[Are there therapeutic approaches of non-alcoholic fatty liver disease and its complications?]. / Gibt es Therapieansätze für die nicht-alkoholische Fettleber und ihre Komplikationen?

As little as 10 years ago, there was scepticism as to weather non-alcoholic fatty liver disease is a clinical condition. With the increasing prevalence of obesity, diabetes mellitus and the metabolic syndrome in the general population, non-alcoholic fatty liver disease has become a household diagnosis in clinical practice of several medical specialities. Meanwhile, it is the primary cause for elevated liver enzymes of unknown cause in clinical practice. Treatment is focused on the improvement of insulin resistance and of antioxidative mechanisms, mainly by life-style modifications including weight loss and exercise. Drug therapy cannot be recommended at this time, because studies showing positive effects on morbidity and mortality are still lacking. In addition, issues concerning long term safety and side effects of drugs still have to be resolved.

[Ascites]. / Aszites.

Ascites means accumulation of fluid within the peritoneal cavity, usually in patients with cirrhosis. Diagnostic paracentesis (cell count, albumin, cell culture) is a must. Na-restriction remains the cornerstone of treatment (< 3 g NaCl/d). Spironolactone is the drug of choice, in some patients in addition with proximally acting diuretics. Minimum effective dosage is recommented to reduce side-effects. Pronounced ascites can be treated by large-volume paracentesis with concomitant albumin-infusion. Only very few patients suffer from refractory ascites. TIPS is a treatment modality for this group. However, TIPS may precipitate PSE in some patients with decompensated liver cirrhosis.

[Non-alcoholic steatohepatitis--a new epidemic]. / Die nicht-alkoholische Steato- hepatitis--eine neue Epidemie.

Non-alcoholic steatohepatitis (NASH), the metabolic syndrome of the liver, characterised by the consequences of obesity (insulin resistance, production of free radicals, chronic inflammation) has become a new epidemic in the United States as in Europe. Diagnosis is suspected in patients with obesity, denying alcohol abuse, having typical co-morbitities (Hypertension, Diabetes mellitus, Hyperlipidemia). Liver histology confirms the diagnosis of NASH. Fatty liver without inflammation bears a good prognosis. Liver fibrosis, however, in NASH patients signalizes progression to liver cirrhosis and even HCC. Treatment modalities are limited. Reduction of body weight, physical activity, treatment of co-morbitities, specially Hypertension and Diabetes are of paramount importance. At the moment it remains unclear whether glitazone treatment could be introduced in the therapeutic armentarium.

[Diverticulosis--diverticulitis]. / Divertikulose--Divertikulitis.

Diverticular disease is a common disorder in the western world. The course of the illness is benign: At least 75% of all patients with diverticular disease remain asymptomatic life long. 10-20% develop clinical symptoms, usually painful diverticulitis. Diverticular disease is diagnosed clinically in most cases. Computed tomography (CT) has replaced contrast enema as the diagnostic procedure of choice for acute diverticulitis. Most patients with uncomplicated diverticulitis can be treated as outpatients Bowel rest, intravenous fluid therapy, broad spectrum antibiotics are treatment modelities if a patient has been hospitalized. Close follow-up is mandatory, especially in patients treated as outpatients. Failure to improve with conservative medical therapy warrants a diligent search for complications and surgical consultation. Surgery may be nessasary in a few of hospitalized patients. Commonly, the operation is performed in a single-stage procedure. Once the acute setting has passed, a colonoscopy should be electively performed to exclude competing diagnoses particularly colonic cancer.

[Non-alcoholic liver disease (NASH)]. / Nicht-alkoholische Fettleberhepatitis (NASH).

NASH, an increasingly recognized condition resembles alcohol-induced liver disease, but occurs in patients who do not abuse alcohol. Obesity, insulin resistance and oxidative stress have critical roles in the pathogenesis of NASH. Liver biopsy remains the only modality that can reliably distinguish steatosis from steatohepatitis. Simple steatosis may have the best prognosis. In patients with NASH liver enzymes are insensitive and can not be used reliably to confirm the diagnosis or stage the extent of fibrosis. Currently no effective medical therapy is available. Weight reduction may improve the disease. Liver-transplantation in end-stage liver disease is a potential therapeutic option also in patients with NASH.

[Risk-classification in liver cirrhosis]. / Risikoklassifikationen bei Leberzirrhose.

Prognostic models are useful in estimating disease severity and survivial and are used to make decisions regarding specific medical interventions. These models are developed using analytical methods that involve determining the effects of variables of interest (eg, laboratory values) on specific outcomes such as death. There are two models that are used commonly in the care of patients witch chronic liver disease: the Child-Pugh score and the recently described Model for End-Stage Liver Disease (MELD). MELD score is a prospectively developed and validated chronic liver disease severity scoring system that uses a patient's laboratory values for serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time (INR) to predict survival. The score was proposed as a the most promising alternative to Child-Pugh score. Weather Child-Pugh score should definitely be abandoned for MELD score remains uncertain. The aims of this paper are to summarize and to compare the characteristics, applications and limitations of Child-Pugh and MELD scores.

[Drug therapy in chronic liver disease]. / Medikamentöse Therapie in der Hepatologie.

Treatment of virally induced chronic hepatitis consists of interferons, nucleotide and nucleoside analogues. So far, combination therapies are not superior to a monotherapeutic regimen. If detected early, inherited metabolic diseases (e.g. hereditary hemochromatosis, M. Wilson) can be successefuly treated, leading to a normal life expectancy of the patients. In contrary treatment of cholestatic chronic liver disease, especially of PSC, is far from being satisfying, due to our very limited knowledge of the etiology of this diseases. The same holds true for the therapy of NASH. Weight reduction and treatment of the often underlying diabetes are therapeutic cornerstones in the moment. On the other hand, immuosuppression, some times life-long, remains a (highly successful) treatment option in cases of proven autoimmune-hepatitis.

[The patient with slightly increased liver function tests]. / Der Patient mit gering erhöhten Leberwerten.

The availability of serum blood chemistries for screening both symptomatic and asymptomatic patients has resulted in a marked increase in the number of abnormal liver chemistry tests that must be interpreted by physicians. Usually the first step in the evaluation of a patient with elevated liver enzymes is to repeat the test to confirm the result. If the result is still abnormal, it seems wise to differentiate between a predominant "necrotic pattern" of liver chemistry, as indicated by an elevation of ALT- or AST-activity or a predominant "cholestatic pattern", as indicated by elevated activities of g-GT and alkaline phosphatase. In patients with elevated serum amino transferases hepatic diseases should be excluded primarily with non-invasive serologic tests. The most common causes of elevated amino transferase levels are chronic hepatitis B and C, autoimmunhepatitis, non-alcoholic steatohepatitis, hemochromatosis, Wilson-disease and (only recently recognized) celiac sprue. In the case of a dominant "cholestatic pattern", primary biliary cirrhosis, primary sclerosing cholangitis, but also drugs and granulomatose hepatitis must be excluded. If non-invasive serologic studies remain inconclusive, ultrasound, mini-laparoscopy and liver biopsy will help to establish the final diagnoses.

[Hepatitis: associated diseases. Risk groups -- prevention -- treatment]. / Hepatitis--Hepatitisfolgen. Risikogruppen--Prävention--Therapie.

Active vaccination against HBV-infection results in a very high protection rate. Therefore, all persons at risk should be vaccinated. Acute HBV-infection seems to progress to chronicity in a minority of adults. Unfortunately, treatment of chronic HBV-infection with interferon and Lamivudine is effective only in about 40% of patients, leading to a complete virus elimination. However, relapse-rates are high. Additionally, mutant viruses arise in the case of Lamivudine treatment (YMDD-mutants). Interestingly, Adefovir, a new nucleoside analogue, seems not to induce virus-mutants, at least after a therapy of 48 weeks. HBV-DNA declines rapidly, transaminases normalize in more than 2/3 of the patients, liver histology improves. As mentioned, active vaccination against HBV is very effective in preventing the infection. Unfortunately, this is not the case in HCV-infection. So far, the development of an HCV-vaccine is mainly hampered due to the variability of the HCV (RNA) virus. Untreated, more than 2/3 of the HCV-infected patients with acute HCV-positive hepatitis develop chronicity. Chronic hepatitis C can be treated preferably with a combination therapy (pegylated interferons + Ribavirin). Sustained response rates average 50 per cent (and more). However, treatment of non-responders as well as the treatment of relapsers remain an unresolved problem.

[Phenprocoumon-induced liver failure]. / Phenprocoumon-induziertes Leberversagen.

HISTORY: A 61-year-old woman was referred because of painless jaundice, laboratory tests having indicated hepatitis with impaired liver functions. For the past two years she had been taking phenprocoumon because she had atrial fibrillation. INVESTIGATIONS: Serological tests largely excluded infectious, autoimmune or metabolic etiology, so that the diagnosis of drug-induced hepatic disease was made. Liver biopsy showed necrotic liver cells and mild inflammatory reaction. TREATMENT AND COURSE: A perforating duodenal ulcer required urgent surgical intervention, after which liver functions further deteriorated. The patient having refused liver transplantation she was treated symptomatically (oral vitamin K. lactulose, diuretics), phenprocoumon was discontinued and her condition slowly improved. She was discharged after two months. At subsequent examination she was symptom-free, the INR was 1.41, transaminases were normal and ultrasound merely showed a slightly inhomogeneous internal structure. CONCLUSION: Phenprocoumon can cause liver damage even when the drug has been taken for prolonged periods without any problems. A careful history about previously administered drugs should be taken in any case of hepatitis of uncertain etiology.

[Pantoprazole-induced hepatitis]. / Pantoprazol-induzierte Hepatitis.

HISTORY: A 46-year-old woman presented for an emergency admission because of colic-like upper abdominal pain and markedly impaired general condition. Eight days before admission she had started and continued to take pantoprazole because of symptoms of gastroesophageal reflux. INVESTIGATIONS: Clinical examination and laboratory tests indicated abnormal liver functions suggesting hepatitis. Serology largely excluded an infectious, autoimmunological or metabolic cause. Duplex sonography gave no evidence of bile obstruction or Budd-Chiari syndrome. DIAGNOSIS AND COURSE: The patient's condition and laboratory tests after the drug had been discontinued gradually improved on symptomatic treatment, indicating pantoprazole-induced hepatitis. CONCLUSION: Intake of proton pump inhibitors is a rare cause but should be considered in the differential diagnosis of hepatitis of uncertain etiology.