Interferon in chronic hepatitis B.

In patients with typical chronic hepatitis B (HBsAg, HBeAg, HBV-DNA-positive), treatment with interferon-alpha must be carried out for 4-6 months on an alternate-day basis and dosage should be not less than 5 million units/square meter of body surface. The therapeutic response (i.e., clearance of replicative markers, transaminases normalization, histologic improvement) is achieved in about 40% of treated patients and the long-term beneficial effect is maintained in about 90% of them. Oriental HBV carriers, children, immunodeficient and highly viraemic patients are less likely to respond. Patients given combinations therapy (with steroids, antivirals, stimulators of the immune system) do not appear to gain more benefit from the association in comparison with treatment with interferon alone. Side-effects are usually minor (flu-like symptoms), but in a minority major adverse events have also been reported. In conclusion, interferon-alpha is effective in inhibiting viral replication but new therapeutic regimens and a better selection of patients are needed in order to induce persistent remissions and to reduce the cost benefit ratio.

HLA antigens and clinical manifestations in Crohn's disease.

A clinical, radiological and immunogenetical study was carried out on 51 Crohn's patients. Rheumatological disorders were found in 16 of them, with higher frequency in those with colon involvement only. A statistically significant increase in the frequencies of HLA-A9 and HLA-Cw3 was noted: Cw3 showed a particularly high frequency in males, and A9 in younger patients. The frequency of HLA-B27 was significantly increased in the patients with colon involvement. In the group of 16 patients with rheumatic diseases HLA antigen frequencies were not significantly different from the control population.

IgM antibody against measles virus in patients with inflammatory bowel disease: a marker of virus-related disease?

OBJECTIVE: Viral infections of the mesenteric microvascular endothelium have been hypothesized as pathogenetic factors in inflammatory bowel diseases. The aim of this study was to determine whether immunoglobulin M (IgM) antibody against measles virus is associated with disease. PATIENTS AND METHODS: The IgM antibody was detected by indirect antibody test in 36 patients with evidence of Crohn's disease (23 males and 13 females, median age 40 years, range 20-66), 22 patients with ulcerative colitis (14 males and 8 females, median age 42 years; range 19-65), 59 patients with a chronic active hepatitis (35 males and 24 females, median age 56 years, range 38-77) and 30 blood donors (20 males and 10 females, median age 45 years, range 29-62). RESULTS: Twenty-eight of 36 patients (78%) with Crohn's disease and 13 of 22 patients (59%) with ulcerative colitis tested positive as compared to only 3 of 89 (3.3%) controls (P < or = 0.001). CONCLUSION: The detection of IgM anti-measles virus in the majority of patients with Crohn's disease and in about half of ulcerative colitis patients as compared to a very low prevalence in patients with other chronic inflammatory disease is consistent with the hypothesis that the measles virus has pathogenetic implications in inflammatory bowel diseases.

Monoethyl glycine xylidide (MEGX) test evaluation in primary biliary cirrhosis: comparison with Mayo score.

OBJECTIVE: To evaluate the clinical and prognostic value of the monoethyl glycine xylidide (MEGX) test in patients with primary biliary cirrhosis (PBC) in comparison with the Mayo score (Mayo). DESIGN: A prospective study. METHODS: MEGX determinations at enrolment were compared to the Mayo score as well as to conventional clinical and laboratory parameters in 92 patients with PBC. RESULTS: The MEGX test yielded higher basal values in long-term survivors compared to patients that were transplanted or died during the follow up; patients belonging to the last two groups displayed significantly higher Mayo scores at baseline. Although values for prothrombin time, serum albumin, alkaline phosphatase, cholesterol, cholinesterase, and gamma-glutamyltranspeptidase were significantly different in survivors compared to either transplanted or dead patients at univariate analysis, the multivariate analysis demonstrated an independent prognostic value for the MEGX and the Mayo score solely. The best discrimination between probability of death or survival was achieved with a cutoff value of 25 ng/ml for the MEGX test and of 6 for the Mayo score. When plotting both MEGX test and Mayo score, the point distribution displayed a bimodal trend, and the wide range of values given by the MEGX test was observed to supply a more precise assessment of liver reservoir and a better discrimination of progressive changes in liver function; the limited range of the Mayo score for values below 6 could only identify gross deteriorations. CONCLUSION: Our data show that the asymptomatic progressive functional deterioration occurring during the natural history of PBC can be monitored by the MEGX test because it appears to be able to identify abnormalities prior to the onset of alterations in conventional laboratory and/or clinical parameters which are likely to affect the Mayo score.

Patterns of natural killer cell function activation in response to interferon in chronic HBsAG positive hepatitis: relationship with the state of viral infection and with the early clinical response.

In an effort to define immunobiological parameters identifying "responders" vs "non-responders" to IFN among hepatitis patients, 16 patients with chronic active hepatitis were screened for changes of Natural Killer cell activity (NK). 10/16 patients replicated the hepatitis B virus (HBV-DNA positive) whereas 6/16 replicated the defective B virus associated delta virus (HDV-RNA positive). Patients received 9 MU/3x/weekly/3 months of recombinant IFN alpha A. Mean NK activity of the HBV-DNA patients rose significantly from 29.9 +/- 5.3 to 45 +/- 4.7 during therapy, whereas the 6/16 HDV-RNA positive patients did not show any significant increase of NK activity. Interestingly, individual HDV-RNA positive patients exhibiting boosted NK activity also showed improvement of disease confirmed by clearance of intrahepatic delta antigen at one year. No such a correlation was found amongst the HBV-DNA positive patients. These data indicate that in spite of widespread individual variability, IFN-mediated NK boost may herald delta clearance and help in identifying "responders" and "non-responders" in IFN trials.

Immunohistochemical research of HDV infection in Chinese patients with chronic liver disease.

The prevalence of HDAg in the liver of Chinese patients with chronic hepatitis and hepatocellular carcinoma was determined using direct immunofluorescence and immunoperoxidase. Overall, 6 patients (6.31%) out of 95 HBsAg carriers with inflammatory liver disease and neoplasia were found to be HDAg positive. HDAg was detected in the livers of 6 (7.59%) out of 79 chronic hepatitis patients. The relative frequency of HDAg in cirrhosis-B, CAH-B and CPH-B was 14.3%, 7.1%, and 5.89%, respectively. These results suggest that a sizeable number of HBsAg carriers are also carriers of HDV. In view of the large number of HBV carriers in China, the relatively minor but distinct presence of HDV represents an important health problem.

[Is HCV RNA detectable in the ultrafiltrate?]. / L'RNA dell'HCV è riscontrabile nell'ultrafiltrato?

We investigated by molecular biology the possibility that the HC virus passes by the dialysis membranes into the ultrafiltrate, making the HD monitor a way of HCV transmission. HCV-RNA was tested in blood and in UF samples during 2 HD sessions at T-0, 30, 60, 120 min and at HD end. HCV-RNA was measured by RT-PCR. Viraemia in patients was > 10(-4) gen Eq/ml and remained unchanged along HD, HCV-RNA was not found in whole UF and its x100 concentrates during the HD. We failed to prove the passage of the HCV into the UF, at least in standard conditions.

[Chronic hepatitis: diagnostic and therapeutic problems]. / Epatite cronica: problemi diagnostici e terapeutici

The morphological criteria for diagnosing chronic hepatitis are discussed and criticised. A classification closer to clinical reality than that of De Groote et al 1968 is then proposed. Personal experience in differential laboratory diagnosis between the various forms of chronic hepatitis by means of comparative evaluation of an enzymogram and the measurement of certain proteins in the serum is then reported. Case examples are given to emphasise the possibilities of the immunological approach to the problem of active chronic hepatitis. Finally, the cardinal points of therapy are reviewed.

[Cimetidine in the treatment of peptic ulcer]. / La cimetidina nella terapia dell'ulcera peptica.

Cimetidine, a non-thiourea-containing histamine H2-receptor antagonist, has been employed in the treatment of peptic ulcer. We studied 50 patients, partly with double-blind method, and partly in a free trial. Duodenal ulcers were completely healed in 80% of the cases, at the control endoscopy after a 4-week period of treatment with cimetidine (1000 mg/day). Peptic ulcer in general healed in 76% of the cases. Gastric secretion was significantly reduced after cimetidine. An important improvement in subjective symptoms was noted in every patient. No toxic effect was noted.

[Prevalence of peptic ulcer in patients with various hepatopathies]. / Prevalenza della malattia peptica in pazienti con differenti epatopatie.

Aim of this study was to re-evaluate the overall prevalence of a peptic disease in 350 patients with liver diseases of different etiology and severity. A normal endoscopic picture was found in 82% of cases. Peptic lesions were found in 18% of total cases and were located in the duodenal (10.9%) and gastric (7.1%) wall. On the basis of the 15-20% rate, which most Authors think to be a reasonable estimate of the overall ulcer prevalence in normal population, the prevalence rate in this survey would suggest that there is no association between ulcer and liver disease. Ulcers were more commonly present in cirrhotic than in noncirrhotic patients. Both alcohol intake and cigarette smoking were identified as two ulcerogenic events in these patients while portal hypertension and etiology of liver disease were irrelevant factors. The contemporary occurrence of the three ulcerogenic factors (cirrhosis, smoking, and alcohol intake) in a given patient seems to potentiate each others as ulcerogenic event. It is concluded that patients with liver diseases share the same risk of developing a peptic disease as the general population.

[Intestinal ischemia: nosographic framework and risk factors]. / Ischemia intestinale: inquadramento nosografico e fattori di rischio.

The diagnosis of intestinal ischaemia still presents numerous problems in terms of nosography, epidemiology, diagnosis and treatment with the result that it is more often excluded than diagnosed. The aim of the present study was to discover whether intestinal ischaemia was clinically identifiable by any specific early signs and symptoms and whether there were any concomitant risk factors. The medical reports on 44 patients consecutively admitted to the San Giovanni Battista Hospital, Turin in 1985-86 with suspected intestinal ischaemia were therefore examined. It was found that intestinal ischaemia was only occasionally (30% of cases) diagnosed at the onset of clinical symptoms. In the 10 patients with ischaemic colitis, the risk factor linked to the causes of the disease was systemic hypovolaemia arising in diffuse atherosclerosis. In the 8 cases of chronic ischaemia and the 26 of intestinal infarction the remote anamnesis revealed symptoms that should have aroused suspicion of intestinal ischaemia partly because the patients were suffering from widespread atherosclerosis. In fact a review of the risk factors for the onset of atherosclerosis (i.e. high blood pressure, smoking, dyslipidemia, obesity and age over 65) revealed that about 60% of the patients under study presented 3 or 4 them simultaneously. To conclude, the data emerging from the study indicate the existence of symptoms and risk factors to diffuse atherosclerosis that should permit the early diagnosis of intestinal ischaemia.

[Early gastric cancer. Survival and prognostic factors in 95 consecutive cases]. / Early gastric cancer. Sopravvivenza e fattori prognostici in 95 casi consecutivi.

In order to characterize prognostic factors and therapeutic strategies for EGC, we have studied 95 patients operated on from 1980 to 1988. EGC was limited to the mucosa in 36% and extended to the submucosa in 64% of the cases. Lymph nodes involvement was observed in 13 patients; in 12 of them EGC extended to the submucosa. Gastric resection was performed in 73 and total gastrectomy in 22 patients with a postoperative mortality of 6% and 16% respectively. During the follow-up 8 patients died for causes related to EGC, 8 for unrelated causes. The 5 years survival rate was 79, without differences according to site, type, size and histology of EGC, lymph nodes involvement, type of gastrectomy; only EGC limited to the mucosa was associated with a better survival experience (96% vs 70% of tumors extended to the submucosa p less than 0.05). The prognosis of EGC is good and a curative surgery may be accomplished, especially if the lesion is limited to the mucosa. In EGC extended to the submucosa an accurate lymphadenectomy may further improve the prognosis, while total gastrectomy--de principe--carries a higher postoperative mortality, without significant improvement of the long term prognosis.

[Combined treatment of colorectal polyps with diathermy and the Nd-YAG laser. Our experience]. / Terapia combinata con ansa diatermica e laser ND-YAG nell'eradicazione dei polipi del colon retto. Nostra esperienza.

Among colorectal polyps, those of the sessile and villous type are said to bear a high frequency cancer degeneration. While surgery is considered the cure, alternative choices are to be offered in the presence of contraindications or lack of an informed consent. We analyzed the results of the "combined therapy" that requires the use of the ND-YAG laser following the ablation of the lesion with diathermic snare. We used an EV laser 132 with double wavelength to allow the ablation of flat lesions and minimize the risk of perforation. We included 12 patients with sessile colorectal polyps. In 9/12 complete eradication was obtained over a follow-up 11 months; of the remaining 3, 2 dropped out, 1 did not respond. Owing to the small series, the relationship between the successful eradication and the size of the polyp cannot be evaluated. We conclude that the treatment of sessile colorectal polyps with this combined approach may be a promising one.

[Clinical evaluation of chemical cholelitholysis using methyl tertiary butyl ether in lithiasis of the bile ducts]. / Valutazione clinica della colelitolisi chimica con MTBE nella litiasi delle vie biliari.

Personal experience is reported in the treatment of calculosis of the biliary ways using MTBE and injected through percutaneous biliary drainage catheters placed surgically or endoscopically in 11 patients in whom surgery appeared to be contraindicated or particularly dangerous. In 10 out of the 11 cases chemical cholelitholysis was successful and the technique is therefore proposed as a valid alternative to surgery in ductal cholelitholysis when sphincterotomy and endoscopic removal of the stones cannot cure the conditions.

[Chronic diarrhea: a difficult diagnosis. A rare cause: lymphocytic colitis]. / Diarrea cronica: una diagnostica difficile. Una causa rara: colite linfocitica.

Lymphocytic colitis is a clinicopathological entity, characterized by chronic watery diarrhea, not bloody. Previously termed microscopic, it is now named lymphocytic for histological features, the most important seems to be the diffuse infiltration of intraepithelial lymphocytes, that must be investigated in multiple biopsies during colonoscopy. This review evidences that during endoscopy the mucosa is normal, but this does not exclude a biopsy, only way for take a diagnosis. Ethiologies are unknown too although a correlation with autoimmune diseases as possible. Lymphocytic colitis is a definition histological entity, while the term ''microscopic'' includes different histological entities under the same ''umbrella'', in relation to the concept of no macroscopic changes and multiple different histological specimens. The treatment is based for the first time on mesalazine or sulphasalazine and then in case of non responders, on corticosteroids.

[Endoscopic therapy of giant choledochal calculosis]. / Terapia endoscopica della calcolosi coledocica gigante.

The paper reports the results of conventional endoscopic treatment in 100 consecutive cases of giant lithiasis of the common bile duct. A giant calculus is one whose dimensions exceed 2 cm. Endoscopic therapy proved successful in 73% of cases, with an 8% incidence of complications. The success of endoscopic treatment is related to the anatomical conditions of the biliary tract and the diameter of calculi. Mechanical lithotripsy has proved efficacious in all cases where it was used, whereas poor results were obtained using MTBE infusion through a naso-biliary tube. ESWL provided encouraging results. Cases which were not resolved using endoscopic methods were treated using intervention radiology or surgery, or both.

Day Bed Unit at the Department of Gastro-enterology. Experience of a study group.

Day Bed Unit at the Department of Gastroenterology. Experience of a study group. We analyzed the activity of the Day-Bed Unit at the Department of Gastroenterology of Turin Hospital (Molinette). The quality of the service provided and the days of stay in hospital for each admission were evaluated in terms of cost benefit ratio. The average stay in hospital for each admission was 2.57 days as opposed to 9.3 in the in patient ward. Patients were divided in subsets according to the cause of admission. Stratifying the patients according to diagnosis showed a hospital stay of 2.73 days for liver disease and of 2.81 for pancreas and biliary disease. Among the admissions for liver disease, pre or posttranspiant patients required 2.89 days as opposed to 2.62 days of those who were treated for esophageal varices. Thus, the cause of admission was a factor influencing length of hospital stay. Patients needing non surgical treatment for liver cancer took 2.22 days if treated with percutaneous ethanol injection; those undergoing chemoembolization required 2.93 days. In conclusion, the day bed unit has proven to be able to provide a service with a good cost benefit ratio. Patients admitted to this service may be withdrawn from the waiting list of the in patient ward, thus reducing the waiting time. Optimization of this service needs integration with the surroudings Units within the Department and in the Hospital.

[Recurring duodenal ulcer. Evaluation of previous complications as a predictive factor of ulcer recurrence after eradication of Helicobacter pylori]. / Ulcera duodenale recidivante. Valutazione della pregressa complicanza come fattore predittivo di recidiva ulcerosa dopo eradicazione dell'Helicobacter pylori.

Duodenal ulcer is a chronic disease, punctuated by acute relapses. The pathogenic mechanism in 90-100% of cases is infection by Helicobacter pylori. Two major strains exist of this bacterium: I strain, which secretes a vacuolating cytotoxin (Vac-A), and another protein named cytotoxin-associated (Cag-A) and type II strain, unable to produce both proteins and unable to produce duodenal pathology. We sought to identify the natural history of relapsing duodenal ulcer after cure of the bacterial infection. In particular, we followed the outcome of patients who repeatedly had bled from their recurrent ulcer disease, after success in eliminating the microorganism from the stomach. None of 12 repeated bleeders had an ulcer recurrence after the cure of Helicobacter pylori infection. Only 3 (5%) of 60 frequent relapser had a new episode of duodenal ulcer during a follow-up reinfection by Helicobacter pylori. We demonstrated that the cure of bacterial infection is also the cure of duodenal ulcer recurrence, but for a few cases, in the latter, event one could hypothesize a defect in the production of growth factors (Epidermal Growth Factor, Fibroblast Growth Factor) or of cellular polyamines synthesis. It is important to improve the diagnosis of reinfection by implementing the urea breath test.

[Somatostatin in severe peptic ulcer hemorrhage]. / La somatostatina nelle severe emorragie da ulcera peptica.

Somatostatin was compared with intensive antacid and thrombin in a randomised controlled study on 15 patients with severe haemorrhages of the upper digestive tract deriving from peptic ulcers and identified endoscopically in order to assess the efficacy of the two drugs. The results in both groups were similar but somatostatin appeared more effective than antacids and thrombin in terms of blood transfusions required and the average time it took to stop the bleeding. The insignificance of these results is in contrast with the data from similar studies using other drugs (anti-H2) and reported by others. This shows the need for controlled polycentric studies conducted on large groups of homogeneous patients.