Non-Invasive Assessment of Graft Fibrosis After Living Donor Liver Transplantation: Is There Still a Role for Liver Biopsy?

Non-invasive methods have evolved as a surrogate for liver biopsy such as indirect markers (aspartate transaminase to platelet ratio index, fibro-α score), transient elastography (TE), and magnetic resonance elastography (MRE). The aim of this study is to prospectively compare the value of MRE, TE, and indirect markers in detecting and staging allograft fibrosis compared to liver biopsies in patients who have undergone living donor liver transplantation for complications related to hepatitis C virus. A total of 31 living donor liver transplantation recipients with hepatitis C virus recurrence underwent a liver biopsy, TE, and MRE within 3 months of a liver biopsy. Fibrosis was assessed according to the biopsy and staged according to Metavir criteria. There was a significant correlation between both MRE and fibro-α scores, as well as histologic classification by liver biopsy (P = .02, .002). The diagnostic accuracy of MRE and fibro-α scores in diagnosing significant fibrosis (F ≥ 3) was measured as the area under the curve (.708 and .833, respectively). Both methods showed good diagnostic performance. TE and aspartate transaminase to platelet ratio index were insignificantly correlated with the degree of fibrosis in liver biopsy (P value of .134, .535). At a cutoff value of 5.5 kPa, MRE predicted graft fibrosis (Metavir stage ≥ 3) with 71.43% sensitivity, 75% specificity, 45.5% positive predictive value, and 90% negative predictive value; at a cutoff value > 1.47, fibro-α scores predicted significant graft fibrosis (Metavir stage ≥ 3) with 85.7% sensitivity and 70.83% specificity, with a positive predictive value of 46.2% and a negative predictive value of 94.4%. These data suggest that non-invasive methods could be considered a reliable tool in assessing significant graft fibrosis post-living donor liver transplantation.

Prognostic role of serum interleukin-18 in Egyptian patients with hepatitis c virus-related hepatocellular carcinoma treated by radiofrequency ablation.

Aim: The aim of this study is to identify the prognostic value of serum interleukin (IL)-18 level in hepatitis C virus (HCV) -related hepatocellular carcinoma (HCC) patients. Materials and Methods: This study was conducted in Tropical Medicine department and HCC unit in Ain Shams University Hospitals. It included 35 patients with HCV associated HCC fit for radio frequency ablation and 20 healthy control subjects. Serum IL-18 level was measured for all participants at the beginning of the study. Patients were followed-up for 1 year then serum IL-18 re-measured at the end of the follow-up period. Results: Pre-intervention serum IL-18 level was significantly higher in patients than healthy control subjects and was associated with bad clinical, laboratory or radiological prognosis. Post follow-up mean value of IL-18 level was significantly lower than pre-intervention level. Conclusion: Higher pre-intervention serum IL-18 level in HCV -related HCC patients level was associated with bad prognosis either clinically, laboratory or radiologically.

Isolation and antibiotic susceptibility of Salmonella, Shigella, and Campylobacter from acute enteric infections in Egypt.

While Campylobacter, Salmonella, and Shigella remain major contributors to acute enteric infections, few studies on these pathogens have been conducted in Egypt. From January 1986 to December 1993, 869 Salmonella, Shigella and Campylobacter strains were isolated from stool specimens from 6,278 patients, presenting to the Abbassia Fever Hospital, Cairo, Egypt, with acute enteric infections. Salmonella predominated, totalling 465 isolates, followed by Shigella with 258 isolates, and Campylobacter with 146 isolates. Of the Shigella isolates, 124 were Shigella flexneri, 49 were S. sonnei, 47 were S. dysenteriae (mainly serotype 1, 2, and 3), and 38 were S. boydii. Campylobacter spp. comprised 92 Campylobacter jejuni and 54 C. coli isolates. Isolation of Salmonella was highest during the months of February-March, June-July, and October-November, while that of Shigella was maximal from July to October. Isolation of Campylobacter increased during May-June and again during August-October. Although Salmonella was sensitive to amikacin, aztreonam, ceftriaxone, and nalidixic acid, it was, however, resistant to erythromycin, streptomycin, ampicillin, chloramphenicol, and tetracycline. Shigella (> 80%) was sensitive to amikacin, ceftriaxone, cephalothin, sulphamethoxazole-trimethoprim (except S. sonnei), aztreonam, and nalidixic acid. Resistance (> 50%) was noted only for ampicillin, chloramphenicol, and tetracycline. C. jejuni and C. coli were resistant to cephalothin, aztreonam, and streptomycin. Some of the above antibiotics were employed to characterize the Egyptian isolates, but did not have any clinical utility in the treatment of diarrhoea. Significant differences (p < 0.05) were observed in the resistance profiles of Shigella and Salmonella between late 1980s and early 1990s. The results suggest the use of fluoroquinolones or a third-generation cephalosporin as an empirical treatment of enteric diseases. However, alternative control strategies, including the aggressive development of broadly protective vaccines, may be more effective approaches to curbing morbidity and mortality due to acute enteric infections.

A study on the relation between proton pump inhibitor and gastric giardiasis.

Thirty patients treated with proton pump inhibitor and still having symptoms related to gastritis or peptic ulcers were subjected to upper gastrointestinal endoscopy and gastric biopsy for detection of giardiasis in these cases. Results showed presence of 3 (10%) cases of gastric giardiasis, intestinal metaplasia and presence of H. pylori in these cases. It is concluded that there may be a relation between the presence of gastric giardiasis and the intake of proton pump inhibitor. The endoscopists have to search for gastric giardiasis especially in the presence of H. pylori and/or intestinal metaplasia.

Differentiation of Campylobacter isolates on the basis of sensitivity to boiling in water as measured by PCR-detectable DNA.

Differential sensitivity for the release of PCR-detectable genomic DNA upon boiling in water is reported for 45 Campylobacter jejuni and Campylobacter coli strains isolated in Egypt. All of the strains released PCR-detectable DNA when treated with proteinase K and sodium dodecyl sulfate. When DNA was extracted from these strains by boiling in water, nine (20%) of the strains were PCR negative or resistant to boiling, suggesting the presence of boiling-sensitive and boiling-resistant phenotypes.

Characterization of Campylobacter spp. using restriction fragment length polymorphism and SDS-polyacrylamide gel electrophoresis.

Twenty four Campylobacter jejuni and coli isolates obtained from Egyptian children were characterized using restriction fragment length polymorphism (RFLP) of flagellin genes and polyacrylamide gel electrophoresis of whole cell and glycine-extracted proteins. The isolates were found to fall into nine polymorphism groups, eight of which were reported previously in Egypt but one group displayed by 3 isolates represented a new group that was not reported before. Furthermore, the relative prevalence of polymorphic groups in the population studied is different from that reported previously. Analysis of whole-cell and acid glycine-extracted proteins showed that the profiles of these isolates are typical profiles of Campylobacters isolated from other humans.

Causes of minimal hepatic periportal fibrosis present in Egypt.

This study aimed to elucidate the common causes of minimal periportal fibrosis in Egypt. Out of 50 patients having minimal periportal fibrosis, 22 (44%) had schistosomiasis as a sole aetiology, 33 (66%) had combined schistosomiasis with both HBV and HCV. Rare causes were tuberculosis in 4% of the patients and HIV in 2%. No cause could be elicited in 14% of the patients. It is concluded that although schistosomiasis is the commonest cause of minimal hepatic fibrosis in Egypt, yet it is not the sole aetiological factor.

Murine intranasal challenge model for the study of Campylobacter pathogenesis and immunity.

Campylobacter jejuni infection of mice initiated by intranasal administration was investigated as a potential model for studies of pathogenesis and immunity. By using a standard challenge (5 x 10(9) CFU), C. jejuni 81-176 was more virulent for BALB/c (72% mortality) than for C3H/Hej (50%), CBA/CAJ (30%), or C58/J (0%). Intranasal challenge of BALB/c was used to compare the relative virulence of three reference strains; C.jejuni 81-176 was more virulent (killing 83% of challenged mice) than C. jejuni HC (0%) or C. coli VC-167 (0%). The course of intranasally initiated C. jejuni 81-176 infection in BALB/c was determined. C. jejuni was recovered from the lungs, intestinal tract, liver, and spleen at 4 h after challenge, the first interval evaluated. After this initial interval, three distinct patterns of infection were recognized: (i) a progressive decline in number of C. jejuni CFU (stomach, blood, lungs), (ii) decline followed by a second peak in the number of organisms recovered at 2 or 3 days postchallenge (intestine, liver, mesenteric lymph nodes), and (iii) persistence of approximately the same number of C.jejuni CFU during the course of the experiment (spleen). Intranasally induced infection initiated with a sublethal number of bacteria or intranasal immunization with killed Campylobacter preparations resulted in both the generation of Campylobacter antigen-specific immune responses and an acquired resistance to homologous rechallenge. The model was used to evaluate the relative virulence of nine low-in vitro-passage (no more than five passages) isolates of C. jejuni species from patients with diarrhea. The patient isolates were differentially virulent for mice; one killed all exposed mice, three were avirulent (no deaths) and the remainder showed an intermediate virulence, killing 17 to 33%. Mouse virulence of Campylobacter strains showed a trend toward isolates originating from individuals with watery diarrhea; however, no association was found between mouse virulence and other signs or symptoms. There were no observed relationships between mouse virulence and bacterial Lior serotype or Fla polymorphic group. Intranasal challenge of BALB/c with C. jejuni is a useful model for the study of infection and vaccination-acquired immunity to this agent.

Detection of enterotoxigenic Escherichia coli, Shigella and Campylobacter spp. by multiplex PCR assay.

Three oligonucleotide primers were used in a polymerase chain reaction (PCR) assay for the simultaneous amplification of regions of the invasive plasmid antigen (ipaH) of Shigella spp., flagellin gene (flaA) of Campylobacter spp., and heat-labile enterotoxin (LT) of enterotoxigenic Escherichia coli (ETEC). The multiplex assay was performed using DNA extracted by a chaotropic method directly from diarrhoeal stools. The diagnostic efficacy of the assay was analyzed by agarose gel electrophoresis. This assay shows a novel approach for the diagnosis of diarrhoea caused by Shigella spp., ETEC, and Campylobacter spp.

Restriction fragment length polymorphism of flagellin genes of Campylobacter jejuni and/or C. coli isolates from Egypt.

The conservation of flagellin genes from thermophilic Campylobacter spp. strains isolated in Egypt was evaluated by a restriction fragment length polymorphism (RFLP) assay. The flaA and flaB genes were amplified from 59 independent clinical isolates and digested with EcoRI and PstI, and the resulting patterns were compared with each other and with previously described RFLP groups. The results indicate that the isolates fell into 14 groups for flaA and 11 groups for flaB, 9 of which have been described, and that considerable genetic variability exists among isolates belonging to the same LIO serogroup. In most cases, the flaB gene displayed the same RFLP pattern as that of the flaA gene of the same strain, although some variability was observed. The data suggest that more variability of flagellin genes exists within the LIO serogroups common to Campylobacter field isolates from Egypt than has previously been reported for North American isolates.

Prevalence of antibiotic resistance among Egyptian Salmonella typhi strains.

This report describes the resistance of 537 Salmonella typhi isolates identified in Egypt between 1990-1994. Results indicated a high isolation rate for multiple resistant S. typhi (> 71% of isolates collected in 1992-93), particularly to the three standard drug regimens of the clinically relevant antibiotics; ampicillin, chloramphenicol and trimethoprim-sulfamethoxazole. This adds to the complexity and difficulty of treating infections caused by these organisms. Resistance of S. typhi was associated with a transferable 120 MD plasmid. The organism was sensitive to amikacin, aztreonam, cephalothin, ceftriaxone, gentamicin and nalidixic acid, suggesting the use of aztreonam and ceftriaxone as alternative therapeutic drugs for the treatment of multidrug-resistant S. typhi. These results may provide a clinically useful evaluation of the spread and acquisition of resistance among S. typhi strains in Egypt.

Schistosomiasis as an important determining factor for the response of Egyptian patients with chronic hepatitis C to therapy with recombinant human alpha-2 interferon.

The aim of the present study was to compare the response to recombinant human alpha-2 interferon therapy in 2 groups of Egyptian patients having chronic hepatitis C with or without associated schistosomiasis. Group 1 included 36 patients with associated intestinal schistosomiasis, and group 2 included 24 patients without schistosomiasis. All patients had abnormal serum aminotransferase levels and were negative for hepatitis B surface antigen and anti-hepatitis core antibody, but positive for hepatitis C virus antibody in serum. All patients received interferon at a dose of 3 million units subcutaneously 3 times a week for 6 months and were followed up clinically, biochemically and haematologically during this treatment period and for 6 months thereafter. A second liver biopsy was obtained from every patient after the completion of interferon therapy. Both the percentage of complete response with return to normal of alanine aminotransferase levels during therapy and the overall response rate at 6 months (when patients with a partial response were also included as responders) were significantly lower (P < 0.001) in group 1 (14% and 33% respectively) than in group 2 (63% and 71% respectively). The liver histology also improved significantly in group 2 (46%) compared with group 1 (14%) after completion of therapy (P < 0.05). On the other hand the overall relapse rate in responders, by 6 months after cessation of therapy, was significantly higher (P < 0.05) in group 1 (92%) than in group 2 (59%). These results show that the presence of associated schistosomiasis has to be considered as an important factor in determining the response of Egyptian patients with chronic hepatitis C to therapy with interferon.

Short-term course of corticosteroids in the treatment of resistant ascites complicating schistosomal liver disease.

The aim of this work was to evaluate the effect of short-term corticosteroids in resistant ascites complicating schistosomal liver disease after 4 wk or more on standard treatment. Thirty-seven patients were randomly allocated to two groups: Group I (18 patients) was put on 40 mg furosemide and 200 mg spironolactone, in addition to a 15-day, tapering dose of prednisone (15, 10, 5 mg). Group II (19) patients received the same diuretics without steroids, and served as controls. At the end of a 2-wk course of therapy, the mean variations were as follows: body weight in patients in Group I ("cases") decreased by 9.8 kg, compared with 4.3 kg in controls; abdominal girth decreased by 7.4 cm in cases, compared with 3.6 cm in controls; urine output increased by 635.9 ml in cases, compared with 364.6 ml in controls; urinary sodium excretion increased by 16.5 mEq/day in cases, compared with 4.1 mEq/day in controls. These differences between cases and controls were found to be statistically significant (p less than 0.01). On the other hand, there were insignificant differences as regards decrease in blood urea (3.2 g/dl for cases and 2.7 g/dl for controls), decrease in serum creatinine (0.2 mg/dl for both cases and controls), increase in serum albumin (0.3 g/dl in cases and 0.2 g/dl in controls), increase in serum sodium (3.2 mEq/L in cases and 2.7 mEq/L in controls), and increase in serum potassium (0.2 mEq/L in cases and 0.4 mEq/L in controls). We conclude that a short-term course of corticosteroids in conjunction with standard diuretics has proved to be an effective, safe, and economical modality to relieve resistant hepatic ascites. It can be considered a temporary alternative to paracentesis with albumin infusion.

Histological changes of the esophageal mucosa in bleeding versus non-bleeding varices.

There is considerable controversy as regards the exact cause of bleeding from esophageal varices. This study examined changes in the mucosa of such patients in an effort to understand the underlying mechanisms. Fifty patients were studied, 20 with a history of variceal bleeding and 30 without who served as controls. Endoscopic biopsies were taken from the inter-variceal mucosa within 5 cm from the cardia and were examined histopathologically. The results showed dilated intra-epithelial blood-filled channels within the squamous epithelium and the lamina propria in all bleeders, and in 50% of the non-bleeders. Evidence of esophagitis was also more pronounced in bleeders (50%) than in non-bleeders (23.3%). It is our opinion that esophagitis and the presence of dilated blood-filled channels may play a role in the initiation of variceal bleeding.