Hepatomegaly / Splenomegaly / Hepatosplenomegaly

Scoring systems in acute alcoholic hepatitis

*Maddrey's discriminant function test* was described by Maddrey and colleagues in 1978 to predict prognosis in alcoholic hepatitis: It is calculated by: 4.6 x [PT:control value (sec)] + serum bilirubin (mg/mL) During the episode, a score of >32 carries a 50% mortality rate and is an indication for treatment with steroids, whereas > 90% of patients with a score <32 will survive. The *Mayo End stage Liver Disease (MELD) score* has been applied to alcoholic hepatitis. This is a composite score derived from the serum bilirubin, creatinine and INR and predicts survival probability over 90 days. In one study, patients with a score ≤ 11 had a 30-day survival of 96% whilst the 30-day survival in those with a score ≥ 11 was 45%. The *Glasgow alcoholic hepatitis score* on day 1 has an overall accuracy of 81% when predicting 28-day outcomes.

Signs and conditions associated with hepatosplenomegaly

- Anaemia: myeloproliferative disorders - Lymphadenopathy: lymphoproliferative disorders, infective causes (EBV, TB), sarcoidosis - Parkinsonism, dysarthria, Kayser-Fleischer rings, neuropsychiatric: Wilson's - Xanthoma and xanthelasma: PBC - Arthropathy: haemochromatosis - Yellow-brown skin pigmentation, pingueculae, eye movement disorders, myoclonus, early dementia: Gaucher's disease (lysosomal storage disease). - Learning difficulties: Niemann-Pick disease (sphingomyelinase deficiency), Wilson's disease

Cardiac manifestations of Wilson's diseaes

- Cardiomyopathy - Sudden cardiac death

GI manifestations of Wilson's disease

- Chronic active hepatitis - Fulminant hepatitis - Chronic liver disease with cirrhosis

Renal manifestations of Wilson's disease

- Fanconi syndrome - Renal stone disease and nephrocalcinosis (thought to be due to the renal tubular acidosis and hypercalciuria arising from proximal tubular dysfunction).

Haematological manifestations of Wilson's disease

- Haemolytic anaemia (rare)

Opthalmological manifestations of Wilson's disease

- Kayser-Fleischer rings in Descemet's membrane - Sunflower cataracts

MSK manifestations of Wilson's disease

- Osteopenia - Arthropathy - Chondrocalcinosis

Psychiatric manifestations of Wilson's disease

- Personality change - Emotional lability - Intellectual impairment - Psychosis and affective disorders

Neurological manifestations of Wilson's disease

- Resting or intention tremor - Parkinsonism - Dysdiadochokinesia - Dystonias - Choreoathetosis - Ataxia - Epilepsy

Causes of isolated splenomegaly (common)

1. Chronic malaria 2. Kala-azar 3. Schistosomiasis 4. Lymphoproliferative diseases (but usually also includes lymphadenopathy +_ hepatomegaly)

Uncommon causes of isolated splenomegaly

1. Felty's syndrome 2. Chronic haemolytic anaemia 3. Infective endocarditis 4. Left-sided portal hypertension - portal vein or splenic vein thrombosis (e.g. due to pancreatic malignancy or pancreatitis).

Clinical manifestations of Wilson's disease

1. GI 2. Neurological 3. Psychiatric 4. Ophthalmological 5. Musculoskeletal 6. Renal 7. Cardiac 8. Haematological Accumulation of copper in the liver is at first an asymptomatic process. Most patients therefore present from the 2nd decade of life onwards.

Common causes of hepatosplenomegaly

1. Infective 2. Myeloproliferative and lymphoproliferative diseases 3. Cirrhosis with portal hypertension

Causes of a low platelet count in alcoholic liver disease

1. Splenomegaly associated with portal hypertension results in platelet sequestration and thrombocytopenia. 2. In addition there is a direct toxic effect of alcohol on production, survival time and function of platelets. Folate deficiency may contribute. Platelet counts may begin to rise after 2-5 days' abstinence from alcohol. A platelet count of <50 x109/L is an indication for platelet transfusion in the presence of bleeding, particularly from varices.

Uncommon causes of hepatosplenomegaly

1. Wilson's diseaes 2. Haemochromatosis 3. Glycogen storage disorders

Left lobe liver enlargement

Alcoholic hepatitis Budd-Chiari syndrome

Schistosomiasis

Bilharzia is a parasitic disease caused by several species of fluke of the genus Schistosoma. Schistosomiasis is often a chronic illness with a low mortality rate but high morbidity relating to irreversible damage to internal organs such as the liver and urinary tract. Chronic infection causes granulomatous reactions and fibrosis in affected organs, resulting in portal hypertension with hepatosplenomegaly (particularly with S. mansoni and s. japonicum). Schistosomiasis is readily treated using a single oral dose of the drug praziquantel.

Biochemical features of Wilson's disease.

Cardinal features: Low serum caeruloplasmin High urine copper levels Both copper and caeruloplasmin are acute phase reactants and their levels increase in the presence of an acute phase response. Therefore, levels should be interpreted in the context of the patient's overall condition.

Malaria

Chronic malaria is seen in both Plasmodium vivax and P. ovale because they have hepatic lifecycles, but no in P. falciparum which does not have a lifecycle outside of the circulation. Nevertheless, P. falciparum may also be associated with hepatosplenomegaly.

Felty's syndrome

Felty's syndrome is defined by the presence of 3 conditions: 1. Rheumatoid arthritis 2. Splenomegaly 3. Neutropaenia. It affects 1% of patients with RA. Cause unknown. The frequency of Felty's syndrome increases with the duration of rheumatoid arthritis. People with this syndrome are at risk of infection (lung and skin mainly) on account of neutropenia. Complications of Felty's syndrome include: - recurrent infection, - hypersplenism causing anaemia and thrombocytopenia, - skin hyperpigmentation - cutaneous ulceration.

Clotting factor abnormalities associated with hepatic amyloidosis

Hepatic amyloidosis is characteristically associated with loss of the clotting factors IX and X. In addition, infiltration with amyloid protein contributes to vascular fragility. There is a significant risk of bleeding if percutaneous liver biopsy is performed and spontaneous hepatic rupture has been described.

Histological features of alcoholic liver disease

Hepatic steatosis - accumulation of fat in liver cells. This is not related to the total alcohol exposure alone. Alcoholic hepatitis - acute inflammation and hepatocyte necrosis (usually hepatocytes affected by steatosis). Hepatic cirrhosis - fibrosis of liver tissue. Cirrhosis is irreversible and if progressive can lead to liver failure, but both steatosis and hepatitis are potentially reversible following abstinence from alcohol.

Hepatosplenomegaly top tips

If other stigmata of CLD are present, the diagnosis is likely to be cirrhosis with portal hypertension. Ascites does not usually occur in myeloproliferative and lymphoproliferative disorders. Lymphadenopathy elsewhere makes the diagnosis of lymphoproliferative disorder more likely. Jaundice associated with hepatosplenomegaly may be due to haemolysis rather than hepatitis or cholestasis.

Pre-sinusoidal portal hypertesnion

In schistosomiasis caused by S. mansoni and S.japonicum, schistome eggs become trapped in the portal tracts where they cause a granulomatous reaction and subsequent fibrosis. Since this involves the last branches of the portal veins, portal hypertension ensues. However, the liver sinusoids are not affected and the liver synthetic function is unaffected.

Visceral leishmaniasis

Known also as kala-azar, this is the most severe for of leishmaniasis. Leishmaniasis is caused by protozoan parasites of the Leishmania genus and is the second-largest parasitic killer in the world (after malaria). The parasite is spread by sandflies and migrates to the internal organs such as liver, spleen and bone marrow and, if left untreated, will almost always result in the death of the host. signs and symptoms include fever, weight loss, anaemia and substantial swelling of the liver and spleen.

Most common worldwide causes of hepatosplenomegaly

Malaria. Visceral leishmaniasis (kala-azar) Schistosomiasis (bilharzia)

Genetic basis of Wilson's disease

Mutation of the adenosine triphosphatase 7B (ATP7B) gene. This gene is a key element in the transport of copper into the secretory pathway of the cell for incorporation into copper-containing enzymes and excretion of excess copper in the bile. Mutation of this gene therefore leads to accumulation of free copper in hepatocytes, followed by eventual 'spill-over' into the serum and thence to the urine. Simultaneously, the levels of copper-containing enzymes, such as caeruloplasmin, decrease.

CML chromosomal abnormality

The Philadelphia chromosome is the hallmark of CML, where it is found in >90% of cases. Cytogenetically it results from a chromosomal translocation: t(9;22)(q34;q11). This molecular rearrangement expresses a bcr-abl hybrid mRNA transcript that encodes an altered bcr-abl protein with enhanced in vitro tyrosine kinase activity. The fused bcr-abl protein interacts with the interleukin 3 receptor subunit. The transcript is continuously active and does not require activation by other cellular messaging proteins. Bcr-abl activates proteins which control the cell cycle, speeding up cell division and inhibiting DNA repair.

Differentiating a splenic and renal mass

The four characteristics of a splenic mass are: 1. Dull to percussion 2. Not ballotable 3. Palpable splenic notch 4. The palpating finger cannot get above a splenic mass.

Management of acute alcoholic hepatitis

The mainstays fo management are supportive and include: abstinence from alcohol, adequate nutrition and treatment of any intercurrent infections. Liver biopsy may be indicated to confirm the diagnosis. Maddrey's discriminant function score of > 32 is an indication for treatment with steroids. 40mg oral pred is frequently used. Other drugs which may be useful include pentoxifylline.

Clinical exam of liver

The surface marking of the upper border of the liver is the right 5th interspace and is best determined by percussion. The liver may be palpable in normal subjects on deep inspiration. The liver may be transiently enlarged in acute alcoholic hepatitis. This can cause hepatomegaly affecting either the whole of the liver or occasionally only he left lobe. The latter presents as an epigastric mass. Hepatomegaly in the absence of signs of CLD is unlikely to be due to cirrhosis. Consider a malignancy instead. Chronic myeloid leukaemia may present with jaundice secondary to an autoimmune haemolytic anaemia. The jaundice is pre-hepatic, giving the sclera a lemon yellow tinge.

Hepatomegaly causes

Top 3 causes: 1. Congestive cardiac failure 2. Malignancy 3. Lymphoma

Spleen exam

Usual abdominal exam. In addition: - Look for signs of RA - Look for signs of underlying carcinoma which may be associated with splenic vein thrombosis. The differential diagnosis of an enlarged spleen is usually a palpable left kidney. The spleen cannot be balloted, is dull to percussion, has a notch and you should be able to 'get above' it.

Hepatomegaly presentation

V. common worldwide, usually due to infection (malaria, hepatitis, leishmania) or malignancy. Patients may be referred: 1. Asymptomatically: 2. Symptomatically: - Features of underlying malignancy - Abdominal pain - usually due to rapid enlargement, necrosis of an enlarging tumour, or heart failure. Pain may be referred to the right shoulder. - Jaundice with enlarged liver.

Causes of splenomegaly

Worldwide common: - Chronic malaria - Kala-azar - Schistosomiasis. Splenomegaly is nearly always present in chronic myeloid leukaemia and myelofibrosis and may be massive (>20 cm). Enlargement to 4-8cm is found in: - lymphoma, - chronic lymphotic leukaemia (CLL) - cirrhosis with portal hypertension - CML - myelofibrosis If the spleen is just palpable consider CML, myelofibroiss, lymphoma, CLL, cirrhosis in addition acute infections such as EBV, CMV and subactue bacterial endocarditis. 'Left-sided' (sinistral) portal hypertension is commonly caused by splenic vein compression or thrombosis as a result of, for instance, a pancreatic tumour. Compression causes increased pressure in the left portal venous system leading to gastric varices.