Allan G. Redeker

The Prevention of Hepatitis B with Vaccine: Report of the Centers for Disease Control Multi-Center Efficacy Trial Among Homosexual Men

A randomized, double-blind, vaccine/placebo trial of the Merck 20-micrograms hepatitis B virus (HBV) vaccine was done among 1402 homosexual men attending venereal disease clinics in five American cities. Vaccination was followed by only minimal side effects. Two doses of vaccine induced antibody in 80% of vaccine recipients. A booster dose 6 months after the first dose induced antibody in 85% of recipients and markedly increased the proportion of recipients who produced high antibody titers. The incidence of HBV events was markedly less in the vaccine recipients compared to that in the placebo recipients (p = 0.0004). Between month 3 and 15 after the first dose, 56 more significant HBV events (hepatitis, or hepatitis B surface antigen positive, or both) occurred in the placebo group while only 11 occurred in the vaccine group. Ten of the 11 HBV events in the vaccine recipients occurred in hypo- or nonresponders to the vaccine. This vaccine appears to be safe, immunogenic, and efficacious in preventing infection with hepatitis B virus.

Direct Transhepatic Measurement of Portal Vein Pressure Using a Thin Needle: Comparison with wedged hepatic vein pressure

A technique for the direct measurement of portal vein pressure in fully conscious patients is described. This uses a percutaneous transhepatic approach with a thin Chiba needle and is shown to be simple and safe. The technique has been applied to 123 patients with a variety of liver disorders and the pressure measurements have been compared with those obtained by the indirect technique of wedge hepatic vein catheterization. Close agreement was found between portal vein pressure and wedged hepatic vein pressure in quiescent alcoholic liver disease and alcoholic hepatitis. In chronic active hepatitis, portal vein pressure tended to be higher than wedged hepatic vein pressure, indicating a presinusoidal component to the portal hypertension. This technique is shown to be useful in assessing idiopathic protal hypertension and in demonstrating hepatofugal flow.

Fulminant B Viral Hepatitis: Role of Delta Agent

The prevalence of delta-markers among 71 patients with fulminant B viral hepatitis was found to be 33.8%. The majority of the patients with delta-markers showed serologic evidence of simultaneous acute delta-infection and B viral infection. Only 5 of the 24 patients with serologic markers of acute delta-infection in this fulminant group were presumably infected chronically with hepatitis B virus as shown by the absence of immunoglobulin M antibody to hepatitis B core antigen. A study of serologic markers of acute delta-infection among 118 patients with nonfulminant acute B viral hepatitis, in contrast, revealed only 4.2% incidence. This significant difference in the prevalence of simultaneous acute B and delta viral infections between the fulminant and the nonfulminant acute hepatitis groups indicates a higher morbidity rate associated with simultaneous infection. When the fulminant group was divided into acute B viral infection without delta-markers (subgroup 1), simultaneous acute B and delta-infections (subgroup 2), and chronic asymptomatic B with acute delta-infections (subgroup 3), for comparison of survival data, the mortality rate was not significantly different in the first two groups when the patients were age matched.

Short-term prednisone therapy affects aminotransferase activity and hepatitis C virus RNA levels in chronic hepatitis C

BACKGROUND/AIMS The effects of corticosteroids on chronic hepatitis B have provided insight into the mechanism of liver cell injury caused by hepatitis B. In this study, this model was applied to investigate the effects of prednisone on alanine aminotransferase (ALT) and hepatitis C virus (HCV) RNA levels in chronic hepatitis C. METHODS Ten patients with chronic hepatitis C who had increased levels of ALT and HCV RNA detectable in serum were given a 7-week course of a tapering dose of prednisone. Quantitation of serum HCV RNA was determined by polymerase chain reaction (PCR) and by branched-chain DNA amplification. RESULTS ALT levels decreased in 8 of 10 patients during therapy. Mean ALT levels of all 10 patients decreased from 184 to 84 U/L (P = 0.002) and then rebounded in 7 of the 8 patients after discontinuation of prednisone. HCV RNA was detectable by the branched DNA technique in 9 of 10 patients. These values increased in all 9 patients during prednisone therapy. The mean serum HCV RNA levels increased from 40.9 before treatment to 414.3 Eq/mL x 10(5) during treatment (P = 0.043). Using PCR, HCV RNA titers increased one log-fold in 8 of 10 patients (geometric mean of 1:4420 to 1:23410). HCV RNA levels decreased to pretreatment values within a mean of 2.8 weeks (range, 1-5) after discontinuation of prednisone. CONCLUSIONS These responses in ALT and HCV RNA suggest the participation of an immune-mediated mechanism in the liver cell injury in chronic hepatitis C.

Etiology of sporadic hepatitis B surface antigen-negative hepatitis.

We studied serologically 45 adults who had sporadic acute viral hepatitis that was hepatitis B surface antigen (HBsAg) negative. Two cases were due to hepatitis B virus, as demonstrated by the appearance of antibody to hepatitis B core antigen. In three other patients, the serologic pattern was inconclusive. Of 40 non-B cases, 20 were type A hepatitis and 20 were non-A, non-B hepatitis. Clinically, type A and non-A, non-B hepatitis were indistinguishable; one case of fulminant disease occurred in each group. The type A cases were more frequent in young adults; non-A, non-B disease predominated in women 35 years or older. Epidemiologic backgrounds were generally similar, including illicit self-injection; but four transfusion-associated cases were limited to the non-A, non-B group. We conclude that relatively few HBsG-negative cases are due to hepatitis B virus, and that hepatitis A virus and non-A, non-B viruses are both important in acute non-B disease.

Factors Predicting Relapse and Poor Outcome in Type I Autoimmune Hepatitis: Role of Cirrhosis Development, Patterns of Transaminases During Remission and Plasma Cell Activity in the Liver Biopsy

AIM:To determine factors predicting relapse and poor outcome in patients with type I autoimmune hepatitis (AIH).METHODS:Patients with AIH were retrospectively recruited. Definitions—remission: AST/ALT < 2 ULN; relapse: AST/ALT ≥ 2 ULN; poor outcome: cirrhosis complications, transplantation (OLTx), and death; abnormal transaminases: AST/ALT > ULN but within the remission range; abnormal transaminases index (ATI): number of occasions AST/ALT abnormal/years of remission. Liver biopsies were assessed by Ishak system, and additional score given for portal and parenchymal plasma cells. Data are presented as median (range).RESULTS:Seventy-one patients were identified. Twenty (28%) had cirrhosis at presentation, 14 (20%) developed it during follow-up of 52 months (18–336). Of the 14, four had histological confirmation, and the remainder had clinical/radiological evidence of cirrhosis. Factors independently associated with cirrhosis development were inability to have consistently normal transaminases during remission, OR 19.3 (95% CI 2.2–40), p= 0.002. Treatment was discontinued in 40/69 patients of whom 30 (75%) relapsed within 2 months (1–23), culminating in one death. Factors independently associated with relapse were: time to initial remission, OR 5.5, 95% CI 1.3–22, p= 0.01; failure to have consistently normal transaminases during remission OR 11.8, 95% CI 1.3–100, p= 0.02; and portal plasma cell score (PPCS) OR 10.6 (95% CI 1.0–107), p= 0.04. Time to remission ≥ 5 months, PPCS ≥ 3 and ATI ≥ 2 was associated with >90% probability of relapse (PPV 100%). Fifteen percent had a poor outcome. Independent predictors of poor outcome were: globulins at onset OR 3.4 (95% CI 1.1–10.1), p= 0.02 and cirrhosis development, OR 23 (95% CI 1.7–307), p= 0.CONCLUSIONS:Seventy percent of patients with AIH relapse upon drug cessation. Time to remission ≥ 5 months, ATI ≥ 2 and PPCS ≥ 3 were associated with >90% probability of relapse. Factors predicting poor outcome were globulins at onset and cirrhosis development.

Hepatitis B Virus Infection in Dentists

To evaluate viral hepatitis as a hazard in general dentistry, we surveyed participants in an annual health-screening program at the 1972 American Dental Association session. Of 1245 practitioners, 0.9 per cent were positive for hepatitis B surface antigen, and 12.7 per cent were antibody positive. Of those who had had clinical hepatitis while studying or practicing dentistry, 43 per cent were seropositive. The frequency of evidence for prior infection with hepatitis B virus increased uniformly with increasing years of professional experience. The proportion of seropositive dentists did not vary with geographic region of the United States, or size of community. Only 10.5 per cent recognized illicit self-injection among patients, and their infection rate was not increased. These data indicate an increased frequency of infection with hepatitis B virus among general dentists, and are compatible with relatively uniform endemicity of subtype/ad strans of that agent in the general population for several decades.

Relation of alpha-fetoprotein in acute hepatitis to severity and prognosis.

Abstract Serums of 104 patients with acute hepatitis of variable severity were tested for alpha-fetoprotein by counterelectrophoresis. Among 51 patients with fulminant hepatitis and coma, alpha-fet...

Cyclosporine therapy in patients with steroid resistant autoimmune hepatitis

Autoimmune hepatitis is a form of chronic liver disease characterized by progressive hepatocellular inflammation, which usually responds to treatment with corticosteroids. However, 10% of patients with autoimmune hepatitis are refractory to corticosteroids and develop progressive liver disease and cirrhosis. We describe five patients with autoimmune hepatitis who did not respond to conventional corticosteroids and azathioprine therapy who were then treated with cyclosporine A. Cyclosporine A was started at 2–3 mg/kg/day and induced biochemical remission in four of five patients within 3 months. One of the four responders relapsed within 1 month of discontinuing cyclosporine on two occasions. Each time, liver tests promptly normalized after reinitiation of cyclosporine. Two responders were managed with cyclosporine alone. The single patient who did not respond to cyclosporine developed progressive liver failure, underwent orthotopic liver transplantation, and subsequently died of disseminated cytomegalovirus infection. Cyclosporine was generally well tolerated and none of the patients developed renal insufficiency. These data and review of 11 cases in the literature show that cyclosporine can induce remission of liver disease in patients with autoimmune hepatitis who are refractory to corticosteroids.

Liver transplantation for advanced liver disease with alpha-1-antitrypsin deficiency

ALPHA-1-antitrypsin deficiency associated with chronic obstructive airway disease was recognized in 1963 by Laurell and Ericksson.1 In 1969, Sharp2 described the first cases of alpha-1-antitrypsin-...