The clinical importance in differentiating portal from mesenteric venous thrombosis.

AIM: To relate the extent of portomesenteric thrombosis to the risk of intestinal infarction, concomitant venous thromboembolism and underlying diseases. METHODS: Identification of patients with mesenteric (MVT) and portal vein thrombosis (PVT) at Malmö University Hospital from a clinical series from 2000 - 2006 as well as an autopsy cohort of 24000 consecutive autopsies from 1970 - 1982. RESULTS: In the clinical comparative study, MVT (n=51) was associated with more thrombophilic disorders (P=0.040) and intestinal infarctions (P=0.046), whereas patients with PVT without extension to the superior mesenteric vein (n=20) more often had liver disease (P<0.001). At autopsy, 270 patients with portomesenteric venous thrombosis were found; twenty-nine out of the 31 cases with MVT had intestinal infarction. None (0%) of the 239 patients with PVT without extension into the superior mesenteric vein had intestinal infarction. Portomesenteric venous thrombosis and intestinal infarction was associated with concomitant venous thromboembolism (O. R. 6.1 [95% CI 1.8-21]). CONCLUSION: MVT carries a high risk of developing intestinal infarction and is associated with concomitant venous thromboembolism, whereas PVT is associated with liver disease.

Clinical trial: colectomy after rescue therapy in ulcerative colitis - 3-year follow-up of the Swedish-Danish controlled infliximab study.

BACKGROUND: The long-term efficacy of infliximab as rescue therapy in steroid-refractory ulcerative colitis is not well described. AIM: To examine the long-term efficacy of infliximab as a rescue therapy through a 3-year follow-up of a previous placebo-controlled trial of infliximab in acute steroid-refractory ulcerative colitis. METHOD: In the original study, 45 patients were randomized to a single infusion of infliximab 5 mg/kg or placebo, and at 3 months, 7/24 patients given infliximab were operated vs. 14/21 patients given placebo. Three years or later, patients were asked to participate in a clinical follow-up. RESULTS: Another seven patients underwent colectomy during follow-up: five in the infliximab group and two in the placebo group. After 3 years, a total of 12/24 (50%) patients given infliximab and 16/21 (76%) given placebo (P = 0.012) had a colectomy. None of eight patients in endoscopic remission at 3 months later had a colectomy compared with 7/14 (50%) patients who were not in remission (P=0.02). There was no mortality. CONCLUSION: The benefit of rescue therapy with infliximab in steroid-refractory acute ulcerative colitis remained after 3 years. The main advantage of infliximab treatment occurred during the first 3 months, whereas subsequent colectomy rates were similar in the two groups. Mucosal healing at 3 months influenced later risk of colectomy.

Ribavirin dosage in patients with HCV genotypes 2 and 3 who completed short therapy with peg-interferon alpha-2b and ribavirin.

BACKGROUND: The optimal dose of ribavirin to be used in combination with Peg-IFN in patients with HCV genotypes 2 and 3 undergoing short treatment has not been established. AIM: To explore the relationship between starting ribavirin doses, expressed as mg/kg body weight and both rapid viral response at treatment week 4 (RVR) and sustained virological response (SVR) in patients treated for 12-14 weeks with peg-interferon alpha-2b and ribavirin. METHODS: A post hoc analysis of data collected from two multicenter clinical trials was performed. Multiple regression analyses were employed to identify independent baseline and on-treatment predictors of RVR and SVR. For each dose of ribavirin, the empirical estimated probability of response was computed and the continuous exposure index was dichotomized by using a recursive partitioning and amalgamation method. RESULTS: A nonlinear relationship was ascertained between ribavirin dose and RVR, but not SVR. A dose of 15.2 mg/kg was selected as the best splitting value for discriminating RVR vs. non-RVR. Regression analysis identified low baseline viraemia, genotype 2 and high ribavirin dose as independent prognostic factors for RVR. The likelihood of an SVR was not correlated with baseline ribavirin dose, but was independently predicted by adherence to the full dose throughout treatment and normal platelet counts. CONCLUSIONS: Starting high ribavirin doses appears capable of increasing the rate of RVR in patients with HCV genotypes 2 and 3 undergoing short treatment. Maintenance of the full planned dose throughout treatment is essential for achieving optimal SVR rates.

GB virus C/hepatitis G virus infection in patients investigated for chronic liver disease and in the general population in southern Sweden.

Serum samples from patients referred for liver biopsy for investigation of suspected chronic liver disease (n = 286) and from healthy middle-aged volunteers (n = 445) were analyzed for markers of exposure to GB virus C/hepatitis G virus (GBV-C/HGV), hepatitis B virus and hepatitis C virus. GBV-C/HGV analyses included GBV-C/HGV PCR for detection of viremia and GBV-C/HGV enzyme-linked immunosorbent assay for anti-GBV-C/HGV E2 antibodies. Liver biopsies were re-evaluated by a hepatopathologist. GBV-C/HGV markers were detected in 97/286 (34%) patients (GBV-C/HGV RNA = 26; anti-GBV-C/HGV E2 antibodies = 74) compared to 86/445 (19%; p < 0.0001) controls (GBV-C/HGV RNA = 7, anti-GBB-C/HGV E2 antibodies = 79). A significantly higher proportion of GBV-C/HGV-exposed subjects in the patient group were viremic compared to controls (27% vs. 8.1%; p = 0.0015). GBV-C/HGV markers were more commonly found in patients with chronic hepatitis B and C. In patients with GBV-C/HGV viremia, a higher occurrence of bile duct degeneration was detected than in non-viremic patients. Markers of GBV-C/HGV infection were over-represented among patients investigated for chronic liver disease, and ongoing GBV-C/HGV viremia was more common in this group than in controls. Apart from a higher prevalence of bile duct degeneration in viremic patients, infection with GBV-C/HGV did not confer any specific histological characteristics.

Clinical spectrum of hepatitis C-related liver disease and response to treatment with interferon and ribavirin in haemophilia or von Willebrand disease.

Our aim was to evaluate the severity of liver disease resulting from chronic hepatitis C in haemophilia or von Willebrand disease and the efficacy of 6 months treatment with interferon alpha and ribavirin. Fifty-five liver biopsies were performed in 43 patients without any bleeding complications, as seen with ultrasound immediately after the biopsy and 48 h thereafter. Histological changes were mild, with low scores for both inflammation and fibrosis, in spite of long exposure to blood products (mean 27 years). Two patients had compensated cirrhosis. Thirty-five out of 39 included patients completed study treatment. Hepatitis C virus (HCV)-RNA was negative in 77% (30/39) of patients at the end of treatment, and 36% (14/39) achieved a complete sustained response at follow-up 6 months after treatment. Treatment failure was more frequent in patients with virus genotype 1 compared with non-1 (P = 0.0003). The response rate correlated well with that of non-haemophilic patients. In summary: (1) liver biopsy was safe with our regimen; (2) liver disease in our patients was usually mild and had a slow progress; (3) only HCV genotype 1 predicted treatment failure; (4) our treatment results agreed with those from non-haemophilic patients.

Prevalence and clinical spectrum of chronic viral hepatitis in a middle-aged Swedish general urban population.

BACKGROUND: Although abundant data are available regarding the prevalence of chronic hepatitis B or C virus (HBV, HCV) among both blood donors and patients with liver diseases, corresponding data for the general population are scarce. Accordingly, this study was designed to investigate the prevalence and clinical spectrum of HBV and HCV in a general Swedish middle-aged urban population. METHODS: Demographic data and blood samples were collected from subjects enrolled in a prospective study of cancer development in the city of Malmö (population 250,000). The participation rate in the preliminary examination was 46.2%. From 12,445 individuals born between 1926 and 1945 and included in the study, a statistically representative subsample of 6103 persons was selected. Blood samples were available from 5533 of these. The mean age of the subjects in the series was 58.5 +/- 5.9 years, and 59% were women. The HBV markers used were anti-HBc and HBsAg. HCV antibodies were detected with a third generation anti-HCV ELISA, followed by immunoblotting (RIBA 3) if the test was positive. Immunoblot-reactive samples were analysed for HCV-RNA by polymerase chain reaction and genotyped. In all patients with signs of chronic HBV or HCV, epidemiological data were evaluated and liver biopsies obtained. RESULTS: Of the series as a whole (n = 5533), 4.2% (n = 211) tested positive for anti-HBc and 0.2% (n = 10) for HBsAg. RIBA 3 analysis showed 0.37% (18/5533) to be anti-HCV-positive, of whom 83% (15/18) were HCV-RNA-positive. Apart from two (both from HBsAg carriers) with normal histology, all liver biopsies manifested various degrees of inflammation and fibrosis. Among anti-HCV-positives, median grade was 6 and median stage 1 (Knodell score). CONCLUSION: The prevalence of both chronic HBV and HCV is low in the Swedish general urban middle-aged population. Nonetheless, the long-term effects on the population and the health care system may be significant.

Anti-neutrophil cytoplasmic antibodies in patients with chronic liver diseases: prevalence, antigen specificity and predictive value for diagnosis of autoimmune liver disease. Swedish Internal Medicine Liver Club (SILK)

BACKGROUND: Anti-neutrophil cytoplasmic antibodies (ANCA) against proteinase 3 are diagnostic of Wegener's granulomatosis, but ANCA occur also in patients with other inflammatory disorders, such as ulcerative colitis, primary sclerosing cholangitis (PSC) and autoimmune hepatitis. As their predictive value for autoimmune liver disease remains unknown, we analysed the prevalence and antigen specificity of ANCA in patients with various chronic liver diseases (CLD). METHODS: We studied sera from 100 patients with primary biliary cirrhosis (PBC), from 76 with PSC and from 279 with various CLD, consecutively drawn during a 5-year period at the time of liver biopsy. The ANCA were detected by indirect immunofluorescence (IIF) while the antigen specificity was characterized by ELISA by using lactoferrin, neutrophil elastase, cathepsin G and BPI (bactericidal/permeability increasing protein) as antigens. RESULTS: In PBC, ANCA were detected by IIF in 39 patients (39%). The antigen reactivity by ELISA was lactoferrin in seven, elastase in 15, BPI in 20 and cathepsin G in four patients. Four patients had reactivity against more than one antigen. In PSC, IIF demonstrated ANCA in 49 patients (65%). The antigen reactivity was lactoferrin in 17, elastase in 14, BPI in 20 and cathepsin G in four patients. Twelve patients showed reactivity against more than one antigen. In CLD, ANCA were observed in sera from 55 patients (20%). Nineteen of 45 patients (42%) with autoimmune liver disease were ANCA positive versus 36/234 (15%) with non-autoimmune liver disease (P = 0.0002). Among IIF-positive patients, antibody reactivity against lactoferrin was noted in 14, elastase in 28, BPI in 25 and cathepsin G in five patients. Twenty-one patients had reactivity against more than one antigen. Elastase and BPI antibodies occurred more frequently in patients with autoimmune compared to non-autoimmune liver disease (P < 0.01). CONCLUSIONS: Anti-neutrophil cytoplasmic antibodies are prevalent in patients with chronic liver diseases, but although they occur more frequently in patients with autoimmune liver disease their specificity and sensitivity for autoimmune liver disease is low. The predominant antigens are lactoferrin, elastase and BPI, but the correlation between IIF findings and ELISA reactivity against these antigens is weak.

Hepatocellular carcinoma in Sweden: its association with viral hepatitis, especially with hepatitis C viral genotypes.

Viral markers of chronic hepatitis were tested for in 95 frozen serum samples from 299 patients from Malmö, Sweden, with hepatocellular carcinoma (HCC), diagnosed between 1977 and 1994. Hepatitis B analysis included anti-HBc, HBsAg and, if anti-HBc positive, HBV DNA. Hepatitis C infection analysis included anti-HCV screening, RIBA, HCV RNA and HCV genotyping. HCV genotyping was also carried out in 9 HCV-viraemic HCC-patients from Gothenburg. HCV genotype distribution in HCC cases was compared with Swedish HCV-infected blood donors. Among the 95 patients from Malmö, 28 (29%) had anti-HBc, but only 5 (5%) were chronic HBV carriers, compared with 16 (17%) with chronic hepatitis C (p = 0.021). HCV-related HCC was more common among immigrants (8/16 vs. 8/79; p < 0.001). Genotyping of 25 HCV-infected cases showed genotype 1a in 6 (24%), genotype 1b in 13 (52%), genotype 2b in 4 (16%), and genotype 3a in 2 (8.0%) patients. Genotype 1b was more common among HCC patients than among blood donors (p < 0.001), but 8 of 13 genotype 1b-infected patients were from countries where genotype 1b is predominant. Among native Swedes there was no difference between the HCV genotypes infecting blood donors and those found in HCC patients.

The prevalence of gallstones in chronic liver disease is related to degree of liver dysfunction.

BACKGROUND/AIMS: Earlier studies have indicated an elevated risk for gallstone disease in patients with cirrhosis. This study aimed to evaluate the prevalence of gallstones in patients with chronic liver disease (CLD) with respect to sex, etiology, and severity of liver disease. METHODOLOGY: Four hundred and thirteen adults (176 women), mean age 51.2+/-14 years, with CLD, who had undergone liver biopsy during 1978-1993, and from whom sera were available, were investigated retrospectively. The results were compared with a population-based ultrasonography study of 556 healthy men and women, in their 40s and 60s. RESULTS: The prevalence of gallstones in patients with CLD did not differ from that in the control population. An increased frequency was observed in patients with CLD initially classified as cryptogenic, of whom the majority (60%) later were reclassified as chronic hepatitis C. The frequency of gallstones was also high in PiZ-heterozygotes for alpha1-antitrypsin deficiency (5/21, 24%) compared to non-PiZ-carriers (17/389, 4.8%), (p<0.001). In 67 patients with histologic evidence of cirrhosis, 30% (20/67) had gallstones (vs. 15% in the general population, p<0.01). The prevalence of gallstones increased significantly from Child's class A (16%) to C (56.2%). The difference was significant in males (18.2% vs. 62.5%, p=0.033), but not in females. Fifty percent of the patients with gallstones were symptomatic. CONCLUSIONS: Progressive liver dysfunction is a risk factor for gallstones particularly in males. HCV infection and PiZ carriership may further increase biliary lithogenesis.

Extrahepatic manifestations of chronic hepatitis C infection and the interrelationship between primary Sjögren's syndrome and hepatitis C in Swedish patients.

OBJECTIVE: To analyse the frequency of some extrahepatic manifestations of chronic hepatitis C virus (HCV) infection in northern European patients, including a postulated association between HCV and primary Sjögren's syndrome (SS). DESIGN: Cohort study. SETTING: Department of Medicine, Malmö University Hospital, Sweden. PATIENTS: Twenty-one patients with HCV infection and 53 with primary SS (according to the Copenhagen criteria). MAIN OUTCOME MEASURES: Cryoglobulins were analysed in all patients, while patients with primary SS were investigated with regard to markers of HCV infection, and HCV patients with objective tests of SS (Schirmer-1 test, break-up time, van Bijsterveld score, sialometry, labial salivary gland biopsy) and antibodies against nuclear antigens, smooth muscle (SMA) and mitochondria (AMA). HCV antigens in small salivary glands from lower lip biopsies were detected by immunohistochemical analysis. RESULTS: Only one of the SS patients had detectable cryoprecipitates, while another was HCV-positive. None of the 21 HCV patients had cryoprecipitates. A total of 14/21 (67%) patients with HCV infection had at least one abnormal objective test suggestive of xerostomia or keratoconjunctivitis sicca, while eight (38%) had objective evidence of both eye and salivary gland involvement. HCV antigens were not detected in affected glands. Only two patients had clinical symptoms of SS, and two fulfilled the Copenhagen criteria for SS. None of the HCV-positive patients had detectable antibodies against SS-A, SS-B, RNP, Jo-1, PCNA or Scl-70, and the frequency of ANA/SMA/AMA was low. CONCLUSIONS: While involvement of salivary and lacrimal glands was common in Swedish patients with HCV infection, cryoglobulinaemia was not observed. The pathogenetic mechanism responsible for glandular inflammation appears to be different from that in primary SS. HCV infection does not seem to be an aetiological factor for primary SS in this population. These observations suggest that viral, genetic or possibly environmental factors may be responsible for the reported high frequencies of systemic complications associated with chronic hepatitis C infection in southern Europe.

[Alendronate-induced severe esophagitis. A rare and severe reversible side-effect illustrated by three case reports]. / Alendronatutlöst svår esofagit. Ovanlig och allvarlig men reversibel biverkan belyses med tre fall.

The bisphosphonate, alendronate sodium (e.g. Fosamax), a bone resorption inhibitor used to treat osteoporosis, has occasionally been reported to cause severe oesophagitis. The characteristic endoscopy findings include oesophageal ulceration with discoloured exudate, a narrowed lumen and denuded, haemorrhagic mucosa. The oesophagitis heals on discontinuation of alendronate medication, and the institution of gastric acid suppression treatment. The article consists in discussion of such adverse reactions, illustrated by three case reports. As many of the patients selected for alendronate treatment are elderly and handicapped, to minimise the risk of serious side-effects it is important not only to give detailed instructions regarding medication, but also to ensure that they are properly understood. As a history of swallowing problems was a feature of all three cases reported, caution is recommended before treating such patients with alendronate sodium.

Long-term outcome of chronic hepatitis C infection in a low-prevalence area.

BACKGROUND: Although hepatitis C virus (HCV) infection is recognized as an important causative factor in the development of liver cirrhosis and hepatocellular cancer (HCC), the strength of this correlation has been difficult to confirm in low-prevalence areas. METHODS: Stored serum samples from 987 consecutive (1978-88) patients with chronic liver disease were tested with an enzyme-linked immunosorbent assay for anti-HCV and further confirmed by immunoblot. To evaluate the long-term outcome, the cohort was followed up until 1995, for a median observation time of 10 years. RESULTS: Anti-HCV, confirmed by immunoblot, was found in 9.5% (94 of 987) of the patients, and at inclusion most patients were asymptomatic irrespective of anti-HCV status. Of the 445 patients who died during the study period, 44 were HCV-positive. A liver-related cause of death was far commoner and the age-adjusted survival shorter among HCV-positive patients than among HCV-negative ones. At death 68% (30 of 44) of the HCV-positive subgroup had developed cirrhosis, and 30% (13 of 44) had concurrent HCC, as compared with 36% (142 of 393) (P = 0.001) and 8% (31 of 393) (P = 0.001), respectively, of the HCV-negative subgroup. HCV infection (P < 0.001), alcohol abuse (P < 0.001), and immigrant status (P = 0.045) were independent factors with regard to the development of cirrhosis, whereas HCV infection (P = 0.040) and immigrant status (P = 0.012) were independent factors with regard to HCC. CONCLUSIONS: HCV infection is common among patients with chronic liver disease, even when clinical evidence of viral infection is sparse, and constitutes a significant cause of death even in a low-prevalence area.

Factors associated with cirrhosis development in chronic hepatitis C patients from an area of low prevalence.

The aim of this study was to evaluate the importance of different endogenous and exogenous factors associated with cirrhosis development among hepatitis C virus (HCV)-positive individuals from an area of low prevalence. We studied 106 consecutive HCV RNA positive patients who had undergone liver biopsy. Each patient was assessed with special attention to risk factors for hepatitis C infection, average daily alcohol consumption and analysis of plasma levels of alpha1-antitrypsin (alpha1AT) and alpha1-antichymotrypsin (alpha1ACT). Viral RNA, amplified from serum with the polymerase chain reaction (PCR) technique, was used for genotyping. Liver biopsies were assessed according to conventional histopathological criteria, and for necroinflammatory activity (grade) and fibrosis (stage) according to a numerical scoring system. The presence of cirrhosis (stage 4) was used as the dependent variable in multivariate logistic regression analysis. Alcohol abuse (P = 0.007), age at entry (P < 0.001), immigrant status (P = 0.017) and a low alpha1ACT level (P = 0.008) were all independent determinants of progression to cirrhosis whereas HCV genotype 1, estimated duration of HCV infection and positivity for antibodies to hepatitis B core antigen (HBcAb) were not. Cirrhosis occurred at a significantly younger age (P = 0.00(5) among alcohol abusers. Hence, both endogenous and exogenous factors such as subnormal alpha1ACT levels and alcohol appear to contribute to the rate of progression to cirrhosis among HCV-positive patients.

Serine protease inhibitors in patients with chronic viral hepatitis.

BACKGROUND/AIMS: This study aimed to determine whether deficiency of the major serine protease inhibitors (alpha1-antitrypsin (AAT) or alpha1-antichymotrypsin (ACT)) is associated with increased risk for chronic hepatitis B or C virus (HBV or HCV) infection. METHODS: We studied 709 adults with chronic liver disease who had undergone liver biopsy during the 14-year period 1978-92. Anti-HCV testing was carried out with second-generation ELISA and immunoblot assays (RIBA 2). HBV markers were tested with commercially available radioimmunoassays. ACT and AAT concentrations in plasma were measured with electroimmunoassay and immune nephelometry. Plasma samples were screened for the AAT PiZ deficiency with ELISA technique and phenotyped by isoelectric focusing. The 229Pro-->Ala mutation for ACT deficiency was identified by PCR techniques. RESULTS: Of the 709 patients, 132 (18.6%) were positive for anti-HCV according to RIBA 2. PiZ AAT deficiency was found in 44 (6.2%) of patients (one PiZZ, 38 PiMZ, and PiSZ), while subnormal ACT levels were found in 33 (4.6%) patients, frequencies that were higher than expected in the general population (p=0.0375 and p<0.0001, respectively). Of the PiZ-carriers, 8/44 (18%) were found to be anti-HCV positive according to RIBA 2, as compared to 123/662 (19%) non-PiZ-carriers (p>0.05). One of these patients had cirrhosis, four chronic active hepatitis, and three chronic persistent hepatitis. In contrast, 17/33 (51.5%) of the patients with subnormal ACT were anti-HCV positive (OR=5.2, CI=2.6-10.6; p<0.0001). No relationship was found between HBV infection and AAT deficiency or subnormal ACT levels. Only one patient with subnormal ACT levels was heterozygous for the 229Pro-->Ala mutation of ACT deficiency. There was no significant difference in the histological findings when the patients with subnormal ACT levels or PiZ allele were subgrouped according to HCV status. CONCLUSIONS: There is no overrepresentation of chronic HBV or HCV in heterozygous AAT deficiency, although an association with more severe liver disease in such patients cannot be excluded. In contrast, low plasma levels of ACT that may be acquired or hereditary, due to mutations other than 229Pro-->Ala, are frequent in HCV infection.

Non-invasive assessment of inflammatory activity and fibrosis (grade and stage) in chronic hepatitis C infection.

BACKGROUND: Much effort has been expended in finding non-invasive alternatives to percutaneous liver biopsy for assessing the histological extent of liver damage. METHODS: We have evaluated the relationship between various histological features of liver of biopsies and plasma levels of immunoglobulin G (IgG), procollagen III propeptide (PIIIP) and type-IV collagen (CL-IV) in 109 patients with chronic hepatitis C (HCV) infection. RESULTS: The serum IgG level was the best single marker for distinguishing chronic persistent hepatitis (CPH) from chronic active hepatitis (CAH). The mean serum levels of PIIIP and CL-IV increased with the progression of liver disease, though the three variables manifested considerable overlap in individual values as markers of CPH, CAH and cirrhosis. The various biochemical markers correlated weakly but significantly to both histological grade and stage of liver disease, as assessed with the scoring system of Knodell. The correlation appeared to be non-specific and to reflect inflammatory activity as well as fibrogenesis. CONCLUSIONS: Serum levels of PIIIP. CL-IV and IgG are of limited use in predicting the histological grade and stage of liver disease in patients with chronic HCV infection.

Alcohol abuse exaggerates autonomic dysfunction in chronic liver disease.

BACKGROUND: Advanced chronic liver disease is characterized by peripheral arterial vasodilation and increased plasma catecholamine concentrations. These haemodynamic alterations may reflect impaired vascular responsiveness due to autonomic nerve dysfunction. METHODS: Three established non-invasive tests based on the heart reactions to deep breathing (expiratory/inspiratory (E/I) ratio) and to tilt (acceleration and brake indices) were used to evaluate age-related autonomic nerve function in 27 patients with chronic alcoholic and non-alcoholic liver disease. Liver function was estimated by demethylating capacity. The results were compared with a control group consisting of 56 healthy individuals. RESULTS: Overall, 12 patients (52%) had autonomic neuropathy (10 of 13 (77%) patients with alcoholic and 2 of 14 (14%) with non-alcoholic liver disease). Variance analysis showed that the age-corrected E/I ratio, but not the acceleration and brake indices, was significantly decreased compared with controls both in patients with alcoholic and non-alcoholic liver disease, indicating vagal nerve dysfunction (P < 0.0001 and 0.0133, respectively). The decrease in E/I ratio was also significantly more pronounced (-1.77 (0.62) (median (interquartile range)) versus 0.76 (0.70); P = 0.049) in patients with alcoholic compared with non-alcoholic liver disease. Furthermore, in contrast to non-alcoholics, patients with alcoholic liver disease were unable to increase their diastolic blood pressure after return to upright from a tilted position, indicating additional sympathetic neuropathy. CONCLUSIONS: Autonomic, mainly vagal, nerve dysfunction is common in patients with liver diseases and is further exaggerated by alcohol abuse. Autonomic neuropathy may contribute to altered vascular responsiveness in patients with chronic liver diseases.

Intravenous drug abuse--the major route of hepatitis C virus transmission among alcohol-dependent individuals?

As the prevalence of hepatitis C virus (HCV) antibodies has been reported to be high among alcohol-dependent individuals, we screened prospectively 310 consecutive non-selected alcoholic outpatients for HCV and possible routes of transmission. Using a second-generation enzyme-linked immunosorbent assay test and retesting all positive sera with a second-generation recombinant immunoblot assay, we found the prevalence of anti-HCV to be 14.5% (45 of 310). Of the 45 anti-HCV-positive individuals, 39 (88.7%) had a history of intravenous drug abuse, 2 had received blood transfusions, and only 4 lacked an identifiable source of infection. The magnitude of alcohol consumption, number of hospital admissions, duration of alcohol dependence, or presence of tattooing could not be shown to be factors of importance for the transmission of HCV infection. Our results suggest that a history of intravenous drug abuse is a common phenomenon and the predominant route of HCV transmission among alcoholics. True community-acquired infection would appear to be rare.

Hepatitis C in chronic liver disease: an epidemiological study based on 566 consecutive patients undergoing liver biopsy during a 10-year period.

We analysed the presence of hepatitis C virus (HCV) antibodies in 566 patients undergoing liver biopsy. While over 20% of the patients were anti-HCV positive according to ELISA, only 13.8% had HCV antibodies when tested with a four-antigen recombinant immunoblot assay (RIBA 2). At the time of inclusion in the study, most patients were asymptomatic, irrespective of whether they were HCV-positive. Histological findings in anti-HCV-positive patients were chronic persistent hepatitis, chronic active hepatitis or cirrhosis in greater than 75% of cases. Only four of the patients who were anti-HCV-positive according to the RIBA 2 had autoimmune chronic active hepatitis. Risk behaviour could be identified in the majority of cases. Community-acquired sporadic cases were rare (12%). Of the 153 patients who died during follow-up, 23 subjects were anti-HCV positive. Although age- and sex-adjusted survival was not shorter in anti-HCV-positive patients than in anti-HCV-negatives, the risk of hepatocellular cancer was higher (P = 0.01). We conclude that HCV infection is associated with chronic liver disease, even when critical evidence of viral aetiology is slight. Truly sporadic cases are rare. Patients infected with HCV are at increased risk of developing hepatocellular cancer.