Quantitative assessment of fibrosis and steatosis in liver biopsies from patients with chronic hepatitis C.

BACKGROUND: Hepatic fibrosis is one of the main consequences of liver disease. Both fibrosis and steatosis may be seen in some patients with chronic hepatitis C and alcoholic liver disease (ALD). AIMS: To quantitate fibrosis and steatosis by stereological and morphometric techniques in patients with chronic hepatitis C and compare the results with a control group of patients with ALD. In addition, to correlate the quantitative features of fibrosis with the Ishak modified histological score. MATERIALS AND METHODS: Needle liver biopsies from 86 patients with chronic hepatitis C and from 32 patients with alcoholic liver disease (disease controls) were analysed by stereological and morphometric analyses using the Prodit 5.2 system. Haematoxylin and eosin and Picro-Mallory stained sections were used. The area fractions (A(A)) of fibrosis, steatosis, parenchyma, and other structures (bile duct and central vein areas) were assessed by stereological method. The mean diameters of fat globules were determined by morphometric analysis. RESULTS: Significant differences were found in the A(A) of fibrosis, including fibrosis within portal tract areas, between chronic hepatitis C patients and those with ALD (mean (SD): 19.14 (10.59) v 15.97 (12.51)). Portal and periportal (zone 1) fibrosis was significantly higher (p = 0.00004) in patients with chronic hepatitis C compared with the control group (mean (SD): 9.04 (6.37) v 3.59 (3.16)). Pericentral fibrosis (zone 3) occurred in both groups but was significantly more pronounced in patients with ALD. These results correlate well with the modified Ishak scoring system. However, in patients with cirrhosis (stage 6) with chronic hepatitis C the A(A) of fibrosis varied between 20% and 74%. The diameter of fat globules was significantly lower in patients with hepatitis C (p = 0.00002) than the ALD group (mean (SD): 14.44 (3.45) v 18.4 (3.32)). Microglobules were more frequent in patients with chronic hepatitis C than in patients with ALD. In patients with chronic hepatitis C, the fat globules had a zonal distribution in comparison with pan steatosis in ALD. CONCLUSION: Quantitative, stereological techniques are simple and reliable for evaluating hepatic fibrosis and steatosis in chronic hepatitis C. They are most useful for assessing the origin, location, and the stage of fibrosis. Stereology and morphometry are recommended for the quantitation of fibrosis and steatosis, particularly for the evaluation of new treatment strategies in patients with chronic hepatitis C.

Resolution of gastritis induced by Helicobacter pylori 4-5 weeks after successful eradication of infection using a triple therapy regimen of pantoprazole, amoxycillin and clarithromycin for one week.

UNLABELLED: This open-label study was designed to determine the extent of histological resolution of gastritis induced by Helicobacter pylori infection 4-5 weeks after successful eradication of the infection. Eradication was achieved using a triple therapy regimen consisting of a twice daily dose of pantoprazole 40 mg, clarithromycin 500 mg, and amoxicillin 1,000 mg taken for 1 week only. No other medications were given thereafter. Four biopsies were processed for histological examination of each patient, two from the antral and two from the corporeal mucosa, first at the start of the study and then again 4 weeks after cessation of the medication trial. Scoring for H. pylori colonization and the severity of gastritis was determined for each patient according to the Sydney system. 53 of 57 patients in this study had their H. pylori infection successfully eradicated by the regimen mentioned and could be histologically evaluated. According to the severity of gastritis in the antral mucosa, patients were studied in 3 groups: mild, moderate and severe gastritis. 17 of 19 cases with mild gastritis showed complete resolution of the inflammation, with residual inflammatory changes persisting in 2 cases only. 22 of the 26 cases with moderate gastritis showed almost complete recovery except for minor residual inflammatory changes as judged by irregularity of intracytoplasmic mucine storage. Persistent residual inflammatory changes in the lamina propria were detected in 4 cases. Of the 8 cases with severe gastritis 5 showed subsidence of the inflammatory changes, but the mucosa in these cases revealed some scarring, distortion of the glandular epithelium and atrophy. In 3 cases residual inflammation persisted. CONCLUSION: One-week therapy with a twice daily dose of pantoprazole 40 mg, clarithromycin 500 mg and amoxicillin 1,000 mg, used to eradicate H. pylori causing active inflammation of the gastric mucosa, has led to subsidence of the acute inflammatory changes in all the cases with residual inflammation persisting in 17%. Severe gastritis may cause irreparable damage to the gastric mucosa. The density of H. pylori colonization does not appear to be related to the severity of gastritis, nor to the successful eradication achieved.

One-week triple regime therapy consisting of pantoprazole, amoxicillin and clarithromycin for cure of Helicobacter pylori-associated upper gastrointestinal diseases.

This study was designed to determine the efficacy and safety of 1-week triple therapy regime consisting of pantoprazole, amoxicillin and clarithromycin in the cure of Helicobacter pylori infection leading to duodenal ulcer disease and/or gastritis. Sixty-one patients (47 males, 14 females with a mean age of 34 years) belonging to different ethnic groups suffering from H. pylori-associated duodenal ulcer and/or gastritis for an average of 2.46 years were recruited. Having satisfied primary selection criteria, patients received pantoprazole 40 mg b.i.d., clarithromycin 500 mg b.i.d. and amoxicillin 1,000 mg b.i.d. for 7 days. All medications were stopped there after H. pylori eradication was determined 4-6 weeks after treatment by a repeat endoscopy, a rapid urease test, H. pylori culture and histology assessment as indicators of cure. All three tests must be negative to consider the infection to have been successfully eradicated. Fifty-seven patients completed the efficacy analysis per protocol. Dramatic symptomatic improvement was noted in most patients immediately after stopping treatment and it was sustained at 6 weeks. At the end of the study, the healing rate of duodenal ulcers (complete re-epithelialization) following 1-week treatment only, as indicated above, and without any maintenance therapy was 66.7%, that of gastritis was 55.7%, and that of erosions was 64.3%. The overall eradication rate for H. pylori, however, was 93% (95% CI 83.0-98.1%). Furthermore, histologic evaluation revealed a remarkable resolution in the activity of gastritis in all the patients who had successful eradication of the infection.

Hepatitis C virus genotypes in a cohort of Middle Eastern patients.

BACKGROUND: The epidemiology of hepatitis C virus infection has been well characterized in Western Europe, North America and Japan. Less is known about it in other regions of the world. In order to fully understand the relationship between host and virus, it is important to study the effect of virus infection in all regions of the world. In this report, we have analyzed patients from the United Arab Emirates, Egypt and Jordan. DESIGN AND METHODS: Serum from 81 Middle Eastern HCV ELISA-2-positive patients was analyzed for the presence of HCV RNA by PCR. RNA-positive patients were genotyped by selective hybridization of amplicons to HCV genotype-specific oligonucleotides (InnoLipa2, Innogenetics, Belgium). Where possible, data was also obtained on racial origin, liver histology, serum ALT, prothrombin time, albumin, and risk factors for infection. RESULTS: Sixty-five of 81 patients were HCV RNA-positive. A higher proportion of Middle Eastern patients were genotype 4 compared to equivalent studies from Western Europe, USA and Japan. However, the most common genotype was 1a. No significant difference in genotype was found between patients with chronic hepatitis and patients with cirrhosis. CONCLUSIONS: Eight of 65 (12%) patients were genotype 4, but the most common genotype was 1a, a âWesternâ genotype (24/65, 37%). The mean age of cirrhotics was low compared to Western studies. This may be due to infection in early childhood or race-related host factors. Twelve of 65 patients (18%) were not classifiable for genotype using InnoLipa2. This may be due to multiple infecting genotypes in these patients, or unusual, non 13 HCV genotypes which cannot be classified by InnoLipa2.

Visceral leishmaniasis in Gizan, Saudi Arabia.

Visceral leishmaniasis is endemic in southern Saudi Arabia. We prospectively evaluated 121 patients with visceral leishmaniasis at King Fahad Hospital in Gizan. All patients were infants and children. Seasonal variation was observed with more cases presenting in late spring and summer and few in winter. The predominant clinical features in these patients were chronic fever, abdominal distention, weight loss and hepatosplenomegaly. Lymphadenopathy was rare in contrast to African kala-azar. Common laboratory abnormalities included anemia, leukopenia, thrombocytopenia, hypoalbuminemia and hypergammaglobulinemia. Liver function tests were deranged in one-third of patients. Leishmania hemagglutination test was positive in all patients and all of them had positive bone marrow smear or culture for Leishmania donovani. Patients responded well to stibogluconate (Pentostam) therapy with a cure rate of 96.7%. Four patients died in the first few days of therapy. Jaundice and grossly deranged liver function tests were found to be bad prognostic signs.

Some unusual presentations of hepatic amoebiasis in Enugu, Nigeria.

Eighty-two cases of hepatic amoebiasis were diagnosed and treated at the University of Nigeria Teaching Hospital during a 4-year period. Typical or classical features were observed in 75 (91.4%) of the cases while the remaining seven presented atypically or unusually. These were obstructive jaundice (three cases), coma (two cases) and pyrexia of unknown origin (two cases). All the cases had positive gel diffusion precipitation test for amoebic antibodies, and in all but one there was demonstration of an abscess cavity. In the three cases of obstructive jaundice, the abscess cavities were located close to the hilum and compressed the main bile duct. There was no mortality recorded especially in the jaundiced cases despite the grave prognosis associated with jaundice in hepatic amoebiasis. This study demonstrates the need to consider hepatic amoebiasis in an area when patients present with either obstructive jaundice, coma or pyrexia of unknown origin and to do ultrasonography as an initial investigation in such patients.

Intestinal permeability in diabetic diarrhoea.

Small intestinal permeability to mannitol and lactulose was studied in 12 patients aged 36-70 (mean 56) years with diabetic diarrhoea (DD). Ten uncomplicated diabetics aged 24-56 (mean 37) years and 25 normal subjects aged 22-60 (mean 37) years served as controls. Permeability was assessed by measuring urinary recovery of the test substances after oral ingestion. Mean lactulose excretion in patients with DD was significantly lower than in normal controls but was not significantly different from the uncomplicated diabetics. Mean lactulose excretion was not significantly different in the three groups. However, lactulose to mannitol excretion ratios (LMER) were significantly higher in patients with DD compared to the controls or the uncomplicated diabetics. LMER in seven patients with DD were outside the normal range. LMER in patients with DD did not correlate with blood urea, small intestinal transit time, faecal fat excretion, small intestinal bacterial overgrowth, duration of diabetes or duration of diarrhoea. Jejunal morphology was normal in all patients with DD. It was concluded that small intestinal permeability was abnormal in some patients with DD and that this might be a factor in the aetiology of the diarrhoea.

Liver biopsy: experience at Enugu, eastern Nigeria.

A retrospective analysis of liver biopsies done at the University of Nigeria Teaching Hospital, Enugu, between January 1980 to December 1985 was done to determine the indications, level of preparation and investigation of the patients, biopsy techniques and failure rate, complications and histopathological results. The register of all biopsies sent to the Morbid Anatomy Department and the clinical records of the patients were used for the analysis. Of the 154 biopsies done, the Menghini technique was used in 128 cases (83.1%), the rest was by exploratory laparotomy. The commonest indication was unexplained hepatomegaly with or without splenomegaly 46 cases (29.8%). Adult cases accounted for 132 cases (85.7%) with male/female distribution of 3:1. Histologically proven cases of hepatocellular carcinoma accounted for 38 cases (14.2%). Pain requiring analgesics occurred in 8 cases (5.2%). The need for adequate clinical documentation of patients is emphasized.

Gastric acid secretion studies in Enugu, using pentagastrin stimulation.

Mean acid output was studied in forty-three Nigerian subjects (twenty controls and twenty-three duodenal ulcer patients). 6 micrograms/kg body weight of pentagastrin was given to each after 1 hour basal acid output (B.A.O.) collection. Maximal and peak acid outputs (M.A.O. and P.A.O.) were measured in mmol/hr using the indicator-titration method. Gastric juice volume was measured in mls. For the control the B.A.O., M.A.O. and P.A.O. in mmol/hr were (Mean 1 S.D.) 1.7 +/- 1.6; 13.5 +/- 4.61 and 15.1 +/- 5.3 respectively. The corresponding figures for the duodenal ulcer patients was 3.2 +/- 2.7; 25.1 +/- 8.5; 28.4 +/- 11.1. P less than 0.05, P less than 0.001 and P less than 0.001 respectively). The mean stimulated gastric juice volume of 131.3 +/- 29.6 ml in the controls differed significantly from the volume 198.2 +/- 54.9 in the duodenal ulcer patients (P less than 0.001). 182 mls of gastric juice was found to be the volume above which is duodenal ulcer may be suspected. Acid values are compared with published data and reasons for any differences discussed.

Dose response studies of gastric acid secretion in Nigerians using pentagastrin stimulation.

To determine the does of pentagastrin required for maximal gastric acid secretion, 6, 8, and 10 micrograms/kg body weight of intramuscular pentagastrin were given to twenty Nigerian subjects (ten controls and ten duodenal ulcer patients). The different doses of pentagastrin were administered to each subject on different days. 8 micrograms/kg body weight of pentagastrin caused the highest gastric acid output in all the subjects followed by 6 and lastly 10 micrograms/kg body weight. Significant differences in the mean stimulated acid output by 6 and 8 micrograms/kg body weight to pentagastrin were found only in the duodenal ulcer patients (Maximal Acid Output (M.A.O.).

Small intestinal permeability in normal Sudanese subjects: evidence of tropical enteropathy.

Small intestinal permeability to mannitol and lactulose was studied in healthy English and apparently healthy Sudanese subjects to determine whether any differences were apparent. Permeability was assessed by measuring urinary recovery of the test substances after oral ingestion. The mean excretion of lactulose was significantly higher and the mean excretion of mannitol was significantly lower in the Sudanese than in the English subjects. Lactulose to mannitol excretion ratios were significantly higher in the Sudanese. These data demonstrate abnormal intestinal permeability in the Sudanese subjects and indicate the presence of an asymptomatic enteropathy.

Small intestinal permeability as an indicator of jejunal mucosal recovery in patients with celiac sprue on a gluten-free diet.

Lactulose/mannitol excretion ratios were measured in 13 patients with celiac disease at diagnosis and after 5-8 months on a gluten-free diet. Jejunal biopsies were assessed histologically at diagnosis and during treatment. The excretion ratios in untreated patients were significantly higher than in 25 normal controls (P less than 0.01). On the diet, the excretion ratios fell in every patient, but in only eight did the ratio return to normal. There was a good correlation between the ratio and jejunal histological grading. During treatment, the ratios significantly inversely correlated with jejunal villous height/mucosal thickness ratios (P less than 0.001). Therefore, excretion ratios provide a well-tolerated noninvasive means of assessing the jejunal mucosa in patients with celiac disease on a gluten-free diet.

Small intestinal permeability to mannitol, lactulose, and polyethylene glycol 400 in celiac disease.

Mannitol (molecular weight 182), lactulose (342), and polyethylene glycol 400 (range 242-550) absorption was studied in 25 controls, 22 untreated celiacs, and 13 treated celiacs. Untreated celiacs absorbed less mannitol and more lactulose than controls. Absorption of higher as well as lower molecular-weight polyethylene glycols was reduced in untreated celiac disease. Absorption returned towards normal on treatment. Polyethylene glycol and lactulose absorption was enhanced by administering them in a hypertonic solution. Polyethylene glycol 400 but not lactulose or mannitol was lipid soluble in vitro. It was concluded that the mucosa in untreated celiac disease was more "leaky" than normal. Polyethylene glycol 400 absorption data suggested that its absorption may largely be determined by its lipid solubility and was decreased in celiac disease because of the reduced surface area of the small intestine. Polyethylene glycol 400 cannot be recommended as a suitable marker for permeability studies of the small intestine.

Small intestinal permeability to sugars in patients with atopic eczema.

Absorption of lactulose and mannitol was measured in eleven patients with atopic eczema and lactulose/mannitol excretion ratios were calculated. Mean lactulose absorption was increased in the patients with exzema and their excretion ratios were higher than those of controls. There was no correlation between either eczema extent or severity and the excretion ratio. We conclude that small intestinal passive permeability is increased in some patients with atopic eczema.

Abnormal small intestinal permeability to sugars in patients with Crohn's disease of the terminal ileum and colon.

The absorption of lactulose and mannitol in 20 patients with Crohn's disease limited to the ileum or colon was studied, and lactulose/mannitol excretion ratios were calculated. The results were compared to those from 16 normal controls and 6 patients with ulcerative colitis. The 13 patients with ileal Crohn's disease had significantly higher lactulose/mannitol excretion ratios than the controls (p less than 0.01) or ulcerative colitics (p less than 0.01). Similarly, the 7 patients with Crohn's disease limited to the colon had significantly higher excretion ratios than the controls (p less than 0.01) or ulcerative colitics (p less than 0.01). The results provide support for the concept that Crohn's disease may be more extensive than is apparent macroscopically.

Serum lysozyme activity in coeliac disease: a possible aid to athe diagnosis of malignant change.

Serum lysozyme activities were measured in 34 control subjects, 13 untreated adult coeliac patients, 21 adult coeliac patients on gluten-free diet, and eight coeliac patients with a histiocytic lymphoma. Serum lysozyme activities were raised in three untreated patients, three patients treated with a gluten-free diet, and in only two patients with coeliac disease and lymphoma. Serum lysozyme estimations cannot be recommended as an aid to the diagnosis of lymphoma in patients with coeliac disease.