Need for vaccination of susceptible food handlers against hepatitis A in Taiwan.

BACKGROUND: With the improvement in the socioeconomic situation and general hygiene standards in Taiwan, the prevalence of antibodies to the hepatitis A virus (anti-HAV) in the general population has declined markedly in recent years. To avoid food-borne outbreaks of HAV infection caused by susceptible food handlers in Taiwan, we investigated the seroprevalence of anti-HAV among the target population and also evaluated the immunogenicity and reactogenicity of the inactivated hepatitis A vaccine in this study group. METHODS: Two hundred and forty-four food handlers employed in four restaurants at Taipei Veterans General Hospital participated in the anti-HAV serologic screening program in July 1997. Of them, 48 susceptible food handlers received three doses of 720 enzyme-linked immunosorbent units of inactivated hepatitis A vaccine at 0, 1 and 6 months. RESULTS: Of the 244 food handlers who underwent anti-HAV serologic screening, 169 (69.3%) were anti-HAV positive. The seroprevalence of anti-HAV was related to age: 91.5% of food handlers over 30 years of age were positive for anti-HAV but only 22.8% of food handlers younger than 30 were anti-HAV positive. Anti-HAV response was observed in all vaccinees after a booster vaccination at month 6. The response persisted to 1 year. The side-effects of the vaccinations were minimal. CONCLUSIONS: Susceptible food handlers should receive hepatitis A vaccination. Hepatitis A vaccine is safe and immunogenic in this target population.

Hepatitis B vaccination in patients with chronic hepatitis C.

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.

A two dose combined hepatitis A and B vaccine in Chinese youngsters.

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.

Long-term follow-up of hepatitis A vaccination in children.

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.

Control of hepatitis B virus infection by vaccination: the Taiwan experience.

Hepatitis B virus infection poses a serious health problem in Taiwan, and plays an important role in the development of chronic hepatitis, liver cirrhosis and hepatoma; the latter two are among the 10 leading causes of death in Taiwan. The success from a mass hepatitis B vaccination program, which began in 1984 and first included high-risk neonates, has seen the hepatitis B carrier rate among children in Taiwan drop from 10% to less than 2%, and the annual incidence of childhood hepatoma has also decreased significantly in recent years. Prior to this vaccination program, a series of viral epidemiologic surveys, transmission pattern studies and pilot immunization trials proved the clinical, economic and strategic benefits of mass immunization and provided the impetus for the Taiwan government to implement a mass vaccination program. This is one of the most remarkable success stories in the field of public health.

Safety and immunogenicity of inactivated hepatitis A vaccine in patients with chronic liver disease.

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 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 (> or = 33 mIU/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 mIU/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.

Endoscopic variceal ligation in prophylaxis of first variceal bleeding in cirrhotic patients with high-risk esophageal varices.

To determine the efficacy of endoscopic variceal ligation (EVL) in prophylaxis on the rate of first esophageal variceal bleeding, we conducted a prospective, randomized trial in 126 cirrhotic patients with no history of previous upper gastrointestinal bleeding and with esophageal varices endoscopically judged to be at high risk of hemorrhage. The end-points of the study were bleeding and death. Life-table curves showed that prophylactic EVL significantly diminished the rate of variceal hemorrhage (12/62 [19%] vs. 38/64 [60%]; P = .0001) and overall mortality (17/62 [28%] vs. 37/64 [58%]; P = .0011). The 2-year cumulative bleeding rate was 19% (12/ 62) in the EVL group and 60% (38/64) in the control group. The 2-year cumulative mortality rate was 28% (17/62) in the EVL group and 58% (37/64) in the control group. Comparison of Kaplan-Meier estimates of the time to death of both groups showed significantly lower mortality in the ligation group (P = .001). Patients undergoing EVL had few treatment failures and died mainly of hepatic failure. The lower risk in the EVL group was attributed to a rapid reduction of variceal size. Prophylactic EVL was more efficient in preventing first bleeding in patients with good condition (Child A) than in those with decompensated disease (Child B and C). We conclude that prophylactic EVL can decrease the incidence of first variceal bleeding and death over a period of 2 years in cirrhotic patients with high-risk esophageal varices.

Single dose-inactivated hepatitis A vaccination schedule for susceptible youngsters.

OBJECTIVE: To investigate the feasibility of a single-dose primary hepatitis A vaccination for young travelers. METHODS: One hundred and nineteen susceptible youngsters, 9-18 yr old, received a dose of 720 ELISA units of the inactivated hepatitis A vaccine at month 0, and then a booster at month 6. RESULTS: Antibodies to hepatitis A virus (anti-HAV) seroconversion ( > or = 20 mIU/ml) in these vaccinees was 91% (106/117) on day 15, and reached 99% (118/119) 1 month after the single-dose vaccination. At month 6 before the booster, 97% (110/113) of the vaccinees still had detectable anti-HAV. All vaccinees (113/113) had measurable titers of anti-HAV 1 month after booster vaccination, and were still seropositive (68/68) at month 12. The anti-HAV response was found to be slower in vaccinees positive for hepatitis B surface antigen (11/16, 68.8%), compared with noncarrier vaccinees (95/101, 94.1%; p < 0.01) 15 days after the priming dose. After initial vaccination, the geometric mean titers of anti-HAV among vaccine responders were 220, 255, 117, 3308, and 1094 mIU/ml at day 15 and months 1, 6, 7, and 12, respectively. CONCLUSION: These results suggest that a single dose of hepatitis A vaccine could be a good alternative to immune serum globulin administration for immunoprophylaxis in young healthy travelers.

Caffeine clearance test: a quantitative liver function assessment in patients with liver cirrhosis.

BACKGROUND: Quantitative assessment of live function is an important work-up for patients with liver cirrhosis. The aim of the present study was to clarify the role of caffeine clearance test in the quantitative measurement of metabolizing capacity of the liver. METHODS: Twenty-eight patients with liver cirrhosis and 28 normal healthy volunteers were enrolled in this study. After an overnight fast, the first blood sample was collected at 8 a.m., immediately followed by an oral administration of 150 mg caffeine. Subsequent samples of venous blood were obtained at 8.30 a.m., 9 a.m., 11 a.m., 2 p.m. and 5 p.m. The caffeine clearance was determined using two caffeine concentrations from blood samples taken at 2 p.m. and 5 p.m., which were then measured by an enzyme multiple immunoassay technique. RESULTS: The serum caffeine clearance was significantly higher in the control group than in the patient group (1.72 +/- 1.06 vs. 0.78 +/- 0.77 ml/min/kg, p < 0.0001). Elimination half-life was significantly prolonged in the patient group (3.74 +/- 1.05 vs. 2.69 +/- 0.75 hours, p < 0.0001). The influence of cigarette smoking was also evident: higher clearance and shorter half-life of caffeine were noted in the smoking subjects. In the non-smokers, caffeine clearance was 1.30 +/- 0.90 and 0.51 +/- 0.47 ml/min/kg and half-life of caffeine was 2.89 +/- 0.78 and 4.06 +/- 0.93 hours, respectively (control vs. patient, p < 0.05). In the smokers, caffeine clearance was 2.30 +/- 0.98 and 1.13 +/- 0.96 ml/min/kg and half-life of caffeine was 2.41 +/- 0.63 vs. 3.31 +/- 1.06 hours, respectively (control vs. patient, p < 0.05). During the mean six-month period of follow-up, the mortality rate was significantly higher in those patients with caffeine clearance less than 0.5 ml/min/kg than in those with clearance more than 0.5 ml/min/kg (46.1% vs. 6.7%, p < 0.05). A significantly negative correlation between the serum caffeine clearance and the Child-Pugh's score was also demonstrated (r = -0.851, p < 0.0001). CONCLUSIONS: Serum caffeine clearance determined at two points of blood concentration is a useful method to evaluate the severity of liver disease and predict short-term survival of cirrhotic patients. It offers another choice for the quantitative measurement of liver functional reservoir.

A pilot, open-labelled, phase II study using oral ribavirin in the treatment of patients with chronic active hepatitis B.

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 < 0.01 when compared to mean baseline value). Seven (29%) patients seroconverted from HBeAg positive to anti-HBe positive but no patients lost hepatitis B surface antigen (HBsAg) during the 8 weeks of follow-up. At the end of 4 weeks of ribavirin treatment, serum levels of alanine aminotransferase (ALT) decreased in all but 1 patient; only 1 patient normalized serum ALT at this time. The mean serum ALT decreased significantly from 416+/-72 IU/l at baseline to 179+/-35 IU/l at the end of 4 weeks of treatment (p = 0.001). Eight weeks after cessation of therapy, the mean serum ALT value was 151+/-32 IU/l (p < 0.001 when compared to mean baseline value) and 5 (21%) patients normalized serum ALT at this time. During ribavirin treatment, the main side effect was a decrease in the hemoglobin level which returned to the pretreatment level in each instance within 2 months after discontinuance of therapy. CONCLUSIONS: Results of this pilot study indicated that oral ribavirin was well tolerated in CAH-B patients and resulted in lowering of serum ALT and HBV DNA values. A randomized controlled trial is needed to fully evaluate the beneficial effects of ribavirin in CAH-B patients.

Hepatitis B vaccination alone is not adequate for the categorizing of adult subjects with isolated anti-HBc.

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)

Endotoxemia in patients with chronic liver diseases: relationship to severity of liver diseases, presence of esophageal varices, and hyperdynamic circulation.

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, p < 0.05) and patients with cirrhosis (7.0 +/- 0.7 pg/ml, n = 126, p < 0.05) 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, p > 0.05) but lower than those in chronic hepatitis patients with acute exacerbation (4.6 +/- 0.5 vs. 10.1 +/- 1.3 pg/ml, p < 0.05). Endotoxemia (plasma endotoxin level > 5.7 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, p < 0.05). In contrast, plasma endotoxin levels were comparable between patients with cirrhosis with and without esophageal varices (p > 0.05). Chronic hepatitis patients with acute exacerbation (no collaterization) had much higher plasma endotoxin levels than those in patients with cirrhosis and large varices (p < 0.05), whereas compensated patients with cirrhosis and large esophageal varices had plasma endotoxin levels similar to those seen in chronic hepatitis patients (no collaterization) (p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative branched DNA assay and genotyping for hepatitis C virus RNA in Chinese patients with acute and chronic hepatitis C.

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.

Long-term follow-up of hepatitis B virus carrier infants.

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 alanine 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) DNA 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.

A randomized controlled trial of recombinant interferon alpha-2b in the treatment of Chinese patients with acute post-transfusion hepatitis C.

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 (p < 0.01). 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 (p < 0.001). 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)

A double-blind randomized controlled trial of colchicine in patients with hepatitis B virus-related postnecrotic cirrhosis.

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; p < 0.05). 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.

Correlation of serum HCV RNA and alanine aminotransferase levels in chronic hepatitis C patients during treatment with ribavirin.

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)

Total paracentesis in non-alcoholic cirrhotics with massive ascites: mid-term effects on systemic and hepatic haemodynamics and renal function.

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.

Transjugular liver biopsy: comparison with percutaneous liver biopsy.

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.

Prolonged bleeding time in cirrhotic patients: relationship to peripheral vasodilation and severity of cirrhosis.

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 (P < 0.001) and a longer prothrombin time (P < 0.001) and activated partial thromboplastin time (P < 0.001) 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, P < 0.001). Patients with decompensated cirrhosis had a longer bleeding time in comparison to patients with compensated cirrhosis (621 +/- 39 vs 478 +/- 27 s, respectively, P < 0.01). The prolonged bleeding time was also discovered in 25% of 83 cirrhotic patients with a platelet count > 80 x 10(9)/L and a prothrombin time < 17 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, P < 0.001), whereas both groups had similar hepatic venous pressure gradient (16.2 +/- 1.2 vs 18.1 +/- 1.4 mmHg, respectively, P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)