Long-term liver-related morbidity and mortality related to chronic hepatitis C virus infection in Swedish patients with inherited bleeding disorders.

INTRODUCTION: Hepatitis C virus (HCV) infection is common in patients with inherited bleeding disorders treated with clotting factor concentrates prior to the introduction of viral inactivation of these products. The long-term consequences of hepatitis C infection in Swedish patients are not fully understood. AIM: To examine the impact of HCV infection on liver-related morbidity and mortality in Swedish patients with inherited bleeding disorders. METHODS: We retrospectively collected data on 183 patients with inherited bleeding disorders infected with HCV who attended the Coagulation Unit at Karolinska University Hospital, Sweden. Data regarding end-stage liver disease (ESLD), defined as presence of ascites, encephalopathy, variceal bleeding, hepatocellular carcinoma or liver-related death, were collected from the patient records and the national registers. RESULTS: The median follow-up time was 35.9 years (IQR 29.0-41.2). A total of 41% had achieved sustained virological response (SVR) after treatment. In total, 14.2% developed ESLD at the median age of 52.6 years (IQR 46.5-64.7). Nineteen (35.8%) of all deaths were due to liver-related causes. Co-infection with human immunodeficiency virus (HIV), older age at time of infection and severe form of bleeding disorder was associated with higher risk of developing ESLD, while SVR was a strong protective factor. CONCLUSIONS: This study demonstrated that liver-related morbidity and mortality was significant in patients with bleeding disorders and HCV infection in Sweden. Patients with HCV-infection should be candidates for treatment with the new highly effective antiviral drugs, since SVR proved to be a strong protective factor.

Historical epidemiology of hepatitis C virus (HCV) in selected countries.

Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6,358,000 cases in 2008 and Brazil with 2,106,000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.

Strategies to manage hepatitis C virus (HCV) disease burden.

The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV-related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3-5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.

The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm.

The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing.

Risk of pancreatic cancer among individuals with hepatitis C or hepatitis B virus infection: a nationwide study in Sweden.

BACKGROUND: A few studies indicated that hepatitis C and hepatitis B virus (HCV/HBV) might be associated with pancreatic cancer risk. The aim of this nationwide cohort study was to examine this possible association. METHODS: Hepatitis C virus- and hepatitis B virus-infected individuals were identified from the national surveillance database from 1990 to 2006, and followed to the end of 2008. The pancreatic cancer risk in the study population was compared with the general population by calculation of Standardized Incidence Ratios (SIRs), and with a matched reference population using a Cox proportional hazards regression model to calculate hazard ratios (HRs). RESULTS: In total 340 819 person-years in the HCV cohort and 102 295 in the HBV cohort were accumulated, with 34 and 5 pancreatic cancers identified, respectively. The SIRHCV was 2.1 (95% confidence interval, CI: 1.4, 2.9) and the SIRHBV was 1.4 (0.5, 3.3). In the Cox model analysis, the HR for HCV infection was 1.9 (95% CI: 1.3, 2.7), diminishing to 1.6 (1.04, 2.4) after adjustment for potential confounders. CONCLUSION: Our results indicated that HCV infection might be associated with an increased risk of pancreatic cancer but further studies are needed to verify such association. The results in the HBV cohort indicated an excess risk, however, without statistical significance due to lack of power.

The burden of hepatitis C in Sweden: a national study of inpatient care.

The spread of hepatitis C virus (HCV) in Sweden in the 1970s indicated that serious liver complications (SLC) would increase in the 2000s. The aim of this study was to analyse the burden of HCV-associated inpatient care in Sweden, to demonstrate the changes over time and to compare the findings with a noninfected population. The HCV-cohort (n: 43,000) was identified from the national surveillance database 1990-2006, and then linked to national registers to produce an age-, sex-, and region-matched noninfected comparison population (n: 215,000) and to obtain information on demographics, cancers, inpatient care and prescriptions. Cox regression was used to estimate the likelihood (hazard ratios) for admission to hospital in the HCV compared with the noninfected cohort. The hazard ratios were 4.03 (95% CI: 3.98-4.08) for all care, 77.52 (71.02-84.60) for liver-related care and 40.74 (30.58-54.27) for liver cancer care. The admission rate in the HCV-cohort compared with the noninfected cohort, the rate ratio (age- and sex-adjusted) for all inpatient care was 5.91 (95% CI: 5.87-5.94), and the rate ratio for liver-related care was 70.05 (66.06-74.28). In the HCV-cohort, 45% of all episodes were for psychiatric, mostly drug-related, care. Inpatient care for SLC increased in the 2000s. To conclude, drug-related care was common in the HCV-infected cohort, the demand for liver-related care was very high, and SLC increased notably in the 2000s, indicating that the burden of inpatient care from serious liver disease in HCV-infected individuals in Sweden is an increasing problem.

The epidemiology of hepatitis C virus infection in Sweden.

In Sweden, infection with hepatitis C virus (HCV) has been a notifiable disease since 1990, when diagnostic methods became available. Blood donor screening indicated that about 0.5% of the Swedish population (9 millions) had been HCV infected. Here we present the Swedish hepatitis C epidemic based on data from all the HCV notifications 1990-2006. During this time about 42,000 individuals (70% men) were diagnosed and reported as HCV infected. The majority (80%) were born in 1950 or later, with a high percentage (60%) born in the 1950s and 1960s. Younger people, 15-24 years old at notification, were reported on the same level each year. The main reported routes of HCV transmission were intravenous drug use in 65%, blood transfusions/products in 6%, and sexual in 2%, though unknown or not stated in 26%. Approximately 6,000 of all notified individuals have died during the study period. To conclude, the Swedish HCV epidemic is highly related to the increase of intravenous drug use in the late 1960s and 1970s, with a high proportion of people now chronically infected for more than 25 years, resulting in an increase of severe liver complications in form of cirrhosis and hepatocellular carcinoma. Furthermore the unchanged number of notifications of newly infected younger people indicates an ongoing HCV epidemic.

Coccidioidal spondylitis: MR findings in 15 patients.

OBJECTIVE: MR imaging studies of 15 patients with documented vertebral column coccidioidomycosis infection were retrospectively reviewed to determine the MR imaging features of coccidioidal spondylitis. CONCLUSION: On MR imaging, coccidioidal spondylitis may be unifocal or multifocal. Involvement of an intervertebral disk, vertebral body marrow, and adjacent epidural and soft tissue is generally seen.

Virological, biochemical and histological effects of human lymphoblastoid interferon in Swedish patients with chronic hepatitis C.

Thirty-eight Swedish patients with chronic hepatitis C were randomly assigned to receive either 3 million units (MU) or 5 MU of human lymphoblastoid interferon-alpha-n1 (Wellferon) three times per week for either 6 or 12 months. The patients were monitored biochemically, histologically and by quantitative polymerase chain reaction for circulating HCV RNA, during therapy and for the following year. Overall, 22 (58%) of the patients lost detectable hepatitis C virus (HCV) viraemia during therapy but eight of these patients relapsed during follow-up, leaving 14 (37%) sustained responders. Patients infected with HCV non-type 1 genotypes were significantly more likely to achieve a sustained response than were those infected with HCV type 1 (63% vs 10.5%, P = 0.001). Sustained virological responses were also associated with lower pretreatment viraemia level, younger age, absence of cirrhosis and the higher interferon dosage regimens but these associations failed to reach statistical significance. In 97% of patients there was concordance between virological and biochemical responses, and a statistically significant (P = 0.005) improvement in the Knodell histological activity index was observed in the virological sustained responders.

Transmission of hepatitis C virus by transfusion in Orebro County, Sweden, 1990-1992.

A retrospective study of hepatitis C virus (HCV) transmission by transfusion was conducted in Orebro county. Out of the 7,900 active, registered blood donors, 21 repeatedly anti-HCV reactive (RIVA 2 positive or indeterminate) donors were diagnosed. Their 84 recipients from January 1990 through June 1992 were identified and 41 (49%) were alive in December 1992. A total of 13 anti-HCV reactive (RIBA 2 positive or indeterminate) were diagnosed in 39 investigated recipients. Of these 11 were previously undiagnosed, and seven were HCV RNA-positive. In the donor population 1.03% were anti-HCV-positive by ELISA, but only 0.09% were RIBA and HCV RNA-positive. In 1990, 0.06% of the blood components came from the HCV RNA-positive donors, and none during the first 6 months of 1992. In order to identify transfusion-transmitted HCV infections that took place before the introduction of tests for anti-HCV antibodies, patients with a history of transfusion and symptoms and signs of liver dysfunction or damage should be thoroughly tested.

Intracranial cryptococcosis in immunocompromised patients: CT and MR findings in 29 cases.

CT and MR scans of 29 immunocompromised patients (28 with AIDS or ARC, one with diabetes mellitus) who had documented intracranial cryptococcal infection were reviewed retrospectively. All patients had CT studies; 26 received iodinated contrast agent. CT findings included normal results in nine of 29, atrophy only in 13 of 29, nonenhancing lesions in three of 29, enhancing lesions in two of 20, and foci of leptomeningeal calcification in two of 29. Ten patients had both CT and MR studies, and four received gadopentetate dimeglumine. Among these 10 patients, five had normal CT studies and one showed moderate central atrophy. All 10, however, had abnormal MR findings. We observed four patterns: (1) parenchymal cryptococcoma (3/10); (2) numerous clustered tiny foci that were hyperintense on T2-weighted images and non-enhancing on postcontrast T1-weighted images, located relatively symmetrically in the basal ganglia bilaterally and in midbrain, representing dilated Virchow-Robin spaces (4/10); (3) multiple miliary enhancing parenchymal and leptomeningeal nodules (1/10); and (4) a mixed pattern, consisting of dilated Virchow-Robin spaces with mixed lesions such as cryptococcoma and miliary nodules (2/10). In the group of six patients with dilated Virchow-Robin spaces (patterns 2 and 4), two received gadopentetate dimeglumine, but the Virchow-Robin space lesions did not enhance; among the remaining four patients, two received gadopentetate dimeglumine (one with pattern 1 and one with pattern 3) and the lesions did enhance. Three patients in our study subsequently died and autopsies were performed. The postmortem results revealed dilated Virchow-Robin spaces filled with fungi in the basal ganglia, which correlated well with MR findings.(ABSTRACT TRUNCATED AT 250 WORDS)

An evaluation of MRI contrast in the uterus using synthetic imaging.

Using a 1.5-T system, we investigated the contrast in MR images of the uterus using a synthetic imaging program that was capable of producing images with TR values of 20 to 10220 ms and TE values of 1 to 511 ms. Synthetic images were calculated from images obtained on six normal women of reproductive age. The synthesized uterine images were essentially indistinguishable from acquired images with the same TR and TE parameters. Cervical and uterine anatomy could be clearly differentiated in synthetic images with a TE = 80 ms when the TR was as low as 100 ms. We conclude that the zonal anatomy of the uterus can be demonstrated using TR values that are much lower than those usually used for demonstrating uterine anatomy.

Radiolabeled fibronectin for the scintigraphic detection of pulmonary emboli in dogs.

Plasma fibronectin, a glycoprotein that is a component of blood thrombi, was evaluated for the in vivo scintigraphic detection of pulmonary emboli in dogs. Fibronectin (canine or human) was labeled with either 131I or with 111In and diethylenetriaminepenta-acetic acid (DTPA) as the bifunctional chelating agent using a modification of the mixed anhydride method. The radiolabeled proteins were administered intravenously 20 to 30 minutes after the embolization of a 99mTc-labeled thrombus. The uptake of radioactivity by the embolus was monitored scintigraphically up to 24 hours. At the end of each experiment, the animal was killed and in vitro tissue counting of radioactivity was performed. Comparative study of the 131I- and 111In-labeled agent is presented with particular reference to their pharmacokinetics. The in vivo uptake of radioactivity by the emboli was limited, indicating that radiolabeled fibronectin is not a good scintigraphic agent for the detection of pulmonary emboli.

A comparison between Bactec aerobic resin and hypertonic blood culture media.

The presence of antimicrobial agents in patients' blood is thought to represent an important source of false-negative blood cultures. This has led to the incorporation of agents with inhibitory effects on antimicrobial drugs into culture medium. In the present study, Bactec aerobic resin-containing blood culture medium was compared with Bactec hypertonic blood culture medium. 504 patients receiving cytostatic and/or antibiotic treatment were studied. Sensitivity calculations on detection of bacteremia in these patients gave 0.91 for the resin medium and 0.79 for the hypertonic blood culture system and showed a significant difference (p = 0.016). In addition, the resin-containing system more rapidly detected positive cultures than the hypertonic system.