Pegylated-interferon-associated retinopathy in chronic hepatitis patients.

PURPOSE: To investigate the clinical features of pegylated-interferon (PEG-IFN)-associated retinopathy in chronic hepatitis patients. METHODS: We examined a consecutive case series of 46 patients who were treated with PEG-IFN for chronic hepatitis C or B between October 2007 and September 2008. All patients underwent regular ophthalmologic examinations every 3 weeks during the 6 months after treatment. RESULTS: Ten of the 46 patients (21.73%) developed retinal abnormalities. PEG-IFN-associated retinopathy occurred a mean of 7.25 +/- 10.28 weeks after treatment and manifested itself as cotton wool spots and retinal hemorrhages. All patients, except for 1 with a retinal vein occlusion, recovered without cessation of treatment. CONCLUSIONS: PEG-IFN-associated retinopathy in chronic hepatitis patients was reversible, and patients recovered without visual complications; however, 1 patient did present with an irreversible visual impairment. This type of retinopathy is usually asymptomatic, and clinicians should closely observe patients for 3 months after treatment.

Liver biopsy assessment in chronic hepatitis.

Liver biopsy has been a major diagnostic tool in the evaluation of individuals with chronic hepatitis for many decades and remains the most direct way of visualizing hepatic necroinflammation and fibrosis. In chronic viral hepatitis B and C, immune attack on hepatocytes bearing viral antigens results in the entry of lymphocytes and other effector cells through the portal tracts from which other lesions may evolve, including interface and lobular hepatitis as well as fibrosis or cirrhosis. Classification systems have been developed in order to provide semiquantitative grading of necroinflammation and staging of fibrosis and include the Scheuer, Batts and Ludwig, Ishak, and METAVIR systems. This review provides an historical perspective on histopathological methods of analyzing chronic hepatitis, describes the essential criteria of each of the major scoring systems and discusses problems related to sampling error, observer variation, and specimen size.

Chronic hepatitis. An update on terminology and reporting.

The terms chronic active hepatitis (CAH), chronic persistent hepatitis (CpH), and chronic lobular hepatitis (CLH) have become obsolete, and their use without further specifications should be discontinued. This recommendation has become necessary because these names have changed from descriptive terms, intended for grading, to terms that are used either as morphologic diagnoses or disease designations or both, depending on individual preferences. Because this practice has caused serious misunderstandings, many authors and two international groups have recommended the use of a clear etiologic terminology. For the reporting practice of pathologists, we recommend that the pathologist routinely sign out biopsy samples with features of chronic hepatitis by indicating etiology, grade, and stage. An example would be autoimmune hepatitis, severe, stage 3. The stage in this case would indicate the presence of well-developed septal fibrosis but no nodular regeneration. Obviously, for the etiologic diagnosis, morphologic findings must be integrated with clinical and laboratory data. If this information is not available, clear morphologic diagnoses should be reported. Thus, instead of CPH, the diagnosis should be portal hepatitis, cause undetermined. This reporting practice eliminates ambiguous terminology and avoids the risk of inappropriate treatment as might occur, for example, when a term such as CAH is used to describe Wilson's disease and is misunderstood to mean autoimmune hepatitis. For a transitional period and to facilitate relearning, the terms CAH, CPH, and CLH can be reported in parentheses behind the etiologic diagnosis.

Scoring of chronic hepatitis.

Grading of the severity of chronic hepatitis and staging of its structural consequences are widely used in clinical trials of therapy and in research. Simple and complex methods are available. Intra- and interobserver variation can be reduced but not eliminated, because grading and staging are essentially subjective. The data are categorical rather than numerical and must be treated accordingly. Morphometry of fibrous tissue offers a different approach to biopsy assessment.

Pathologic features of chronic hepatitis. A review and update.

The general histopathologic changes of chronic hepatitis and those related to the various causes are reviewed. Consideration also is given to underlying or associated diseases and to mixed infections in chronic viral hepatitis. Changes occurring in exacerbations or relapses are described. Selected histopathologic changes are illustrated. The nomenclature is reviewed briefly, with emphasis on separation of activity from stage of disease.

Chronic hepatitis C associated with anti-liver/kidney microsome-1 antibody is not a subgroup of autoimmune hepatitis.

To determine whether "autoimmune hepatitis type IIb" should be categorized as a subgroup of autoimmune hepatitis, we conducted a clinicopathological study of 25 adult Japanese patients who were positive for anti-liver/kidney microsome-1 (anti-LKM-1) anti-body and infected with the hepatitis C virus (HCV). Anti-LKM-1 was determined by indirect immunofluorescence and by the double immunodiffusion assays we have developed. Twenty-two patients did not present any unusual symptoms or any associated diseases during the course of their chronic HCV infection. The spectrum of HCV genotypes of these patients did not significantly differ from that of anti-LKM-1-negative Japanese patients with chronic hepatitis C. Histological examination of liver biopsy specimens showed the usual characteristics of chronic hepatitis C and lack of characteristics of autoimmune hepatitis type I. No disease-specific HLA haplotypes were noted, and HLA-DR4, which is detectable in 88.7% of Japanese patients with autoimmune hepatitis type I, was detected in only 50.0% of our group, the same rate as the background frequency. Prednisolone was effective in none of the six patients treated, but interferon was effective in six of ten treated patients (60%). From these results, we conclude that "autoimmune hepatitis type IIb" should not be categorized as autoimmune hepatitis, and that this subgroup is essentially chronic hepatitis C in which an autoantibody has been produced during the course of chronic HCV infection.

Autoimmune diseases of the liver.

A loss of tolerance against autologous liver tissue is regarded as the principal pathogenetic mechanism in autoimmune liver disease. Autoimmune type chronic hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis are the three major autoimmune liver diseases. This article discusses recent advances in the diagnosis and treatment of these diseases. Topics include diagnosis and classification, clinical features and pathology, etiology and pathogenesis, immunogenetics, and therapy.

Chronic hepatitis in the dog--a review.

Chronic hepatitis is a heterogeneous group of inflammatory-necrotizing diseases of the liver. There is controversy in both human and veterinary medicine about the classification of chronic hepatitis and this is likely to remain until a classification based on aetiology rather than on morphology is introduced. Controversy exists as to whether chronic hepatitis in dogs is comparable to the human disorder. The aetiology of chronic hepatitis in dogs is poorly understood, whereas in humans an increasing number of viral causes have been found. Liver biopsy is essential for the diagnosis of chronic hepatitis both in dogs and in humans. Histopathological evaluation of the liver is required to make the diagnosis, which is based on the presence of liver cell necrosis and inflammatory reaction. The proposed criteria for the classification of hepatitis in dogs are then as follows: aetiology is the primary denominator (infectious, drug induced, autoimmune, or, if unknown, idiopathic). The other criteria are histopathological, with severity reflecting the severity of the necro-inflammatory activity (minimal, mild, moderate or severe) and chronicity reflecting the extent of fibrosis (none, mild, moderate, severe or cirrhosis).

Computer image analysis of ultrasound images for discriminating and grading liver parenchyma disease employing a hierarchical decision tree scheme and the multilayer perceptron neural network classifier.

Differential diagnosis of liver parenchyma disease and grading of the hepatic disease on ultrasound is a common radiological problem that influences patient management. The aim of this study was to apply image analysis methods on ultrasound images for discriminating liver cirrhosis from fatty liver infiltration and for grading hepatic disease, which is important in the management of the patients. Ultrasound images of histologically confirmed 18 livers with cirrhosis, 37 livers with fatty infiltration, and 24 normal livers of healthy volunteers were selected and were digitized for further computer processing. Twenty two textural features were calculated from small matrix samples selected from the ultrasound image matrix of the liver parenchyma. These features were used in the design a three level hierarchical decision tree classification scheme, employing the multilayer perceptron neural network classifier at each hierarchical tree level. At the first tree level, classification accuracy for distinguishing normal from abnormal livers was 93.7%, at the second level the accuracy for discriminating cirrhosis from fatty infiltration was 90.9%, and at the third level the accuracy in distinguishing between low and high grading liver cirrhosis or fatty infiltration was 94.1% and 84.9% respectively. The proposed computer software system may be of value to the radiologists in assessing liver parenchyma disease.

[Clinical features of chronic hepatitis]. / Características clínicas de las hepatitis crónicas.

We review the clinical characteristics of the different forms of chronic active hepatitis, the classification and subclassification of the disease. The natural course and prognosis in the chronic active liver disease has been modified by the appearence of new serologic markers and better definition of clinical characteristics. The disease can be silent or asyntomatic. In an autoimmune chronic active hepatitis, the patients have clinical and biochemical features different from other types of chronic hepatitis, autoantibodies specific, and non specific. Early diagnosis by liver biopsy is very important by the risk of cirrhosis. The natural history of the disease has been modified by the use of immunospressive drugs, steroids and recently, antiviral therapy. Long-term prognosis in chronic active hepatitis is poor.

[Possibilities and perspectives of the prevention of viral hepatitis]. / A vírushepatitis megelözésének lehetöségei és perspektívái.

Six district hepatotrop viruses causing viral hepatitis have been identified. Hepatitis A and E viruses are enterically transferred with feco-oral transmission, the others (hepatitis B, C, D and G viruses) produce the infection parenterally with blood, blood products and body fluids. All the hepatitis viruses are able to cause acute hepatitis. Chronic carrier state and chronic hepatitis can develop in case of infections with hepatitis B, C, D, and G viruses. In the prophylaxis the hygienic rules should be applied in all forms of infections. Passive immunisation and active vaccination have been safety developed til now only in hepatitis A and B infections. To prevent the hepatitis C, D, E and G infections the modalities of prophylaxis are in experimental stages.

[Evaluation of the new international classification of chronic hepatitis]. / Otsenka novoi mezhdunarodnoi klassifikatsii khronicheskogo gepatita.

Evaluation of the new international classification of chronic hepatitis recommended by International congress of gastroenterologists in 1994 is given. Positive aspects of the classification cover the necessity of indicating etiological trend, process activity, the disease staging. Some negative points are also mentioned.

[Does alcoholic chronic hepatitis exist?]. / Sushchestvuet li alkogol'nyi khronicheskii gepatit?

Alcoholic chronic hepatitis (ACH) can be considered as an independent nosological entity. This conclusion can be made basing on the literature devoted to the mechanisms of ethanol effects on the liver and clinicomorphological features of hepatic ethanol damage. ACH should be included into the new 1994 International classification of chronic hepatitis. Special attention is paid to a higher incidence of combined liver damage induced by alcohol and hepatotropic viruses, especially by hepatitis C virus. Combined virus-alcoholic liver damage will become, in the author's opinion, one of the most important hepatology problems in the coming millenium.

[Viral hepatitis. Insurance medicine observations]. / Die Virushepatitiden. Versicherungsmedizinische Betrachtungen.

The major cause of liver diseases world-wide are the infectious hepatitis A-E which are due for different viruses. Most of the cases are clinically asymptomatic and without jaundice with a high rate of cure. The diagnosis and the differentiation of the various clinical syndromes are based mainly on serological markers of the involved antigen-antibody-systems. For insurance purposes the chronic hepatitis B, C and D are of great importance. Where chronic persistent hepatitis has a nearly normal life expectancy, chronic active hepatitis which may develop into cirrhosis and/or hepatocellular carcinoma has an increased mortality.

[Problem of chronic hepatitis (classification, pathogenesis and treatment]. / Problema khronicheskogo gepatita (klassifikatsiia, patogenez, lechenie).

Update information is added to classification of chronic hepatitis. A new form--chronic lobular hepatitis is described as well as characteristic features of immune response to hepatitis B virus (HBV). The findings enable the authors not only to relate autoimmune abnormalities to HBV infection, but to consider them an essential component of this infection. The leading role in pathogenesis of viral hepatic lesions is played by cellular immunity. A sound subpopulation analysis of immunocompetent blood cells was carried out for chronic active hepatitis and hepatic cirrhosis in correlation with HBsAg. It is emphasized that a biological cycle of HBV development determines the type and power of the macroorganism immune response and should be allowed for when designing policy of treatment of chronic hepatic viral diseases. Criteria are proposed for deciding on immunomodulators and immunodepressants for chronic viral and autoimmune hepatitis.

[The clinico-immunological characteristics of chronic lobular hepatitis]. / Kliniko-immunologicheskie osobennosti khronicheskogo lobuliarnogo gepatita.

A total of 156 patients with chronic hepatitis were examined, among whom 55 had chronic persistant hepatitis, 42 chronic active and 59 lobular hepatitis. It is for the first time that clinicoimmunologic characteristics of chronic lobular hepatitis are fully detailed. The latter was found to take intermidiate place between chronic persistant and chronic active hepatitis in respect of its clinical picture as well as markedness of biochemical and immunological changes. The value of the R-protein titre determination as a sensitive test in the diagnosis of the hepatocellular inflammation in all clinical types of hepatitis was demonstrated.