Historical epidemiology of hepatitis C virus (HCV) in select countries - volume 2.

Chronic hepatitis C virus (HCV) infection is a leading cause of liver related morbidity and mortality. In many countries, there is a lack of comprehensive epidemiological data that are crucial in implementing disease control measures as new treatment options become available. Published literature, unpublished data and expert consensus were used to determine key parameters, including prevalence, viremia, genotype and the number of patients diagnosed and treated. In this study of 15 countries, viremic prevalence ranged from 0.13% in the Netherlands to 2.91% in Russia. The largest viremic populations were in India (8 666 000 cases) and Russia (4 162 000 cases). In most countries, males had a higher rate of infections, likely due to higher rates of injection drug use (IDU). Estimates characterizing the infected population are critical to focus screening and treatment efforts as new therapeutic options become available.

Strategies to manage hepatitis C virus (HCV) infection disease burden - volume 2.

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 15 countries, and the relative impact of two scenarios was considered: (i) increased treatment efficacy while holding the treated population constant and (ii) increased treatment efficacy and increased annual treated population. Increasing levels of diagnosis and treatment, in combination with improved treatment efficacy, were critical for achieving substantial reductions in disease burden. In most countries, the annual treated population had to increase several fold to achieve the largest reductions in HCV-related morbidity and mortality. This suggests that increased capacity for screening and treatment will be critical in many countries. Birth cohort screening is a helpful tool for maximizing resources. In most of the studied countries, the majority of patients were born between 1945 and 1985.

The present and future disease burden of hepatitis C virus (HCV) infections with today's treatment paradigm - volume 2.

Morbidity and mortality attributable to chronic hepatitis C virus (HCV) infection are increasing in many countries as the infected population ages. Models were developed for 15 countries to quantify and characterize the viremic population, as well as estimate the number of new infections and HCV related deaths from 2013 to 2030. Expert consensus was used to determine current treatment levels and outcomes in each country. In most countries, viremic prevalence has already peaked. In every country studied, prevalence begins to decline before 2030, when current treatment levels were held constant. In contrast, cases of advanced liver disease and liver related deaths will continue to increase through 2030 in most countries. The current treatment paradigm is inadequate if large reductions in HCV related morbidity and mortality are to be achieved.

Brain natriuretic peptide (BNP) in differential diagnosis of dyspnea.

BACKGROUND: The differentiation of congestive heart failure from pulmonary cause of dyspnea is of extreme importance in patients presenting with acute shortness of breath. It seems that the use of B-type natriuretic peptide (BNP) can speed up the diagnostic process significantly. MATERIAL AND METHODS: 79 patients (46 men - 58.2%, average 71.9, range 43-92; 33 women - 41.8%, average 75.5, range 51-93). In each of them we measured BNP concentrations by means of rapid fluorescent immunoassay. RESULTS: We divided the patients according to BNP results into two groups: BNP positive and BNP negative. There were 28 BNP negative patients -35.40% (13 men, 15 women). BNP positive patients (51) were divided into NYHA I-IV groups in accordance with BNP results. CONCLUSION: The rapid, highly sensitive and specific measurement of BNP concentrations in the patients with dyspnea can significantly help to differentiate the cardiac and pulmonary causes of dyspnea (Tab. 1, Fig. 1, Ref. 24).

[Liver biopsy in Slovakia]. / Biopsie pecene na Slovensku.

INTRODUCTION: Liver biopsy is the most specific diagnostic modality in hepatology, but information about its application in Slovakia is rather obscure. METHODS: The authors performed a correspondence study with the aim to find out how many biopsy examinations has been done in Slovakia in 2001, for which indications, what kind of techniques have been applied and which small or great complications were encountered. RESULTS: It was established that in the year 2001, 400 biopsies for diffuse liver diseases were performed. There were 296 percutaneous biopsies, 82 laparoscopic biopsies and 22 trans-jugular biopsies forming the survey. Acute viral hepatitis was the most frequent indication, whereas non-alcohol steatohepatitis was a rare indication in spite of the high prevalence. The frequency of great complications was 0.00025%. No death associated with this procedure was reported. CONCLUSION: Liver biopsy has been done in Slovakia in indications, ways and with the frequency of complications, which were comparable with data from literature.

[Percutaneous biopsy of the liver]. / Perkutánna biopsia pecene.

Percutaneous liver biopsy represents the most specific examination of the nature and severity of liver diseases. P. Ehrlich was the first physician in history having done the intervention in 1880. The new history begins with the Menghini's publication on s.c. one-second biopsy in 1957. The present paper deals exclusively with diffuse diseases of the liver including the most frequent ones--virus hepatitis, alcohol and non-alcohol steatohepatitis. The contraindications include mainly coagulation disorders and non-cooperative patients. The percutaneous biopsy is mostly executed after ultrasonographic examination or under the control of various image-forming techniques and by means of various types of needles; the authors analyze advantages and disadvantages of individual techniques. If the contraindications are respected, the percutaneous biopsy is a safe method of examination, which may be done on out-patient basis. A large series of complications exists, but their frequency is generally low. Morbidity is referred in 0.2% of patients, the most frequent complications being pain and hypotension from vaso-vagal reactions, extensive intraperitoneal bleeding and hemobilia. Mortality is extremely low, the mean in large studies being 0.001%.

Caffeine metabolism before and after liver transplantation.

AIM: To study drug metabolism in patients before and after liver transplantation using caffeine as a probe drug. Forty-five patients undergoing liver transplantation for various liver diseases and who had well documented dossiers were selected for the study. Before the liver transplantation and 1 month, 1 year, and 6 years after liver transplantation, they were given 200 mg of caffeine by the oral route in the morning after voiding their bladder. Twenty-four-hour urine samples were collected and caffeine and metabolites were determined by HPLC: 1-methylurate (1U), 1-methylxanthine (1X), 1.7-dimethylurate (17U), 1.7-dimethylxanthine (17X), 7-methylxanthine (7X), 3-methylxanthine (3X), 1.3-dimethylurate (13U), 3.7-dimethylxanthine (37X), 1.3-dimethylxanthine (13X), 1.3.7-trimethylxanthine = caffeine (137X). Indices of enzyme activities were calculated from the following urinary elimination ratios: (AFMU+1U+1X)/17U for CYP1A2, 17U/17X for CYP2A6, 1U/1X for xanthine oxidase (XO), AFMU/(AFMU+1U+1X) for N-acetyltransferase (NAT-2). RESULTS: Compared with results obtained in a group of 70 healthy subjects, caffeine metabolism before liver transplantation was deeply depressed with a decreased elimination rate in the case of all metabolites and a decreased CYP1A2 activity. Caffeine metabolism began to return to the control values one month after transplantation. One year and 6 years after liver transplantation, quantitatively, the metabolism of caffeine was stable and not different from control, but with qualitative modifications. CYP1A2 activity was decreased with reduced urinary elimination rates of 1X and 17X. XO and CYP2A6 activities and 1U and 17U urinary elimination rates were increased. Immunosuppressive treatment was possibly responsible for the metabolic pathway changes. Almost the same modifications were observed in 9 patients after bone marrow transplantation who had been treated with the same immunosuppressive drugs, cyclosporine and azathioprine. During severe rejection phases in 6 of the liver transplant patients, caffeine metabolism was progressively decreased when the usual liver function tests showed moderate but uniform changes. CONCLUSION: Despite an apparent normal drug-metabolic function, immunosuppressive treatment induces stable variations in drugmetabolic pathways after liver transplantation which can be detected from the changes in caffeine metabolism.

A twenty-year history of alveolar echinococcosis: analysis of a series of 117 patients from eastern France.

OBJECTIVES: Alveolar echinococcosis of the liver is a very rare and severe parasitic disease due to the growth of the larva of Echinococcus multilocularis. The aim of this paper was to describe a 20-year study of the epidemiological, clinical and therapeutic aspects of alveolar echinococcosis in eastern France. DESIGN: One hundred and seventeen consecutive cases, diagnosed and followed in our liver unit, were studied from 1972 to 1993. METHODS: Data from 85 patients followed since 1983 (period B) were compared to data from a first series of 32 patients (period A) collected from 1972 to 1982; 1983 was chosen as the cut-off year because of the numerous changes that occurred in the diagnosis, follow-up and treatment of the disease at this time, in particular the introduction of parasitostatic benzimidazoles. RESULTS: The results of patient follow-up were evaluated in December 1997. The cumulative prevalence was 2.5 per 100,000 persons in period A whereas it reached 6.6 per 100,000 in period B. The annual incidence in period B was 7.3 on average, compared with 2.7 in period A. Twenty-nine per cent of patients from period B were asymptomatic at the time of diagnosis compared with 10% in period A. This change was correlated with less advanced liver lesions, and was related to the extensive use of abdominal ultrasound, and from 1987, serological screening. Curative resections were performed in 24% of the cases in period B versus only 3% in period A. From 1986, liver transplantations were performed in eight patients from period A and 13 patients from period B. In period B, palliative surgery was frequently replaced by radiological non-operative procedures to treat abscesses and jaundice. From 1982, 73 patients received benzimidazoles for a period of time ranging from 4 to 138 months. Stabilization of the lesions was observed in two-thirds of the patients. Episodes of jaundice or digestive haemorrhage due to portal hypertension were 31.5 and 11 times less frequent respectively in patients from period B compared with period A. Actuarial survival at 5 years improved from 67% in period A to 88% in period B in patients of similar age. CONCLUSIONS: Radical changes in the diagnosis and the management of alveolar echinococcosis have occurred during the last decade. Together they have contributed to an improvement in the status of the patients affected by this very severe parasitic disease.

Primary disease recurrence after liver transplantation for alveolar echinococcosis: long-term evaluation in 15 patients.

Between 1986 and 1991, 21 patients received liver grafts in our center for incurable alveolar echinococcosis (AE). The aim of this study was to analyze the long-term results in 15 of these 21 patients who survived more than 1 year after undergoing a liver transplantation (LT). The follow-up, mainly aimed at the diagnosis of recurrence, consisted of repeated radiological and specific immunological investigations. The role of pre- and post-LT benzimidazole (BZM) therapy was also evaluated. Among the 15 patients, 8 patients had a palliative LT related to previously known pulmonary AE metastases and/or inextirpable abdominal parasitic foci. In the 7 remaining patients, LT was considered curative. In June 1998, the mean follow-up duration was 96 months (range: 28-138 months). Five late deaths occurred, 2 of them were directly related to residual AE. A reinfection of the graft was observed in 4 patients. Preoperative BZM therapy seemed useful in preventing or delaying the parasitic recurrence. Post-LT BZM was able to stabilize and even to reduce residual AE. The anti-Em2 enzyme-linked immunosorbent assay (ELISA), which is the standard test used in patient follow-up after partial liver resection for AE, did not appear useful in detecting recurrence here; however, an ELISA, using a crude heterologous antigen (Echinococcus granulosus) allowed early diagnosis of residual AE. In conclusion, primary disease recurrence is not rare after LT for AE. Immunosuppressive therapy may favor larval growth in extrahepatic sites; therefore, an extensive extrahepatic radiological check-up has to be performed before LT. BZM therapy seems to stabilize residual foci. Anti-Eg immunoglobulin G (IgG) follow-up is the most useful test for early diagnosis of parasite recurrence.

[Elastic band ligation in secondary prevention of esophageal varices hemorrhage]. / Elastická ligácia pri sekundárnej prevencii krvácania z pazerákových varixov.

BACKGROUND: Sclerotization of esophageal varices may result in serious esophageal destruction. Elastic band ligation of esophageal varices is recently used in similar indications. AIM: The aim of the study was to evaluate in a pilot study the efficacy and safety of elastic band ligation for secondary prevention of bleeding from esophageal varices in patients who experienced life-threatening and were not yet treated with elastic band ligation. PATIENTS AND METHODS: Saeed's method of elastic band ligation was used in 10 patients (5 men and 5 women) aged from 16-60, who had already experienced life-threatening esophageal varices hemorrhage. One patient awaiting liver transplantation underwent preventive ligation. RESULTS: Esophageal varices were eradicated in 5 patients, minimum range residual varices remained in 4 patients after ligation. Haemorrhage recurrence was observed in 4 patients and was successfully treated by single urgent sclerotization. Two patients developed neo-varices. The ligation program was stopped in one female patient with mitral stenosis and tricuspidal insufficiency because of stenocardias occurring during ligation. In one session, 4.5 elastic bands in average were applied. The treatment of one patient required 4 sessions during 2.5 months in average. CONCLUSION: Elasic band ligation is an effective and safe method for the treatment of esophageal varices. Short term results are promising. (Tab. 1, Fig. 1, Ref. 18.)

[Acute cytolytic hepatitis caused by coumarin. 2 cases]. / Hépatite aiguë cytolytique à la coumarine. Deux cas.

Coumarin is a drug which is extensively used to treat lymphedema. We report two cases of acute hepatitis probably due to coumarin. Two women, 40 year and 45 year-old, were treated with 90 mg/d of coumarin for 5 months. Clinical features included jaundice, pruritus, and diarrhea. A marked increase in serum aminotransferases was observed (ALT: 30 and 100 times the upper limit of normal, respectively). Coumarin withdrawal was rapidly followed by a favorable outcome in both cases. Rechallenge in one case induced a relapse of symptoms and liver test abnormalities. Coumarin can induce acute cytolytic hepatitis.

[Imaging of the transplanted liver]. / Zobrazenie transplantovanej pecene.

The study brings about the newest information on possibilities of imaging the liver, its vessels, biliary ducts and further organs in coincidence with liver transplantation. (Fig. 7, Ref. 39.)

[Indications and contraindications for liver transplantation]. / Indikácie a kontraindikácie transplantácie pecene.

Liver transplantation (LT) is a therapeutic method in many, otherwise infaust diseases of the liver. During the recent decade the experimental therapeutic procedure has become a routine therapeutical method. The stage of clinical experiment was ultimated by the Washington Conference held on the consensus in LT indications (1983). Large centries (USA, England, Germany) yield 80-100 liver transplantations per year. The recent years have recorded a change in some principal opinions on LT. It is possible to state that liver transplantation is being abstained from cases with more extensive primary neoplamatic affliction of the liver. Conservative therapy in primary biliary cirrhosis of the liver by means of ursodeoxycholic acid has shifted the LT indication into the later stages of the disease. The opinions on the meaning of LT in alcoholic cirrhosis remain still unsettled. LT remains unambiquously indicated in life-endangering fulminant and subfulminant liver failures. Among the viral diseases, attention is paid to liver cirrhosis caused by infection by the hepatitis C virus. Cirrhosis due to hepatitis B has a better prognosis, owing to the complex antiviral therapy. Liver transplantation represents, beside the main indications, the therapy of first selection, e.g. also in Wilson's disease, alpha-1-antitrypsin deficiency, alveolar echinococcosis etc. (Tab. 1, Fig. 2, Ref. 54.)

[Cost-effectiveness analysis of the treatment of chronic hepatitis C]. / Analyse coût-efficacité du traitement de l'hépatite chronique C.

OBJECTIVES: Chronic active hepatitis C is an important public health issue because of its prevalence, evolution, and overall cost. Treatment by recombinant alpha-interferon is both expensive and exacting and its effectiveness is limited. We report the results of a cost-effectiveness analysis of alpha-interferon treatment in patients with chronic active hepatitis C. METHODS: Direct medical costs of caring for patients with chronic active hepatitis C and its complications, based on treatment or no treatment, were assessed with retrospective data collected from the files of 137 hospital patients. Seventy-seven patients were treated with alpha-interferon between 1988 and 1994. The overall costs of caring for chronic active hepatitis C patients, without treatment or with alpha-interferon treatment (3 millions units three times a week) for 6 months (strategy A), 12 months (strategy B), or 12 months but discontinuing treatment when there was no response (strategy C), was reported and compared to the respective effectiveness of each. RESULTS: With an actualization rate of 5%, the real overall cost of caring for a chronic active hepatitis C patient was 143290 FF. Considering the contraindication rate (15%), the treatment acceptance (85%), the response rate to treatment (50%), and the prolonged response rate (25 to 30%), treating patients with strategy A induced a real overall cost of caring to 140731 FF to avoid 0.11 cases of cirrhosis, to 150277 FF to avoid 0.13 cases of cirrhosis with strategy B, and to 136947 FF to avoid 0.13 cases of cirrhosis with strategy C. CONCLUSION: Alpha-interferon treatment in patients with chronic active hepatitis C provides a long-term saving compared to cases which receive no treatment. Strategy C was the most cost-effective, inducing the reduction of both the number of cases of cirrhosis and the cost of care.

[Treatment of viral hepatitis]. / Liecba vírusových hepatitíd.

Chronic forms of viral B,C and D hepatitis and fulminant hepatitis represent a serious healthcare problem. The study deals with the changes in the strategy in treating these diseases. During the chronic active hepatitis caused by the B hepatitis virus, the main aim of treatment is to cease multiplication of viruses, eliminate the clinical symptoms, prevent the development of cirrhosis, or the origin of hepatocellular carcinoma. The authors analyze the possibilities of the application of corticosteroids, viricidal drugs (vidarabin and interferons) and other medicaments (acyclovir, zidovudin, duramin, gancyclovir, chinacrin, and others) besides corticosteroids, interleukin 2 and tymozin from the group of immunomodulators were tested. The testing included the factor stimulating the colonies of granulocytes and myeloblasts and other substances. The therapy of acute protracted B hepatitis by means of interferon still requires controlled studies. Superinfection by D virus in chronic carriers of HBsAG causes chronic hepatitis which quickly leads to the development of cirrhosis. The therapy on basis of alpha interferon decreases the RNA virus D hepatitis serum level and leads to an improvement in the development of chronic hepatitis in half of the patients. Therapy of chronic C hepatitis on basis of corticosteroids is ineffective, and can be dangerous. Acyclovir is proved to be ineffective as well. The open study indicated certain positive results in application of interferon. The fulminant hepatitis can be defined as a development of encephalopathy and a decrease of the prothrombin time to less than 50% in the course of acute hepatitis. The break-point in the therapy of fulminant hepatitis took place in association with the performance of the transplantation of the liver. Impossibility to transplant the liver means that the effect of therapy of fulminant hepatitis is merely of supportive value. Majority of patients die due to neurologic complications, namely unmanageable oedema of the brain. But still, neither the antioedema therapy, e.g. on basis of manitol, as well as by means of corticosteroids, hemodialysis, hemofiltration, plasmapheresis and hemoperfusion, nor the treatment on basis of E1 prostaglandine improved the survival of patients. (Tab. 2, Ref. 82).

[Regeneration of transplanted human liver: gene expression at the time of graft implantation]. / Régénération du foie humain transplanté: expression génique au moment de l'implantation du greffon.

The liver tissue mRNA expression of protooncogenes c-fos, c-myc, c-Ha-ras, c-met and c-erb B1, and TGF alpha and TGF beta genes is sequentially and temporarily increased in the early stages after partial hepatectomy, ischaemia or other mitogenic stimuli. These gene expressions were studied in 38 samples of liver tissue from 24 patients who underwent orthotopic liver transplantation, at different evolution stages. Eleven samples were obtained from surgical liver biopsies before graft implantation at day 0 (Group A), 14 samples from percutaneous liver biopsies during the post-operative period from day 9 to day 48 (Group B) and 13 samples in the long-term follow-up period from day 102 to day 1,382 (Group C). Gene expression was studied using 32P-labeled cDNA and oligonucleotidic probe hybridization in slot blots. A GAPD gene was used as a control gene. All expression values of protooncogenes were related to those of the GAPD gene. After cold ischaema, the relative gene expression (quantity of specific mRNA/quantity of GAPD mRNA ratio) tended to diminish in most cases. The relative expressions of c-fos, c-myc, c-Ha-ras, c-met and TGF alpha gene were correlated at day 0. During and after the liver transplantation, an overexpression of c-fos, c-myc, c-Ha-ras, c-met and TGF alpha was observed in different pathological conditions such as cold ischaemia and conservation injury, acute rejection, and cytomegalovirus infection. In three cases the relative expression values of c-fos, c-myc and c-Ha-ras increased over long-term follow-up without any associated acute pathology. These results suggest the necessity of an intercellular mediation--by means of graft reperfusion--in induction of hepatocyte proliferation and regeneration of the transplanted liver.

[The clinical picture and development of aortic aneurysms in older persons]. / Klinický obraz a prubeh aneurysmat aorty u osob vyssího veku.

The authors discuss 11 patients with aortal aneurysms (AA) which they diagnosed in the course of 1983-1988. In seven instances the abdominal aorta was affected; once the ascending part and once the arch; twice the descending part and once the whole aorta. In four patients the aneurysm had a dissecting character. Patients of advanced age were involved (73.9 +/- 9.7 years) with multiple morbidity and frequently also general advanced atherosclerosis which was the main cause of development of aneurysms. The authors analyze the clinical picture and course of AA in different patients and draw attention to their great variability. In the discussion they deal with the position of diagnostic methods, analyze critically the causes, course and prognosis of AA incl. interpretation of their own group of patients. In view of the frequent (and rising) incidence of AA in old age, the authors consider it important to pay attention to this problem also from the aspect of clinical gerontology.

[Ultrasonography of echinococcosis, toxocariasis and cysticercosis of the liver]. / Ultrasonografia echinokokózy, toxokarózy a cysticerkózy pecene.

The diagnosis of tissue parasitoses has remained complicated until the present time for variability of clinical picture. Their incidence been increasing due to aimed and accidental findings of foci in parenchymal organs employing new methods of visualization such as computer tomography and especially ultrasonography whose advantage is a good detection rate, availability and a possibility to follow the dynamics of parasitosis development. The authors present a survey of ultra-sonographic findings of the liver in cases of tissue parasitoses occurring in Czechoslovakia, while using their own image documentation. If a focal affection in the liver is established the differential diagnosis considerations should also take into account a tissue parasitosis, whose ultrasound picture may be nonspecific.