Diverticular disease of the colon: ethnic differences in frequency.

BACKGROUND: Colonic diverticular disease is more common in Western populations than in developing countries. AIM: To determine whether the frequency of colonic diverticular disease is different in British patients of Indian-subcontinent Asian origin compared with other ethnic groups. METHODS: All colonoscopies performed over a 3-year period in a London hospital were studied. Patients of Indian-subcontinent Asian origin were identified by name. RESULTS: Five of 134 Indian-subcontinent Asian males (4%) had colonic diverticular disease, compared with 278 of 1268 patients of other ethnic groups (22%; P < 0.001). Five of 91 Indian-subcontinent Asian females (6%) had colonic diverticular disease, compared with 333 of 1486 patients of other ethnic groups (23%; P < 0.001). Although patients of Indian-subcontinent Asian origin (54.8 +/- 15.8 years) were younger than those of other ethnic groups (60.3 +/- 17.8 years; P < 0.0001), the ethnic difference in the frequency of diverticular disease persisted even when age was taken into account. CONCLUSION: There is a lower frequency of colonic diverticular disease in Indian-subcontinent Asians presenting for colonoscopy, compared with other ethnic groups. This cannot be explained by sex or age differences. Our findings require confirmation, but may provide opportunities for research into the aetiology of colonic diverticular disease.

Gallstones--an increasing problem: a study of hospital admissions in England between 1989/1990 and 1999/2000.

BACKGROUND: The number of operations for cholelithiasis increased from the 1950s to the 1990s. AIMS: To determine the time trends in cholelithiasis for hospital admissions, operations and in-hospital case fatalities in England between 1989/1990 and 1999/2000, and population mortality rates between 1979 and 1999. METHODS: Hospital Episode Statistics for admissions were obtained from the Department of Health and mortality data were obtained from the Office for National Statistics. RESULTS: Between 1989/1990 and 1999/2000, age-standardized hospital admission rates for cholelithiasis increased by 30% for males and 64% for females. The proportions of admissions undergoing an operation declined progressively over the study period. In 1999/2000, the frequency of operation was approximately 50-60% for most age groups, but decreased progressively with advancing age at > or = 65 years. The proportions of admissions undergoing therapeutic endoscopy increased several-fold, especially amongst older individuals. Case fatality rates declined. Mortality rates declined from 1979 to 1988, but showed no further change from 1989 to 1999. CONCLUSIONS: There has been a steady increase in admission rates for cholelithiasis over the study period. Whilst the frequency of operation has declined, the proportion of patients undergoing therapeutic endoscopy has increased.

Tropical aspects of viral hepatitis. Hepatitis C.

This paper reviews our current understanding of hepatitis C infection in tropical countries. Since its discovery in 1989, hepatitis C has been recognized as an important disease in many tropical countries. In Egypt the prevalence in some sections of the population may-exceed 20%. In most tropical areas, however, the epidemiology of hepatitis C infection is poorly defined. There are clear variations in the distribution of genotypes in different areas and this may be one of the factors which influence the natural history of infection in different regions of the world. Routes of infection in tropical countries are poorly defined, most carriers having no clear risk factors for infection. There is some speculation that inadequate sterilization of medical equipment may be a route of infection in some areas. A combination of factors may result in an increased risk of hepatocellular carcinoma developing in patients from the tropics infected with hepatitis C and the prognosis may be worse due to co-infection with hepatitis B and human immunodeficiency virus, both of which may lead to accelerated liver disease. Prospects for disease control are poor due to the difficulty of developing a vaccine to the virus.

Liver transplantation for haemophiliacs with hepatitis C cirrhosis.

BACKGROUND: Experience of liver transplantation in haemophiliacs with end stage hepatitis C liver disease is limited and particularly difficult questions are raised when there is also HIV infection. AIMS: This is the first report in Great Britain to describe the operative replacement therapy and initial outcome in four haemophiliacs with end stage HCV cirrhosis. PATIENTS: Two patients had factor VIII, one had factor IX, and one had factor X deficiency. One patient had also contracted HIV infection from factor replacement but had no AIDS defining illnesses. METHODS: Intraoperatively patients were given either factor VIII infusions, factor IX bolus, or fresh frozen plasma, according to formulae devised to calculate exact clotting factor requirements. Baseline preoperative coagulation studies included prothrombin time, activated partial thromboplastin time, fibrinogen concentrations, and factor VIII, IX, and X concentrations. Factor concentrations were then assayed at 12, 24, 48, and 72 hours postoperatively. RESULTS: Postoperatively all patients had coagulation factor concentrations sustained within the normal ranges by 72 hours unsupported (137, 125, 95, 104 IU/dl), representing de novo synthesis by the graft. Transfusion requirements during the operative and immediate post-transplant period were no greater than those of patients without clotting disorders. Two patients had episodes of bleeding postoperatively, one of which was fatal, occurring at the site of a previous untreated subdural bleed. In both instances the bleeding occurred in the presence of normal concentrations of clotting factor. The remaining three patients are at 6, 6, and 12 months post-transplant and remarkably improved clinically with sustained factor concentrations. One patient has evidence of graft dysfunction from HCV recurrence and all have evidence of recurrent viraemia with HCV on polymerase chain reaction studies. CONCLUSIONS: Orthotopic liver transplantation should be considered in haemophiliac patients with end stage liver disease from hepatitis C infection with or without concomitant HIV infection. Their clinical condition is likely to be greatly improved by orthotopic liver transplantation and the haemophilia cured with only a small risk of severe graft dysfunction from recurrent HCV infection.

Evidence that the HLA DQA1*03 allele confers protection from chronic HCV-infection in Northern European Caucasoids.

In the search for factors which may influence susceptibility to and outcome from chronic hepatitis C virus (HCV) infection, few studies have considered the influence of host genes. In the present investigation we have performed HLA DRB1, DQA1, DQB1, and DPB1 genotyping on 104 northern European patients with chronic HCV infection and 177 racially and geographically matched controls. Three HLA class II alleles, DRB1*0403, DQA1*03, and DQB1*0302 were present at a significantly lower frequency in patients compared with controls (4.9% vs. 13%, 20.7% vs. 41.2%, and 11.4% vs. 30.5%, respectively) though only two DQB1*0302 and DQA1*03 were significant after correction for multiple testing (pc = 0.038, and pc = 0.046, respectively). No further HLA associations with chronic HCV infection were observed and there was no correlation between stage of disease and HLA genotype. These data provide the first suggestion that susceptibility to chronic HCV infection may be influenced by the hosts' HLA DQ alleles.

Liver function tests in adults with Plasmodium falciparum infection.

This study examines the levels of serum bilirubin, aspartate transaminase and alkaline phosphatase in adults with Plasmodium falciparum malaria. One hundred and six sets of liver function tests were obtained, and 63 (59.4%) patients had one of the above indices elevated outside the local reference range. Serum bilirubin and aspartate transaminase were relatively higher than alkaline phosphatase. Neither duration of illness nor severity of infection showed any significant correlation with any of the indices measured.

Usefulness and limitation of phylogenetic analysis for hepatitis C virus core region: application to isolates from Egyptian and Yemeni patients.

We report here the nucleotide sequences of the core region of HCV isolates from Egyptian and Yemeni patients and the method for classifying these HCV isolates by phylogenetic analysis. Sequence comparison suggested that the genotypes of these isolates were the same. Preliminary phylogenetic analysis of the HCV core region indicated that the genotypes of both isolates were 1c. However, an additional phylogenetic tree of the HCV core region constructed using a greater number of HCV isolates than that used in the preliminary analysis and on the basis of alignment of nucleotide sequences in an appropriate length indicated that the genotypes of these isolates were 4 and not 1c. For a more detailed analysis, the nucleotide sequences of the HCV E1 region as well as the core region for the same Yemeni patient were determined. A phylogenetic tree of the E1 region confirmed that the genotype of the HCV isolate from the Yemeni patient was 4. These data indicate that even when classifying HCV isolates using phylogenetic analysis, the misclassification would occur if care is not taken regarding the number and sequence lengths of the isolates included in the analysis.

Stenosis of the pouch anal anastomosis following restorative proctocolectomy.

PURPOSE: To compare the incidence of stenosis after hand-sewn and stapled ileoanal anastomosis. Stenosis of the ileoanal anastomosis occurs in 5-16% of patients undergoing a restorative proctocolectomy but the incidence using a stapled technique is unknown. METHODS: Between 1976 and 1990, 266 patients underwent restorative proctocolectomy or proctectomy at one hospital. In two hundred and eighteen the anastomosis was hand sewn and stapled in 48 (single 33; double 15). RESULTS: Stenosis occurred in 31 (14.2%) of the hand-sewn and in 19 (39.6%) of the stapled anastomoses. This difference was highly significant (P < 0.001). Stenosis was not related to the size of the staple head used or to the stapling technique. There was no relationship between the development of stenosis and pelvic sepsis. Twenty six (hand-sewn 16, stapled 10) of the 48 patients with stenosis needed dilatation under general anaesthetic. CONCLUSION: Stapled anastomoses may result in a high incidence of anastomotic stenosis.

Serum intercellular adhesion molecule-1 levels in chronic hepatitis C: association with disease activity and response to interferon alpha.

Soluble intercellular adhesion molecule-1 (sICAM-1) is probably released from a variety of cells, including leukocytes and endothelial cells at sites of inflammation or in the circulation, and serum levels may therefore be used to give an indication of immune activation and inflammatory processes. In the present study, an ELISA was used to measure serum ICAM-1 levels in 43 patients with chronic hepatitis C and these were correlated with histological changes in the liver and the response to interferon alpha treatment. Serum ICAM-1 levels were significantly higher in patients with chronic hepatitis C infection than in normal subjects and correlated positively with the grade of histological activity, in particular the degree of portal, periportal, and lobular inflammation, but not with the presence of lymphoid aggregates. There was also a weak but significant positive correlation between sICAM-1 and serum aspartate aminotransferase activities, and sICAM-1 levels were substantially greater in patients with than those without cirrhosis. Serum ICAM-1 levels fell significantly in 11 responders out of 19 patients treated with interferon alpha, whereas levels remained unchanged in the non-responder group. sICAM-1 levels correlate with the clinical status of patients with chronic hepatitis C infection and fall with successful interferon treatment.

Does hepatitis C contribute to liver injury in alcohol abusers in the west of Scotland?

OBJECTIVE: To test the hypothesis that many patients with alcoholic liver disease have coexisting hepatitis C virus (HCV) infection which promotes the development of cirrhosis. DESIGN: Prospective, two-centre study comparing patients with alcoholic liver disease with HCV-positive blood donors identified by the Regional Blood Transfusion Service. SETTING: Two teaching hospitals in Glasgow, UK. PATIENTS: Sixty patients admitted to hospital with a diagnosis of alcoholic liver disease on the basis of clinical and histological tests. For comparison, a group of 50 anti-HCV-positive subjects identified from 305,012 blood donors during the same period (1991-1993) were questioned about their alcohol consumption and liver biopsy specimens are taken. MAIN OUTCOME MEASURES: The prevalence of HCV infection was determined by a second generation enzyme-linked immunosorbent assay (ELISA) for anti-HCV and by liver histology. RESULTS: No patients with alcoholic liver disease were anti-HCV-positive. Of the blood donors with chronic HCV infection, 11 (22%) reported previous or continuing consumption of more than 80 g alcohol daily for at least 2 consecutive years but liver histology in all 50 cases showed features characteristic of chronic HCV. There was no difference in liver histology between donors with a history of high alcohol consumption [mean grade 2.6 (range, 1-5), stage 0.4 (range, 0-2)] and abstinent, anti-HCV-positive donors [grade 2.8 (0-5), stage 0.5 (range 0-1)]. CONCLUSIONS: The absence of anti-HCV in this population of patients with alcoholic liver disease shows that HCV is not a necessary or a common cofactor in the development of alcoholic liver disease in the west of Scotland.

Ribavirin therapy for hepatitis C infection following liver transplantation.

Hepatitis C infection following orthotopic liver transplantation may lead to progressive chronic graft dysfunction. In this study, seven liver transplant recipients with chronic allograft dysfunction due to hepatitis C infection (one acquired and six recurrent infections) were treated with oral ribavirin for 6 months. Symptoms of lethargy, nausea and anorexia improved in all patients within 2 weeks of starting the drug, with a fall in serum AST of at least 40% by this time. Ribavirin-induced haemolysis was clinically significant in three patients, necessitating a reduction in the daily dose of ribavirin from 1.2 g to 0.2 g. Comparison of the pre- and post-treatment biopsy specimens in the four patients who tolerated the full dose of ribavirin and who had normal AST levels at the end of 6 months of treatment showed significant histological improvement with reduction in either lobular or periportal inflammation in all of the patients and a reduction in periportal fibrosis in one patient. HCV RNA remained detectable in serum in all of the patients at the end of the study.

Effects of ribavirin on intrahepatic and extrahepatic expression of hepatitis C virus in interferon nonresponsive patients.

Response to ribavirin therapy (1,000-1,200 mg/day for 6 months) was evaluated in nine patients with chronic hepatitis C virus (HCV) infections who had previously failed to respond to a 6-month course of alpha-interferon. All had chronic active hepatitis with elevated serum aminotransferase activities (mean +/- SD = 138 +/- 66IU/I). During ribavirin therapy, three showed a complete response (normalized serum aminotransferase), although in one patient this returned to the pretreatment level 2 months after treatment was stopped. Three others showed a partial response (serum aminotransferase reduction by > or = 50%) and the remainder showed no response. There were no consistent changes in HCV-RNA (positive strand) in serum, liver, or peripheral blood mononuclear cells during therapy, but two patients lost HCV-RNA from serum and three of five patients with negative strand HCV-RNA in their livers lost this putative replicative form of the virus. The findings suggest that ribavirin may exert its effects by suppressing viral replication rather than by eradicating the virus, at least in this group of patients, and that the drug may have some benefit in selected cases of chronic hepatitis C that are resistant to interferon. However, peripheral blood mononuclear cells represent a major extrahepatic reservoir of HCV and the present regimen of ribavirin therapy did not significantly affect this situation. More prolonged therapy may be required to eradicate the virus from this large pool of cells with the potential to continually reinfect the liver.

Liver transplantation for acute and chronic viral hepatitis.

Hepatotrophic viruses are responsible for a substantial proportion of cases of both end-stage chronic liver disease and of acute liver failure which are treated by liver transplantation. We review here current practice in transplantation for viral-induced liver disease addressing, in particular, the selection of patients for transplantation and the increasingly recognized problem of recurrent disease in liver grafts.

Methods of transmission of hepatitis C.

The route of transmission of hepatitis C virus is still controversial. Parenteral exposure via blood or blood products leads to infection in the majority of cases, and the majority of intravenous drug users become infected by repetitive exposure to contaminated injection equipment. The risk of infection from a single needlestick injury is 5-15% and may depend on the size of the innoculum. Other parenteral routes of transmission may include traditional healing practices and the use of contaminated medical equipment. Transmission is less common within a family but the prevalence of hepatitis C viral antibodies is higher in family members and sexual partners of carriers than in the general population. There are some well-documented instances of acute hepatitis C occurring after a defined sexual exposure. Vertical transmission is rare unless the mother has high levels of circulating HCV RNA as may occur in those also infected with HIV. The detection of hepatitis C in saliva and the higher than expected prevalence of infection in dentists may point to the possibility of transmission by salivary contamination. There remain large numbers of hepatitis C carriers in whom no route of infection can be identified.

Viral causes and management of acute liver failure.

Infection with an identified hepatotrophic virus accounts for 13-50% of acute liver failure (ALF) in Europe, and an additional 16-17% of cases have non-A non-B or indeterminate hepatitis in whom a viral aetiology is presumed. Hepatitis C is rarely responsible for acute liver failure in Europe and North America but accounts for a higher proportion of cases in Japan, and hepatitis E may lead to ALF, particularly in pregnant women. The survival in cases of acute liver failure associated with hepatitis A is 70%, whereas less than 30% of those with non-A non-B hepatitis survive without a transplant. Management depends on intensive care support and careful selection of patients likely to benefit from transplantation. Recurrence of hepatitis A and non-A non-B hepatitis has been reported following transplantation for ALF, and hepatitis B recurs less frequently in these circumstances than after transplantation for chronic infection.