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.

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.

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.

High prevalence of hepatitis C virus in the normal Libyan population.

The prevalence of hepatitis C virus (HCV) in Libya has been investigated by seeking evidence of HCV infection in 266 healthy Libyan subjects (147 females, 119 males; age range 1-78 years), 76 of whom were registered blood donors. None had any history of blood transfusions, surgery, homosexuality, drug misuse or other risk factor for viral hepatitis. Sera from all subjects were tested for anti-HCV antibodies by enzyme-linked immunosorbent assay against synthetic structural and non-structural HCV peptides from the HCV core, envelope, NS1, NS3/NS4 and NS5 regions. Eighteen (6.8%), all of whom were seronegative for hepatitis B surface antigen (HBsAg), were found to be anti-HCV positive (including 5 blood donors). The patterns of reactivity against the individual peptides varied between subjects as follows: core (14 subjects), envelope (11), NS1 (9), NS3/NS4 (10), and NS5 (6). Fourteen of the 18 had elevated serum aminotransferase activities (AST/ALT) but so also did 9 other subjects who were seronegative for both HBsAg and anti-HCV. Twelve of the 18 anti-HCV positive subjects, including 3 of the 5 anti-HCV positive blood donors, had circulating HCV RNA detected by the polymerase chain reaction. HCV RNA was also detected in 3 of the 9 anti-HCV negative cases with elevated AST/ALT. The finding that 21 (7.9%) of the 266 subjects had evidence of HCV infection indicates that there is a very high frequency of 'community-acquired' HCV in the normal Libyan population, and this has major implications for blood transfusion in that country.

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.

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.

Delta hepatitis in Kiribati: a pacific focus.

From the Pacific Republic of Kiribati, 90/130 (69%) of hepatitis B-infected individuals carry antibodies to hepatitis delta virus. The prevalence of delta infection varied between geographically isolated subgroups in the population and delta antibodies were found more frequently in subjects over the age of 10. It is unlikely that delta superinfection in this population is associated with an acute hepatic illness. The prevalence of delta infection is the highest recorded from the Pacific region and thus migrants from Kiribati may have provided the source of infection in other population in this region.

Hepatitis B, tropical ulcers, and immunisation strategy in Kiribati.

The seroepidemiology of hepatitis B was studied in Kiribati (formerly the Gilbert Islands). Six hundred and two (98%) of the population studied showed evidence of current or previous infection. The prevalence of hepatitis B surface antigen was 31% (188/615) and of the e antigen was 9% (58/615). Infection was acquired early in life, and the prevalence of both antigens declined with age. The rates of infection were similar in all age groups examined (0-70) including early childhood. Both hepatitis B surface antigen and e antigen were detected in exudates from tropical ulcers, which may be a source of environmental hepatitis B. Concordance of antigen presence was higher in pairs of siblings than in mother-child pairs. All Gilbertese children should receive hepatitis B vaccine at birth or soon after if the long term consequences of hepatitis B infection are to be minimised.

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.

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.

Temporary loop ileostomy for restorative proctocolectomy.

The aim of a defunctioning ileostomy after restorative proctocolectomy is to mitigate the consequences of pelvic sepsis, should it occur. However, there are complications related to the ileostomy itself. Of 310 patients (174 male and 136 female; mean age 33.2 years) who underwent restorative proctocolectomy between 1976 and 1990, 296 had a covering ileostomy and 14 did not. The stoma has been closed in 263 (88.9 per cent) at a median interval from formation of 12.0 weeks. Ileostomy-related complications before closure occurred in 17 patients (5.7 per cent). Laparotomy for obstruction due to the ileostomy was required in seven patients (2.4 per cent). Retraction requiring revision occurred in three patients (1.0 per cent), an abscess behind the stoma in one (0.3 per cent) and miscellaneous appliance problems in seven (2.4 per cent). Following closure, 59 patients overall (22.4 per cent) developed an ileostomy-related complication. There were 30 cases of small bowel obstruction, treated conservatively in 19 (7.2 per cent) and by laparotomy in 11 (4.2 per cent). Peritonitis requiring laparotomy occurred in three patients (1.1 per cent) and two (0.8 per cent) developed an enterocutaneous fistula. There were 14 (5.3 per cent) wound infections and 16 (6.1 per cent) other miscellaneous problems. Significant complications associated with a temporary ileostomy were less frequent in this series than in some other reports. Obstruction was the most common complication and fistula was rare.

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.

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.

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.

Prevalence of hepatitis C in tropical communities: the importance of confirmatory assays.

The prevalence of antibody to hepatitis C virus (HCV) was estimated in 3 tropical populations using 2 screening ELISAs to detect antibody to the c100-3 antigen and 2 supplementary assays designed to test the specificity of these tests. Two hundred and eighty-six of 385 (74.2%) sera from Kiribati, 17 of 138 (12.3%) sera from Vanuatu, and 39 of 173 (22.5%) sera from Zaire were reactive in the initial screening assay. The proportion of reactive sera which were also reactive in the second screening ELISA varied between populations (55.1% in Kiribati, 85.1% in Vanuatu, and 39.2% from Zaire). Reactive sera were selected at random for confirmatory testing. Only 3 of 49 (6.12%) of sera from Kiribati and 1 of 14 (4.76%) of sera from Vanuatu positive in the initial ELISA were reactive in the confirmatory assays. The proportion of confirmed positive sera from Zaire was higher 8 of 28 (28.5%). Based on the results of these supplementary assays the estimated prevalence of anti-HCV in these populations is 4.8% in Kiribati, less than 1% in Vanuatu, and 6.4% in Zaire. Reliance on a single screening ELISA to estimate the prevalence of anti-HCV in stored sera from tropical communities may lead to a gross over-estimate of the true prevalence in these populations.

Recurrence of hepatitis C following orthotopic liver transplantation: a polymerase chain reaction and histological study.

Hepatitis C virus was sought by nested polymerase chain reaction in the preoperative biopsy or the explanted liver of 100 consecutive adult patients undergoing orthotopic liver transplantation. In those found to be positive preoperatively, polymerase chain reaction was performed on subsequent biopsies. Of the 12 patients in whom HCV-RNA was identified in the liver by polymerase chain reaction preoperatively, viral recurrence was documented in ten of the 11 with posttransplant liver tissues available for study. In the one exception, hepatitis C virus was undetectable in the liver graft despite repeated co-amplification of albumin mRNA as an internal control, which may indicate viral clearance. In eight of the ten positive cases, HCV-RNA was also detectable in serum postoperatively, while HCV-RNA was undetectable in serum in both the cases in whom HCV-RNA was undetectable in tissue and in the patient who declined post-transplant biopsy. Two of the 12 patients infected with hepatitis C virus preoperatively have died during the follow-up period from causes unrelated to hepatitis C virus infection. While biochemical liver function in seven of those remaining has been excellent, histological evidence of at least mild chronic active hepatitis has been present in all ten cases for whom long-term biopsies are available. Three cases have progressed to severe, symptomatic chronic active hepatitis within 2 years of transplantation. Recurrent hepatitis C is associated with progressive liver disease and appreciable morbidity in a significant proportion of patients.

Hepatic and extrahepatic hepatitis C virus replication in relation to response to interferon therapy.

Response to a 1-yr course of interferon-alpha 2b was assessed in 18 patients with chronic hepatitis C virus infection in relation to clinical, biochemical and histological parameters and to the presence or absence of hepatitis C virus RNA and the presumed replicative form of the virus (negative-strand hepatitis C virus RNA) in serum, liver and peripheral blood mononuclear cells. The findings were compared with those in seven untreated patients studied over the same period. At the start of the study, positive-strand hepatitis C virus RNA was found in sera of all 25 patients, in livers of 24 and in peripheral-blood mononuclear cells of 19 of 22 tested; negative strand was found in livers of 11 and in peripheral-blood mononuclear cells of 15 of 22. Negative-strand hepatitis C virus RNA was not found in the serum of any patient at any stage. All of the five treated patients considered to show complete response during the study period cleared hepatic hepatitis C virus RNA, and four also became seronegative, but three had evidence suggestive of viral replication in their peripheral-blood mononuclear cells; two of these last patients subsequently relapsed. Loss of hepatic hepatitis C virus RNA was the only significant difference between these five and the seven partial and six nonresponders, but it is uncertain whether the observed changes were due specifically to interferon-induced modulation of virus expression because similar (apparently spontaneous) changes were seen in four of the untreated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Cellular and humoral immune reactions against autoantigens and hepatitis C viral antigens in chronic hepatitis C.

BACKGROUND/AIMS: Previous reports have suggested that the hepatitis C virus (HCV) may induce autoimmune hepatitis. The aim of this study was to examine this hypothesis by investigating humoral and cellular immune responses to HCV-related antigens and various autoantigens in patients with chronic HCV infections. METHODS: Lymphoproliferative responses in vitro and/or circulating antibodies to an HCV core peptide, the putative autoantigen GOR, the liver-specific hepatic asialoglycoprotein receptor (ASGP-R), and other autoantigens were investigated in 27 adults with chronic hepatitis C. RESULTS: Five patients with HCV (18.5%) showed cellular immune responses to ASGP-R and two others had antibodies to ASGP-R, whereas 6 of 14 patients (42.8%) showed cellular responses to GOR and 7 of 14 patients (50%) showed responses to HCV core. Other autoantibodies were detected in three patients (11%). Nine patients with autoimmune hepatitis studied concurrently for comparison showed cellular and/or humoral responses to ASGP-R but not to GOR. Only 2 of 11 patients with other chronic liver disorders showed immune responses to any antigen tested. CONCLUSIONS: Specific immunocompetence against HCV-related antigens can often be shown in patients with chronic hepatitis C but is infrequently accompanied by autoreactions against liver-specific or nonspecific antigens. A reported association between T-cell responses to HCV core and lack of liver damage could not be confirmed.