Liver enlargement is a relatively common situation in outpatient pathology.
ANATOMY:
The liver is located at the top and right of the digestive tube, supramesocolic floor. It almost entirely occupies the right hypochondrium.
Its upper face fits exactly in the right diaphragmatic dome. The left end has a tapered shape and thus falls outside the center line, up to and spleen.
The liver has a firm but crumbly, it is enveloped by the liver capsule.
It is projected at its upper edge under the fifth right intercostal space on the nipple line, its lower edge not normally exceed the costal margin.
Hepatic vascularisation has three systems:
– Portal vein brings venous blood, it is derived from the junction superior mesenteric vein, splenic vein and inferior mesenteric vein. It also receives other collateral veins of different digestive viscera;
– Hepatic artery arises from the celiac trunk, it is usually divided into two right and left branches. However, be aware that there is a great variability of hepatic arterial vascularization;
– The hepatic veins that provide true venous drainage of the liver, they are the result of the convergence of central veins.
These hepatic veins are three in number (right, middle and left) and empty into the inferior vena cava.
The liver is a principal organ of metabolism:
– Carbohydrate metabolism due to its glycolytic capacity, glycogen synthesis, of glycogenolysis and of gluconeogenesis;
– Protein metabolism by the breakdown of amino acids, the synthesis of non-essential amino acids, uréogenèse, protein synthesis (all proteins except the immunoglobulins);
– Lipid metabolism with the synthesis of fatty acids, triglycerides, cholesterol and lipoproteins.
Is a glucose storage member (glycogen), iron (ferritin), copper, liposoluble vitamins and vitamin B12 … but also a detoxifying organ through the metabolism of xenobiotics (cytochrome) and alcohol . It biliary function by the synthesis and secretion of bile acids, and immune function played by the Kupffer cells.
DIAGNOSIS:
Clinical examination:
Inspection can sometimes reveal swelling of the right upper quadrant.
Palpation:
Palpation is usually done with the patient in supine strict, slightly bent legs. The doctor puts the patient’s right side and asks him to take a deep breath.
Highlighting hepatomegaly based on the detection of the liver edge that normally is not palpable.
Palpation must be done from the bottom up with the hand flat and obliquely upwards and inwards.
You start in the right flank and gradually go back to the costal margin. If despite this, the lower edge of the liver was not palpated; we can introduce the hand under the costal margin in order to feel the lower edge of the liver come into contact during deep inspiration.
Another examination technique uses the radial side of the hand placed parallel to the costal margin.
Following this review, it is important to note the consistency of the liver and its edge, the existence of a hépatalgie, and enjoy the liver overhang compared to costal margin.
Percussion:
The percussion used to assess hepatic arrow corresponding to a dullness on the mid-clavicular line, the arrow usually is 8 to 10 cm in women and 10 to 12 cm in men.
Examination:
Before hepatomegaly, it is important to look for signs of heart failure, portal hypertension and / or hepatocellular insufficiency, changes in skin color, the color of excreta, stunted growth, food intolerance, taking drugs or toxic, the same old trips, family history.
Fever is an important symptom to be determined.
It is also useful to assess the length of symptoms (less or more than 6 months).
Finally, the calculation of body mass index and waist circumference measurement should be performed.
Liver imaging:
She is currently based on three high-performance tests: ultrasound, CT and MRI.
The simple radiograph (abdomen without preparation) has no interest in shareholders liver disease, can sometimes guess the shade or hepatic calcifications intra parenchymal or aerobilia.
Ultrasound:
The ultrasound, non-invasive, remains excellent for assessing the size, the state of the parenchyma, hepatic lesions (cysts, nodules, hemangiomas), the gallbladder and bile ducts.
It is often coupled to a Doppler hepatic vessels searching for thrombosis, portal hypertension signs. However it is a very operator-dependent examination.
The size of the liver is assessed from longitudinal sections of reference: one passing through the vena cava (normally less than 10 cm) and that passing through the right kidney (normally less than 14 cm).
Signs of portal hypertension on ultrasound is a trunk door caliber exceeding 15 mm, the disappearance of respiratory variations of his caliber, an associated splenomegaly, highlighting bypass roads, the presence of ascites.
Scanner:
Hepatic scanner should ideally be achieved with injection and study of three successive time liver: arterial and venous door.
It has become a very powerful examination with very fine resolution for accurate analysis of the parenchyma and vessels.
MRI:
Liver MRI, less available, is useful for characterizing certain lesions secondarily.
Another interest was recently established to quantify intrahepatic iron and using high-performance software for correlating the signal intensity in liver iron concentration. The performance of this technique has helped significantly reduce liver biopsy indications in hemochromatosis.
ETIOLOGY TREATMENT:
The diagnosis of hepatomegaly is often easy, aided by imaging.
However, some situations are particularly difficult requiring careful analysis of clinical and laboratory data.
They can be classified according to their pathophysiology:
– Liver inflammation;
– Vascular congestion;
– Hepatic infiltration;
– Storage diseases;
– Biliary diseases.
Infectious liver inflammation:
Bacterial hepatomegalies:
Leptospirosis:
It is caused by bacteria of the genus Leptospira. Human contamination occurs accidentally due to a bite or contact with contaminated water (farmers, sewer workers, farmers and recreational freshwater). Rodents (rats) are the main reservoir.
The clinical picture is noisy with high fever, aches and diffuse mucocutaneous manifestations.
The liver injury is the most frequent visceral involvement. Liver enlargement is usually painful and is accompanied by a frank jaundice. Leptospirosis can achieve hepatorenal table associating jaundice and acute renal failure.
Liver biology especially shows a predominant cytolysis. Diagnosis can be made by blood cultures during the first five days, serology is of interest only from the 12th day. PCR can be useful.
Doxycycline (200 mg / d) may be proposed in early treatment in the absence of renal failure. Amoxicillin (100 mg / kg / day) intravenously or ceftriaxone (1 g / day) IV for 7 to 10 days apart may be used.
Vaccination is offered as a preventive measure in high-risk situations.
Brucellosis:
This is an infection with a gram-negative bacillus of the genus Brucella. It is a zoonosis that primarily affects ruminants. Contamination is professional (farmers, butchers …) or food (milk or unpasteurized cheese).
The spread of the germ is lymphatic.
Liver enlargement is present in a third of cases the acute phase that achieves the classic table sudoroalgique fever (undulant fever, arthralgia, headache, myalgia and abundant night sweats). Biology at this stage finds a mixed hepatitis.
Diagnosis is based on blood cultures in the primary phase and serology.
Antibiotic treatment should involve a tetracycline (doxycycline 200 mg / day) and rifampicin (15 mg / kg / d) (Rifadine®) for 30 to 45 days, or doxycycline for 6 weeks with an aminoglycoside (streptomycin 1 g / d) for 15 to 21 days. In children and pregnant women, tetracycline can be replaced with cotrimoxazole.
Syphilis:
The liver is achieved in the secondary and tertiary syphilis.
During secondary syphilis, liver damage concerns 10% of cases. This is called a tender hepatomegaly; he joins in a roséoliforme rash on the trunk, generalized polyadenopathies firm and general signs.
In tertiary syphilis, nodular hepatomegaly possible, while the liver is the seat of a granulomatous infiltrate with syphilitic gum. This syphilitic gum gives lacunar images on ultrasound and CT.
Diagnosis is based on serology: TPHA ( Treponema pallidum Hemagglutinations Assay ), VDRL ( Venereal Disease Research Laboratory ), abs-FTA ( Fluorescent treponemal Antibody Absorption ), which are all positive at the secondary stage.
The treatment of late forms includes: Extencilline® 2.4 MU intramuscularly, 3 injections a week apart.
In case of allergy to penicillin, there is possibility of doxycycline 100 mg × 2 / day or erythromycin 500 mg x 4 / day for 28 days.
Typhoid fever:
Major salmonella ( typhi and paratyphi ) may be the cause of liver damage with hepatomegaly in 67% of cases, sometimes liver abscess. This is currently an import pathology.
The antibiotic therapy is recommended in adults fluoroquinolones (ofloxacin 200 mg × 2 / day or ciprofloxacin 500 mg × 2 / day) for 5-7 days.
Ceftriaxone (75 mg / kg / day) for 5 days is used in children.
Bacillary angiomatosis:
Caused by Bartonella henselae in immunocompromised especially AIDS patients, which may be responsible for a histologically liver bacillary peliosis. Very close tables are also described with Bartonella quintana (cat scratch disease agent).
Liver enlargement is accompanied by fever, poor general state, splenomegaly and cutaneous vascular lesions that can mimic a sarcoma. Liver biology is mainly characterized by an increase in alkaline phosphatase (up to 10 times normal).
Diagnosis is based on serology, Polymerase Chain Reaction (PCR) and possibly liver biopsy.
Treatment is difficult and is based on long-term use of tetracyclines or macrolides (eg, erythromycin for 3 months).
Bacterial liver abscess:
They manifest as hepatomegaly and sometimes painful epigastric mass when it comes from an abscess in the left lobe.
Liver enlargement is associated with fever, chills, poor general condition, pain increases with inspiration and coughing.
The diagnosis is confirmed by imaging (ultrasound, CT), blood cultures and culture of the abscess pus. He frequently is a polymicrobial infection. The starting point is often bile, digestive, and then then a remote household (endocarditis).
Treatment should involve a broad spectrum antibiotic suitable for suspected the door and must cover the anaerobes.The recommended time is 4 to 6 weeks. A local action on or abscesses can type puncture-drainage under radiological control.
Other:
Organic liver damage and / or histological is classic over the rickettsial, Q fever, miliary tuberculosis. Liver enlargement is against rare.
_ Parasitic hepatomegaly
Hepatic amoebiasis (or hepatic amoebiasis):
It is an infection with Entamoeba histolytica form histolytica . Contamination occurs through water and food route. It usually occurs within six months traveling in endemic countries but sometimes much later.
The frequency of liver injury during invasive amebiasis is difficult to estimate but can be up to 25%. It leads to areas of necrosis evolving centrifugal and confluent fashion.
The clinic is often a painful and febrile hepatomegaly (Fontan triad).
He joins in anorexia, weight loss, nausea and asthenia. Concomitant diarrhea is rare.
Liver enlargement is often mild but can become large, normal or firm, rarely dented. It is sensitive to palpation. There may be a phrenic syndrome when higher abscess development.
The imagery is very evocative. Ultrasound shows a hypoechoic area with a painful passage of the probe. The scan finds a fluid density of necrotic zone with a wall which takes the contrast and surrounded by a halo of edema. The NFS found hyperleukocytosis neutrophils.
The stool examination should always be done but it is rarely positive at this stage. Serology is of great diagnostic value. The diagnostic biopsy of the abscess amebic is little used (search for antigens of E. histolytica ).
Treatment should be initiated promptly upon suspicion, indeed the appropriate treatment allows healing without sequelae. Clinical improvement is rapid, however, there is a radiological delay.
The drugs used are imidazole derivatives such as metronidazole 2 g / day for 10 to 15 days, but this molecule has an imperfect amoebicide activity in the colonic lumen.
It is therefore necessary consecutive use of a luminal amoebicide as tibroquinol-tiliquinol Association (Intetrix®: 2 capsules morning and evening for 10 days).
The evacuation of amoebic collection is possible (puncture evacuative, transparietal drainage, surgery). It is indicated if significant pain, worsening under treatment or risk of breakage (diameter> 10 cm).
Hepatic hydatid disease:
It is caused by Echinococcus granulosus .
A toxic origin is suspected with aflatoxin B1, which is produced by Aspergillus flavus type of yeast but alsoPenicillium type. His interest is that it is a common contaminant of food in hot and humid countries.
There are also anabolic steroids that give hepatic adenomas may turn these hepatocarcinomas have the particularity not to elevation of alpha-fetoprotein.
Hepatomegaly is present when it comes to large tumors, it is sometimes blower. It may be associated with impaired general condition, fever and ascites. However the clinical examination is usually normal and diagnosis of small lesions is done on a systematic imaging.
The alpha-fetoprotein is increased in 75% of cases, levels above 500 ng / mL are specific and customs clearance of the biopsy, lower rates can be seen in various situations with hepatic aggression.
Concerning the treatment, surgical resection should be discussed whenever it is possible (partial hepatectomy or transplantation).
Local treatments available are chemoembolization, radiofrequency and alcohol consumption; currently it is the radio frequency which is preferred because of the results at least as good as the alcohol with a much better tolerance, chemoembolization has poor results.
Hormone therapy (tamoxifen) seems irrelevant.
Chemotherapies have not shown yet their usefulness.
Other primary liver tumors:
Other malignant liver tumors can be revealed by hepatomegaly, we cite the cystadenocarcinoma, hepatic sarcomas and can be intrahepatic cholangiocarcinoma.
These are rare tumors.
By cons, we must think of hepatoblastoma in children before a quick installation hepatomegaly, this is the most frequent hepatic tumor in children. Accurate diagnosis is useful because chemotherapy and surgery significantly improves the healing prognosis with near 70%.
Among the benign tumors, only the hepatic adenoma may manifest as hepatomegaly; its frequency is increased in women taking estrogen plus progestin oral contraception.
Treatment involves simply stopping the pill and monitoring.
Liver metastases:
The secondary liver can give irregular hepatomegaly, hard and sometimes nodular on palpation. Pain in the right hypochondrium are possible.
Laboratory abnormalities often boil from a anictérique cholestasis (elevated γ-GT and alkaline phosphatase).
Many tumors are responsible for liver metastases: digestive (colon, pancreas, stomach), breast, broncho-pulmonary, kidney, melanoma …
Hematologic:
Hodgkin’s disease, non-Hodgkin lymphomas and lymphoproliferative low grade (such as chronic lymphocytic leukemia) may be accompanied by hepatomegaly.
This is rarely revealing events.
Note that in Hodgkin’s disease, hepatomegaly is not always synonymous with tumor infiltration since the liver may be the seat of a granulomatous process (non-tumor).
The liver damage as hepatomegaly is more common in hairy cell leukemia.
Myeloproliferative disorders (chronic myeloid leukemia, polycythemia vera, essential thrombocythemia and myelofibrosis) are also hepatomegaly especially idiopathic myelofibrosis etiology. We can bring the super eosinophilic syndrome in his myeloproliferative variant and is sometimes accompanied by hepatomegaly. Diagnosis is by blood count.
The liver is rarely the seat of a primary liver lymphoma, then it is a high-grade B-cell lymphoma. The review found often nodular hepatomegaly with right upper quadrant pain and net general signs. The imagery is not specific but shows nodules or diffuse infiltration. The treatment is based on chemotherapy.
Histiocytosis:
This is Langerhans cell histiocytosis which is accompanied by hepatomegaly in its systemic form.
Non Langerhans histiocytosis as Erdheim-Chester disease usually give no liver damage.
Mastocytosis:
Systemic mastocytosis are accompanied by abnormal and uncontrolled proliferation of mast cells in many tissues.
Hepatomegaly be met in at least 50% of systemic forms.
Overload diseases:
Amyloidosis:
These are rare diseases. This is amorphous deposits consist of an amyloid protein coupled to a glycoprotein common to all types of amyloidosis: amyloid P.
There are several amylose varieties depending on the nature of amyloid protein: AL amyloidosis (light chain), AA amyloidosis (due to the infl ammatory protein Serum Amyloid A or SAA protein) amyloidosis ß2M (due to β2- microglobulin that accumulates in dialysis), genetic amyloidosis (transthyretin …).
It is especially the AL and AA amyloidosis who have a tropism for the liver, are also the two most common types of amyloidosis. However the clinical expression is significantly rarer than histological lesions.
Hepatomegaly was found in 24% of AL amyloidosis but it is not always due to amyloid deposits, cardiac liver is possible.
When present, it is a bulky hepatomegaly, smooth, non edged, painless bottom edge. In a third of cases, it exceeds 10 cm below the costal margin.
The liver function test abnormalities are discrete and contrast with the importance of hepatomegaly, which is evocative.
Liver biopsy should be avoided due to a high risk of bleeding. The diagnosis must be on less risky samples (accessory salivary glands, abdominal fat, rectal biopsy …).
Treatment depends on the type, so in AL amyloidosis treatment is modeled on that of myeloma with whenever possible an intensified therapeutic cation with stem cell reinfusion, in cases where this is not possible c is the association and corticosteroids
melphalan orally is preferred.
In AA amyloidosis, treat and control the inflammatory disease in question (rheumatoid arthritis, spondylitis, periodic disease …) The theoretical goal is a rate of SAA less than 10 mg / L.
Genetic hemochromatosis (see Hyperferritinemia):
The type 1 hemochromatosis is the most common.
It is caused by two possible mutations, C282Y and H63D. C282Y homozygosity is the most common situation. More rarely are diagnosed in compound heterozygotes C282Y / H63D and H63D homozygotes.
The classic clinical picture makes a sometimes severe hepatomegaly, firm and sharp edge. It is associated with hyperpigmentation, arthritis, diabetes and heart disease. The diagnosis is made, however, currently before asthenia above the other symptoms.
Typically, serum iron, ferritin and transferrin saturation coefficient are high. Is the saturation coefficient that is the most sensitive screening.
The diagnosis is confirmed by the search for mutations. In some cases where the therapeutic decision is not obvious, we can help the liver MRI assessment of liver iron concentration, this makes many unnecessary liver biopsy in hemochromatosis.
The juvenile hemochromatosis manifests itself at an early age (the second and third decades).
Treatment is simple, it is the subtraction of iron by phlebotomy (weekly phlebotomy 400-500 mL). The injectable chelators do not belong because of their safety profile and methods of administration.
Oral chelation has not been evaluated in this indication.
Secondary Hemochromatosis:
Specifically secondary iron overloads, following a significant alcoholism, hemoglobinopathies, repeated transfusions.
Liver enlargement is common, the context is evocative.
Treatment is primarily preventive in patients receiving multiple transfusions, the current preference is for oral chelators.
Wilson’s disease:
This is an autosomal recessive disease due to mutations in ATP7B gene located on chromosome 13 and which encodes a transmembrane copper carrier. It currently has more than 300 listed mutations.
About 59% of patients present with liver damage. It may be acute forms with acute or fulminant hepatitis manifested by jaundice, fever and sometimes signs of encephalopathy; hepatomegaly is special because it is hard. The Kayser-Fleischer ring is not always present.
Chronic forms take on the appearance of chronic hepatitis or silent with a diagnosis made at the stage of cirrhosis.Other manifestations are encountered neurological, psychiatric, hemolysis.
Biological diagnosis relies upon the measurement of ceruloplasmin is reduced in 95% of cases (but normal in 5%), it is also a nonspecific abnormality. The urinary copper is constantly increased. The cuprémie is usually lowered.
The measurement of free copper is the difference between the total and the copper bound to ceruloplasmin (50 micromol copper / ceruloplasmin 1 g), the free cuprémie is usually increased.
One can also determine the concentration of hepatic copper, this requires a liver biopsy.
The imagery is not specific.
Genetics can be done but there is a large number of mutations, the absence of the most common mutations does not rule out the diagnosis.
Treatments available are three in number:
– D-penicillamine (Trolovol®) which acts in two ways, chelating copper and decrease in intracellular toxicity. The effective dosage is 1800 mg / day to achieve gradually. This drug however has many side effects;
– Triethylenetetramine (Trientine®) which acts as copper chelator and by decreasing intestinal absorption of copper.Available by temporary authorization for use must be kept cool (4 ° C). The effective dosage is 1 to 1.5 g / day in 2 or 3 doses;
– Zinc (zinc sulfate or Wilzin®) which acts by decreasing the intestinal absorption of copper and incidentally increasing the fixation of the copper to the liver metallothioneins. The effective dosage is 150 mg / d.
Current recommendations are for D-penicillamine in first intention if symptomatic form. In case of intolerance or side effect choice is trientine.
In pauci or asymptomatic forms, it is more logical to use zinc.
Deficiency α 1-antitrypsin:
It is not strictly speaking an overload condition. Anyway, liver damage is rare as it concerns only 10% of homozygous genotypes PiZZ.
Liver enlargement is rare.
It now has a replacement therapy with weekly or biweekly infusion (Alfalastin®).
Non-alcoholic liver Stéatopathies:
Fatty liver corresponds to an excess of lipids in the liver parenchyma (> 5% of liver weight). Histology found lipid droplets in the hepatocytes.
NASH are distinguished (NASH in English Literature) which partners with steatosis, inflammatory infiltrate, hepatocellular necrosis and fibrosis.
Obviously we should exclude other liver diseases before retaining this diagnosis.
Fatty liver is associated with obesity, diabetes, excessive alcohol consumption, hypertriglyceridemia, certain medications.
The natural history seems steatosis, steatohepatitis, steatohepatitis with fibrosis and cirrhosis.
The simple steatosis and NASH can be integrated in the metabolic syndrome that combines several of the following: hypertension, obesity, insulin resistance, hyperlipidemia.
Criteria:
They are detailed in Boxes 1 and 2 (see hyperglycemia).
Box 1. Criteria of the European Group for the Study of Insulin Resistance
Insulin resistance defined by a insulin levels exceeding 25% of the normal rate.
And at least 2 of the following criteria:
Abdominal obesity defi ned by a waist circumference ≥ 94 cm in men and 80 cm for women.
Dyslipidemia defi ned by triglycerides> 2 mmol / L or HDL <1 mmol / L.
Hypertension (≥ 140/90 mmHg or need for treatment)
Plasma glucose> 6.1 mmol / L.Box 2. Criteria formulated by the American National
Cholesterol Education Program in 2001
At least 3 of the following criteria:
Abdominal obesity defi ned by a waist circumference> 102 cm in men and> 88 cm in women.
Triglycerides ≥ 1.7 mmol / L.
HDL cholesterol <1 mmol / L for men and <1.3 mmol / L in women.
Hypertension (≥ 135/85 mmHg or need for treatment).
Fasting glucose ≥ 6.1 mmol / L.
Hepatomegaly without semiotic particularity is present in 30-50% of cases. There is often a pain in the right upper quadrant.
There is a moderate and predominant extended cytolysis on alanine aminotransferase, there is also an increase in γ-GT and alkaline phosphatase.
Imaging allows the diagnosis of steatosis without prejudging the origin.
The histological diagnosis of NASH remains.
Treatment:
The treatment consists of comprehensive care.
The lifestyle measures are prominent: weight reduction, regular physical activity (> 30 minutes of walking daily).
The lipid lowering are to be used according to the recommendations on the management of cardiovascular risk factors.
Several drugs have been tried to influence steatosis: fibrates and statins have no own effectiveness, vitamin E have a positive effect on biochemical and histological abnormalities, ursodeoxycholic acid at 10-15 mg / kg / day demonstrated efficacy on biological anomalies, metformin at a dose of 1.5 g / day improved biological parameters but histological evaluation, glitazones have not demonstrated histologic improvement.
It is also desirable to reduce or stop alcohol consumption. We must identify and treat a possible iron overload due to real or secondary hemochromatosis to insulin resistance.
Stauffer syndrome:
This is a paraneoplastic syndrome that is manifested by fever, weight loss, hepatomegaly, elevated transaminases and decreased prothrombin. Icteric a variant has been described.
There are no liver metastasis.
This syndrome occurs with kidney cancers, few observations have been reported with other tumors.
Inborn errors of metabolism:
GSD:
These are the GSD Ia, Ib, Ic, III, IV, VI, VIII and X which are accompanied by a rapid onset hepatomegaly after birth, often with varying severity of hypoglycemia fast growth retardation.
It is autosomal recessive conditions except glycogenosis VIII as X-linked
Treatment is based on nutritional assistance until the end of adolescence, liver transplantation is an option.
Carbohydrate metabolism Fructose intolerance:
This is a rare, autosomal recessive gene located on chromosome 9q13, incidence 1/20 000. There is a shortage of aldolase B (normally present in liver, kidney and intestines).
Clinical manifestations appear after the age of six months, that is to say after the introduction of fructose. There is always hepatomegaly with in half the cases stunted, bleeding tendency and sometimes ascites, edema and jaundice.
The major biological anomaly is hypoglycaemia after ingestion of fructose, which is the basis of the diagnostic test;hypoglycemia in these patients is not corrected by glucagon.
Other anomalies are cytolysis, a decrease of coagulation factors, hypophosphataemia after ingestion of fructose, renal tubular acidosis.
The treatment is relatively simple, we must exclude all foods containing fructose.
Most abnormalities regress after a well-led regime, but hepatomegaly can persist for long periods.
Anyway, in diet, life expectancy is normal.
Transferase deficiency galactosemia:
It is an autosomal recessive disorder, gene on 9p18, incidence between 1:10 000 and 1:70 000.
Include hepatomegaly in 90% of children with jaundice in 80%. Other symptoms include growth retardation and psychomotor, vomiting and cataract.
Biology shows galactosemia and high galactosurie, hyperchloraemic acidosis,
albuminuria and aminoaciduria and sometimes liver failure.
The diagnosis is made by assaying the activity of galactose transferase in erythrocytes or fibroblasts, it is then collapsed while heterozygotes have a reduced activity by 50%.
Treatment involves the rapid ouster of galactose allowing regression of abnormalities and normal development.Sequels are possible: neurological, hypogonadism in girls, osteoporosis.
Metabolism of amino acids:
Hereditary tyrosinemia is the only to liver damage, the expression can be acute or chronic. The gene is located at 15q23-25. There deficiency fumarylacetoacetase.
The acute form occurs when a month of life, and it is fatal in 3 to 9 months.
The chronic form is slower and progressive installation combining hepatomegaly, splenomegaly, growth failure, vomiting, diarrhea and jaundice. A misbehaving treatment results in early hepatocellular carcinoma.
Biology found cytolysis, hyperbilirubinemia, hepatic failure, tubulopathy and a membrane hemolytic anemia.
Treatment involves a diet low in phenylalanine and tyrosine, NTBC (2- (2-nitro-4-TRIFLUOROMETHYLBENZOYL) -1,3-cyclohexanedione) available temporary authorization for use and is most effective when it is started early. Liver transplant is possible.
Lysosomal storage diseases Gaucher disease:
Due to a deficiency in β-glucocerebrosidase leading to the accumulation of glucosylceramide. The gene is located on chromosome 1q21.
It recognizes three types based on clinical manifestations.
Hepatomegaly was found in type I, which is also the most common, is found in 80% of patients.
Other manifestations are bone (osteonecrosis, deformities and pain) and spleen (splenomegaly, hypersplenism and splenic infarction).
The diagnosis is suggested by the presence of Gaucher cells in the bone marrow aspirate (non-specific), the measurement of the enzymatic activity of β-glucocerebrosidase and the search for the mutation by PCR (for the five most common mutations).
Treatment is based on the substitution with imiglucerase (Cerezyme) in intravenous infusion every 15 days to the initial dose of 60 IU / kg to secondarily adapted according to clinical response.
A new treatment is currently available, miglustat (Zavesca®) which is a chaperone molecule whose mechanism is to reduce the rate of the substrate β-glucocerebrosidase. The Zavesca® is given orally, though it is less effective than replacement therapy.
It is indicated in moderate forms and in the event of poor tolerance of parenteral treatment.
Niemann-Pick disease:
We know three types: A, B and C. The common mechanism is an accumulation of sphingomyelin.
Type A begins early in childhood and is characterized by hepatomegaly and neurological, it progresses to death at the age of three years.
Type B is manifested initially by hepatomegaly and splenomegaly, there are no neurological signs but appears belatedly lung damage type alveolar infiltration. The liver damage may progress to cirrhosis with ascites and portal hypertension.
Type C is characterized by a neurodegenerative disease with a variable hepatomegaly.
The most effective treatment is bone marrow transplant. Note that miglustat (Zavesca®) was granted marketing authorization in the type C.
Other conditions:
Alongside these two conditions, there are some other much rarer being involved in hepatomegaly as Wolman disease whose symptoms appear soon after birth and end at death before the sixth month. There is also the cholesterol esters overload which are diagnosed in early childhood or in young adults with constant sometimes hepatomegaly with splenomegaly, the prognosis is better.
Bile salt metabolism:
This is rare conditions:
– The familial intrahepatic cholestasis (types I and II);
– Alagille syndrome is a complex malformation syndrome with hypoplasia of the bile ducts, a firm hepatomegaly, and abnormal facies, cardiac abnormalities, ocular and vascular …
Cystic fibrosis:
Hepatomegaly may be an especially calling point in adolescents. It is still a rare event since it oscillates between 2 and 16% depending on the series. Liver enlargement is often accompanied at diagnosis of portal hypertension.
CONCLUSION:
Keep in mind that the etiological diagnosis of hepatomegaly is often easier assisted by history and imaging. The epidemiological context that currently in France the main causes of hepatomegaly are alcohol, steatosis and chronic viral hepatitis.
There are some unusual situations should not be overlooked because of the positive impact of rapid therapeutic.
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