The clinical characteristics of primary biliary cirrhosis in China: a systematic review / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To summarize the clinical features, diagnosis and treatment of patients with primary biliary cirrhosis (PBC) in China.</p><p><b>METHODS</b>Systematic analysis of clinical characteristics by searching the Chinese literatures.</p><p><b>RESULTS</b>From 1955 to 2007, 2740 PBC patients were reported in 103 papers (duplicated reports were deleted). The detailed information of 985 patients from 16 papers were collected. Female : male was 6.82:1. The age range was 42 to 56.2-year-old. The time from onset to diagnosis was 12 to 98.4 months. The most common symptoms were fatigue (72.40%), jaundice (67.41%), anorexia (68.58%) and pruritus (45.60%). 20% patients were asymptomatic at onset. The most frequent physical signs were splenomegaly (57.53%), hepatomegaly (43.56%) and ascites (18.45%). Serum alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (GGT) levels were markedly elevated in most of these patients. The immunological marks of AMA and M2 were positive in 88.98% and 82.65% patients, respectively. The most common comorbidity were Sjögren syndrome (9.14%), rheumatoid arthritis (3.95%) and diabetes type II (2.54%). Of the 507 patients treated with ursodeoxycholic acid (UDCA), 345 patients got complete or partial clinical biochemical response. The common complications were gastrointestinal bleeding (41.67%) and liver failure (41.67%). Liver transplantation was the only effective way for the treatment of the end-stage liver disease.</p><p><b>CONCLUSION</b>The clinical feature of primary biliary cirrhosis in China was similar to the overseas literatures. Further research should focus on epidemic investigation, early diagnosis, long term follow up of asymptomatic patients, immunological mechanism and the efficacy of liver transplantation.</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>

A study of the dosage and efficacy of entecavir for treating hepatitis B virus / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the antiviral activity and safety of entecavir in patients with chronic HBV infection as a preliminarily step in selecting 0.1 mg or 0.5 mg as a better dosage for a further large scale clinical trial.</p><p><b>METHODS</b>This was a randomized, double-blinded, placebo-controlled and dose-ranging trial of entecavir usage in 212 patients with chronic HBV infection. The patients were randomly assigned to 3 groups: 0.1 mg entecavir (69), 0.5 mg entecavir (72) and, placebo (71) groups and treated for 28 days. The patients were then followed for 56 days without treatment.</p><p><b>RESULTS</b>The proportion of subjects who achieved the primary endpoint at day 28, with their HBV DNA level decreased >2 log or undetectable, was significantly greater in the entecavir 0.1 mg and 0.5 mg dose groups compared with the placebo group (P < 0.01 for both comparisons). The mean change from baseline in HBV DNA levels at day 28 was greater for entecavir 0.1mg and 0.5 mg groups compared with the placebo group (both P < 0.01). The mean change from baseline in HBV DNA levels at day 28 for entecavir 0.5 mg group was greater than that of the entecavir 0.1 mg group (P < 0.01). During the 56-day post-dosing follow-up phase, the entecavir 0.5 mg group was associated with greater and more sustained suppression of viral replication than the entecavir 0.1 mg group (P < 0.01). There were no clinically meaningful differences in the incidence of any adverse events between the entecavir dosing and the placebo groups.</p><p><b>CONCLUSION</b>Entecavir at both 0.1 mg and 0.5 mg doses demonstrated superior antiviral activity compared with a placebo. Since the entecavir 0.5 mg dose appears to have greater antiviral activity than the 0.1 mg dose and with a comparable safety and tolerability profile, the 0.5 mg entecavir dose could be used in further trials.</p>

Durability of HBeAg seroconversion in lamivudine treatment of chronic hepatitis B patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the factors which may affect the rate of HBeAg seroconversion and its durability after long-term lamivudine therapy in chronic hepatitis B patients.</p><p><b>METHODS</b>81 patients were treated in a phase III clinical trial with lamivudine 100 mg daily for up to 5 years. The mean period of treatment was (48.84+/-10.52) months (range: 16 approximately 60 months). When HBeAg seroconversion occurred in the patients, which was defined as loss of HBeAg and detection of anti-HBe antibody, HBV DNA level less than 10 mEq/ml more than two times (once every 3 months), the lamivudine treatment was stopped and they were followed-up for another 6 approximately 12 months. The HBV DNA level was detected using Branched DNA assay (Chiron). The HBV markers were detected using IMX assay (Abbott). HBV genotyping was performed using type-specific PCR. The data were analyzed using logistic multivariant analysis.</p><p><b>RESULTS</b>(1) The distribution of HBV genotypes was as follows: type B, 17 (20.97%), type C, 62 (76.54%), and type B+C, 2 (2.47%). (2) 26 patients achieved HBeAg seroconversion (32.10%). The annual seroconversion rates were 16.05% (13/81) in the 1st year, 19.75% (16/81) in the 2nd, 27.16 % (22/81) in the 3rd, 28.40% (23/81) in the 4th and 32.10% (26/81) in the 5th year. Four patients had a reappearance of HBeAg and an elevation of HBV DNA. Therefore the stability ratio was 84.62% (22/26). The mean baseline ALT and HBV DNA levels in those who were seroconvered were (104.8+/-86.3) U/L and (940.1+/-1123.7) mEq/ml, respectively. Mean baseline ALT and HBV DNA of non-seroconverters were (48.3+/-46.9) U/L and (2152.3+/-3063.5) mEq/ml. There was a significant difference between the two groups shown by Kruskal-Wallis Test (P < 0.05). Analysis by logistic multivariate analysis showed that the rate of HBeAg seroconversion and its durability rate correlated with a high baseline ALT. In contrast, a relatively low seroconversion rate and durability rate was observed in patients with high baseline HBV DNA. The durability rate also correlated with additional lamivudine treatment after HBeAg seroconversion.</p><p><b>CONCLUSION</b>Continuation of lamivudine therapy for more than 6 months after HBeAg seroconversion might increase the durability of response.</p>

Efficacy and safety in chronic hepatitis B adolescent patients with lamivudine therapy / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To analysis the efficacy and safety of lamivudine (made in China) therapy for 52 weeks in adolescent patients with chronic hepatitis B (CHB).</p><p><b>METHODS</b>One hundred and five teenage CHB patients were treated with lamivudine 100 mg once daily for 52 weeks. Patients with elevated ALT at baseline were in group 1 and those with normal ALT were in group 2. The changes of HBV DNA, HBV seromarkers and ALT at the end of 12, 24 and 52 weeks after lamivudine therapy were compared with those at baseline. Adverse events were recorded and evaluated.</p><p><b>RESULTS</b>At the end of 52 weeks of lamivudine therapy, HBV DNA-ve, HBeAg loss and anti-HBe seroconversion were observed in 92.0%, 24.4% and 22.0% in group 1 patients and 76.1%, 14.2% and 14.2% in group 2 patients respectively. No significant differences were found between two groups. At 12, 24 and 52 weeks, normalization rates of ALT were 59.0%, 66.7% and 76.0%, normal ALT with undetectable HBV DNA were 44.9%, 64.1% and 70.7% at the same time. During 52 weeks lamivudine treatment 26 mild adverse events were observed in 18 patients.</p><p><b>CONCLUSION</b>Lamivudine can inhibit HBV replication rapidly and normalize ALT in majority adolescent CHB patients. HBeAg loss or seroconversion of anti-HBe was observed in some of these patients. All patients in this study were safety and well tolerated.</p>

Liver histological changes after lamivudine treating in chronic hepatitis B patients with HBeAg positive / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To investigate the histological changes in liver biopsy tissues taken from chronic hepatitis B patients with HBsAg and HBeAg positive and ALT abnormal after lamivudine therapy for one year.</p><p><b>METHODS</b>Lamivudine was given orally at the dose of 100 mg once a day for one year. 101 patients were enrolled into this open-label study. Paired liver biopsies from patients with hepatitis B before and after therapy with lamivudine were studied. Blinded biopsies were evaluated by a histopathologist and scored according to Knodell's histology activity index(HAI).</p><p><b>RESULTS</b>53.5% (54/101), 51.5% (52/101) and 31.7% (32/101) patients had a reduction of their total hepatic HAI score, necroinflammation and fibrosis scores by >or=2 points or 1 points at the end of one year of lamivudine therapy, compared with their pretreatment values, respectively. There were significant reduction of HAI score, necroinflammation and fibrosis scores from 8.0+/-4.7 to 5.2+/-3.3 (t=7.358, P<0.01), from 5.9+/-3.8 to 3.6+/-2.5 (t=7.298, P<0.01), and from 2.1+/-1.2 to 1.6+/-1.2 (t=3.827, P<0.01), respectively. The histological improvement was independent on the HBeAg seroconvertion during the therapy.</p><p><b>CONCLUSION</b>Significant improvement in liver histology, both necroinflammation and fibrosis, can be obtained in the majority of patients treated with lamivudine for one year.</p>

Chronic hepatitis B treated with domestic manufactured lamivudine in 2200 patients: a phase IV study / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To further verify the efficacy and safety of locally manufactured lamivudine on patients with chronic hepatitis B (CHB).</p><p><b>METHODS</b>2200 patients with CHB were recruited and received lamivudine orally 100 mg once daily for 12 months. The efficacy assessments included virologic response rate (defined by the absence of serum HBV DNA, HBeAg loss and HBeAg/HBeAb seroconversion), percentage of patients with normalization of alanine aminotransferase (ALT). Meanwhile improvement of quality of life (QOL) measured by mos SF-36 QOL questionnaire and liver histology evaluation were conducted in some patients. The safety assessments included adverse events, serious adverse events and laboratory abnormalities. All 2200 patients received at least one dose of medication and were all included in the safety population.</p><p><b>RESULTS</b>Ninety seven percent of patients (2137/2200) recruited were HBV DNA positive by dot blot (sensitivity GRT or equal to 1.0 pg/ml) at baseline. At the end of 12 months treatment, HBV DNA was undetectable in 80% patients (1538/1920) with HBV DNA positive before treatment. Among the 79%(1744/2200) of the patients recruited had positive HBV DNA accompanied abnormal ALT levels at baseline, 72% patients became ALT normal. And among the 84% (1843/2200) of the patients recruited were HBV DNA and HBeAg positive, anti-HBe negative, 16% (269/1650) patients achieved HBeAg/HBeAb seroconversion after 12 months of lamivudine treatment. The HBeAg/HBeAb seroconversion rate was positive correlation to the ALT level before treatment. A total of 304 patients completed the health-related QOL questionnaire. After 12 months treatment, lamivudine improved both their physical and mental health, especially for their mental health. 133 evaluable, paired liver biopsies were obtained for histological assessment, among whom 115 patients had abnormal ALT levels at baseline. Compared with pre-treatment most of their liver injury got alleviated (51.9%) or no further deterioration (36%), only 12% worsening. During the 12 months treatment, 9% patients withdrew from the study and 17% patients showed at least one adverse event, mild or moderate. There were no obvious difference between this study and the previously reported lamivudine Phase II or III study with regard to the kinds, incidence and severity of adverse events.</p><p><b>CONCLUSION</b>The efficacy and safety profile of the locally manufactured lamivudine 100 mg tablets are similar with those of the previously reported available lamivudine tablets imported in treating Chinese chronic hepatitis B patients.</p>

Drug induced liver injury associated with Chinese herbal medicine and herbal related food supplements / 中华消化杂志

Objective To investigate the drug induced liver injure(DILI)associated with Chinese herbal medicine and herbal related food supplements.Methods From 1982 to 2005.8.9 consecutive pa- tients were diagnosed as DILI based on their medication history,clinical manifestation,liver function and other laboratory tests.The final retrospection confirmatory diagnosis was made according to the interna- tional scoring system for DILI.Results The 82 DILI patients(28 men,54 females,age ranging from 16 to 81 years old)accounted for 2.2% of hospitalized patients with liver dysfunction.Among those patients with DILI,30.5% was caused by weight reducing drugs or food supplements,12.2% by drugs of derma tology,8.5% by drugs for cardiovascular disease,8.5% by drugs of rheumatology,7.3% by drugs of gynecology,6.1% by drugs for liver disease,6.1% by blood-lipids modulators,3.7% by drugs for thy- roid disease,3.7% by drugs for hyperplasia of mammary glands and 13.4 % by the others.The duration of medication was from 6 clays to 6 months and the incubation period was from 6 days to 3 months.DILI could be classified as acute hepatocellular injury(36.59%),acute cholestasis(39.02%)and mixtures (24.39%).About 10% patients were accompanied by allergic manifestations.All patients recovered rap- idly after stopping the relevant medicine.Conclusion Chinese herbal medicine and herbal related food supplements are a common cause of DILI in China.The awareness and monitoring improving DILI during herbs treatment is a critical issue in daily practice.