Overview of important diseases
- Hepatitis A
- Hepatitis B
- Hepatitis C
- Hepatitis D
- Hepatitis E
- Non-alcoholic steatohepatitis (NASH)
- Autoimmune hepatitis
- Liver tumors
- Diabetes mellitus
Hepatitis A
Hepatitis A virus (HAV) infection occurs worldwide and is usually transmitted fecal-orally. It is estimated that 80 - 90% of the world´s adult population have had an HAV infection. Due to improved hygienic standards, the infection rate in western countries is low. Since HAV can "survive" up to 4 hours on the surface of the skin, washing hands is very important. Severe courses of the disease are rare (0,1%), hepatitis A never becomes a chronic disease. There is no causal therapy, however, a vaccination exists. Two injections at intervals of 6 months cause an immunity for up to 10 years. In addition, a combined vaccination against hepatitis A and B is available.
[ Back to overview ]Hepatitis B
An estimated 350 Millionen people are chronically infected with the hepatitis B virus (HBV). Thus, HBV infection seems to be the most frequent chronic viral infection in the world. About 2 billion people have had an HBV infection. One million people die every year due to HBV induced liver cirrhosis and 320.000 people die due to HBV induced hepatocellular carcinoma (HCC). In Austria an estimated 25.000 - 40.000 (0.3 - 0.5% of the population) are chronically infected with HBV. In our country, the routes of HBV transmission are predominantly sexual, intravenous drug use and piercing or tattooing under unhygienic conditions. In developing countries, perinatal HBV transmission from mother to child plays the most important role. The risk of chronic HBV infection depends on the point of time of infection: with perinatal infection the risk of a chronic course of the disease is 90%. Infection during adulthood is associated with a risk of 5 - 10%.
There are 2 types of medication for the treatment of chronic hepatitis B:
1. Pegylierted interferon-alpha can be administered subcutaneously for a limited period of time and should transform patients from the highly replicative state to the inactive carrier state due to its antiviral and immunmodulatory properties.
2. Nucleoside and nucleotide analouges are administered as pills and selectively supress viral replication without affecting the immune system. Tenofovir or entecavir should be used due to their high antiviral efficiency and their high barrier to resistance.
Hepatitis C
About 170 million people are chronically infected with the hepatitis C virus (HCV). In Austria an estimated 50.000 - 70.000 (0.6 - 0.8% of the population) are chronically infected with HCV. Of the 6 viral genotypes only the genotypes 1 - 4 play a role in our region. Since HCV infection becomes a chronic disease in 50 - 80% and may cause liver cirrhosis after years or decades, chronic HCV infection (CHC) is one of the main causes for liver transplantation. In the seventies and eighties, HCV was mainly transmitted via donation of plasma as well as blood and blood products. Nowadays, the main route of infection is intravenous drug use and piercing or tattooing under unhygienic conditions. In every second patient the route of infection remains unclear. A vaccination against HCV is still unavailable.
Treatment of CHC has changed in the past years. After treatment consisted of pegylated interferon and ribavirin for more than 10 years, the first 2 direct acting antivirals (DAAs) were approved in 2012. These two first generation protease inhibitors increased the cure rates in genotype 1 patients from 40 - 50% to 70%. However, severe adverse events and drug-drug interactions limited their use. Actually, several other DAAs (Sofosbuvir, Ledipasvir, Paritaprevir, Ombitasvir, Dasabuvir) with better tolerance and interaction profile are available. With these drugs, CHC can be cured within 12 weeks in more than 90% of patients without interferon. These promising strategies should give us the possibility to treat patients with advanced liver disease, too, for whom interferon-containing regimens are contraindicated. So, the incidence of severe complications of advanced liver disease, e.g. hepatocellular carcinoma (HCC) or liver failure should decrease.
Hepatitis D
Hepatitis D occurs only in patients who have hepatitis B, since the hepatitis D virus (HDV) requires the envelope of the hepatitis B virus (HBV). Thus, the best prevention of hepatitis D is vaccination against hepatitis B. The routes of HDV infection are parenteral, sexual or perinatal from mother to child. It makes a difference, whether HBV and HDV infection occur at the same time (HBV/HDV coinfection) or HDV infection occurs after HBV infection (HDV superinfection). In the case of a coinfection, chronic courses of hepatitis D are rare compared to superinfection. However, severe courses of the disease are more frequent in cases of coinfections. Each patient with chronic hepatitis B should be checked for HDV anibodies at least once. Treatment of chronic HDV infection is difficult. Interferon-alpha can lead to normalization of liver enzymes in some patients, however, a durable supression of HDV replication is a rare event.
[ Back to overview ]Hepatitis E
Similar to the hepatitis A virus (HAV) the hepatitis E virus (HEV) is transmitted fecal-orally, too. Formerly, it was estimated that HEV is only present in tropical regions and that HEV infection never becomes a chronic disease. Nowadays, we know that HEV is present in our region, too, and that chronic courses of the disease are possible in patients with impairments of the immune system, especially in recipients of organ transplants. Severe courses of HEV infection are rare (0.5%). However, in pregnant women the rate of severe courses of the disease rises up to 25%. Treatment of HEV infection is not necessary in most cases. In patents under immunosuppression and chronic disease ribavirin can be helpful. A vaccination against HEV exists, however, up to date it is only approved in China.
[ Back to overview ]Non-alcoholic steatohepatitis (NASH)
Non-alcoholic fatty liver disease (NAFLD) is present when fat makes up more than 5% of the weight of the liver, daily alcohol consumption is below 20 g and other causes of fatty liver (e.g. chronic viral hepatitis, drugs) are excluded. In western countries NAFLD is the most frequent liver disease and affects 20 - 40% of the population. In non-alcoholic steatohepatitis (NASH) additional inflammation of the liver tissue is present. Insulin resistance and the accompanying alterations in carbohydrate and lipid metabolism seem to play a crucial role in the development of NASH. Today, NASH is regarded as hepatic manifestation of the metabolic syndrome and thus, is frequently associated with adiposity, hyperlipidemia, hypertension and impairments in the carbohydrate metabolism. In about 10% of cases NASH leads to liver cirrhosis and is thought to be responsible for the majority of cryptogenic cirrhosises. In addition, patients with NASH have an increased risk for cardiovascular events and cancer.
Liver biopsy is still the gold standard in the diagnosis of NASH. However, recent data suggest, that functional magnetic resonance imaging could possibly differentiate between NAFLD without inflammation and NASH non-invasively in the future. In addition, many studies try to predict the presence of NASH using different biomarkers, to date without the required efficacy. Liver enzymes are frequently increased with NASH, typically with a GOT/GPT ratio below 1. However, normal liver enzymes neither exclude NASH nor advanced liver fibrosis.
Many compounds, e.g. metformin, pioglitazone, statins, vitamin E, pentoxifylline and many others have been investigated in patients with NASH. Up to date, none of these coumpounds could show a longterm improvement of liver fibrosis or a reduction of liver-associated mortality. A healthy life style with regular sports, weight normalization and a healthy diet remains still the most effective strategy to prevent or treat NASH.
Autoimmune hepatitis
Autoimmune hepatitis (AIH) is a cronic inflammatory liver disease that is usually associated with increased gamma globulins and auto antibodies in the serum. The disease occurs more frequent in women and may be associated with other autoimmune diseases outside the liver, such as ulcerative colitis, diabetes mellitus, rheumatoid arthritis or autoimmune thyreoiditis. AIH may also accur together with other autoimmune diseases of the liver (primary biliary cirrhosis or primary sclerosing cholangitis) as overlap syndrome.
There are 4 differents types of manifestation of AIH:
1. Patient asymptomatic, diagnosed due to randomly detected elevated liver enzymes.
2. Acute hepatitis in about 40%.
3. Severe hepatitis with acute liver failure in about 5%.
4. Liver cirrhosis at diagnose in up to 25%.
Since there is no single parameter that proves the presence of AIH, diagnosis is based on the combination of serologic and histologic findings as well as the exclusion of other chronic liver diseases. A liver biopsy should be done whenever AIH is suspected, even though histology is not evidentiary for the disease.
Therapeutic targets are durable normalization of liver enzymes, histology and gamma globulins. To get and remain a remission, corticosteroids are used allone or in combination with azathioprine. The combination therapy allows lower concentrations of corticosteroids to be used. Budesonide, a synthetic steroid, has been shown to be effective in the treatment of AIH with a lower rate of side effects. However, when liver cirrhosis is present, budesonide is contraindicated. Other therapeutic options in case of failure or intolerance of standard treatment are mycophenolat mofetil (MMF), tacrolimus oder cyclosporin A.
After having achieved complete clinical, histological and biochemical remission, the immunosuppressive therapy should be stopped at the earliest after 2 or better 4 years since treatment duration is one of the most important predictors of disease recurrence.
Liver tumors
There are benign and malign liver tumors.
Benign liver tumors:
- Hämangioma
- Focal nodular hyperplasia (FNH)
- Adenoma
- Cyst
- Hepatocellular Carcinoma = HCC)
- Cholangiocellular Carcinoma = CCC)
- Liver metastases
Diabetes mellitus
Diabetes mellitus (DM) is a disease of the carbohydrate metabolism where the body´s own hormone insulin is produced in too little amounts and/or its effect is reduced.
There are different types of diabetes:
- Type 1 diabetes mellitus (type 1-DM) = juvenile diabetes because it occurs in younger age in most cases. The destruction of the insulin producing ß-cells of the pancreas by the body´s own immune system leads to a deficit of insulin. Thus, insulin has to be substituted by subcutaneous injections. Less than 10% of all patients with diabetes have type 1-DM.
- Type 2 diabetes mellitus (type 2-DM) = adult diabetes because formerly, it occured primarily in older age. Nowadays, the age at onset of disease is decreasing more and more and there are many cases of type 2-DM in very young people. At the beginning of the disease there is no deficit of insulin, however, the effects of the hormone are decreased. Therefore, the pancreas secrets more and more insulin to regulate the carbohydrate metabolism. As a consequence of this excess work, the ß-cells of the pancreas are decaying and are not able any longer to produce the required amount of insulin. This leads to increased levels of blood glucose. In the early stage of the disease, the blood glucose levels can be decreased with pills. In advanced stages, injection of insulin or other types of medication might become necessary. Type 2-DM is caused by a genetic disposition and an unhealthy lifestyle with adiposity, lack of sports and unhealthy nutrition. More than 90% of all patients with diabetes have type 2-DM.
- Other types of diabetes, e.g. inflammation of the pancreas, endocrine disorders.
- Gestational diabetes = every newly diagnosed impairment of the carbohydrate metabolism during pregnancy. Gestational diabetes is caused by the endocrine alterations during pregnancy and disappears after delivery in most cases. However, it reappears frequently during further pregnancies and women with gestational diabetes have a higher risk for the development of type 2-DM in the following years and decades. An optimal blood glucose management during pregnancy is very important for the fetus.
The target of all treatments of diabetes is to avoid complications, such as diabetic coma, myocardial infarction, apoplexia, blindness, renal failure and amputations of the lower limb.
[ Back to overview ]