilor = 2 and ALPor = 2.5 ULN were determined as good responders. The treatment results between the two groups were compared.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).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.

To evaluate the virological, serological and biochemical outcomes of 3 years of entecavir (ETV) treatment in nucleoside-naive chronic hepatitis B patients.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 foror= 24 weeks), or those experienced viral breakthrough or relapse, entered a 48-week entecavir rollover study.96 weeks after the treatment, 79% of ETV treated and 46% of LAM treated patients had HBV DNA less than 300 copies/ml (P0.0001), 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.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.

To evaluate the effect of portal hypertension on prognosis in patients with decompensated liver cirrhosis.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.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 (P0.01). 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.The portal hypertensive syndromes have significant effect on the prognosis of the patients with decompensated cirrhosis, hepatic encephalopathy is the worst one.

Hepatitis B and C viruses (HBV and HCV) are two clinically distinct but related diseases. Pooled data from five studies of peginterferon alpha-2a in patients with chronic HCV infection (CHC) were compared with two studies of the drug in patients with chronic HBV infection (CHB).The HBV studies included both hepatitis B e antigen (HBeAg)-positive (n=271) and HBeAg-negative (n=177) patients; 791 patients took part in the HCV trials. In all studies, patients were treated with 180 microg peginterferon alpha-2a monotherapy once weekly for 48 weeks. The number of adverse events (AEs), discontinuations and dose modifications were documented. Health-related quality of life (HRQL) was assessed using the Short-Form 36 questionnaire. Safety was assessed throughout the treatment period. A 24-week treatment-free follow-up period was also included.Differences (HBV vs HCV) were observed in the incidence of AEs (88-89 vs 96-100%), serious AEs (4-5 vs 7-16%) and treatment withdrawals (6-8 vs 17-33%). The frequency of depression-related events was lower in CHB patients (4 vs 22%, P0.001), as was the impact of treatment on HRQL.The safety and tolerability of peginterferon alpha-2a in patients with CHB compares favourably with that observed in CHC patients, with a lower incidence of common interferon-related AEs and a significantly lower incidence of depression.

The aim of this paper was to investigate the factors associated with viral response and HBeAg seroconversion and the relationship between them at different stages of interferon treatment in HBeAg-positive chronic hepatitis B patients.PEG-IFN alfa-2a was injected subcutaneously in doses of 180 microg once a week for 48 weeks to HBeAg-positive chronic hepatitis B patients, and the patients were followed for another 24 weeks after the treatment. The serum HBV DNA load was measured by real-time quantitative PCR assay. Microparticle enzyme immunoassay analysis (MEIA) was then carried out by an automatic enzyme immunoassay analysis instrument to measure HBeAg and anti-HBe. Virological response and HBeAg seroconversion rates, and the factors associated with them were analyzed.The differences in ALT baselines between viral responding and non-responding groups were significant at treatment time and at the end of the follow-up period. These differences were also significant in patients with HBeAg seroconversion at 12 weeks and at the end of the follow-up period compared with the non-conversion group. No significant difference of HBV DNA baseline was observed between the HBeAg seroconversion and non-conversion group. At 12, 24 and 48 weeks, in patients with viral response during the treatment, their HBeAg seroconversion rates were 43.8%, 21.4% and 18.9% respectively; their respective HBeAg seroconversion rates remaining at 72 weeks were 42.9%, 33.3% and 27.6%. HBeAg seroconversion was related to HBV DNA negativity at 48 weeks treatment in the multivariate analysis (OR=2.15, 95.0% CI=1.744-2.664, P less than 0.01).Viral response and early and sustained HBeAg seroconversion were associated with pretreatment ALT levels. HBeAg seroconversion was related to viral response during IFN treatment, but not to the baseline HBV DNA load.

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.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.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.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.

To analyze the frequency and the clinical and virological features of HBeAg-negative and HBeAg-positive chronic hepatitis 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.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 (P0.01) 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%, P0.01]. 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 (P0.05), 53.2% patients of HBeAg-negative group and 44.5% patients of HBeAg-positive group had a fibrosis score ofor= S3.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.

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.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 aor = 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.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, P0.01). 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.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.

To discuss the diagnostic value of an ultrasonic assessing system for detecting the severity of hepatic fibrosis in patients with chronic hepatitis B (CHB).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.The areas under the curve of the scoring system for different liver fibrosis stages wereor= 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, P0.001). 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%.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.

To investigate the relationship between hepatitis C virus (HCV) genotype, serum viral load and ALT levels, and the factors associated with the viral relapse after IFN treatment in patients with chronic hepatitis C.The HCV RNA levels were determined with Cobas Amplicor Monitor Test, version 2.0, and HCV genotypes were examined by means of PCR products of 5' NTR digested with restriction endonucleases. The patients with chronic hepatitis C were treated with PEG-IFN alpha -2a and Roferon-A for 24 weeks. Those with a viral response after 24 week treatment were followed for an additional 24 weeks. The association of clinical characteristics, such as sex, age, the way of the HCV infection, IFN treatment history and platelet counts, and the HCV genotype, virus load and medicine used for the viral relapse after IFN treatment were analyzed.Of the 208 chronic hepatitis C patients, the ALT levels were not related to HCV RNA levels (r = 0.093, P0.05). No difference of ALT levels between HCV genotypes was found, and the HCV RNA load was also of no difference between HCV genotype 1 patients and non 1 patients. Of the 119 patients with viral response after 24 week treatment, 58 cases (48.7%) relapsed after another 24 week's follow-up. Relapse was not significantly related to the clinical characteristics, such as sex, age, mode of the infection, treatment history of IFN, AST/ALT ratio, platelet counts and the baseline viral load. Among patients with genotype 1 virus, the relapse rate was significantly higher than those patients with non-genotype 1 virus (54.5% vs 32.1%, P=0.039). The relapse rate after PEG-IFN alpha -2a treatment was lower than that of Roferon-A treatment (47.0% vs. 52.8%), but not significantly.The viral relapse of chronic hepatitis C patients after IFN treatment was significantly associated with the genotypes of the HCV.

To evaluate the efficacy and investigate the influencing factors of the interferon (IFN) retreatment for patients with chronic hepatitis C relapsed after a previous IFN treatment.A retrospective study was designed to analyze the retreatment with IFN of 60 relapsed chronic hepatitis C patients. All patients were from a randomized, opened and multi-center clinical trial about the efficacy and security of PEG-IFNalpha-2a compared to CIFNalpha-2a in the treatment of chronic hepatitis C in China. There were 35 patients treated with PEG-IFNalpha-2a and 25 with CIFNalpha-2a. The main parameter to evaluate the efficacy was sustained viral response (SVR) rate. The influence of viral concentration in serum, genotype and drug categories on the responses to IFN were analyzed.For all the patients, the end of treatment virus response (ETVR) and SVR rates were 55.00% and 35.00% respectively. ETVR rate of PEG-IFNalpha-2a was significantly higher than that of CIFNalpha-2a (74.29% and 28.00% respectively, P0.01). SVR rate of PEG-IFNalpha-2a was also markedly higher than that of CIFNalpha-2a (45.71% and 20.00% respectively, P0.05). However, there was no significant difference between the high and low viral load groups. Among the patients with genotype 1, ETVR and SVR rates of PEG-IFNalpha-2a (75.00%, 45.83%) were significantly higher than those of CIFNalpha-2a (22.22%, 11.11%), (P0.01, P0.05 respectively), but in patients with genotype non-1, there were no such differences between the two groups.Some relapsed patients were not responsive to the IFN retreatment. The efficacy of PEG-IFNalpha-2a was superior to CIFNalpha-2a. The conventional IFN was not suggested to be used in the relapsed cases with genotype 1. The viral load was not associated with the efficacy of IFN retreatment.

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.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.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).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.

To study the efficacy of the protocol of combination of lamivudine with low dosage hepatitis B immuno-globulin (HBIG) to prevent HBV reinfection and of the treatment for HBV reinfection after liver transplantation.From December 2000 to May 2003, 11 patients (follow-up is more than 1 year) had been transplanted due to HBV related end-stage liver disease or hepatocellular carcinoma. All patients received the protocol of combination of lamivudine with low dosage HBIG to prevent HBV reinfection after liver transplantation. Lamivudine was administered for more than 2 weeks. Preoperatively patients with HBV-DNA(-) and HBeAg(-) accepted HBIG 2000 IU intramuscular injection. Patients with HBV-DNA(+) or HBeAg(+) before operation accepted HBIG 4000 IU intramuscular injection, and patients with both HBV-DNA(+) and HBeAg(+) before operation accepted HBIG 6000 IU intramuscular injection. All patients took long-term lamivudine postoperatively. They accepted HBIG 800 IU/d for 1 week after transplantation. Two weeks after operation, dosage of HBIG was adjusted so that the titer of HBsAb was higher than 500 IU/L, but lower than 1000 IU/L, and this treatment lasted for 6 months. 6 months after operation, dosage of HBIG was adjusted so that tite of HBsAb higher than 300 IU/L but lower than 500 IU/L, and this treatment lasted for 6 months. One year after operation, dosage of HBIG was adjusted so that tite of HBsAb was higher than 100 IU/L but lower than 300 IU/L, and this treatment lasted for a long time. Examinations of liver function, HBV-DNA and hepatitis B were regularly taken. To observe the early turning to be negative rate, the later HBV reinfection rate, and the efficacy of the treatment for HBV reinfection.HBsAg, HBeAg and HBV-DNA in all patients turned to be negative in 1-4 days after operation. All patients responded to HBIG, and level of titer of HBsAb was elevated gradually. All patients was alive during the observation time. The regular examination of HBsAb showed that of HBsAb was in line with our expectation. Hepatitis B recurrence occurred in 1 patient 25 months after transplantation. Through using adefovir and adding the dosage of HBIG, the hepatitis B is in control.The protocol of combination of lamivudine with low dosage HBIG proved to be highly effective and safe in preventing the recurrence of HBV after liver transplantation. It also reduced the cost obviously.

This study was undertaken to investigate the predictive factors of sustained viral response in roferon-A or pegasys treated chronic hepatitis C patients after logistic regression analysis of the factors that might be associated with the therapeutic effects of interferon (IFN).All patients enrolled into this randomized, open and multi-center controlled trial were divided into two groups randomly and treated with pegasys and roferon-A for 24 weeks, then followed up for another 24 weeks. Before treatment, hepatitis C virus (HCV) genotype was determined, and HCV-RNA in serum was detected before and at the end of treatment and follow-up. HCV-RNA turning negative was considered the major index for evaluating the therapeutic effect. The clinical characteristics including gender, age, infection route of HCV, treatment with IFN, platelet count, AST/ALT ratio and treatment drugs were analyzed by logistic regression.Intention to treat (ITT) and per-protocol (PP) population groups have 208 and 197 patients respectively. In the PP group, after treatment for 24 weeks, the response rates of female patients aged less than 50 years, infected through non-transfusion, relapsed after IFN treatment, and presented with a AST/ALT ratio/=1, virus load less than 8 x 10(5) IU/ml, and non genotype 1 HCV infection, and treated finally with pegasys were higher than those of male patients, aged more than 50 years, infected by transfusion, treated firstly with IFN, presented with a AST/ALT ratio/=1, virus load equal or more than 8 x 10(5) IU/ml, and genotype 1 infection, and treated finally with roferon-A. But, at the end of follow-up, the patients with a AST/ALT ratio/=1 and virus load more than 8 x 10(5) IU/ml had a higher rate of sustained response than did those with a AST/ALT ratio/=1 and virus load less than 8 x 10(5) IU/ml. Logistic regression analysis and control of the promiscuous factors showed that the genotype of HCV was not related to the response rate at the end of treatment (OR 0.604, 95% CI 0.271-1.349, P=0.219), but was the independent predictive factor of virus sustained response to IFN treatment (OR 0.408, 95% CI 0.189-0.881, P=0.023). The form of IFN was significantly related to viral response at the end of treatment (OR 0.105, 95% CI 0.052-0.212, P0.001), and pegasys were an intensely predictive factor for sustained response(OR 0.255, 95% CI 0.123-0.529, P0.001).HCV genotype and pegasys are the predictive factors for IFN response to the IFN treatment of patients with chronic hepatitis C.

To investigate the diagnostic value of coagulation factors in assessing the severity degree of liver cirrhosis caused by hepatitis B.Fifty-eight patients with liver cirrhosis and twenty healthy persons as control were enrolled. Prothrombin time activity percentage (PTA), activated partial thromboplastin time, coagulation activity of factor II, V, VII, VIII, IX and X were detected with clotting assay. Antithrombin-III (AT-III) was detected with colorimetric assay. The biochemical markers were also detected.The differences of PTA, factor II, VII and AT-III among Child-Pugh A, B, C in patients with liver cirrhosis were statistically significant (P0.01). Through receiver operating characteristic curve analysis, when 64% and 50% were used as cut-off values for PTA and factor VII in diagnosing Child-Pugh B, the area under the curve (AUC) was 0.689 and 0.610, the sensitivity was 76.9% and 61.5%, the specificity was 62.2% and 55.6%; when 54% and 39% were used as cut-off values for PTA and factor VII in diagnosing Child-Pugh C, the AUC was 0.924 and 0.942, the sensitivity was 80.0% and 86.7%, the specificity was 88.4% and 90.7%. Stepwise linear regression was done between Child-Pugh grade and coagulation factors. PTA, cholinesterase (Che), total bilirubin (TBil), albumin (Alb), factor VII were included in regression equation, Y = 15.008 - 0.018 x PTA - 0.288 x Che + 0.264 x TBil - 0.988 x Alb - 0.034 x VII, R(2) = 0.871. Patients whose Y was less than 8 were classified as grade "a", between 8 - 10 as grade "b", more than 10 as grade "c", the diagnostic accuracy was 84.5%.Coagulation factor VII may serve as a helpful marker in diagnosing the severity degree of liver cirrhosis.

Clinical features of 30 cases of amyloidosis, a rare disease in China, were analyzed in order to improve the recognition of the disease here.30 cases of biopsy-proven amyloidosis, admitted to Beijing Friendship Hospital from July 1980 to December 2003 were retrospectively reviewed.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.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.

To investigate the efficacy and safety of secreted interferon in treatment of chronic hepatitis B.A multi-center randomized open-label controlled clinical trial was carried out. The patients of the study group were treated by secretory human interferon alpha-2a, and the patients of the control group were treated with an ordinary interferon.ALT normalization rate in the secreted interferon group was 48.3% and it was higher at the end of treatment than that of the control group, but there was no difference between the two groups at the end of the follow-up. HBV DNA dropped more in the study drug group, but there was no difference in the normalization rate between the two groups. HBeAg seroconversions in secreted interferon group and in the control interferon group were 19.0% and 18.4% respectively. The safety of the two types of interferon was satisfactory.Secreted interferon was superior to ordinary interferon in ALT normalization and HBV DNA drop at the end of treatment in chronic hepatitis B patients, but there was no difference at the end of the follow-up. There was also no difference in HBeAg negative and HBeAg seroconversion between the two groups.

To investigate the predictors of IFN therapy in patients with chronic hepatitis C through making the multivariate logistic regression analysis.The patients in the opened, randomized and controlled trial were enrolled into two group, pegasys and Roferon-A group, and were given 24 weeks of pegasys (injection of 180 microg a week), and Roferon-A (injection three times of Roferon-A 3 MU a week) therapy, and followed 24 weeks. The HCV RNA content was determined at the time before, end of treatment and at the followed-up. The association of the response to the treatment with the clinical characteristics including age, gender, way of HCV infection, history of IFN treatment, planet count, AST/ALT ratio, HCV RNA level, HCV genotype and treatment drugs was made trough multivariate logistic regression analysis.The PP population containing 197 cases was analyzed. After controlling for age, gender, way of HCV infection, history of IFN treatment, planet count, AST/ALT ratio, HCV RNA level and treatment, the HCV genotype was not predictor of the end of treatment viral response (ETVR) to IFN therapy (OR 0.604, 95% CI 0.271-1.349, P = 0.219), but was the independent predictor of sustained viral response (SVR) (OR 0.408, 95% CI 0.189-0.881, P = 0.023). After controlling for other characteristics, the treatment drug was the predictors of ETVR (OR 0.105, 95% CI 0.052-0.212, P0.001) and SVR (OR 0.255, 95% CI 0.123-0.529, P0.001).The pegasys using and HCV genotype were the independent predictors of the response to antiviral therapy in chronic hepatitis C.

To further assess the clinical antifibrotic efficacy of Cpd 861 on chronic hepatitis B related fibrosis and early cirrhosis using a randomized, double blind, and placebo controlled clinical trial.Total 136 patients with HBV-related fibrosis and early cirrhosis were allocated randomly into Cpd 861 treatment group and placebo group for 24 weeks treatment. Serum fibrosis markers including hyaluronic acid (HA), IV collagen (IV-C), amino terminal propeptide of type III procollagen (PIIIP), and laminin (LN) and serum MMP1, 2, 9, TIMP1, 2 level were determined before and after 24 weeks treatment. Liver biopsies before and after 24 weeks of treatment were assessed according to modified Scheuer and Chevallier's scoring system.Total 52 patients in Cpd 861 treatment group and 50 patients in placebo-controlled group completed the 6 months. ALT level decreased from 68.2 U/L+/-68.6 U/L to 45.9 U/L+/-26.1 U/L, AST level decreased from 60.4 U/L+/-62.6 U/L to 46.7 U/L+/-39.0 U/L (P0.05) after 24 weeks treatment, whereas there was no significant change in placebo group (ALT: 65.3 U/L+/-48.3 U/L to 85.4 U/L+/-115.5 U/L; AST: 60.4 U/L+/-44.6 U/L to 77.6 U/L+/-89.6 U/L, P0.05). Serum fibrosis markers, including HA, IV-C, PIIIP, and LN were decreased after treatment, but there is no statistically significant compared with placebo group. Compared with placebo group, serum TIMP1 and MMP9 level decreased significantly (TIMP1 172.0 ng/ml+/-79.6 ng/ml vs 133.5 ng/ml+/-66.8 ng/ml; MMP9 116.1 ng/ml+/-88.2 ng/ml vs 80.4 ng/ml+/-79.0 ng/ml), and the ratio of TIMP1/MMP1 (48.3+/-96.3 vs 19.9+/-28.0) were also decreased after 861 treatment. In patients treated with Cpd 861, hepatic inflammatory score (from 14.0+/-6.0 to 10.2+/-6.1), fibrosis score (from 11.9+/-6.5 to 8.2+/-4.5), and relative content of collagen (from 18.9%+/-9.5% to 14.9%+/-8.4%) decreased significantly. In contrast, there was no significant change in placebo group. The reversal (fibrosis score decreaseor = 2) rate of fibrosis in Cpd 861 group was 38.9% in S2, 53.3% in S3 (precirrhotic) and 78.6% in S4 (cirrhosis), significantly higher than those in placebo group (14.3%, 25.0%, and 41.7%, respectively). The overall reversal rate was 52.0% in Cpd 861 group, and 20.0% in placebo group (P0.05). No serious adverse effects were observed during Cpd 861 treatment.Liver fibrosis and early cirrhosis due to HBV infection in man could be definitely reversed by herbal remedy Cpd 861.

Some factors have been reported to be associated with a greater likelihood of sustained viral response (SVR) in the interferon (IFN) treatment of chronic hepatitis C. The factors include HCV genotype, HCV RNA level in serum, state of liver disease, baseline body weight, age, sex, and race. The aim of this trial was to investigate the influence of HCV genotype on the IFN treatment of patients with chronic hepatitis C.The genotypes of HCV virus were determined in the patients with chronic hepatitis C from several hospitals of China enrolled into the randomized, opened and controlled trial of Peg-IFN alpha-2a (pegasys) treatment, controlled with IFN-alpha-2a (roferon-A). The serum ALT levels and HCV RNA concentrations of the patients were detected before and at the end of treatment and during the follow-up. The influence of HCV genotype on the IFN treatment of patients with chronic hepatitis C was analyzed in intention-to-treat (ITT) population.The HCV genotypes of 202 patients were determined. Of these patients, 158(78.22%) were infected with genotype 1 HCV and 44(21.78%) with genotype non-1. The viral response at the end of treatment (ETVR) and sustained viral response (SVR) rates were 53.80% and 25.32% respectively in patients with genotype 1 HCV, but they were 61.36% and 43.18% in patients with genotype non-1. The difference of SVR between patients with genotype 1 HCV and those with genotype non-1 was significant (P=0.021). After being grouped by the used drugs, the ETVR rates of patients infected with genotype 1 and non-1 HCV were 76.83% and 80.95% in the patients treated with pegasys (P=0.686); but their SVR rates were 35.37% and 66.67% (P=0.01). The viral relapse rate of genotype 1 HCV (55.56%) was significantly higher than that of genotype non-1 HCV (23.53%) (P=0.02). In roferon-A group, the ETVR and SVR rates of patients with genotype 1 HCV were 28.95% and 14.47% respectively, which were lower but not more significant than those of patients with genotype non-1 HCV (43.48% and 21.74%). Moreover, the viral relapse rate of genotype 1 HCV (72.73%) was higher but not more significant than that of genotype non-1 HCV (50.00%) (P=0.21).HCV genotype could affect the efficacies, mainly sustained responses, of IFN treatment in patients with chronic hepatitis C, and the effects of IFN are related to drugs and therapeutic course.

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.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.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).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.

To determine the reason of thrombocytopenia in patients with liver cirrhosis, we studied the relationship among platelet counts, serum thrombopoietin (TPO) level and spleen index.Serum TPO, platelet counts and spleen index were measured in 71 cirrhotic patients. TPO was measured with ELISA method, spleen index were measured on ultrasonography by the same doctor.Platelet counts in patients with cirrhosis were lower than that of healthy group [(109.20+/-53.39) vs (169.63+/-26.60) x 10(12)/L, P0.05]. Serum thrombopoietin level in patients with cirrhosis was similar to that of healthy group [(436.42+/-258.97) vs (412.63+/-132.80) pg/ml, P0.05]. However, serum thrombopoietin level decreased as liver disease aggravated, [(526.13+/-317.44) pg/ml in Child-Pugh grade A, (445.22+/-214.90) pg/ml in grade B and (311.45+/-182.66) pg/ml in grade C, grade A vs. Grade C, P0.05]. However, decline in platelet counts was accompanied with incline in spleen index coordinately. 35 of 71 cirrhotic patients had normal platelet counts whereas 36 of them had thrombocytopenia. Thrombopoietin levels were higher in non-thrombocytopenia group than in thrombocytopenia group [(529.43+/-282.64) vs. (351.27+/-228.25)pg/ml, P0.01]; but spleen index of two groups showed no difference [(29.65+/-12.00) vs. (36.35+/-12.68) cm2, P0.05]. Correlation was found between thrombopoietin level and platelet counts (r=0.252, P=0.025); no correlation was found between spleen index and platelet counts (r=-0.238, P=0.062).The decline serum TPO levels might play an important role for thrombocytopenia in patients with liver cirrhosis.

To investigate the relationship between Transitional CK19 positive cells and hepatic precancerous lesion in chronic hepatitis B patients.We observed the expression of CK19 in liver tissue of chronic hepatitis B patients by LSAB immunohistochemical staining, and examined serum AFP and ultrasonography one time per 3 months for one year.We observed a population of CK19 positive cells-with size and structure between those of human oval cells and mature hepatocytes-that usually occurred along with oval-cell proliferation. It was suggested that these transitional cells may partly account for the elevation of serum AFP. One patient occurred hepatic carcinoma, another patient had low-echogenic nodules in liver parenchyma within the 1 year follow-up period.Transitional CK19 positive cells could be regarded as a new possible pathological marker of hepatic precancerous lesion.

This was an open, random, control and multicenter clinical trial. In the study, the anti-hepatic fibrosis effect of rhIFN-gamma and its side reactions were evaluated.A total of 289 patients enrolled in clinical trial, 153 patients in trial group and 136 patients in control group. The routine strategy is given in all patients. In addition, every patient in trial group received rhIFN-gamma at a dose of 1 MU intramuscularly daily for the first three months and 1 MU every other day for the following six months. Patients of two groups were followed up for another three months after the treatment. Histological indices, serum hepatic fibrosis indices, ultrasound B and symptoms and signs evaluated the effect. For patients who accepted two liver biopsies before and after treatment, the effect was determined by semiquantitative score system while for patients who did not accepted liver biopsy, serum hepatic fibrosis indices and ultrasound B were major criteria.The efficient of treatment were 66% in trial group vs. 16.2% in control group and the obviously efficient of treatment was 27.8% in trial group vs. 7.4% in control group (P0.001). For patients who accepted two liver biopsies before and after treatment, the efficient of treatment was 63% in trial group vs. 24.1% in control group and the obviously efficient of treatment was 27.8% in trial group vs. 13.8%. For patients who did not accepted liver biopsy, the efficient of treatment was 67.7% in trial group vs. 14.0% in control group and the obviously efficient of treatment was 22.2% in trial group vs. 5.6%. None of patients emerged serious side reactions during clinical trial.The results confirmed that rhIFN-gamma have a better anti-hepatic fibrosis effect to patients with chronic hepatitis B.

To investigate the clinical usefulness of noninvasive diagnostic methods in evaluating liver fibrosis in hepatitis B virus (HBV) patients.102 patients with chronic hepatitis B (CHB) were enrolled from Beijing Friendship Hospital Affiliated to Capital University of Medical Sciences. Noninvasive diagnostic methods including ultrasonography, CT, serum markers of liver function and fibrosis, and HBV DNA were performed and compared with histological fibrotic changes in order to establish a noninvasive method for detecting the degree of liver fibrosis.The total score of liver surface, edge, parenchyma echogenicity, intrahepatic vessels, and the size of spleen had a coefficient of 0.822 with fibrotic stage. By receiver operating curve (ROC) analysis, the sensitivity to distinguish cirrhosis from CHB was 86.1% and the specificity was 95.5% if the total ultrasonic score was more than 10. The CT imaging diagnosed liver cirrhosis with a specificity of 100% and a sensitivity of 48.5%. The change of CT values in cirrhotic patients was lower than that in controls and no cirrhotic patients (F=5.805, P0.01), when the voltage was increased from 100 KV to 140 KV. Except normal controls and S1 group, S2 and S3 group, the level of HA and collagen IV between the other groups were statistically different. The cut-off value of HA to diagnose cirrhosis was 108 (microg/L) with a sensitivity of 72.2% and a specificity of 80.3%. The cut-off value of collagen IV to diagnose cirrhosis was 188 (microg/L) with a sensitivity of 72.2% and a specificity of 78.8%. When ultrasonography was combined with serum markers, the sensitivity was 72.2% and the specificity was 80.3%.Both ultrasonography and serum markers are useful to diagnose cirrhosis. The combination of the two examinations is more valuable than any one alone. The characteristic CT imaging has high specificity but low sensitivity in diagnosing early cirrhosis. HA and collagen IV are correlated more closely with the stage of fibrosis, and can reflect the severity of fibrosis.