[Dihydralazine hepatitis. Morphologic and clinical criteria for diagnosis]. / Die Dihydralazin-Hepatitis. Morphologische und klinische Kriterien für die Diagnose.

70 cases of acute dihydralazine-associated hepatitis with centrolobular or confluent necroses, registered in the files of the Berlin-Friedrichshain Institute of Pathology, between 1981 and 1985, were classified into 3 types of diagnostic probability for differential diagnosis versus virus hepatitis. Classification was conducted according to recommendations given by a working group of pathologists, specialised in liver pathology. 42 cases out of this material had come from Prenzlauer-Berg Hospital, Department of Infectious Diseases, and were re-examined under clinical aspects. 6 of them were discarded from evaluation. Type I proved to be of high diagnostic reliability, as was seen from 61% of all cases. Only 3 cases had to be discarded from that group and were associated with other drugs, such as halothane, methyldopa, and propranolol. The following clinical parameters proved to be of particular value for definite assessment of drug-induced hepatitis: time of exposure (for analysis of co-medication), time of recovery, and re-exposure test. Only circumstantial evidence so far can be provided for all histological types to causative relationship between drug ingestion and hepatitis. Compliance with mandatory notification should be ensured in all cases, since suspicious cases are explicitly included. Higher sex-related disposition of women to drug-induced hepatitis was confirmed in our material, with the female-to-male ratio being 3:1.

[Liver parenchyma damage in immunosuppressed patients: diagnostic differentiation]. / Leberparenchymschäden immunsupprimierter Patienten: Diagnostische Differenzierung.

Liver abnormalities are common complications in patients with immunosuppressed state iatrogenic or infectious induced. They are caused by infections due to hepatotropic viruses or by other infectious complications, drug induced or caused by rejections in patients after transplantation. Hepatic neoplasms have been associated with liver abnormalities, too. Problems in evaluation of liver abnormalities in these patients are discussed.

[Drug-induced liver damage from the morphologic viewpoint]. / Medikamentöse Leberschäden aus morphologischer Sicht.

An overview about drug-induced liver injury is presented. The most frequent changes of the hepatocytes are those of the organelles, which are adaptive at the beginning, but in later stages they can develop to degenerative alterations leading to necrosis. Cases of drug-induced hepatitis simulating all types of non-suppurative hepatitis are a major problem of diagnosis. Bile duct lesions can include pure cholestasis, cholangiolitis and destruction of intrahepatic ducts. Drug-induced vascular lesions including tumours can be found as isolated phenomenon or in association with other signs of drug-induced liver damage. Hyperplasia (focal or diffuse) and neoplasia of the liver can develop in the course of a longstanding application of some drugs.

[Liver changes caused by drugs--a challenge for puncture biopsy pathology]. / Leberveränderungen durch Arzneimittel--eine Herausforderung für die Punktatmorphologie.

Drug-induced liver lesions are on a steadily rising trend and raise diagnostic problem which make for a challenge to liver biopsy interpretation. History, nomenclature, and present status of this branch of hepatology are briefly discussed. The main part is devoted to problems of histological diagnosis and typing of virus hepatitis, such as drug-induced hepatitis, the clinical data necessary for judgement of these cases and the two types of drug-related idiosyncrasy so far known.

[The nomenclature and typing of drug-induced liver changes. The opinion of a group of pathologists]. / Zur Nomenklatur und Typisierung arzneimittelbedingter Leberveränderungen. Stellungnahme einer Arbeitsgruppe von Pathologen.

A working group of histopathologists with specialised liver training has established guidelines for a nomenclature of drug-induced liver lesions. It is recommended to use the term of drug-induced hepatitis for all cases of virus hepatitis-like picture. The most frequent type is that of hepatitis with confluent necrosis. This type of hepatitis was subdivided into three subtypes of diagnostic probability for differential diagnosis versus virus hepatitis.

[Chronic drug-induced hepatitis caused by dihydralazine]. / Chronische Arzneimittelhepatitis durch Dihydralazin. Bericht über 2 Fälle.

Two cases are described, which revealed the picture of a dihydralazine-induced chronic aggressive hepatitis bioptically. One case was laparotomized under the clinical diagnosis of obstruction jaundice, the other exhibited no symptoms and was detected by elevated transaminases only. The time of exposure was 2-3 years. After withdrawal of dihydralazine the patients recovered within 2-3 months. Elevated transaminases (more than 1 mumol) should given occasion for withdrawing the drug or for performing of liver biopsy. In a total of 6,581 liver biopsies within five years an acute dihydralazine-hepatitis was seen more frequent than a chronic one (ratio 77:2).

[Bone marrow aplasia: a rare complication in virus-induced hepatitis]. / Knochenmarkaplasie: seltene Komplikation virusbedingter Hepatiden.

Bone marrow aplasia associated with acute viral hepatitis is a rare, in the rule late complication. A prognostic relation between the latency of acute hepatitis and the development of aplastic anemia is described. We report a case of nearly symptomless hepatitis in a 25 year old women with a fatal course of aplastic anemia. First clinical symptoms were caused by aplastic anemia. The pathogenesis of aplastic anemia associated to viral hepatitis is obscure. Genetic and immunological causes are discussed. A direct viral action is possible. Because the main part of the described cases is caused by non-A, non-B hepatitis, it seems apparent that at least a non-A, non-B virus strain could have an affinity to bone marrow cells. Ensuring this, relations will be impossible up to the identification of the virus.

[Effects of oral contraceptives on liver function and structure]. / Auswirkungen oraler Kontrazeptiva auf Leberfunktion und -struktur.

PIP: This is a broad review (140 literature citations) of the possible effects of oral contraceptives on the liver. The oral contraceptives considered consist of combined preparations of estrogens and progestogens although the so-called "minipills" contain only a progestogen. The effects are divided into 1) decrease in excretory liver function; 2) influence on bile acid formation, including cholesterol metabolism; 3) increased synthesis of various transport proteins (ceruloplasmin, transferrin, thyroxine-binding protein, and cortisol-binding protein); 4) the effects of increased tissue circulation caused by sexual hormones and anabolic steroids as a cause for more frequent cavernous angiomas and peliosis hepatis; 5) interference with the metabolism of other drugs by the competitive action of the hepatic metabolites of steroid hormones. This includes the increased formation of delta amino levulinic-acid synthetase, the key enzyme for porphyrin synthesis. The gestagen component of oral contraceptives is responsible for enzyme induction in the smooth endoplasmic reticulum. Morphological liver changes caused by oral contraceptives include parenchyma changes, hepatosis, reactive hepatitis, hepatitis resembling viral hepatitis, vascular changes, sinusoid ectasia, Budd-Chiari syndrome, hyperplasias and neoplasias, focal nodular hyperplasia, adenoma and liver cell carcinoma.^ieng

[Delta virus superinfection in a patient with chronic viral hepatitis B]. / Delta-Virus-Superinfektion bei einem Patienten mit chronischer Virushepatitis B.

Hepatitis-Delta virus is a defective RNA virus enclosing the Delta antigen and genome within a coat of hepatitis B surface antigen (HBsAg). Prevalence of Delta virus is limited to individuals with hepatitis B infection. Two modes of infection have been identified: coinfection with hepatitis virus B of healthy individuals and superinfection of HBsAg carriers. In a prospective study of 485 liver biopsies from HBsAg seropositive patients, 320 non-replicative HBsAg carriers (without evidence of core antigen) were discovered. In only one of these cases could a Delta virus superinfection be confirmed by immunohistology. It caused a shift from a preexisting chronic persistent to a chronic active hepatitis. This is the first case of chronic Delta virus infection confirmed by immunhistology in the G.D.R.

[Patho-histological liver diagnostics-yesterday and today]. / Pathoihistologische Leberdiagnostik--gestern und heute.

The development of the so-called one second liver biopsy method of Menghini in 1957 resulted in rapid progress in the field of liver pathology. Indeed a new sub-discipline of pathology was created based on the interpretation of needle biopsy findings. In order to achieve the current high level of diagnostic and prognostic accuracy it was necessary to provide special histopathological training and to emphasize clinical-pathologic cooperation. The full potential of this technique has not yet been universally realized.

[Morphology of alcoholic liver damage]. / Morphologie des alkoholinduzierten Leberschadens.

As a result of the ability to examine successive biopsy specimens, the process of progression of liver damage resulting from ethanol abuse is well appreciated. The ten most important tissue and cellular changes are described in the present paper. The staging system promulgated by the author since 1977 is reviewed: 1) Alcohol-induced liver damage without fibrosis, 2) Alcoholic hepatopathy with fibrosis, 3) Alcoholic hepatopathy with cirrhosis. Staging by this system provides clinically valuable prognostic information. Women with stage 1 changes have a two to threefold liklihood of advancing to stage 3 than do men with the same degree of initial damage.

[Detection of alcohol abuse and monitoring of alcoholic abstinence using sideroblastic index and gamma-glutamyltransferase]. / Erfassung von Alkoholmissbrauch und Monitoring der Alkoholabstinenz mittels Sideroblastenindex und Gamma-Glutamyltransferase.

45 hospitalised patients with chronic alcohol abuse observed immediately until that time preceding hospitalisation were examined with the aim of finding out whether examinations of the bone-marrow and gamma-glutamyltransferase (GGT) i.s. may be used for recording the consumption of alcohol and for monitoring the abstinence from alcohol. Bone-marrow puncture was made within 3 days after hospitalisation and was repeated at n = 35 after two weeks on an average. Simultaneously, GGT was determined. Disturbances of iron utilization, which were divided according to frequency and kind of sideroblasts into 4 degrees of seriousness, represented by far the most constant hematological findings. An sideroblastic+ index (SI) was counted, which, in addition to the count of sideroblasts, takes into account even qualitative disturbances. The sideroblastic+ index was increased in 91% (41/45) of patients irrespective of the presence or extent of an anemia so far as iron stores had not been completely depleted because of bleedings. In 71% (32/45) of the patients, gamma-glutamyltransferase (GGT) remained within the pathological range, thus lying significantly (p less than 0.05) below the sensitivity of the sideroblastic index (SI). By taking the increase of SI or GGT as a basis, the rate of recording alcoholics could be improved to 98% (44/45). Abstaining from alcohol caused a highly significant decrease of SI and GGT (p less than 0.005). Thereby, the sideroblasts index predominantly normalised in the period of examination, whereas gamma-glutamyltransferase fell below the pathological range only by way of exception. No significant decrease in the control value of SI and GGT was observed in those patients who did not abstain from alcohol. In comparing the differences of average values between abstaining and non-abstaining persons only SI revealed significant differences (p less than 0.005). SI and GGT complement each other in the control function of drinking behaviour. Under the given circumstances a simultaneous examination enables alcohol abuse to be recorded with nearly 100% of probability. SI is more sensitive and is able to differentiate more clearly between abstaining and non-abstaining. Due to its slower response GGT can indicate former alcohol abuse over a longer period. Concerning doubtful or potentially hepatotoxic+ substances at places of work, the sideroblastic+ index could provide an essential aid in deciding whether alcohol is a disturbing factor.

[Paracetamol poisoning--clinical aspects and pharmacokinetics]. / Parazetamolintoxikation -- Klinik und Pharmakokinetik.

The analgesic and antipyretic effect of paracetamol and phenacetin is to be traced back to the same pharmacologic active substance. When no therapeutic doses are applied, paracetamol causes severe lesions of the liver parenchyma with often fatal termination. It is reported on the paracetamol intoxication of a 38-year-old landlady, in whom as a sequel of the intoxication a severe lesion of the liver parenchyma and an acute toxic renal failure developed. The understanding of the paracetamol-conditioned lesions takes the knowledge of the course of the reaction of its biotransformation for granted. Since the pharmacokinetics underlies numerous influence factors, there is no foreseeable correlation between toxicity and doses. It seems that also in therapy paracetamol does not cause less side-effects than phenacetin. The discussed use of paracetamol instead of phenacetin is, therefore, critically to be considered.

[Causes and types of cholestasis from a biopsy viewpoint]. / Ursachen und Formen der Cholestase aus bioptischer Sicht.

In a total number of 1,400 internal biopsies within a year we found 186 (14%) cases of cholestasis. The most of them were caused by virus hepatitis (93), followed by alcoholic liver injury in all three stages (39) and drug induced cholestasis (19). The special bioptical problems of these diseases were discussed. Most important are adverse reactions to contraceptive, antirheumatic, antihypertensive and antikonvulsive agents.

[Dihydralazine-induced hepatitis with bridging necrosis. A clinico-pathologic survey of 20 cases]. / Hepatitis mit konfluierenden Nekrosen durch Dihydralazin (Depressan). Eine klinisch-pathologische Studie an Hand von 20 Fällen.

A hepatitis with bridging necrosis following dihydralazine therapy has been diagnosed bioptically in 20 cases, preferably in women. The duration of drug intake ranged from 2 weeks to 11 months. A relapse following drug re-exposure occurred in 3 cases, one of them had the fifth relapse within 10 years. Histologic features were centrolobular confluent necrosis with inflammatory infiltration in the adjacent liver parenchyma. The periportal parenchyma showed no or slight alteration. The knowledge of the hepatitis with bridging necrosis is important in order to avoid misdiagnosis as chronic or cirrhotic liver processes. 2 cases had been misdiagnosed as extrahepatic obstruction and were laparotomised. After drug withdrawal the liver damage was reversible and had no tendency to a chronic course even in severe cases.