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— The acute effects of Nifedipine on hepatic venous pressure gradient (HVPG) and estimated hepatic blood flow (EHBF) were investigated in six patients with HBsAg-positive cirrhosis and portal hypertension by simultaneous hepatic venous catheterization. The mean arterial pressure significantly decreased by 18% at 1 h after sublingual administration of 10 mg Nifedipine. Significant increases in heart rate (13%) and cardiac output (20%) were also demonstrated in our patients 1 h after administration of Nifedipine. However, there were no significant changes in HVPG and EHBF after Nifedipine. We conclude that in patients with HBsAg-positive cirrhosis who receive Nifedipine, EHBF is maintained despite a substantial change in systemic hemodynamics, and that Nifedipine is not effective in acutely reducing HVPG.

The aim of the study was to evaluate the safety, immunogenicity, and possible therapeutic effect of hepatitis B vaccine in patients with chronic hepatitis C. The subjects studied included three groups: group I, 26 patients with chronic hepatitis C who were susceptible to hepatitis B virus infection; group II, 35 healthy subjects who were susceptible to both hepatitis B and hepatitis C virus infection; and group III, 30 patients with chronic hepatitis C receiving no hepatitis B vaccination as controls. Three 20 microg/dose of recombinant hepatitis B vaccines were given to subjects of groups I and II in months 0, 1, and 6. Blood samples from the subjects were collected before and 1 month after each dose of vaccination for serological testing. The subjects of groups I and II had similar antibody to hepatitis B surface antigen (anti-HBs) response rates after the first (30.8% vs. 17.1%), second (61.5% vs. 60.0%), and third (88.5% vs. 91.4%) doses of vaccination. Also, their geometric mean titers of anti-HBs did not differ much when vaccination completed in 7 months (360 vs. 581 mIU/ml). During vaccination period, patients with chronic hepatitis C demonstrated no significant change of serum cytokines and HCV RNA levels, but significantly lowered ALT levels after three doses of vaccination. Hepatitis B vaccination is safe and immunogenic in patients with chronic hepatitis C. It did not significantly affect their levels of HCV RNA, but tended to lower ALT levels.

This open, randomized study was conducted in healthy Chinese youngsters, aged between 10 and 19 years to compare the reactogenicity and immunogenicity of two vaccines: the combined vaccine against hepatitis A and B was administered in a two-dose schedule with the profile of the corresponding monovalent vaccines, while the concomitant vaccine was administered also on a two-dose schedule but simultaneously in opposite arms. All vaccinees had antibodies against hepatitis A (anti-HAV) after the 2-dose administration, whereas all but four in the first and two in the second group had protective titres against hepatitis B (anti-HBs). At month 7, the geometric mean titres for both antibodies were more than double for the group of subjects receiving the combined vaccine: 3,701 vs. 1,705 mIU/ml for the anti-HAV, and 1,524 vs. 720 mIU/ ml for the anti-HBs response. Injection site pain was the most commonly reported local symptom and headache was the most reported general symptom. It is concluded that this combined vaccine against hepatitis A and B, administered according to a two-dose schedule, is well-tolerated and highly immunogenic.

We conducted this follow-up study to evaluate the long-term immunogenicity of an inactivated hepatitis A vaccine in children. Ninety-six children who had seroconversion to antibody to HAV (anti-HAV) after receiving a three-dose schedule of inactivated hepatitis A vaccine were enrolled into this study. Sixty months after the initial vaccination, all vaccinees who received annual follow-up still had protective levels of anti-HAV. The geometric mean titer (GMT) of anti-HAV, peaking at month 7 (4133 mIU/mL), kept declining throughout the follow-up period. The GMTs in months 12, 24, 36, 48 and 60 were 1722, 896, 896, 645 and 403 mIU/mL, respectively. Nine of the vaccinees were hepatitis B virus carriers. Their anti-HAV titers tended to be lower than those of the remaining vaccinees at all time-points, but the difference was not significant (p > 0.05). Natural booster was noted in one vaccinee during the follow-up period. In conclusion, inactivated hepatitis A vaccine is safe and immunogenic in children, the duration of protection against HAV infection is longer than five years.

The safety and immunogenicity of inactivated hepatitis A vaccine was evaluated in patients with chronic liver disease. Sixty hepatitis A virus antibody (anti-HAV) seronegative patients A virus antibody (anti-HAV) seronegative patients with chronic liver disease (56 chronic hepatitis B and four chronic hepatitis C) and from 17 to 47 years of age received a dose of 1440 ELISA units of the inactivated hepatitis A vaccine at month 0, and a booster at month 6. Anti-HAV seroconversion (⩾ 33 mlU/mL) was 57.6% (34/59) on day 15, and reached 93.2% (55/59) 1 month after primary vaccination. At month 6, the seropositivity of anti-HAV decreased before the booster to 69.0% (40/58). All vaccinees had measurable titers of anti-HAV 1 month after booster vaccination, and were still seropositive at month 12. After initial vaccination, the geometric mean titers of anti-HAV among vaccine responders were 158, 264, 74, 1309, and 409 mlU/ml at day 15 and months 1, 6, 7, and 12. Overall, 59.7% (71/119) of the vaccine doses administered were followed by mostly minor reactions. The majority of symptoms reported were local, all of which resolved within 3 days after vaccination. No significant changes in serum liver enzyme levels were detected after vaccination. Thus, an inactivated hepatitis A vaccine was safe in patients with chronic liver disease while the immune response was inferior to that observed in healthy subjects reported in a previous study. J. Med. Virol. 52:215–218, 1997. © 1997 Wiley-Liss, Inc.

Plasma endotoxin levels were investigated using a quantitative Limulus assay in patients with chronic liver diseases and correlated with the severity of liver diseases, the presence of esophageal varices, and hemodynamic parameters. The plasma endotoxin levels were significantly higher in chronic hepatitis patients with acute exacerbation (10.1 +/- 1.3 pg/ml, n = 13, p0.05) and patients with cirrhosis (7.0 +/- 0.7 pg/ml, n = 126, p0.05) than in healthy subjects (2.9 +/- 0.2 pg/ml, n = 45). Chronic hepatitis patients (n = 30) had plasma endotoxin levels which were similar to those in healthy subjects (4.6 +/- 0.5 vs. 2.9 +/- 0.2 pg/ml, p0.05) but lower than those in chronic hepatitis patients with acute exacerbation (4.6 +/- 0.5 vs. 10.1 +/- 1.3 pg/ml, p0.05). Endotoxemia (plasma endotoxin level5.7 pg/ml) was found in 27%, 85% and 41% of patients with chronic hepatitis, chronic hepatitis with acute exacerbation, and cirrhosis, respectively. In patients with cirrhosis, the plasma endotoxin levels progressively increased in relation to the severity of liver dysfunction (Pugh's class A/B/C = 4.9 +/- 0.5/7.9 +/- 1.4/10.2 +/- 2.0 pg/ml, p0.05). In contrast, plasma endotoxin levels were comparable between patients with cirrhosis with and without esophageal varices (p0.05). Chronic hepatitis patients with acute exacerbation (no collaterization) had much higher plasma endotoxin levels than those in patients with cirrhosis and large varices (p0.05), whereas compensated patients with cirrhosis and large esophageal varices had plasma endotoxin levels similar to those seen in chronic hepatitis patients (no collaterization) (p0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

We tested serum samples from 25 fulminant hepatitis and 7 subfulminant hepatitis patients for hepatitis A, B, C, D and E viral markers and nucleic acids by means of polymerase chain reaction to determine the role of each virus on such catastrophic events in an area endemic for hepatitis B. Of these 32 patients, 14 (44%) were hepatitis B virus carriers with hepatitis D virus superinfection (1 with hepatitis C virus infection), 3 others had coexisting hepatitis B virus and hepatitis C virus infections, 6 had reactivation of underlying chronic hepatitis B, 4 had acute hepatitis B, 2 had acute hepatitis C and 1 had acute hepatitis E

Recently, with an available serological hepatitis E virus diagnostic kit, the prevalence of IgG antibody to hepatitis E virus among Chinese subjects in Taiwan was evaluated by means of a solid-phase enzyme-linked immunoassay based on two recombinant hepatitis E virus antigens. The overall prevalence of hepatitis E virus antibody was 10.7% among 384 healthy subjects older than 20 yr but only 0.3% among 600 schoolchildren and young adolescents younger than 20 yr (p

To evaluate the efficacy of recombinant interferon alpha-2b in the treatment of patients with acute post-transfusion hepatitis C, a randomized controlled trial was conducted in 33 acute post-transfusion hepatitis C patients; 16 patients received 3 million units of subcutaneously injected recombinant interferon alpha-2b 3 times a week for 3 months and 17 patients without specific treatment were used as controls. At the end of the interferon treatment, 13 (81%) patients in the interferon-treated group normalized serum alanine aminotransferase compared with only six (35%) patients in the control group (p0.01). One year after completion of the interferon treatment, nine (56%) patients in the interferon-treated group and six (38%) patients in the control group normalized serum alanine aminotransferase (p = 0.35). Serum HCV-RNA measured by reverse transcription-polymerase chain reaction was positive in all patients at the time of enrollment and then became undetectable in 13 (81%) patients in the interferon-treated group and two (12%) patients in the control group at the end of interferon treatment (p0.001). One year after completion of the interferon treatment, seven (44%) patients in the interferon-treated group and two (13%) patients in the control group had persistent undetectable serum HCV-RNA (p = 0.08). Using a logistic regression model, the lower pretreatment level of serum HCV-RNA measured by quantitative branched DNA signal amplification assay was the only predictor for a favorable response to the interferon treatment in acute hepatitis C patients.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of octreotide on postprandial hemodynamic responses were evaluated in 20 patients with postnecrotic cirrhosis. They were randomly assigned to receive either a 100-micrograms bolus with a 100-micrograms/h infusion of octreotide or a placebo. Placebo administration did not affect any of the hemodynamic values. However, after a liquid meal of 500 kcal, postprandial increases in the hepatic venous pressure gradient and hepatic blood flow were observed in patients receiving placebo, while the systemic hemodynamic values remained unchanged. In contrast, in patients receiving octreotide, the hepatic blood flow was significantly decreased 30 min after administration, while the hepatic venous pressure gradient and the systemic hemodynamic values were not affected. After ingestion of a meal, the mean values of the hepatic blood flows were not significantly different from basal values. Moreover, the wedged hepatic venous pressure, the hepatic venous pressure gradient and the systemic hemodynamic values were not affected by meal ingestion. However, during octreotide infusion, hepatic blood flow 30 min after the meal had a tendency to increase compared to before the meal. In conclusion, octreotide inhibited the postprandial increase in portal pressure in patients with postnecrotic cirrhosis. In addition, octreotide decreased hepatic blood flow in the fasting state. When given before a meal, the increase in blood flow induced by the meal restored the hepatic blood flow to basal levels.

The preliminary results of a prospective double-blind controlled trial of colchicine in 100 patients with hepatitis B virus-related cirrhosis are reported. The patients, 94 males and 6 females, aged 32-80, were assigned to receive either 1 mg of colchicine or an identical placebo orally on a daily basis. The duration of the follow up ranged from 15 to 51 months (median 26 months). Seventy percent had histological proof of cirrhosis. On entry, 80 patients were in Child-Pugh class A, 19 were in class B, and one was in class C. Compared to the placebo group, there was no improvement in the colchicine group after a 24-month follow up in any of the biochemistry data, for example, serum albumin, alkaline phosphatase, alanine and aspartate aminotransferase, bilirubin, and prothrombin time. The difference in the cumulative survival rates at 51 months did not reach statistical significance (p = 0.8) in either group. There was no histological improvement in 30 patients who were willing to undergo repeated liver biopsies. No trend toward improvement of the hepatic pressure gradient was observed in these patients. The serum levels of aminopropeptide of type III procollagen increased significantly in patients in both groups after 24 months of therapy (1.07 +/- 0.06 vs. 1.36 +/- 0.06 U/ml in the colchicine group, 0.93 +/- 0.09 vs. 1.25 +/- 0.07 U/ml in the placebo group; p0.05). In addition, neither the clinical deterioration of cirrhosis nor death was prevented in patients receiving colchicine therapy. This report indicates that colchicine has no effect in the treatment of HBV-related postnecrotic cirrhosis.

To evaluate the effectiveness of screening test for antibody to hepatitis C virus (anti-HCV), the incidence of acute post-transfusion HCV infection in patients who underwent cardiovascular surgery and received blood transfusion was studied. All patients were followed prospectively with serum biochemistry tests and viral hepatitis markers before and periodically for at least 6 months after cardiovascular surgery. None of them had history of liver disease and none tested positive for anti-HCV prior to blood transfusion. Before blood donors were screened for anti-HCV with a second-generation HCV diagnostic kit, 28 (12.4%) of 226 patients or 0.49% of 5,690 unit transfusion had seroconverted to anti-HCV during a 6-month follow-up. The incidence of post-transfusion hepatitis (PTH) C in 91 patients who had received 1-12 units transfusion was significantly lower than in 135 patients who had received more than 12 units transfusion (6.6 vs. 16.3%, p < 0.05). However, none of the 87 transfused patients, since anti-HCV screening in July 1992, developed PTH C (p < 0.05). The result demonstrates that screening for anti-HCV by a more sensitive second-generation HCV diagnostic assay may protect the patients studied from PTH C. It further provides a firm argument for the necessity of a nation-wide blood donor screening.

Sixty adult patients with acute viral hepatitis B (AVHB) and 93 controls were interviewed to assess potential risk factors of hepatitis B. Heterosexual contact was the only significant factor, and it was associated with 83% of cases. A history of having new sex partners or multiple sex partners within 6 months before the onset of AVHB or first sexual contact before 20 years of age were significantly associated with HBV infection (P < .005, respectively). There was a dose-response relationship between the number of sex partners and the risk of HBV infection. In multivariate analyses, a history of having new sex partners was the most important factor. Moreover, 18 of 24 sex partners of the patients were serum hepatitis B surface antigen- and HBV DNA-positive. Heterosexual contact is, therefore, the predominant route of HBV transmission among adults in Taiwan. Susceptible adults should receive vaccination.

Lidocaine is metabolized to form monoethylglycinexylidide (MEGX) via oxidative N-deethylation in the liver. To assess the clinical value of this lidocaine metabolite as a quantitative liver function test, we measured the serum MEGX concentration 15 min after intravenous administration of a single dose of lidocaine (1 mg/kg) in 24 adults with chronic hepatitis, 47 patients with cirrhosis and 26 normal controls. A fluorescence polarization immunoassay was used to obtain the MEGX value. The MEGX concentration in controls was 67 (54-95) ng/ml (median with 16th-84th percentile in parentheses), which was higher than 43 (23-61) ng/ml in patients with chronic hepatitis and 24 (7-52) ng/ml in those with cirrhosis (P0.05). In addition, the serum MEGX levels are proportional to the galactose elimination capacity, and inversely proportional to Pugh's score, the prothrombin time and indocyanine green retention ratio. If a MEGX concentration of below 54 ng/ml is taken as an indicator of hepatic dysfunction, its diagnostic sensitivity for hepatic disorder is 84.5%, specificity 88.5% and accuracy 85.6%. Furthermore, after a 10-month follow-up, patients with MEGX formation above 30 ng/ml had a higher survival rate than those with a MEGX concentration below this level (P = 0.004). In conclusion, the MEGX formation test reflects the severity of hepatic dysfunction quite well, making it valuable both in the quantitative evaluation of liver function and in the prognostic prediction of adults with liver diseases.

In an attempt to interrupt perinatal and postnatal transmission of hepatitis B virus (HBV) infection, hepatitis B vaccine trials were initiated in October 1981 in Taiwan, starting in neonates of hepatitis B e antigen (HBeAg)-positive hepatitis B surface antigen (HBsAg) carrier mothers and extending to neonates of non-carrier mothers. All neonates had received a four-dose schedule of Pasteur plasma-derived hepatitis B vaccine. Among neonates of HBeAg-positive HBsAg carrier mothers, the protective efficacy rate of vaccination was 75% in those who received vaccine alone and 90% in those who received vaccine plus hepatitis B immunoglobulin (HBIG) at birth. Among neonates of HBeAg-negative HBsAg carrier mothers, the protective efficacy rate was 100% whether they had received vaccine alone or vaccine plus HBIG at birth. The protective efficacy rate was also 100% in neonates of non-carrier mothers. During 6–9 years of long-term follow-up, 12 (6%) responsive vaccinees of HBeAg-positive carrier mothers, one (2%) child of HBeAg-negative carrier mothers and one child (0.4%) of non-carrier mothers had seroconverted to antibody to hepatitis B core antigen (anti-HBc) positivity. ‘Natural booster’ phenomenon, defined as a spontaneous sharp rise in serum antibody to HBsAg (anti-HBs) titres in the absence of anti-HBc and HBsAg, was observed in 7% of vaccinees whose mothers were HBeAg-positive, 6% of vaccinees whose mothers were HBeAg-negative HBV carriers, and 8% in vaccinees of non-HBV carrier mothers. None of the responsive vaccinees had seroconverted to HBsAg. Thus, in the first decade of life, the protective efficacy in neonates who responded to plasma-derived hepatitis B vaccine was 100%.

The hemodynamic effects of octreotide were studied in 20 patients with hepatitis B-related cirrhosis. In patients receiving a 100-micrograms bolus and a 100-micrograms/h infusion, heart rate, cardiac index, and systemic vascular resistance showed no significant changes, whereas right atrial pressure, pulmonary capillary wedge pressure, and inferior vena cava pressure decreased significantly after octreotide infusion compared with basal values. In contrast, in patients receiving a 50-micrograms bolus and a 50-micrograms/h infusion, all the systemic hemodynamic values were unaffected. In both groups of patients receiving two different doses of octreotide, the estimated hepatic blood flow, hepatic indocyanine green clearance, and wedge hepatic venous pressure were significantly reduced at 60 minutes after octreotide administration compared with basal values, whereas the hepatic venous pressure gradient remained unchanged. It is concluded that the two different doses of octreotide administration result in the reduction of the wedge hepatic venous pressure and the hepatic blood flow of a similar magnitude, whereas the hepatic venous pressure gradient is unaffected. Octreotide induces discrepant systemic hemodynamic response; this effect is dose related.

To investigate whether Sengstaken-Blakemore tube tamponade is needed before emergency sclerotherapy, 60 patients with active esophageal variceal bleeding were randomized to receive either immediate injection sclerotherapy (group A) or sclerotherapy preceded by balloon tamponade (group B). Three patients in group A (10%) were completely inaccessible to sclerotherapy. Initial success in stopping bleeding at 24 hours after sclerotherapy was 76% in group A and 81% in group B (p = 0.89). Re-bleeding rate was 27% in group A versus 50% in group B (p = 0.11). Blood requirement was significantly less in group A (3.7 +/- 2.5 units vs. 6.2 +/- 3.2 units, p less than 0.01). Major complications were also significantly less frequently encountered in group A than in group B (14% vs. 39%, p less than 0.05). In-hospital mortality was 24% in group A and 42% in group B (p = 0.14). We conclude that the efficacy of immediate sclerotherapy is comparable to that of delayed sclerotherapy preceded by balloon tamponade. Additionally, significantly less blood requirement and fewer complications were noted in the immediate sclerotherapy group. Thus, emergency sclerotherapy without prior balloon tamponade is feasible and recommended in most patients with acute esophageal variceal hemorrhage.

To evaluate the role of hepatitis C virus (HCV) in Chinese patients with hepatocellular carcinoma (HCC), the antibodies to HCV (anti-HCV) were detected by enzyme immunoassay in 41 (12.6%) of the 326 patients with HCC. However, none of 35 patients with metastatic carcinoma of the liver had detectable anti-HCV. The prevalence of anti-HCV was significantly higher in patients with hepatitis B surface antigen (HBsAg)-negative HCC than those with HBsAg-positive HCC (37.3% versus 4.1%, P < 0.0001). However, the prevalence of anti-HCV was much higher in patients with HCC with negative results for HBsAg and antibody to hepatitis B core antigen (54.5%). The mean age of patients with HCC with positive results for anti-HCV was significantly greater than that of patients with HBsAg-positive HCC (65.1 versus 55.5 years, P c 0.0001). Alpha-fetoprotein levels greater than 20 ng/ml were found in 70.7% of patients with HCC with positive results for anti-HCV and in 73.3% of patients with HBsAg-positive HCC. Of the Chinese patients with HCC, 74.5% had HBsAg-positive results and 96.6% had positive results for antibody to hepatitis core antigen. These data indicate that, although HCV may play an etiologic role in HCC, hepatitis B virus is still the most important causal agent among most Chinese patients with HCC. Cancer 1992: 69:342-345.

In an attempt to investigate the incidence and clinical course of type C viral hepatitis among patients with posttransfusion hepatitis, antibodies to hepatitis C virus (anti-HCV) in sera were measured from 42 prospectively followed cardiovascular surgery patients who developed hepatitis after blood transfusions. Of these, 35 (83.3%) had anti-HCV seroconversion during a 6- to 12-month follow-up period. The mean interval between blood transfusion and onset of active anti-HCV seroconversion was approximately 3 months after the first elevation of serum alanine aminotransferase levels (18.1 vs. 6.4 weeks). There was no correlation between fluctuations in serum alanine aminotransferase levels and anti-HCV titers. Of 26 patients with type C posttransfusion hepatitis who were followed greater than 1 year, 20 (76.9%) continued to have abnormal serum alanine aminotransferase levels. The results indicate that HCV is the major agent of posttransfusion hepatitis in Taiwan. Furthermore, it plays an important role in chronic hepatitis among transfused patients.

The prevalence of antibody to hepatitis C virus among Chinese subjects in Taiwan was evaluated using a commercially available enzyme immunoassay. The overall prevalence of antibody to hepatitis C virus was 0.28% among 1,419 healthy subjects, 0.8% among 500 unselected paid blood donors and 0.4% among 793 pregnant women. The three offspring of the mothers positive for antibody to hepatitis C virus were all found to be positive for antibody to hepatitis C virus at birth but all became negative by the age of 6 mo. Among healthy subjects, none of 1,000 school children and young adolescents had antibody to hepatitis C virus. Among patients in selected "high-risk" groups, antibody to hepatitis C virus was detected in 100% of 9 hemophiliac patients who were positive for antibody to human immunodeficiency virus, in 53% of 115 intravenous drug abusers, in 34.4% of 96 hemodialysis patient and in 15.8% of 19 homosexual men who were positive for antibody to human immunodeficiency virus. Only 7.1% of 196 prostitutes, 5.9% of 34 spouses of patients positive for antibody to hepatitis C virus and 0.5% of 201 brothelgoers had antibody to hepatitis C virus. These findings suggest that hepatitis C virus is transmitted mainly by the parenteral route in Taiwan. Transmission from mother to infant is not an important mode of spread of hepatitis C virus.

It has been suggested that vasopressin given during hemorrhage may be less effective than when given during a stable state in a portal-hypertensive rat model. This study was designed to evaluate the hemodynamic response to vasopressin infusion in 25 HBsAg-positive cirrhotic patients. Nine patients had active variceal hemorrhage before vasopressin infusion, and the other 16 patients were in a stable condition at the time of infusion. The two groups of patients were similar in baseline values except that a higher heart rate was found in patients with hemorrhage (96 +/- 20 vs. 73 +/- 10 beats/min, mean +/- S.D., p less than 0.01). Thirty minutes after vasopressin infusion (0.66 units/min), hepatic venous pressure gradient significantly decreased in both bleeding and stable patients (from 21 +/- 9 to 18 +/- 9 mm Hg, p less than 0.05; and from 18 +/- 4 to 8 +/- 3 mm Hg, p less than 0.0001, respectively). However, the decrease of hepatic venous pressure gradient was less obvious in bleeding patients as compared with stable patients (4 +/- 3 vs. 9 +/- 2 mm Hg, p less than 0.0001). A significant reduction of hepatic venous pressure gradient after vasopressin infusion was found in five bleeding patients without shock (from a median of 16 mm Hg [range = 12 to 26] to 11 mm Hg [range = 6 to 18], p less than 0.05), but not in four bleeding patients with shock (from 28 [range = 15 to 36] to 25 [range = 18 to 33] mm Hg, p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

In an attempt to evaluate the effect of quinidine in the treatment of patients with cirrhosis and muscle cramps, 31 cirrhotic patients with muscle cramps were randomly divided into two groups and given orally 400 mg of quinidine sulfate per day or placebo, respectively. Baseline clinical and laboratory data for these two groups were similar. Four weeks after oral administration of quinidine, the number of cramps significantly decreased from 14.4 +/- 1.7 (mean +/- S.E.) to 4.4 +/- 1.1 episodes (p less than 0.0001), but it remained unchanged in the placebo group (from 11.8 +/- 1.0 to 11.5 +/- 1.5 episodes, p greater than 0.05). In addition, 88% of the 16 patients on quinidine and 13% of the 15 patients on a placebo showed a greater than 50% reduction in the number of cramps during a 4-week treatment period (p less than 0.0001). The peak and trough serum levels of quinidine in patients having received quinidine for 2 weeks were 1.3 +/- 0.1 and 0.7 +/- 0.1 mg/l, respectively. There was a significant relationship between serum quinidine concentrations and attenuation of cramps. No significant adverse effect was observed during the study, except for five (31%) patients who developed mild diarrhea after quinidine therapy. Diarrhea subsided spontaneously or was controlled by medications without the interruption of quinidine therapy. It was concluded that quinidine is a safe and effective drug for the treatment of cirrhotic patients with muscle cramps.

11/323 patients (3.4%) with symptomatic chronic hepatitis B were positive for antibody to hepatitis C virus (anti-HCV). The positive rate of anti-HCV in patients with serum alanine aminotransferase (ALT) levels greater than 200 U/l (n = 219) did not exceed that of the patients with ALT less than or equal to 200 U/l (n = 104) (2.7% vs. 4.8%). Of the 219 patients who were positive for hepatitis B e antigen (HBeAg) and/or hepatitis B virus-DNA (HBV-DNA), 5 (2.3%) had anti-HCV, while 6/104 patients (5.8%) who were positive for antibody to HBeAg (anti-HBe) had anti-HCV (p greater than 0.1). In contrast to the anti-HCV-negative patients, the patients with anti-HCV had a higher percentage of cirrhosis in their liver histological findings (36.4% vs 5.4%, p less than 0.005). In conclusion, the prevalence of HCV superinfection in symptomatic chronic hepatitis B patients is low and HCV superinfection is not an important factor in acute exacerbation of chronic hepatitis B. However, the superinfection with HCV may exacerbate the existing liver disease and accelerate its progression.

Among 30 consecutive patients diagnosed with primary biliary cirrhosis (PBC) in Taiwan, 27 were females and the median age of symptom onset was 54.5 years. Most had similar clinical manifestations to those reported in the Western countries, but ascites and oesophageal varices as commonly found at the late stages of cirrhosis of liver were noted in nine patients (30%) and 13 patients (43%) respectively. Only one patient was asymptomatic. Hyperbilirubinaemia was noted in 21 patients (70%) and hypoalbuminaemia in 8 patients (27%). All patients had elevated serum alkaline phosphatase and alanine aminotransferase and 28 (93%) had antimitochondrial antibodies. Ten out of 21 patients (48%) were positive in antinuclear antibodies, of which most were of speckled type. Sixteen out of 18 patients (89%) had elevated serum IgM levels. Interestingly, only one of 26 patients (3.8%) was positive for hepatitis B surface antigen, in contrast to its high prevalence (15%) in the Taiwan population. Special associated diseases, including systemic lupus erythematosus, scleroderma, malignant lymphoma and hepatocellular carcinoma, were each noted in one patient respectively. Eight patients had a history of gallstones before the diagnosis of PBC. The mean follow-up period was 23.6 +/- 19.8 months, and nine patients died during that period. In conclusion, the clinical manifestations of PBC in Taiwan are similar to those in Western countries, but most of our cases were at later stages.

Focal hepatic fatty infiltration may be mistaken for hepatic neoplasm on ultrasonography. A sonographic feature mimicking "space occupying lesions" was identified in 41 cases with focal fatty liver, which led to the recognition of four sonographic patterns: (1) Ten patients in whom the livers were characterized by irregular configurations of hyperechoic and hypoechoic areas. Although confusing to inexperienced sonographers, all of them were properly interpreted by experienced sonographers. (2) One patient in whom the hepatic sonography revealed a hyperechoic nodule, but which was correctly diagnosed by computed tomography (CT) scan. (3) Six patients in whom the livers were characterized by multiple confluent hyperechoic lesions, which were all misinterpreted by sonographers and misinterpreted following CT scans in 4 cases and angiography in 3 cases. (4) Twenty-four patients in whom the livers revealed focal spared areas, which was misdiagnosed by sonographers in 14 cases, but correctly diagnosed by CT scan in all 24 cases.

We measured the haemodynamic changes following triglycyllysine vasopressin administration and after addition of nitroglycerin in twelve patients with portal hypertension due to hepatitis B-related cirrhosis. A bolus i.v. injection of triglycyllysine vasopressin at a dose of 2 mg reduced the hepatic venous pressure gradient from 18.5 +/- 3.7 (mean +/- S.D.) to 15.6 +/- 4.0 mmHg, p less than 0.001. However, the cardiac index decreased from 4.8 +/- 1.0 to 3.7 +/- 0.8 l/min m2, p less than 0.001; the heart rate decreased from 79 +/- 15 to 71 +/- 13, p less than 0.01; the right atrial pressure increased from 3.2 +/- 1.9 to 5.3 +/- 2.3 mmHg, p less than 0.001; the mean arterial pressure increased from 92 +/- 13 to 103 +/- 13 mmHg, p less than 0.05; and the systemic vascular resistance rose from 939 +/- 182 to 1367 +/- 310 dyn/s cm-5, p less than 0.001. Furthermore, both mean pulmonary arterial pressure and pulmonary capillary wedge pressure showed a significant increase following triglycyllysine vasopressin administration as compared with baseline values (p less than 0.005). The addition of sublingual nitroglycerin at a dose of 0.6 mg returned all the systemic haemodynamic parameters to baseline levels. On the other hand, nitroglycerin administration caused no further change in the hepatic venous pressure gradient. We concluded that although triglycyllysine vasopressin significantly reduced portal pressure in patients with hepatitis B-related cirrhosis, it produced untoward systemic haemodynamic changes similar to those seen with vasopressin. The addition of nitroglycerin improved the detrimental systemic haemodynamic effects produced by triglycyllysine vasopressin without further reducing the hepatic venous pressure gradient.

To elucidate the effects of verapamil on splanchnic haemodynamics in rats with portal hypertension, verapamil was given at a low dose (0.2 mg/kg) and a high dose (2 mg/kg) to the rat model after portal vein ligation. Approximately 10% decrease in arterial pressure was caused by the low dose of verapamil, with significant decreases in cardiac output and portal venous inflow as well as reduced portal pressure; these were all indicative of a rise in portal vascular resistance. In contrast, the marked fall in both arterial pressure and cardiac output in the high dose, accompanied by a significant decrease in the portal pressure and the unchanged portal venous inflow, suggested a reduction in portal vascular resistance. This study shows that the acute effects of verapamil on portal hypertension may vary with the dosage used. These results also demonstrate that, since the therapeutic efficacy and safety of verapamil is only in a very limited range of dose, caution should be taken in its clinical use in the treatment of cirrhosis with portal hypertension.

Hepatitis B, a disease entity currently affecting more than 350 million persons worldwide, is also a serious health problem in Taiwan. Liver cirrhosis and hepatoma, which are both closely correlated with hepatitis B, are among the 10 leading causes of death in Taiwan. A mass hepatitis B vaccination program, conducted by the government of Taiwan, was started in 1984. Prior to this vaccination program, a series of viral epidemiological surveys, transmission pattern studies, and pilot immunization trials proved the clinical, economic, and strategic benefits of mass immunization, thus providing the impetus for the implementation of this mass vaccination program. The success of this program has led to a decline in hepatitis B carrier rates among children in Taiwan from 10% to

One hundred and eight primary school students who had been vaccinated with three doses of a plasma-derived hepatitis B vaccine were randomly divided into two groups, to receive a booster dose of either the same vaccine or of a recombinant yeast-derived vaccine. The pre-booster anti-hepatitis B surface antigen (HBs) geometric mean titres (GMT) were similar in both groups (281.8 mIU ml-1 versus 295.1 mIU ml-1, p greater than 0.5). One month after booster vaccination, all the vaccinees in both groups had a marked elevation in their anti-HBs titres, the anti-HBs GMT in group 1 and group 2 being 19,952.6 and 51,286.1 mIU ml-1 (p less than 0.05), respectively. In conclusion, the recombinant yeast-derived hepatitis B vaccine was able to elicit an excellent booster response in vaccinees who had originally received a plasma-derived vaccine.

To evaluate the meaning of isolated antibody to hepatitis B core antigen (anti-HBc), 88 Chinese subjects with isolated anti-HBc received rescreening of hepatitis B virus (HBV) markers. Eighty (90.9%) of them were still positive for this antibody and 29 were also found to be positive for antibody to hepatitis B surface antigen (anti-HBs). The remaining 51 subjects (58.0%) were positive for anti-HBc alone; 50 of them received a four-dose schedule of hepatitis B (HB) vaccine. After the initial dose, only one vaccinee disclosed an amnestic anti-HBs response, that is, anti-HBs titre > 1000 miu/mL. Forty-five vaccinees completed the vaccination schedule and 44 (97.8%) had anti-HBs response. The anti-HBs responses in 25 of these vaccinees were compared with 25 age- and sex-matched normal susceptible vaccinees. The anti-HBs response rates in both groups were the same (96 vs 96%). However, the geometric mean titre was significantly lower in the vaccinees with isolated anti-HBc (512 mIU/mL vs 4688 mIU/mL, P < 0.001). Prevaccinated sera were available in 49 vaccinees with isolated anti-HBc for detection of antibody to hepatitis B e antigen (anti-HBe) and HBV DNA; 37 (75.5%) of them had one or two of these markers. As we regarded the rescreening of HBV markers, response to hepatitis B vaccination and presence or absence of anti-HBe and/or HBV DNA together for categorizing the 88 subjects with isolated anti-HBc, at least three-quarters of them had past infection of HBV. The subjects with false positive anti-HBc test were a minor group.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine the value of a quantitative branched DNA (bDNA) assay for detection of hepatitis C virus (HCV) RNA, 309 serum specimens were collected from 100 patients with acute or chronic hepatitis C for detection of HCV RNA by bDNA assay and reverse transcription-polymerase chain reaction (RT-PCR) assay. There were 256 samples positive by RT-PCR; 199 (78%) were also positive by bDNA assay. All but 1 of the remaining 53 samples negative by RT-PCR were also negative by bDNA assay. Combination of the two methods clearly demonstrated changes in HCV RNA titers during and after interferon (IFN) treatment. The most common genotype of HCV infection was Okamoto type II (Simmonds type 1b, 60.0%), followed by type III (type 2a, 16.5%) and type IV (type 2b, 8.2%); mixed or underdetermined types were noted in 15.3%. Patients with chronic type II HCV infection tended to have higher HCV RNA titers. These findings suggest that the bDNA assay is a reliable test for HCV RNA.

One hundred twenty-two hepatitis B surface antigen (HBsAg) carrier infants were followed-up for 8–10 years. One hundred eleven had antibody to hepatitis B core antigen (anti-HBc; 83 had been vaccinated) and the remaining 11 were without anti-HBc (7 had been vaccinated). During the follow-up period, 29 (26.1%) carrier infants with anti-HBc had one or more episodes of ala-nine aminotransferase (ALT) elevation and up to 32.8% (21/64) of the carriers in this group lost their hepatitis B e antigen (HBeAg) before the age of 10. In addition, 2 (1.8%) carriers lost their HBsAg at the age of 3 and 8, respectively. No significant symptom or sign was noted during HBeAg seroconversion. In contrast, all the carrier infants without anti-HBc were still positive for both HBeAg and hepatitis B virus (HBV) DMA and none displayed abnormal ALT levels or any symptom related to liver disease. One became anti-HBc positive at the age of 9, and 5 other carriers had inconsistent borderline or weakly positive titers of anti-HBc. The episodes of ALT elevation and the prevalence of HBeAg seroconversion were not significantly different between immunized carrier infants. In conclusion, HBeAg seroconversion may occur in about one third of the anti-HBc-positive carrier infants during the first decade. On the other hand, the anti-HBc-negative HBsAg carrier infants' immune incompetence to the HBV antigens could persist for more than 10 years. Hepatitis B immunization did not have significant effect on the clinical course in carriers. © 1994 Wiley-Liss, Inc.

Single total paracentesis (4.8-11 L) was performed in 23 patients with hepatitis B surface antigen (HBsAg)-positive cirrhosis and massive ascites and its effects on systemic and hepatic haemodynamics and renal function were examined over 5 days. Severe hypotension occurred in six (26.1%) patients from 6 to 54 h after paracentesis. In the remaining 17 patients, compared to the baseline, there was an increase in the cardiac output (6.1 +/- 0.3 vs 6.7 +/- 0.3 L/min, P < 0.001) and a decrease in right atrial pressure (8.8 +/- 0.8 vs 4.3 +/- 0.7 mmHg, P < 0.001), systemic vascular resistance (1160 +/- 61 vs 976 +/- 50 dyne.s.cm-5, P < 0.001), and wedged hepatic venous pressure 30 min after completion of paracentesis. After 5 days, right atrial pressure, systemic vascular resistance and wedged hepatic venous pressure returned to baseline, while the cardiac output dropped to a level lower than the baseline (5.7 +/- 0.7 L/min, P < 0.05). Hepatic venous pressure gradient had returned to baseline after 5 days. Serial tests of serum creatinine level showed an increase from day 3 (1.34 +/- 0.14 vs 1.04 +/- 0.10 mg/dL, P < 0.05). On day 5, creatinine clearance (55.7 +/- 5.4 vs 41.9 +/- 5.3 mL/min, P < 0.05) and effective renal plasma flow (351 +/- 32 vs 293 +/- 29 mL/min, P < 0.05) were decreased, compared to the baseline. Based on these data, infusion of a volume expander may be necessary for total paracentesis to avoid systemic haemodynamic complications in non-alcoholic cirrhosis.

To evaluate the effect of ribavirin on serum hepatitis C virus (HCV) RNA and alanine aminotransferase (ALT) levels, 22 patients with chronic HCV infection were treated with oral ribavirin 1200 mg daily in three divided doses for 4 weeks. At the end of 4 weeks treatment, the serum ALT decreased in all but one patient and became normal in three individuals. The mean pretreatment serum ALT was reduced significantly from 193 +/- 45 i.u./L to 95 +/- 16 i.u./L after 4 weeks therapy (P = 0.009). However, 8 weeks after cessation of treatment, the serum ALT rose to a mean value of 154 +/- 21 i.u./L. The mean pretreatment serum HCV RNA was not significantly decreased at the end of 4 weeks treatment (7.0 x 10(5) vs. 4.1 x 10(5) copies/mL, P > 0.05). However, serum HCV RNA levels were decreased in 12 and increased in 10 patients at the end of 4 weeks therapy. Eight weeks after cessation of therapy, the serum HCV RNA of 22 patients rose to a mean value of 4.9 +/- 10(5) copies/mL. Six patients who continued to have elevated serum ALT and positive HCV RNA after the initial 4 weeks treatment received oral ribavirin at the same dosage for an additional 24 weeks. The serum ALT again decreased in all six patients during therapy, but rose to pretreatment values by 8 weeks after cessation of the treatment. In addition, no significant changes were noted in the mean serum HCV RNA levels during and after 24 weeks of ribavirin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

A prolonged bleeding time (540 s), measured with a Simplate single template device, was found in 0% of 50 patients with chronic hepatitis and 38% of 154 cirrhotic patients. Cirrhotic patients with a prolonged bleeding time (n = 59) had lower platelet counts (P0.001) and a longer prothrombin time (P0.001) and activated partial thromboplastin time (P0.001) compared with cirrhotic patients with a normal bleeding time (n = 95). A weak but significant negative correlation existed between the bleeding time and platelet count in cirrhotic patients (n = 154, r = -0.3668, P0.001). Patients with decompensated cirrhosis had a longer bleeding time in comparison to patients with compensated cirrhosis (621 +/- 39 vs 478 +/- 27 s, respectively, P0.01). The prolonged bleeding time was also discovered in 25% of 83 cirrhotic patients with a platelet count80 x 10(9)/L and a prothrombin time17 s (usually taken as safe limits for invasive procedures). Twenty-seven of the 83 cirrhotic patients received a haemodynamic study by Swan-Ganz catheterization. A lower systemic vascular resistance was found in cirrhotic patients with an abnormal bleeding time than in cirrhotic patients with a normal bleeding time (844 +/- 57 vs 1171 +/- 60 dyne.s.cm-5, respectively, P0.001), whereas both groups had similar hepatic venous pressure gradient (16.2 +/- 1.2 vs 18.1 +/- 1.4 mmHg, respectively, P0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

A transjugular liver biopsy was performed on 60 patients. Specimens were successfully obtained from 57 (95%) patients. Specimens obtained from cirrhotic patients were frequently small-sized/fragmented. The wedge hepatic venous pressure and hepatic venous pressure gradient were higher in patients with small-sized/fragmented specimens than those with non-fragmented specimens (16.3 +/- 6.4 vs 12.3 +/- 4.9 and 10.9 +/- 6.2 vs 7.3 +/- 3.4 mmHg, P < 0.05, respectively). During the same period of time, percutaneous liver biopsies were consecutively performed on 277 patients. The liver specimens by transjugular method were generally smaller (0.63 +/- 0.58 vs 1.50 +/- 0.86 cm, P < 0.001) and more fragmented (63% vs 16%, P < 0.01) than those obtained by percutaneous method. Biopsy specimens obtained for diagnosis by the former method were inadequate from 6 (10%) patients and by the latter route were inadequate from 7 (2%) patients. Subcapsular haematoma in one patient was associated with the transjugular liver biopsy. Minor complications occurred in three patients: neck haematoma in two and paroxysmal supraventricular tachycardia during the procedure in one. In comparison, percutaneous liver biopsy was followed by minor complications in 20 patients and major complications in four patients. It is concluded that transjugular liver biopsy is a safe, valuable and alternative procedure to obtain liver specimens, especially in patients who were contraindicated for percutaneous liver biopsy.

To determine the clinical value of tumour markers in the diagnosis of malignancy-related ascites (not including hepatocellular carcinoma), serum and ascitic fluid levels of carcinoembryonic antigen, cancer antigen 125, carbohydrate antigen 19-9, tissue polypeptide antigen and serum-ascites albumin gradient were determined in 66 patients with cirrhotic ascites, 28 patients with hepatocellular carcinoma and ascites, and 29 patients with malignancy-related ascites. Three tumour markers and serum-ascites albumin gradient showed significant difference between patients with malignancy-related ascites and those without: serum carcinoembryonic antigen (26.4 +/- 31.5 vs 4.8 +/- 4.6 ng/mL, P0.01), ascitic fluid carcinoembryonic antigen (118.4 +/- 196.5 vs 2.0 +/- 1.4 ng/mL, P0.01), ascitic fluid carbohydrate antigen 19-9 (12,933 +/- 25,496 vs 23 +/- 67 U/mL, P0.01) and serum-ascites albumin gradient (1.1 +/- 0.4 vs 2.0 +/- 0.4 g/dL, P0.01). At the best cut-off levels chosen from near 95% of the data in those without malignancy-related ascites, the sensitivity, specificity and accuracy to diagnose malignancy-related ascites were, respectively, 65.5%, 93.6%, 87.0% using serum carcinoembryonic antigenor = 10 ng/mL; 69.0%, 94.7%, 88.6% using ascitic fluid carcinoembryonic antigenor = 5 ng/mL; 65.5%, 93.6%, 87.0% using ascitic fluid carbohydrate antigen 19-9or = 50 U/mL; 62.1%, 98.9%, 90.2% using serum-ascites albumin gradient1.1 g/dL. Although serum-ascites albumin gradient offered the best diagnostic accuracy and specificity, its sensitivity was not good enough. Our study indicates that serum-ascites albumin gradient and tumour markers are not sensitive parameters in the diagnosis of malignancy-related ascites.

Background: Ribavirin is a synthetic purine nucleoside with demonstrated antiviral activity against several DNA and RNA viruses. Objectives: An open-labelled pilot study to evaluate the safety and effect of ribavirin in the treatment of patients with chronic active hepatitis B (CAH-B). Study design: 24 CAH-B patients were treated with oral ribavirin 1200 mg daily in 3 divided doses for 4 weeks. Biochemical and virological parameters were monitored at regular interval during and after treatment. Results: The serum hepatitis B e antigen (HBeAg) and HBV DNA measured by dot-blot hybridization were positive in all patients before treatment. At the end of 4 weeks of therapy, the HBV DNA levels decreased in 15 (63%) patients and became undetectable in 1 (4%) of these individuals. The mean HBV DNA decreased from 288±78 pg/ml at baseline to 219±79 pg/ml at the end of the 4 weeks of treatment (p=0.046). Eight weeks after cessation of treatment, HBV DNA was undetectable in 10 (42%) patients, and the mean HBV DNA was 46±23 pg/ml (p

The diagnosis and treatment of 126 consecutive patients with tissue-proved cholangiocarcinoma which originates in or proximal to the common hepatic duct was reviewed. They are further divided into the hilar type and peripheral type tumours. The clinical presentations were commonly compatible with the hilar type tumour. However, the accurate pre-operative diagnosis of the peripheral type tumour was difficult because of the frequent association with hepatolithiasis (43.3%) and the high prevalence of hepatocellular carcinoma (HCC) in Taiwan; 25% of these patients underwent surgery for chronic cholangitis and 12.5% for HCC rather than cholangiocarcinoma. Among the 40 (31.7%) patients who had tumour resections, 24 were hilar type and 16 were peripheral type. There were no operative deaths and the mean survival time was 36.1 months (27.9 months for the hilar types, 52.2 months for the peripheral types). Sixty-three (50%) patients with hilar type tumours were only suitable for palliative procedures to relieve the jaundice. The 30-day mortality rate was 50 and 33.3% for the patients who received non-surgical and surgical drainages, but zero for the patients who had surgical bypasses. All the bypass patients experienced50% decrease of serum bilirubin, but this effect was obtained in less than half the patients receiving drainage procedures. Surgical resection significantly prolonged the survival (resection vs palliation vs no treatment = 36.1 vs 6.6 vs 3.6 months, P0.05), but no survival advantage was achieved in any of the palliative therapies. Five cases with tumour resection survived5 years. We conclude that surgical resection offers the best prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

To define patients with an ascitic fluid polymorphonuclear cell countor = 250 cells/mm3 oror = 500 cells/mm3 but without spontaneous bacterial peritonitis, 166 patients with sterile cirrhotic ascites, 46 patients with spontaneous bacterial peritonitis, 123 patients with hepatocellular carcinoma, 67 patients with peritoneal carcinomatosis or massive liver metastasis and 12 patients with other miscellaneous diseases were studied. The sensitivity, specificity and accuracy of the diagnosis of spontaneous bacterial peritonitis were 100, 86 and 88% with the cut-off value of an ascitic fluid polymorphonuclear cell countor = 250 cells/mm3; and were 93, 91 and 92% with that valueor = 500 cells/mm3, respectively. With the cut-off valueor = 250 cells/mm3 oror = 500 cells/mm3, the prevalence was 18% or 14% in hepatocellular carcinoma; and 30% or 19% in peritoneal carcinomatosis or massive liver metastasis. The ascitic fluid lactate concentration was insensitive and nonspecific. Among the patients with an ascitic fluid polymorphonuclear cell count greater than the cut-off values, an ascitic fluid erythrocyte countor = 10,000 cells/mm3, a ratio of ascitic fluid erythrocyte to total leukocyte countor = 100, and the ratio of ascitic fluid polymorphonuclear cell to total leukocyte countor = 75% indicated hepatocellular carcinoma, while serum to ascites albumin gradientor = 1.1 g/dl and a ratio of ascitic fluid polymorphonuclear cell to total leukocyte countor = 75% indicated peritoneal carcinomatosis or massive liver metastasis.

To detect hepatitis D virus (HDV) RNA in asymptomatic HDV-infected risk groups, Northern blot hybridization was carried out using a strand-specific riboprobe. Univariate and multivariate analyses were carried out to evaluate factors associated with HDV viremia and elevated transaminase levels in these subjects. Two (15%) of 13 antibody to HDV (anti-HDV) -positive intravenous drug addicts, 15 (33%) of 45 anti-HDV positive prostitutes, and 6 (40%) of 15 anti-HDV positive brothel goers had detectable serum HDV RNA. Older age (31 years old) was negatively associated with HDV RNA (P.04), while hepatitis B e antigen (HBeAg) was positively associated with it (P.002) in univariate analysis. Only HBeAg was still significant in multivariate analysis (P.05). Of the 76 asymptomatic anti-HDV positive case, 28 (37%) had mildly elevated serum ALT levels and only 5 (7%) had ALT levels more than twice normal (80 U/L). HBeAg (P.05) and HDV RNA (P.02) were two factors associated with ALT elevation in univariate analysis, and HDV RNA was the only significant factor in multivariate analysis (P.005). In summary, active replication of HBV seemed to be of help for the assembly of HDV and viremia. However, active replication of HDV was associated mostly with mildly elevated ALT levels in these subjects. These cases may represent a particular group in the disease spectrum of HDV infection.

One hundred and fifty cirrhotic patients with or without esophageal varices and/or gastric varices were investigated by endoscopy and hepatic venous catheterization to evaluate differences in the degree of portal hypertension, main portal venous diameter and frequency of portal systemic encephalopathy. Hemodynamic values were correlated with varices size as assessed by endoscopy. Patients with large gastric varices had wedged hepatic venous pressures and hepatic venous pressure gradients which were lower than patients with esophageal varices only, but similar to patients without varices. In addition, in patients with large gastric varices, a decrease in the diameter of the main portal vein and an increase in the incidence of chronic portal systemic encephalopathy were noted. Our results implied that patients with large gastric varices presented different hemodynamic features including the degree of portal hypertension and the incidence of portal systemic encephalopathy from patients with esophageal varices only.

Variceal recurrence and rebleeding are common after initial obliteration by injection sclerotherapy. To investigate whether propranolol can maintain variceal obliteration by sclerotherapy, 59 patients with oesophageal variceal bleeding after sclerotherapy were enrolled. Patients were allocated to propranolol treatment (30 patients) or served as controls (29 patients). After a mean follow up of 2 years and 4 months, 53 patients completed the study. Fifty-eight per cent of the propranolol group versus 77% of the control group experienced recurrent varices (P = 0.20). Fifteen per cent of the propranolol group versus 11% of the control group developed cardiac varices. Recurrent variceal bleeding was encountered in 27% of the propranolol group and 19% of the control group. Three patients in the propranolol group, compared with two patients in the control group, died of massive variceal bleeding. Eighty per cent of them bled from cardiac varices. Both groups had similar survival rates. We therefore concluded that the use of propranolol after variceal obliteration by sclerotherapy can neither prevent oesophagogastric variceal recurrence nor prevent further rebleeding.

Background: Inactivated hepatitis A vaccine is now becoming available in many countries. Methods: To evaluate the immunogenicity and safety of inactivated hepatitis A vaccine in healthy children, 99 susceptible schoolchildren from 4 to 15 years of age received 360 enzyme-linked immunosorbent assay units of the inactivated hepatitis A vaccine at months 0, 1, and 6. Results: Antibody to hepatitis A virus seroconversion (≥20 mlU/mL) was 97% (96/99) in vaccinees after the first dose and 100% after the second (99/99) and booster (96/96) doses. The geometric mean titers of antibody to hepatitis A virus were 167, 465, and 4133 mlU/mL after each dose of vaccine, respectively. There were no significant side effects during the vaccination. Levels of antibody to hepatitis A virus were also tested in 9 susceptible children at day 7 and months 1 and 4 after the intramuscular injection of 2 mL of immune serum globulin. All children had measurable titers of antibody to hepatitis A virus 1 week after receiving immune serum globulin by sensitive enzyme immunoassay, but measurable titers had disappeared 1–4 months later. Conclusions: The inactivated hepatitis A vaccine is safe and immunogenic in healthy children.

This randomized controlled trial was conducted to compare the efficacy of intravenous infusion of octreotide (a synthetic long-acting somatostatin analogue) with vasopressin in 48 cirrhotic patients with endoscopically proven bleeding esophageal varices. Twenty-four patients received a continuous infusion of octreotide 25 micrograms/h for 24 h after an initial bolus of 100 micrograms and another 24 patients received a continuous infusion of vasopressin 0.4 U/min for 24 h. Bleeding was initially controlled after 6 h of drug infusion in 88% (21/24) and 54% (13/24) of the patients treated with octreotide and vasopressin respectively (p = 0.03). Complete control of bleeding after 24 h of drug infusion was achieved in 15 (63%) patients receiving octreotide and in 11 (46%) patients receiving vasopressin (p > 0.05). Side effects during drug infusion such as headache, chest pain and abdominal pain were significantly lower in the octreotide group (3/24) than in the vasopressin group (11/24). Serum gastrin and insulin levels fell significantly following octreotide infusion, but plasma glucose levels remained unchanged. Mortality related to bleeding esophageal varices was no different between the two groups. This report showed that octreotide infusion was more effective and had fewer side effects than vasopressin in initial controlling of acute esophageal variceal bleeding until an elective endoscopic sclerotherapy could be performed.

The influence of octreotide and somatostatin on liver metabolic activity were studied in 16 patients with cirrhosis that was positive for hepatitis B surface antigen (HBsAg). In patients receiving a 50 µg bolus and a 50 µg/hr infusion of octreotide, the hepatic blood flow, hepatic clearance, and the maximum velocity/metabolic elimination rate constant (Vmax/km) were significantly reduced after octreotide infusion compared with basal values. Similarly, the hepatic blood flow, hepatic clearance, and Vmax/km were significantly decreased in patients receiving a 250 µg bolus and a 250 µg/hr infusion of somatostatin. The extraction ratio and the systemic hemodynamic values, including cardiac index, heart rate, mean arterial pressure, and systemic vascular resistance, showed no significant changes in patients receiving either octreotide or somatostatin. These findings suggest that, as with somatostatin, octreotide reduced hepatic blood flow and impaired liver metabolic activity in patients with HBsAg-positive cirrhosis. These effects may have important clinical implications in the management of bleeding esophageal varices in patients with cirrhosis. Clinical Pharmacology and Therapeutics (1992) 52, 134–138; doi:10.1038/clpt.1992.122

Two hundred and sixty-seven susceptible hospital personnel who had been randomly divided into three groups to receive different doses (5 micrograms, 2 micrograms or 1 microgram) of a plasma-derived hepatitis B vaccine on a four-dose schedule were investigated annually for 4 years. Of them, 251 were vaccine responders. The percentages of persistence of antibody to hepatitis B surface antigen (anti-HBs) in these 3 groups were 95.5% (84/88), 92.3% (72/78) and 95.3% (81/85), respectively (P greater than 0.05). During the follow-up period, 12 of 21 (57.1%) responders with low anti-HBs titres (10-100 miu/mL) and 3 of 48 (6.3%) responders with medium anti-HBs titres (101-1000 miu/mL) were found to be anti-HBs seronegative, while none of the 182 candidates with high anti-HBs levels (greater than 1000 miu/mL) lost their anti-HBs. The 4 year cumulative rate of natural booster in the responders was 11.6% (29/251). None of the candidates became HBsAg positive during the follow-up period. This study revealed that low dose hepatitis B vaccine can provide satisfactory immunogenic response and long-term efficacy in Chinese adults and that the persistence of immunogenicity is not related to the vaccine dose but to the candidate's own initial anti-HBs response.

In a prospective study of 103 consecutive cirrhotic patients a high prevalence (43%) of anorectal varices was found compared with only 2% in 103 age- and sex-matched control subjects (p less than 0.001). However, there was no significant difference between the prevalences of hemorrhoids in cirrhotic patients and in control subjects (79% vs. 83%, p greater than 0.05). The hepatic venous pressure gradient of cirrhotic patients with anorectal varices was similar to cirrhotic patients without anorectal varices (14 +/- 6 mmHg, n = 22, vs. 16 +/- 7 mmHg, n = 39, p greater than 0.05. There was no significant difference in the hepatic venous pressure gradient between cirrhotic patients with and without hemorrhoids (15 +/- 6 mmHg, n = 47, vs. 16 +/- 8 mmHg, n = 14, p greater than 0.05). The prevalence of anorectal varices and hemorrhoids in cirrhotic patients had no relation to Child-Pugh's grading, esophageal varices with and without sclerotherapy and ascites. We conclude that anorectal varices are common in cirrhotic patients. Anorectal varices and hemorrhoids are not related to the degree of portal pressure.

To assess whether the hepatitis C virus plays an important role in Chinese patients with acute and chronic liver disease, antibodies to HCV (anti-HCV) were measured by enzyme immunoassay in 67 patients with type A and B acute viral hepatitis, 165 patients with non-A, non-B (NANB) hepatitis, 438 patients with chronic hepatitis, 200 patients with postnecrotic liver cirrhosis, 72 patients with alcoholic liver disease, 55 patients with non-alcoholic fatty liver, 24 patients with toxic and drug-induced hepatitis, and 20 patients with other chronic liver diseases. Anti-HCV was not detected in sera from patients with type A and B acute viral hepatitis, toxic and drug-induced hepatitis, primary biliary cirrhosis, Wilson's disease, or lupoid hepatitis. The anti-HCV prevalence was found to be highest in patients with NANB hepatitis (59% in sporadic and 73.2% in transfusion-associated), 16.4% in non-alcoholic fatty liver, 5.6% in alcoholic liver disease, 6.8% in chronic hepatitis, and 16% in postnecrotic liver cirrhosis. In patients with chronic hepatitis, the anti-HCV prevalence was significantly higher in HBsAg-negative (15/34, 44.1%) than in HBsAg-positive cases (15/404, 3.7%; P less than 0.0001). The results indicate that HCV is a major agent of NANB hepatitis and plays an important role in HBsAg-negative chronic liver disease in Taiwan.

To delineate the natural clinical course of spontaneous bacterial peritonitis in hepatitis B-related cirrhosis and to determine if it occurs in hepatocellular carcinoma, a prospective survey was conducted in 262 patients over 2 1/2 years. The in-hospital incidence and mortality rates of spontaneous bacterial peritonitis were 21.6% and 36.4%, respectively, in cirrhosis and 7.3% and 50% in hepatocellular carcinoma. In cirrhosis, the cumulative probability of annual recurrence of spontaneous bacterial peritonitis was 47.3%, which was significantly higher than the annual probability of occurrence of 11.3% in those with no previous attack (P less than 0.0001). The cumulative probability of annual survival was 27.6% in the spontaneous bacterial peritonitis patients, significantly lower than the probability of 64.0% in the control group (P = 0.0001). A univariate analysis, with Kaplan-Meier curves compared by the Mantel-Cox test, and subsequent multivariate analysis by stepwise Cox regression procedure were used to evaluate 37 variables recorded immediately after admission. Blood urea nitrogen concentration greater than 10.5 mmol/L urea (greater than 30 mg/dL) and ascitic fluid protein concentration less than 7.35 g/L (less than 735 mg/dL) were found to be the only significant predictors of lower annual survival; ascitic fluid protein concentration less than 7.50 g/L (less than 750 mg/dL) was the only significant predictor of higher annual recurrence. The authors conclude that spontaneous bacterial peritonitis has a high risk of recurrence in hepatitis B-related cirrhosis and that the same disease occurring in patients with hepatocellular carcinoma is related to the underlying cirrhosis rather than the hepatocellular carcinoma.