Long-term prognosis of patients with alcoholic liver cirrhosis: a 15-year follow-up study of 100 Norwegian patients admitted to one unit.

BACKGROUND: Most follow-up studies in patients with alcoholic liver cirrhosis have been for a 5-year period or less. The aim of this study was to assess the long-term mortality and causes of death among patients with alcoholic liver cirrhosis and to identify predictors of mortality. METHODS: One hundred patients with alcoholic liver cirrhosis, consecutively admitted to one medical department, were included in the study from May 1984 until December 1988. All patients had a history of alcohol abuse of at least 100 g ethanol daily for several years. The study comprised 65 men and 35 women with a median age of 58 years (range 34-82). Percutaneous liver biopsies and/or autopsies were obtained on 89 patients. Sixty-seven had ascites at admission and 34% had bleeding oesophageal varices. All patients were followed prospectively until death or until October 2000. RESULTS: During the follow-up period 90% of the patients died, 68 of whom (76 %) had been autopsied. The cumulative actuarial mortality after 1, 3, 6 and 12 months was 18%, 28%, 36% and 49%, respectively and after 5, 10 and 15 years 71%, 84% and 90%, respectively. None of the patients underwent liver transplantation during the study. The causes of death were bleeding, liver failure or a combination of these two conditions in 52 of 90 patients (58%), while 9 (11%) died of hepatocellular carcinoma 0.5 to 73 months after inclusion in the study. Using the Cox regression analysis, age, alcohol abuse and alkaline phosphatase were independent and significant predictors of mortality, but Child-Pugh class was not. CONCLUSIONS: The mortality in a group of patients with advanced alcoholic cirrhosis was extremely high with 5 and 15 years' mortality in 71% and 90%, respectively. Independent predictors of a poor prognosis were high age, continuous alcohol consumption of more than 10 g ethanol per day and high levels of alkaline phosphatase.

Hepatitis C in the general adult population of Oslo: prevalence and clinical spectrum.

BACKGROUND: The prevalence of hepatitis C (HCV) in Northern Europe has not been well described. This study aimed to estimate the prevalence and spectrum of hepatitis C infection in the general adult population of Oslo, Norway. METHODS: The study was part of the Oslo Health Study 2000-2001 and included a random selection of individuals older than 30 years living in Oslo County. Sera from 11,456 participants were screened for anti-HCV (EIA-3), positive samples were confirmed (RIBA-3) and examined for HCV RNA (PCR). All anti-HCV positive patients were offered clinical evaluation. Routine biochemical liver tests were performed. Candidates for HCV treatment were asked to undergo a percutanous liver biopsy. RESULTS: Among 11,456 participants HCV RNA was detected in 62 (0.5%) and HCV RNA with raised serum alanine aminotransferase (ALT) in 46 (0.4%). Anti-HCV was detected in 78 (0.7%) with a peak prevalence of 1.5% among subjects 40 and 45 years old. Being anti-HCV positive was associated with being unmarried, unemployed and having low education. Anti-HCV prevalence was higher among subjects with alcohol-related problems compared to those without (4.4% versus 0.6%, P < 0.001). It was also higher among smokers compared to non-smokers (2.0% versus 0.2%, P < 0.001). In 33 liver biopsies, bridging fibrosis was seen in 8 (24%) and cirrhosis in 1 (3%). The route of transmission was injecting drug use in 67%, transfusion in 6% and unknown in 27%. CONCLUSION: In this population-based survey the prevalence of chronic hepatitis C was 0.5% and ALT was raised in 80% of those with chronic infection.

Raised serum ferritin predicts non-response to interferon and ribavirin treatment in patients with chronic hepatitis C infection.

BACKGROUND/AIM: Previous studies have indicated that response to interferon therapy is inversely proportional to the amount of body iron stores. We have studied the relationship between serum ferritin, transferrin saturation, liver iron, presence of HFE-C282Y gene mutation and response to treatment in patients with chronic hepatitis C infection. METHODS: Two hundred and fifty-six naive, HCV-RNA positive patients (60% males, median age 38 years, range 21-70) were treated with interferon and ribavirin for 6 months. Iron indices and the presence of the C282Y mutation were measured. In 242 (94%) patients iron deposition were determined by Perls staining method. Patients with negative HCV-RNA at 6 months after the end of treatment were defined as sustained viral responders. RESULTS: Non-responders (n = 127) had significantly higher median s-ferritin values compared with sustained viral responders (130 microg/L vs. 75 microg/L P < 0.001). There was no difference in transferrin saturation among the two response groups. Only 23% (4/7) of patients with Perls grade 1 in liver biopsies responded to treatment vs. 54% (122/225) patients without iron deposition (P = 0.02), however, 10/13-non-responders had HCV genotype one. Two patients (0.8%) were homozygous for the C282Y mutation, 36 patients were heterozygous (14%). Among mutation carriers 26/38 achieved sustained response compared with 102/216 non-carriers (68% vs. 48%, P = 0.02). In a multivariate analysis s-ferritin (P = 0.030) and C282Y carrier status (P = 0.012) remained independent predict of sustained response. CONCLUSIONS: Raised s-ferritin values predicate non-response to interferon-ribavirin therapy in hepatitis C patients. Response rate in C282Y mutation carriers seems greater than in non-carriers.

Effect of interferon-alpha induction therapy on genotype 2b/3a and low viral load hepatitis C virus infection. A randomized multicentre study.

BACKGROUND: Interferon monotherapy for chronic hepatitis C virus (HCV) infection leads to sustained viral eradication in a minority of patients. However, in selected groups of patients, sustained virological response is observed in as many as 50% of patients. High initial interferon dose (induction therapy) has been reported to increase the initial response rate. We have studied the effect of interferon induction therapy in patients infected with HCV genotype 2b/3a, low viral load and no cirrhosis. METHODS: A total of 71 treatment-naive HCV RNA-positive patients with biopsy-confirmed chronic hepatitis, with genotype 2b or 3a, viral load < or = 3 million copies per ml and no cirrhosis were randomized to receive either standard interferon therapy (3 MIU interferon-alpha-2a thrice weekly) for 26 weeks or 6 MIU interferon-alpha-2a daily for 4 weeks (induction group) followed by the standard dose (3 MIU thrice weekly) for 22 weeks. Those with persistent HCV RNA at 4 weeks stopped treatment. Patients were monitored for HCV RNA during and following treatment, and data were interpreted according to intention-to-treat analysis. RESULTS: Viral clearance occurred more rapidly (after 4 weeks) in the induction group (33/36 = 92%) compared to the standard interferon group (21/35 = 60%) (P = 0.01). Among the initial responders, 23/33 (induction group) compared to 16/21 (standard group) were persistently HCV RNA-negative at the end of treatment. At 52 weeks (6 months' follow-up), 22/36 (61%) (induction group) compared to 10/35 (29%) (standard group) were HCV RNA-negative. Among initial responders, 22/33 (induction group) and 10/21 (standard group) achieved a sustained virological response. Among end-of-treatment responders, 22/24 (induction group) and 10/16 (standard group) were HCV RNA-negative at 6 months' follow-up (P = 0.013). CONCLUSIONS: In patients infected with HCV genotype 2b/3a, low viral load and without cirrhosis, IFN induction therapy increases the initial viral clearance and reduces the risk of relapse in end-of-treatment responders. A sustained virological response was achieved in 61% of the patients receiving IFN induction therapy.

Effect of combined interferon-alpha induction therapy and ribavirin on chronic hepatitis C virus infection: a randomized multicentre study.

BACKGROUND: The efficacy of interferon-alpha (IFN) induction in combination with ribavirin for chronic hepatitis C virus (HCV) infection is not known. METHODS: A total of 256 treatment-naive HCV RNA-positive patients with biopsy-confirmed chronic hepatitis were enrolled in a randomized multicentre study. The patients received either standard combination therapy with 3 MIU interferon-alpha2b thrice weekly for 26 weeks or 6 MIU interferon-alpha2b daily for 4 weeks and 3 MIU 3/7 days for 22 weeks. All patients received ribavirin 1000 mg or 1200 mg (weight dependent) daily during the 26-week treatment period. Patients were monitored for HCV RNA during and following treatment. RESULTS: The sustained virological response rates (26 weeks after end of treatment) were 54% and 47% for patients receiving IFN induction/ribavirin and standard IFN/ribavirin, respectively (P = 0.35). Among patients infected with genotype 1a/1b, the sustained response rates were 32% and 35%. In patients infected with genotype 2b/3a IFN induction/ribavirin led to a sustained response rate of 80% as compared to 65% in the standard combination therapy group (P = 0.073). Steatosis was more frequently seen in liver biopsies from patients infected with genotype 3a as compared to genotypes la/lb. Among genotype 1a/1b infected patients. steatosis was a highly significant predictor of failure to achieve sustained virological response. Logistic regression analysis (multivariate analysis) showed that independent predictors of sustained virological response were low age, female gender, genotype 2b/3a and HCV RNA negativity at 2 weeks. CONCLUSIONS: IFN induction in combination with ribavirin does not increase the sustained virological response rate among patients infected with HCV. Absence of steatosis is an independent predictor of sustained virological response in patients infected with genotypes 1a/1b.

[Non-alcoholic steatohepatitis]. / Ikke-alkoholisk steatohepatitt.

BACKGROUND: There is a growing interest in nonalcoholic steatohepatitis (NASH), a disease entity which is quite similar to alcoholic liver disease. MATERIAL AND METHODS: We present three patients with nonalcoholic steatohepatitis, and review current opinion on this disease entity. RESULTS: Non-alcoholic steatohepatitis is very often associated with the insulin resistance syndrome. There is also an association with hepatic iron overload. In one of our patients, biochemical improvement occurred after treatment with phlebotomy. Insulin resistance, resulting in fat accumulation, seems to be an important first step in the pathogenesis. Free fatty acids, iron, and other sources of oxidative stress probably result in cell damage. In some patients, these events result in necroinflammation mediated by various cytokines and immunoactive cells. The prognosis in pure steatosis is usually good. Presence of necroinflammation or fibrosis indicates a risk of progressive liver disease, including cirrhosis.

[Carbamazepine-induced hepatitis]. / Karbamazepinindusert hepatitt.

BACKGROUND: Hepatotoxic reactions associated with carbamazepine therapy are well recognised, and it is important that clinicians are aware of this adverse effect. MATERIAL AND METHODS: We present the clinical course in three patients with carbamazepine-induced hepatitis. RESULTS: All three patients had clinical and biochemical signs of hepatitis; improvement occurred immediately after carbamazepine therapy was discontinued. Other causes of hepatitis were excluded. INTERPRETATION: Previous reports concerning this adverse effect are reviewed. Focusing on the liver as the major organ for drug metabolism, we discuss possible pathophysiological mechanisms of drug-induced hepatic injury. A thorough medication history is mandatory in all patients with hepatitis and other liver diseases. The prognosis of carbamazepine-induced hepatitis is usually excellent, but fatal cases have been reported.

The clinical expression of hemochromatosis in Oslo, Norway. Excessive oral iron intake may lead to secondary hemochromatosis even in HFE C282Y mutation negative subjects.

BACKGROUND: The prevalence of hereditary hemochromatosis in Norway is one of the highest reported in the world. However, the clinical presentation in patients with hemochromatosis in Norway seems to be different compared with recent studies elsewhere. The aim of this study was to investigate patients with hemochromatosis in one community hospital in Norway and to study the prevalence of the C282Y mutation. METHODS: One hundred and twenty patients were consecutively admitted to one medical department in Oslo. Serum transferrin and ferritin concentrations were measured in all patients, and a percutaneous liver biopsy was obtained in 108 of 120 (90%) patients. Stainable iron (Perls stain) in hepatocytes was graded from 0 to 4+ and fibrosis from 1 to 4. Genotyping for the C282Y and H63D mutation in the HFE gene was performed by PCR-RFLP. RESULTS: Forty-eight (40%) of the patients suffered from tiredness and astenia and 29 (24%) had typical arthropathy. Only 5 of 105 (4.5%) had biopsy confirmed cirrhosis and 5 had diabetes mellitus. Patients referred from a blood bank had significantly less symptoms and signs compared with other patients. Twenty-one of 120 (17.5%) patients were C282Y mutation negative. Seventeen (81%) of these patients (16 women and 1 man) had a history of extensive oral iron intake lasting from 5 to 50 years. When excluding those with extensive oral iron intake (n = 17), 92 of 103 (89%) were homozygous for the C282Y mutation, 7 (7%) were heterozygous including 3 compound heterozygous and 4 (4%) were mutation negative. CONCLUSIONS: Only a minority of our patients with hemochromatosis had a far advanced disease at the time of diagnosis (less than 5% had cirrhosis) and hemochromatosis in a majority of the C282Y mutation negative patients was associated with excessive oral iron intake for several years.

Treatment with interferon-alpha2a alone or interferon-alpha2a plus ribavirin in patients with chronic hepatitis C previously treated with interferon-alpha2a. CONSTRUCT Group.

BACKGROUND: Preliminary results from combination therapy with interferon-alpha and ribavirin (IFN/Rib) in patients with chronic hepatitis C have been promising, with up to 50% sustained hepatitis C virus (HCV) RNA response. The aim of this study was to investigate whether a sustained HCV RNA response could be obtained with combination therapy in patients who were non-responders or relapsers after IFN treatment. METHODS: In a multicenter study we randomized 53 HCV RNA-positive patients into 2 treatment groups. They all had biopsy-confirmed chronic hepatitis C, and all were recruited from a previous IFN study: 26 were previous non-responders and 27 responders with relapse. Group A received interferon-alpha2a, 4.5 MIU thrice weekly for 6 months, and group B received ribavirin, 1000-1200 mg/day, in combination with the same dose of interferon-alpha2a for 6 months. Median Knodell index was 5.0 in both groups. Genotype 1 was found in 24 (45%), type 2 in 3 (6%), and type 3 in 26 (49%). RESULTS: Sustained clearance of HCV viremia 6 months after interferon-alpha2a treatment stop was obtained in 12 of 53 patients (23%): 6 of 27 in the IFN group (22%) and 6 of 26 (23%) in the IFN/Rib group (NS). Nine of 27 (33%) former responders with relapse, compared with 3 of 26 (12%) non-responders, obtained a sustained HCV RNA response (P = 0.054). In previous relapse patients sustained loss of viremia was more frequent in genotype 3 (50%) than in genotype 1 (11%) patients (P = 0.022). CONCLUSIONS: In a group of previous IFN-alpha2a-treated chronic HCV patients we obtained a similar sustained clearance of viremia when retreated either with IFN-alpha2a alone or with a combination of IFN-alpha2a and ribavirin for 6 months. Previous relapse patients with HCV genotype 3 obtained sustained loss of viremia significantly more often (50%) than type-patients (11%). Previous IFN responders with relapse responded better than previous non-responders.

Fecal calprotectin concentration in patients with colorectal carcinoma.

PURPOSE: The study contained herein was undertaken to investigate fecal calprotectin excretion in a series of patients with colorectal carcinoma and to determine whether the excretion was influenced by localization or stage of the tumor. Furthermore, the effect of surgical treatment on the concentrations was studied. Fecal calprotectin was also compared with plasma concentrations of calprotectin, carcinoembryonic antigen, and C-reactive protein. METHODS: Fecal calprotectin was measured in 119 consecutive patients admitted for treatment of colorectal carcinoma. In 116 (97.5 percent) patients, resectional surgery was performed. Plasma calprotectin was measured in 90 (76 percent) patients, carcinoembryonic antigen in 88 (74 percent) patients, and C-reactive protein in 82 (69 percent) patients. RESULTS: Median fecal calprotectin concentration in the 119 patients was 50 (range, 2-950) mg/l, which was significantly (P < 0.0001) higher than in 125 control patients (median, 5.2 mg/l). In 23 patients studied also after resection, the excretion fell greatly. There were no significant differences in fecal calprotectin concentration among patients with different tumor stages. Elevated plasma calprotectin concentrations were found in 67 of 90 (73.3 percent) patients with colorectal carcinoma, compared with elevated fecal calprotectin in 111 of 119 (93.3 percent) patients, and there was no significant correlation between plasma and fecal calprotectin concentrations. Plasma calprotectin concentrations were significantly lower in patients with T1 or T2 tumors than in those with more advanced stages (P = 0.0025). CONCLUSION: Measurement of fecal calprotectin may become a diagnostic tool in detecting colorectal carcinoma. The specificity in relation to colorectal carcinoma has not, however, been completely investigated. Both neoplastic and inflammatory conditions may be associated with elevated values; therefore, it is unlikely that calprotectin can predict specific colonic disorders.

The effect of treatment with alpha-interferon on hepatitis G/GBV-C viraemia. The CONSTRUCT Group.

BACKGROUND: Hepatitis G virus (HGV) or GBV-C is frequently detected in patients co-infected with hepatitis C virus (HCV). This study investigated host and virologic factors influencing the response to HGV/GBV-C to alpha-interferon treatment. METHODS: HGV/GBV-C was detected and quantified by nested polymerase chain reaction. The influence of variables such as liver biopsy appearance, liver function abnormalities, and response of HCV to interferon treatment was monitored. RESULTS: Fourteen of the 25 HGV/GBV-C-infected patients treated with interferon (3-6 MIU three times a week for 6 months) became non-viraemic during treatment, although all relapsed after treatment withdrawal at 6 months, with no net change in virus load between 0 and 12 months. CONCLUSIONS: Predictive factors for clearance of HGV/GBV-C viraemia by interferon were pre-treatment severity of liver disease (median Knodell score of 4, compared with 7 for non-responders; P = 0.030) and alanine aminotransferase levels (median, 114, 182 for non-responders; P = 0.039). Clearance was associated with the treatment response of HCV. Nine of 13 who cleared HGV/GBV-C also cleared HCV, compared with 3 of 11 HGV/GBV-C non-responders; P = 0.05). The shared susceptibility of HGV/GBV-C and HCV to interferon treatment suggests a link between the mechanism of clearance of the two viruses.

Incidence and prevalence of primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis in a Norwegian population.

BACKGROUND: The relative frequencies of the autoimmune liver diseases primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) have not been studied. We therefore performed an epidemiologic investigation to describe the incidence and prevalence of the three diseases in a defined population. METHODS: Patients with PBC, PSC, or AIH admitted to Aker University Hospital in Oslo were prospectively registered during the 10-year period 1986-95. This hospital serves a defined population of 130,000 inhabitants. The mean yearly incidence and the point prevalences at the end of each year were calculated. RESULTS: During the 10-year period 21 patients with PBC, 17 with PSC, and 25 with AIH were diagnosed. The mean annual incidence per 100,000 was 1.6 for PBC, 1.3 for PSC, and 1.9 for AIH. The point prevalences per 100,000 on 31 December 1995 were 14.6, 8.5, and 16.9 for PBC, PSC, and AIH, respectively. CONCLUSIONS: The prevalences of PBC and AIH are of the same order of magnitude and about twice as high as that of PSC. These epidemiologic data can be used to estimate the number of liver transplantations required due to autoimmune liver diseases.

[Ulcerative colitis. Complications and sequelae in relation to the extent of the disease. A 10-year material]. / Ulcerøs kolitt. Komplikasjoner og følgetilstander i relasjon til utbredelse. Et tiårsmateriale.

Patients with ulcerative colitis in our catchment area were followed over a ten-years period with the focus on the relation between the extent of inflammation and complications. Total colitis was found in 180 out of 334 patients with known extension, while in 154 of the patients the inflammation was classified as left-sided colitis. The frequency of severe colitis, colectomy and cancer was more or less the same as stated in earlier reports. We observed a difference, however, between the patients with extensive colitis and those with left-sided colitis as regards the course of the disease and the complications related to ulcerative colitis. The risk of liver disease, severe colitis and colectomy were significantly higher among the patients suffering from extensive colitis. Extraintestinal manifestations, on the other hand, were equally distributed among both groups of patients. The reasons for the observed differences are unknown.

Prevalence of hemochromatosis among first-time and repeat blood donors in Norway.

BACKGROUND/AIMS: The observed prevalence of hemochromatosis has ranged considerably from 0.05 to 0.37% in studies requiring liver biopsy. We aimed to study the prevalence of genetic hemochromatosis among Norwegian blood donors. METHODS: We studied 10,552 healthy blood donors (5312 women and 5240 men) using serum ferritin as a screening parameter. If serum ferritin concentration was > or = 100 micrograms/l in women and > or = 200 micrograms/l in men, serum iron and transferrin (measured as total iron binding capacity = TIBC) were measured. Blood donors who repeatedly had a transferrin saturation above 40% and a ferritin concentration above these limits were referred to a hepatologist (H.B.). RESULTS: Serum ferritin was > or = 100 micrograms/l in 94/5312 (1.8%) women and > or = 200 microliters in 79/5240 (1.5%) men. Of these, 37 persons had a serum ferritin concentration above 100 micrograms/l (females) or above 200 micrograms/l (males) and a transferrin saturation above 40%. Nineteen of them (13 men and 6 women, median age 36 years, range 28-68) were identified as having hemochromatosis on the basis of increased hepatic iron index. Serum ferritin ranged from 111 to 1980 micrograms/l (median 357 micrograms/l and transferrin saturation from 50 to 100% (median 92%), hepatic iron from 48 to 471 mumol/g dry weight (median 118 mumol/g) and hepatic iron index from 1.5 to 12.1 (median 3.0). One person had cirrhosis and none had diabetes. The prevalence of hemochromatosis was significantly higher among first-time blood donors (12 out of 3500 [3.4/1000]) compared with repeat donors (7 out of 7052 [1/1000]), p < 0.005. CONCLUSIONS: The observed prevalence of hemochromatosis in Norwegian first-time blood donors of 0.34% is comparable to recently observed prevalences in other studies. However, the use of serum ferritin as a first-step screening tool may have failed to detect hemochromatosis in the early stage where iron overload has not yet occurred.

Genotype, viral load and age as independent predictors of treatment outcome of interferon-alpha 2a treatment in patients with chronic hepatitis C. Construct group.

Patients with chronic hepatitis C respond differently when treated with interferon. We randomized 116 patients with chronic hepatitis C in order to compare two dosage regimens of recombinant interferon alpha 2a:3 MIU x 3 per week for 6 months (arm A) or 6 MIU x 3 per week for 3 months and then 3 MIU x 3 per week for 3 months (arm B). There were no significant differences concerning outcome between the two dose regimens: sustained clearance of HCV viremia 6 months after the end of treatment was obtained in 12/59 (20%) in group A compared with 18/57 (32%) in group B (p = 0.24). In patients with genotype 1a, 4/31 (13%), in genotype 1b, none of 9 (0%), 9/15 (60%) in genotype 2, and 17/58 (29%) in genotype 3, showed sustained clearance of HCV viremia 6 months after the end of treatment (p = 0.002). In a stepwise logistic regression analysis, only pretreatment viral load (p = 0.0001), genotype (p = 0.001) and age (p = 0.04) were identified as independent predictors of sustained clearance of HCV viremia. Liver histology as assessed by Knodell index was significantly improved in patients with sustained HCV RNA response 6 months after the end of treatment (5.2 +/- 2.2 vs 2.6 +/- 2.2, p < 0.001), but not in responders with relapse or in non-responders. In conclusion, stepwise logistic regression analysis showed that viral load, HCV genotype and age were the only independent predictors for sustained HCV RNA response.

Assessment of disease activity in ulcerative colitis by faecal calprotectin, a novel granulocyte marker protein.

This study comprised 62 outpatients with ulcerative colitis who underwent 64 colonoscopies. The disease activity was evaluated according to endoscopic and histological criteria. The results revealed a significant correlation between both the endoscopic as well as the histological gradings of disease activity and faecal calprotectin. The median faecal calprotectin levels in the control group (6 mg/l) and in the patients with no or low disease activity (11.5 mg/l) were significantly different (p < 0.0001). The median calprotectin level among patients with active disease was 68 mg/l which was significantly different from the latter group (p < 0.0001). Furthermore, we suggest that the degree of inflammation rather than the extent of the disease determined the faecal calprotectin levels. In conclusion, assessment of faecal calprotectin seems to be a marker of disease activity in patients with ulcerative colitis.

Prevalence of hepatitis C genotypes among patients with chronic hepatitis C in Norway. Construct Group.

Among 116 patients with biopsy-confirmed chronic hepatitis C (Riba 2 or Riba 3 positive) in a multicenter study in southern Norway on interferon, we determined hepatitis C virus genotype by restriction fragment length polymorphism (RFLP) of the 5' NCR. The RFLP method was supplemented by and compared with a serological typing method based on the detection of type-specific antibody to peptide from the NS-4 region. A total of 102/106 (96%) patient sera showed detectable type-specific antibody to NS-4 peptides and corresponded in all cases, except two, to the genotype detected by polymerase chain reaction. Combining the results from RFLP genotyping and serotyping, genotype 1 was found in 40 (35%) (27 with 1a and 10 with 1b, 3 subtypes not determined), genotype 2 in 15 (13%) (subtype 2b in 14 and 1 subtype not determined), and genotype 3 in 58 (50%) of patients. The low mean age of the patients (34 years), the low prevalence of cirrhosis (3.5%), the short duration of the disease, and a high prevalence of intravenous-drug abusers may account for the low prevalence of infection with genotype 1b (9%). The epidemiological features of hepatitis C patients are markedly different from patient groups described in southern Europe in terms of risk factors, age, and genotype distribution.

Inappropriately low levels of gonadotrophins in amenorrhoeic women with alcoholic and non-alcoholic cirrhosis.

We investigated a group of 111 amenorrhoeic females with associated liver disease. These comprised alcoholic cirrhotics (N = 38), non-alcoholic cirrhotics (N = 12), non-cirrhotic alcoholics (N = 21) and those suffering from other chronic liver diseases (N = 40) admitted to our medical department from 1986 to 1991. The serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), oestradiol, testosterone, sex hormone binding globulin (SHBG) and prolactin were measured. Serum LH was decreased below the normal range in 50% of patients with alcoholic cirrhosis and in 42% of patients with non-alcoholic cirrhosis. One third of non-cirrhotic alcoholics also had decreased LH, in contrast to only 8% of patients with other chronic liver diseases (p < 0.01). A close correlation was found between LH and FSH when all patients were pooled (r = 0.91, p < 0.001). A gonadotrophin-releasing hormone (GnRH) injection elicited a clear LH and FSH response in 11 out of 14 patients with cirrhosis, indicating that the hypothalamus rather than the pituitary is the site of disturbance in gonadotrophin secretion. Serum SHBG was within normal limits and similar in all four groups. In nine females with alcoholic cirrhosis who abstained for 3 months, serum SHBG increased significantly from 39 +/- 18 to 70 +/- 25 nmol/l (p < 0.001), while LH increased in five of nine females and was unchanged in four. In conclusion, half of the amenorrhoeic females with alcoholic as well as non-alcoholic cirrhosis had inappropriately low serum LH and FSH levels, indicating dysfunction of the hypothalamo-pituitary axis.(ABSTRACT TRUNCATED AT 250 WORDS)

Mesalazine suppositories versus hydrocortisone foam in patients with distal ulcerative colitis. A comparison of the efficacy and practicality of two topical treatment regimens.

BACKGROUND: Topical treatment is effective in patients with distal ulcerative colitis. This trial compares the efficacy, safety, and practicality of 4 weeks' treatment with 500 mg mesalazine suppositories with those of 178 mg hydrocortisone foam, both given twice daily. METHODS: Seventy-nine patients with distal ulcerative colitis were stratified on the basis of the extent of the disease (proctitis and proctosigmoiditis) and randomized to one of the treatment groups. A disease activity index (DAI) based on symptoms and endoscopic findings was calculated. The patients evaluated the practicality of the treatment regimens, patients compliance was measured, and histologic findings recorded. RESULTS: Of all the patients 22% and 38% were complete responders after 2 and 4 weeks, respectively. Median DAIs in the mesalazine and hydrocortisone groups before and after 2 and 4 weeks' treatment were 14, 6, and 4, and 13, 8, and 6, respectively. The difference between the treatment groups was statistically significant (p = 0.02) due to a better effect of mesalazine in patients with proctitis. Patients' evaluation of practicality and patient compliance were statistically significantly better in the mesalazine group. CONCLUSIONS: Both treatment regimens are effective; mesalazine suppositories seem to be the preferred alternative.

Serum ferritin and transferrin saturation in patients with chronic alcoholic and non-alcoholic liver diseases.

OBJECTIVES: To compare serum ferritin concentration and transferrin saturation in patients with alcoholic and non-alcoholic chronic liver diseases. DESIGN: Consecutive patients with liver diseases. SETTING: The department of internal medicine in a teaching hospital. SUBJECTS: Three hundred and twelve patients with different liver diseases consecutively admitted between 1987 and 1992. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Fasting serum iron, transferrin and ferritin. RESULTS: Serum ferritin was increased above 200 micrograms L-1 in all 18 patients with haemochromatosis (range 310-6500 micrograms L-1), in 64 of 111 alcoholics (58%) and in 30 of 137 (22%) with chronic non-alcoholic liver diseases (P < 0.01). Twelve of 111 alcoholics (11%) had serum ferritin above 1000 micrograms L-1 compared with one of 137 (0.7%) with chronic non-alcoholic liver diseases. In 13 alcoholics who abstained after admission, serum ferritin decreased from 1483 micrograms L1 +/- 1134 to 388 micrograms L-1 +/- 237 (P < 0.001) after 1 1/2 to 6 weeks. The transferrin saturation was increased above 62% in 13 of 18 patients (72%) with haemochromatosis, in 16 of 105 alcoholics (15.2%) and in three of 132 (2.3%) with chronic non-alcoholic liver disease (P < 0.01). CONCLUSION: Serum ferritin is more frequently elevated in abusing patients with alcoholic liver disease than in patients with other chronic liver diseases such as autoimmune liver diseases and hepatitis C. Because serum ferritin decreases rapidly during abstinence, the measurement of ferritin for the detection of haemochromatosis in patients abusing alcohol should be postponed until the patients are abstaining. Most of the patients with increased serum ferritin have normal transferrin saturation values which can be used to separate them from haemochromatosis.