A. S. F. Lok

Seroepidemiological survey of hepatitis E in Hong Kong by recombinant-based enzyme immunoassays

The agent that causes the enterally transmitted form of non-A, non-B hepatitis has been cloned and called hepatitis E virus (HEV). We have carried out a seroepidemiological survey on the prevalence of hepatitis E in Hong Kong. In a retrospective study, serum from 394 patients with acute viral hepatitis and 355 healthy subjects was tested for antibodies to HEV (anti-HEV) with a recombinant-based enzyme immunoassay. 65 (16.5%) patients with hepatitis were positive for IgM anti-HEV and 23 (5.8%) were also positive for IgM anti-HEV. Of 18 patients diagnosed as having acute non-A, non-B, non-C hepatitis, 6 were IgM anti-HEV positive. 17 (6%) patients in whom acute hepatitis A was diagnosed were also infected with HEV. None of 70 patients with acute hepatitis B or C or exacerbation of chronic hepatitis B was IgM anti-HEV positive. 57 (16.1%) of the healthy subjects were positive for IgG anti-HEV. The prevalence of IgG anti-HEV was higher in subjects over 20 years old than in younger subjects (24% vs 4%, p < 0.0001). IgG anti-HEV was detected in 26% of subjects who were positive for IgG antibody to HAV and in 7% of those negative for that antibody (p < 0.0001). We demonstrated the validity of the recombinant-based enzyme immunoassays for the diagnosis of hepatitis E. Our results suggest that hepatitis E accounts for a third of non-A, non-B, non-C hepatitis in Hong Kong and that coinfection of hepatitis A and E can occur.

EFFECT OF OMEPRAZOLE ON DUODENAL ULCER-ASSOCIATED ANTRAL GASTRITIS AND HELICOBACTER PYLORI

This study set out to investigate the effects of omeprazole or ranitidine on the progression of antral gastritis andHelicobacter pylori in patients with active duodenal ulcer. A double-blind, double-dummy trial was performed in 270 patients, 241 of whom were studied histologically for the presence ofH. pylori. Patients were randomized to receive omeprazole, 10 mg every morning, omeprazole, 20 mg every morning, or ranitidine, 150 mg twice a day, for four weeks. Endoscopy was performed on entry and at weekly intervals during the study; at least two antral biopsies were taken on each occasion to assess the activity and degree of chronic inflammation, as reflected by the degree of polymorphonuclear leukocyte infiltration and mononuclear cell infiltration, respectively. Biopsy specimes also were assessed histologically forH. pylori. The sex, age and maximal acid output were comparable in the three treatment groups. The percentages of patients showing an improvement in the activity of gastritis in the four consecutive weeks of treatment were 9%, 40%, 51%, and 53% for omeprazole, 10 mg (N=78); 14%, 42%, 49%, and 53% for omprazole, 20 mg (N=81); and 2%, 23%, 30%, and 33% for ranitidine, 150 mg twice a day (N=82) (life table analysis gaveP<0.01 for both omeprazole regimens compared with ranitidine). The degree of chronic inflammation showed similar changes. The density ofH. pylori decreased significantly after treatment with omeprazole, 10 mg or 20 mg, (both,P<0.00001) but not with ranitidine. The reduction in bacterial density was significantly higher (P<0.003) in those who showed improvement of gastritis than in those who did not. We conclude that effective acid inhibition with omeprazole improves antral gastritis and is accompanied by a reduction in antral bacterial density, suggesting that both acid andH. pylori may be involved in the pathogenesis of antral gastritis.

Sucralfate Overcomes Adverse Effect of Cigarette Smoking on Duodenal Ulcer Healing and Prolongs Subsequent Remission

A unicenter, single-blind, randomized study was conducted on 283 patients with active duodenal ulcer to compare possible factors that may affect healing and relapse in patients treated with a potent antisecretory agent, cimetidine, or a site-protective and cytoprotective agent, sucralfate. The endoscopic healing rates at 4 wk were 76% and 79%, respectively, and cross-over treatment of the failures for a further 4 wk resulted in 68% healing with cimetidine and 69% healing with sucralfate, both differences being not statistically different. Unlike cimetidine, healing by sucralfate was unaffected by cigarette smoking, reluctance to give up smoking, habitual use of alcohol, high maximal acid output, and large ulcer diameter. In particular, the healing rate of smokers treated with sucralfate (82%) was significantly greater than that of smokers treated with cimetidine (63%). Duodenal bulb deformity significantly affected healing in both groups, and was the only offsetting factor identifiable for sucralfate out of 46 factors examined. Of the patients with healed ulcers, 238 participated in a 24-mo follow-up study consisting of interviews at 2-mo intervals and endoscopy at 4-mo intervals or whenever symptoms recurred. The cumulative relapse rate was significantly (p less than 0.007) greater in patients healed with cimetidine than with sucralfate, 50% relapse occurring at 6 and 12 mo, respectively. In both, the cumulative relapse rate was significantly greater in cigarette smokers than in nonsmokers, but smokers and nonsmokers treated with cimetidine relapsed (50% at 4 and 8 mo, respectively) faster than the corresponding smokers and nonsmokers treated with sucralfate (50% at 8 and 18 mo, respectively). Furthermore, in cimetidine- but not sucralfate-healed patients, early ulcer relapse (within 6 mo) was associated with short duration of illness, short remission period, long symptomatic spell, and reluctance to give up smoking. We conclude that smoking adversely affects duodenal ulcer healing by cimetidine and hastens subsequent relapse, and that sucralfate overcomes the adverse effect of smoking on healing as encountered with cimetidine, and results in a subsequent remission period double that of cimetidine.

A RANDOMIZED COMPARATIVE STUDY OF LASER PHOTOCOAGULATION, HEATER PROBE, AND BIPOLAR ELECTROCOAGULATION IN THE TREATMENT OF ACTIVELY BLEEDING ULCERS

A randomized study was performed to compare the efficacy of Nd:YAG laser, heater probe, and bipolar electrocoagulation in the treatment of active bleeding from peptic ulcers. Nine hundred and forty-eight consecutive patients with upper gastrointestinal bleeding underwent endoscopy and 91 patients with active bleeding from peptic ulcer were randomized to receive laser (N = 30), heater probe (N = 31), and bipolar electrocoagulation (N = 30). The angulation of the probe to the ulcer base was assessed at endoscopy. The three treatment groups were comparable in their clinical and endoscopic characteristics. There was no significant difference among patients treated with laser, heater probe, and bipolar electrocoagulation in the rate of re-bleeding (10%, 19.4%, and 10%), duration of hospital stay (4, 4, and 5 days), and proportion requiring emergency surgery (7%, 13%, and 7%), but the cost per patient was higher with laser than heater probe and bipolar electrocoagulation. The angulation of the probe to the ulcer base did not affect the re-bleeding rate. No complication was reported. We conclude that the three modalities were equally effective and safe in endoscopic hemostasis but because bipolar electrocoagulation and heater probe were cheaper, they were recommended for use.

Hepatitis C in renal transplant recipients

Sera from 130 renal transplant recipients were tested for antibody to hepatitis C virus (anti-HCV). Anti-HCV was detected in 6.2% of patients: 15.4% of patients who had maintenance hemodialysis (HD) and 2.2% of those who had continuous ambulatory peritoneal dialysis (CAPD) before transplantation (P<0.05). The similarity in prevalence of anti-HCV with patients currently on dialysis and the absence of transfusion during posttransplant follow-up suggest that most patients acquired HC V infection through transfusion during dialysis. The proportion of anti-HCV-positive patients who had one or more episodes of elevation in serum transaminase level was similar to that of hepatitis B surface antigen (HBsAg)-positive patients, 75% vs. 72.2%. However, anti-HCV was only detected in 25% of HBsAg-negative patients who had recurrent elevations in serum transaminase level. It is not clear whether the low prevalence of anti-HCV in these patients is related to the presence of other non-A, non-B hepatitis virus (es) or a decrease in titer of anti-HCV secondary to immunosuppression posttransplantation.

Clear cell carcinoma of liver. An ultrastructural study

A light microscopic and ultrastructural study of ten consecutive cases each of the clear cell type and nonclear cell type of hepatocellular carcinoma (HCC) showed important differences between the two groups which may help to explain their different biological behavior. The clear cells contained substantial quantities of glycogen and lipid which partly substitute the usual cytoplasmic constituents. An analogy was made between these tumor cells with clear cytoplasm and the clear cells which occurred in the intermediary stages of hepatocellular carcinogenesis in animals in an attempt to explain the better outcome of clear cell HCC.

Efficacy of sucralfate in corpus, prepyloric, and duodenal ulcer-associated gastric ulcers: A double-blind, placebo-controlled study☆

A 12-week study with two weekly endoscopic assessments was performed in 138 patients to compare the efficacy of sucralfate fine granules (900 mg one-half hour before breakfast, lunch, and dinner, and at bedtime) versus placebo in the healing of gastric ulcers prestratified into corpus, prepyloric, and duodenal ulcer-associated. For corpus and prepyloric ulcers, the respective healing rates achieved by sucralfate at six weeks (69 and 80 percent) and at eight weeks (80 and 93 percent) were significantly (p less than 0.005) better than those obtained with placebo (33 and 25 percent at six weeks, and 41 and 33 percent at eight weeks). The design of the study permitted life-table analysis that further demonstrated the efficacy of sucralfate in these two ulcer types (p less than 0.0001). Symptomatic response was likewise significantly better with sucralfate than with placebo. Similar healing rates and symptomatic responses were observed for patients with duodenal ulcer-associated gastric ulcer but were not significantly better with sucralfate than with placebo. From 38 prospectively obtained clinical, personal, physiologic, and endoscopic characteristics, it was found that ulcer size and a history of pain had significant influence on healing with sucralfate. It is concluded that sucralfate is safe and effective for the treatment of corpus and prepyloric ulcers.

Interferon treatment for hepatitis B-associated membranous glomerulonephritis in two Chinese children

Two Chinese boys, aged 3.5 and 5 years, developed nephrotic syndrome and were chronic carriers of hepatitis B virus surface antigen (HBsAg) and hepatitis B virus e antigen (HBeAg). Renal biopsy showed membranous glomerulonephritis and liver biopsy showed chronic persistent hepatitis. They were given interferon-α-2a at a dose of 5 MU/m2 on alternate days for 12 and 16 weeks after 2 years of persistent nephrotic syndrome. Patient 1 showed complete remission and resolution of hepatosplenomegaly, but his serum remained positive for HBsAg, HBeAg and hepatitis B virus DNA. Patient 2 showed only a transient clinical response and seroconversion from HBeAg to anti-HBe status. Although not always successful, interferon treatment should be considered in severe persistent nephrotic states, since there is at present no satisfactory treatment for this form of glomerulonephropathy.

Re-evaluation of α-interferon treatment of chronic hepatitis B using polymerase chain reaction

To re-evaluate the efficacy of 3 treatment trials involving 272 Chinese patients with chronic hepatitis B virus infection, serial serum samples were tested from 60 patients treated with α-interferon with or without prednisone priming and 12 control patients, who were negative for hepatitis B virus deoxyribonucleic acid using dot-blot hybridization. Serial samples were tested using nested polymerase chain reaction with primer sets chosen from the surface and core antigen coding regions. The 19 patients who did not show persistent serological change remained hepatitis B virus deoxyribonucleic acid positive using the polymerase chain reaction assay. Three of the 4 patients (75%) who lost hepatitis B surface antigen and 9 of 51 (17.6%) who lost hepatitis B e antigen became negative from 0 to 60 months after the e-seroconversion. All patients negative for the polymerase chain reaction assay had normal transaminase levels. Pooling the 3 trials together, 11 of 188 (5.9%) treated patients and 1 of 84 (1.2%) control patients became hepatitis B virus deoxyribonucleic acid negative. The difference was not statistically significant. As assayed by the polymerase chain reaction assay, patients who were treated with α-interferon with or without steroid priming and lost hepatitis B e antigen within 12 months were more likely to subsequently lose the virus completely from the serum (11 of 33) than those who lost hepatitis B e antigen after 12 months (none of 13; p = 0.029).

The diagnostic value of the ratio of serum gamma-glutamyl transpeptidase to alkaline phosphatase in alcoholic liver disease

A prospective study of the initial liver laboratory tests was carried out in the following patients: 55 patients with alcoholic liver disease, 53 with cholangitis, 41 with hepatocellular carcinoma, 65 with acute viral hepatitis, and 49 with hepatitis-B surface antigen-positive chronic active hepatitis. There was considerable overlap in the levels of the serum gamma-glutamyl transpeptidase (GT) and alkaline phosphatase (AP) among the five groups. However, the ratio of GT to AP was significantly higher in the group with alcoholic liver disease than in any of the other four groups. When the ratio was higher than 1.4, the diagnostic efficiency for distinguishing the alcohol group from the other four groups was 78% (the normal upper limit for GT and AP being 35 and 115 U/1, respectively). A possible explanation for this higher ratio in alcoholic liver disease is suggested. We conclude that when the GT and AP is greater than 1.4, it is of greater diagnostic value than either variable alone in differentiating alcoholic from other liver diseases.