What is the preferred medicine for hepatomegaly

Polycystic Liver Disease

introduction

Polycystic liver diseases are mostly inherited diseases in which the liver is interspersed with a large number of cysts (fluid-filled and epithelial-lined cavity) of various sizes. The cysts often occur as part of autosomal dominant polycystic kidney disease (ADPKD). Very rarely, only the liver is affected (polycystic liver disease, PLD).

Pathophysiology

Liver cysts arise from malformations of the ductal plate during liver development. The ductal plate is the starting point for the development of the bile duct within the liver. So-called von Meyenburg complexes remain. These consist of enlarged, disconnected bile ducts and connective tissue and can grow in the course and thus become larger cysts.

Both PLD and ADPKD are autosomal dominant inherited diseases. Changes in genes have been identified that can lead to the disease. However, the mutations are only detectable in about 21% of the cases in PLD.

In addition, several activated signal transduction pathways could be identified, which lead to hypersecretion and hyperproliferation. These include around the "Vascular Endothelial Growth Factor" (VEGF), the insulin-like growth factor (IGF-1), estrogens and the cyclic adenosine monophosphate (cAMP).

Epidemiology

The most common cause of polycystic liver disease is ADPKD. This has a prevalence of around 1 / 100,000, with liver involvement in around 67–83% of patients. Exact data on the incidence and prevalence of PLD are not available. In general, cyst growth before puberty is seldom observed; with increasing age, more and more cysts appear or show a growth in size. Women are more often affected with both diseases.

clinic

The clinical symptoms depend on the size of the cysts and thus also on the size of the liver. Smaller cysts (even several) are usually symptom-free and are usually discovered by chance. As the number and size of the cysts increase, symptoms arise that are caused by the increasing space requirement of the liver and thus the displacement of surrounding organs, because the liver can grow up to 10 times its normal size. Typically, there is a feeling of pressure or fullness, restricted mobility and pain (especially when bending over or sitting). In the course of this, nausea, reflux, back and flank jolts, increase in abdominal girth and a rapid feeling of satiety occur. If the findings are advanced, ascites and esophageal varices can also occur due to the developing portal hypertension.

But even at an earlier stage, individual cysts can become symptomatic: a bleeding into a cyst or a rupture is noticeable in sudden severe abdominal pain. Infected cysts can lead to fever, night sweats, and fatigue. In general, the larger the cyst, the higher the likelihood of a complication. In the case of PLD, it can be assumed that approx. 6–8% of the cysts are infected (even without any significant clinical signs).

Diagnosis

The method of choice for diagnosis is sonography. This is almost universally available and can monitor the course of the disease (Fig. 1). Problematic cysts (e.g. bleeding) can also be identified (Figs. 2 and 3). In the case of special questions (resection, transplantation), computed tomography or magnetic resonance tomography may provide additional information.
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Laboratory parameters have no diagnostic value. The changes are rather unspecific: in around 51% an increase in γGT, in alkaline phosphatase in around 17%. It should also be mentioned that the tumor marker CA19-9 can be increased (in approx. 45%), since it is produced by the cyst epithelium.

Only in infected cysts can an increase in leukocytes or C-reactive protein be observed and control the use of antibiotics. Furthermore, if an infectious liver cyst is suspected, the determination of the echinococcal titer is helpful.

Differential diagnostics

The cyst liver shows a typical finding on imaging, differential diagnosis should include:
  • several single liver cysts

  • infectious liver cyst (esp. Echinococcus sp.)

  • Liver abscesses

  • Peliosis hepatis (very rare!)

  • Cystadenoma (rarity)

therapy

The aim of therapy is to reduce or eliminate the above symptoms caused by the cysts. In principle, only symptomatic patients are treated. The following therapy options are available:
  • Partial liver resection

  • Windowing

  • Transarterial embolization

  • Aspiration and sclerotherapy

  • transplantation

  • Medication

Partial liver resection

Partial liver resection can be performed in patients who have cyst-rich areas as well as segments with normal liver parenchyma (at least 25–30%). Resection is usually reserved for patients with severe hepatomegaly and related symptoms and is only performed by a few centers. The changed courses of the vessels (and bile ducts) are sometimes difficult to visualize, even with modern imaging, which makes the operation more difficult. It is also difficult to visualize the veins intraoperatively. This explains the rather high rate of complications with bile leakage, bleeding, ascites and pleural effusion (51%). The mortality is given as 3%. The relieving effect occurs immediately after the operation, but approx. 34% show renewed symptoms over the course of the operation.

Windowing

Using surgical fenestration, multiple cysts can be treated in one operation during one procedure. The laparoscopic procedure is currently preferred. In 22% of the cases, however, a change (laparotomy) is necessary, mainly for technical reasons, because segments VII and VIII are difficult to reach. The mortality is approx. 2%, the morbidity 23% (ascites, pleural effusion, bile leak, bleeding). In 24% of the cases, the cysts (and the symptoms) reappear.

Transarterial embolization

The segments, which are completely cystic, are embolized via a catheter in the hepatic artery. This therapy seems to improve the symptoms in patients with massive cyst liver, but so far there are only a few studies with a small number of cases in the literature. Thus, the value of this therapy must still be shown in the course.

Aspiration and sclerotherapy

This technique is usually performed under local anesthesia from a diameter of 5 cm. The largest cysts in the area of ​​the complaints - and thus the most symptomatic - are treated. Aspiration alone is usually unsuccessful, as the epithelium of the cyst remains and thus fluid can continue to be produced. Therefore sclerotherapy should always follow if possible (Figs. 4 and 5). For this purpose, different substances are specified in the literature (ethanol, tetracyclines, minocyclines). We have had very good experiences with Polidocanol 1%. The cysts reappear in about 22% of the cases. In addition to the advantage of the operation under local anesthesia, it can also be repeated several times without any problems, is cost-effective and offers the possibility of material recovery (e.g. if infected cysts are suspected).
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transplantation

Liver transplantation is the only curative option in patients, especially those with non-treatable or difficult to treat consequences such as portal hypertension with ascites, esophageal varices or weight loss (malnutrition with preserved liver function). The 5-year survival is approx. 85% above other indications. A combined liver-kidney transplant is often performed.

Drug therapy options

Somatostatin analogs

They reduce the cAMP concentration in the cholangiocytes and thus lead to less fluid production. In several studies it has been shown that the liver volume could be reduced by approx. 4% over a period of 6 months and persist for 6 months afterwards, but then grows significantly so that an administration would have to be continuous and is costly in long-term therapy.

mTOR inhibitors

In the animal model of polycystic kidney disease, mTOR is upregulated. This class of drugs is known as an immunosuppressant in organ transplants. So far, the results have not been shown uniformly (between volume reduction and increase). In addition, it is unclear why some patients do not respond and others respond well. The side effect profile compared to other drugs is also worse.

V2 receptor antagonist

They also reduce the cAMP concentration. Completely new drug approach with only a few data so far (for cystic kidneys). Its role in therapy is unclear so far.

course

In principle, it is a benign disease; there is no increased risk of the cysts becoming degenerate. Even in pronounced cases, the liver's synthesis and detoxification functions are retained. The resulting problems arise from the space-occupying growth of the cyst liver and the associated complications.

literature

Chrispijn M, Nevens F, Gevers TJG et al (2012) The long-term outcome of patients with poycystic liver disease treated with lanreotide. Aliment Pharmacol Ther 35: 266-274 CrossRefPubMed

Drenth JPH, Chrispijn M, Nagorney DM, Kamath PS, Torres VE (2010) Medical and surgical treatment options for polycystic liver disease. Hepatology 52 (6): 2223-2230 CrossRefPubMed

Potthoff A, Sandkühler F, Boozari B, Manns MP, Gebel M, Rifai K (2011) Effectiveness of percutaneous ultrasound-guided sclerotherapy using polidocanol in patients with polycystic liver disease (PCLD). Z Gastroenterol 49: 319 CrossRef

Russel RT, Pinson CW (2007) Surgical management of polycystic liver disease. World J Gastroenterol 13 (38): 5052-5059

Temmerman F, Missiaen L, Bammen B et al (2011) Systematic review: the pathophysiology and management of polycystic liver disease. Aliment Pharmacol Ther 34: 702-713 CrossRefPubMed

Torres EV, Chapman AB, Devuyst O et al (2012) Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med 367 (25): 2407-2418 PubMedCentralCrossRefPubMed