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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.

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.

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.

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.

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.

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

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)

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.

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.

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.

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.

Gastric mucosal lesions are common in patients with cirrhosis. Among them, snake skin pattern gastropathy (SSPG) is the most distinguishing one. A prospective study was conducted to investigate the incidence of SSPG in cirrhotic patients, the relationship between the degree of portal pressure and SSPG, and the possible association of SSPG with serum levels of gastrin and pepsinogen I. SSPG was found to be significantly more common in 100 cirrhotic patients than in 100 age- and sex-matched healthy controls (41% vs 0%, P less than 0.0001). Hepatic venous pressure gradient and serum gastrin and pepsinogen I levels were measured in 21 cirrhotic patients with SSPG and 25 cirrhotics without SSPG. There was no significant difference in hepatic venous pressure gradient (16.1 +/- 4.4 mmHg vs 16.1 +/- 4.9 mmHg, P greater than 0.05), serum gastrin level (78.0 +/- 26.7 pg/mL vs 80.1 +/- 32.5 pg/mL, P greater than 0.05) and serum pepsinogen I level (69.5 +/- 26.6 ng/mL vs 65.2 +/- 26.1 ng/mL, P greater than 0.05) in cirrhotic patients with or without SSPG. In conclusion, SSPG is common in cirrhotic patients. Portal pressure per se may not be the only factor causing SSPG--other aggressive factors may be needed together to cause the gastropathy. There is no evidence of correlation between serum gastrin or pepsinogen I level and SSPG.

Forty-one hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA positive Chinese patients with chronic active hepatitis B were randomized to receive either prednisolone or placebo oral for 8 weeks. The prednisolone group received 60 mg daily for 2 weeks, 40 mg for 2 weeks, 20 mg for 2 weeks, 10 mg for 1 week and 5 mg for 1 week. In 18 patients receiving prednisolone, serum HBV DNA levels rose during the course of therapy, but dropped abruptly within 1 month of cessation of treatment. Conversely, their serum alanine aminotransferase (ALT) levels decreased during high doses of prednisolone therapy, and then became transiently elevated during the period of withdrawal of prednisolone. At 1 year from initial treatment, the serum HBV DNA and ALT levels were similar between the groups of patients treated with prednisolone or placebo. In the prednisolone treated group, 66.7% of patients became HBV DNA negative, 50% became HBeAg negative, and 33.3% seroconverted to antibody to HBeAg (anti-HBe). In the placebo treated group, 60.9% of patients became HBV DNA negative, 60.9% became HBeAg negative, and 56.5% seroconverted to anti-HBe. Hepatic decompensation was not noted in any of the prednisolone-treated patients. Thus, the effects of the withdrawal prednisolone therapy on serum ALT and HBV DNA levels was temporary, and no differences in serum viral markers or biochemical parameters of liver inflammation between these two groups were noted at the 1 year follow-up period.

From January 1984–December 1987, 1783 patients received combination therapy of isoniazid, rifampin, and ethambutol for the control of tuberculosis. Forty-two developed symptomatic hepatitis during the period of treatment. Fifteen were hepatitis B virus carriers, and the remaining 27 were noncarriers. The peak serum transaminase and bilirubin levels were higher in carriers. Seven carriers died of fulminant or subacute hepatic failure, and only 1 noncarrier died. Eleven carriers had detectable serum hepatitis B virus deoxyribonucleic acid during the acute stage of hepatitis. The roles of isoniazid-rifampin combination therapy and hepatitis B virus in the adverse outcomes of carriers were discussed.

In an attempt to evaluate the long-term immunogenicity and efficacy of plasma-derived hepatitis B vaccine in preventing hepatitis B virus infection, 199 infants born to hepatitis B e antigen-positive hepatitis B surface antigen-carrier mothers were found to be antibody to HBsAg-positive (greater than or equal to 10 mIU per ml) 2 months after the first booster of hepatitis B vaccination at age 1, and their serum HBsAg and anti-HBs were rechecked annually to ages 3 to 5. Of the nine infants whose initial anti-HBs were low (10 to 100 mIU per ml) in concentration, four (44%) were found to be anti-HBs seronegative at age 3, while none of the 127 vaccine responders with high anti-HBs levels (greater than 1,000 mIU per ml) lost their anti-HBs during the 4-year follow-up period. Also, in 63 infants whose initial anti-HBs titers were around 101 to 1,000 mIU per ml, only two lost their anti-HBs at age 4, and another two at age 5, respectively. Whether the vaccine responders lost their anti-HBs or not, no hepatitis B virus infection occurred in these vaccinees during the follow-up period. Thus, in the first 5 years of life, the protective efficacy in the high-risk infants who responded to plasma-derived hepatitis B vaccine was 100%. Because of the diversity of anti-HBs response in individuals, we suggest testing anti-HBs titer in all vaccinated infants after the first booster vaccination in order to calculate the time of next booster before the minimal protective level is reached.

Wedged hepatic venous pressure, free hepatic venous pressure and cardiac index were measured before and 1 hr after i.v. administration as well as 1 month and 3 months after chronic oral administration of verapamil in 10 patients with HBsAg-positive cirrhosis. The gradient between wedged hepatic venous pressure and free hepatic venous pressure was decreased 14% at 1 hr after i.v. administration of 10 mg verapamil, and the sustained decrease in hepatic venous pressure gradient was also demonstrated in the patients after 1 month, and in six patients after 3 months of continuous oral administration of verapamil. The mean arterial pressure significantly decreased (p less than 0.01) 1 hr after the administration of verapamil. There was no significant change in other hemodynamic values. We conclude that chronic oral administration of verapamil can reduce the hepatic venous pressure gradient in patients with compensated HBsAg-positive cirrhosis and portal hypertension.

Sera from 108 HBsAg carrier mothers at delivery and their respective offspring at birth and at 6 months of age were examined for hepatitis B virus DNA by the dot-blot hybridization technique. Hepatitis B virus DNA was detected in 83% of 88 carrier mothers who were HBeAg positive, and in 10% of 20 carrier mothers who were HBeAg negative. All five infants born to HBeAg-positive carrier mothers with hepatitis B virus DNA levels over 80 pg per 10 microliters of serum were infected by hepatitis B virus, in spite of receiving hepatitis B immunization. All 17 infants without hepatitis B immunization who were born to HBeAg and hepatitis B virus DNA-positive carrier mothers developed hepatitis B virus infection. Of 56 infants born to HBeAg and hepatitis B virus DNA-positive carrier mothers and who had received hepatitis B immunization, a higher hepatitis B virus infection rate was found in a group of infants whose sera hepatitis B virus DNA were positive (15/16, 93.8%) than in infants whose sera were negative (17/40, 42.5%) at birth (p less than 0.0005). These data suggest that the assay for hepatitis B virus DNA in sera of HBsAg carrier mothers at delivery or their infants at birth will predict the efficacy of hepatitis B immunization for prevention of maternal-infant hepatitis B virus transmission.

A total of 128 HBsAg carrier infants born to HBeAg-positive HBsAg carrier mothers were tested for serum HBsAg, HBeAg, hepatitis B virus DNA and anti-HBc. Ninety-three of them had received hepatitis B vaccination. Anti-HBc had been found to be negative in sera of 12 infants who were HBsAg, HBeAg and hepatitis B virus DNA positive during the follow-up period of 3 to 5 years. Liver damage, as measured by serum ALT levels, was found to be normal among the 12 HBsAg carrier infants with serum anti-HBc negativity, whereas 39.7% of the 116 anti-HBc-positive HBsAg carrier infants had abnormal ALT levels during the follow-up period. Anti-HBe and anti-HBs also were not detected in sera of these anti-HBc-negative HBsAg carrier infants. Thus, HBsAg carrier infants with anti-HBc negativity probably result from immune incompetency of the hepatitis B virus antigens.

Portal vein pressure and wedged hepatic vein pressure were measured simultaneously in 21 patients with hepatitis B-related cirrhosis of the liver and were compared to pressure measured in six patients with idiopathic portal hypertension. No significant difference in the portal venous pressure gradient was found between patients with cirrhosis and those with idiopathic portal hypertension (17.3 +/- 4.3 mmHg (mean +/- S.D.) vs. 19.7 +/- 3.1 mmHg, P greater than 0.05). However, the difference between the portal and the hepatic venous pressure gradient was significantly smaller in patients with cirrhosis than in idiopathic portal hypertension patients (1.3 +/- 1.7 vs. 10.8 +/- 2.1 mmHg, P less than 0.001). An excellent correlation was found between portal vein pressure and wedged hepatic vein pressure in hepatitis B-related cirrhosis (r = 0.94, P less than 0.001). There was no linear relationship between the portal venous pressure gradient and varix size or bleeding episodes. We concluded that a close agreement existed between portal vein pressure and wedged hepatic vein pressure in hepatitis B-related liver cirrhosis. Therefore, measurement of wedged hepatic vein pressure reliably reflects portal vein pressure in these patients.

A prospective survey of primary hepatocellular carcinoma (PHC) was conducted in a rural area of Taiwan using a two-site enzyme immunoassay for alpha-fetoprotein (AFP) in dried blood samples collected on filter paper. Of 1894 men over 40 years of age who were tested, 20 (1%) had AFP levels of greater than 20 ng/ml of blood on screening. Nineteen of these men received ultrasound examinations, and small PHCs were detected in 4 (21%). The remaining 15 cases had other types of hepatobiliary tract diseases, and 6 (40%) were also serum HBsAg positive. They should all be closely followed up by AFP determination and ultrasound examination of the liver. In contrast to the low resection rate of PHC in symptomatic patients who were admitted through the outpatient clinic during the period of this survey, the four cases with small PHC discovered by AFP screening had their tumors successfully removed (5/57 vs. 4/4, p less than 0.005). Our preliminary results showed that this method is a simple, sensitive and convenient assay for AFP and may be used as a first-line screening test in mass population surveillance programs for PHC, particularly in areas where PHC is highly prevalent.

A case is described of cholestasis associated with chlordiazepoxide therapy, and 3 previously reported cases are reveiwed. Chlordiazepoxide should be included in the ever-growing list of commonly used medications that are considered in the differential diagnosis of cholestasis.