Jetra
i bilijarni trakt
Rada
Ješić, *Božina Radević, *Dragan Sagić, Djordje Ćulafić, Aleksandra Pavlović,
Tamara Cvejić, Radmila Šarenac, Vladislava Bulat, Miodrag Krstić.
Institute for
Digestive Diseases, Clinic of Gastroenterology and Hepatology, Clinical Center
of Serbia, Belgrade, *Institute of Cardiovascular Diseases “Dedinje”, Belgrade.
( accepted November 1st, 2002 )
Address
correspondence to: Professor Dr Rada Ješić
Institute for Digestive Diseases
Clinical Center of Serbia
6
Koste Todorovića St.
YU-11000 Belgrade, Serbia
Yugoslavia
..........................................................
...................................................................
Treatment of hypersplenism in cirrhosis Gastroenterološka sekcija SLD-
01736, 2002.
Abstract
Clinical
manifestations of portal hypertension are primarily caused by the development
of collateral circulation and passive spleen congestion. In some centers
decompressive shunt surgery combined with partial spleen resection became an
essential part of the management of portal hypertension complicated with
varices, massive splenomegaly and hypersplenism. From 1995 until 2002, 63
consecutive patients with compensated liver cirrhosis, portal hypertension,
massive splenomegaly and symptomatic hypersplenism enrolled this study. All
patients underwent subtotal spleen resection combined with latero-lateral
splenorenal (L-L SR-H), mesocaval (MC-H) or selective distal splenorenal (SDSR)
Waren shunt. In the majority of them (45 cases,71%) all haematologic indices
improved significantly. Median follow-up
was 4.3 years. During this time all haematological parameters remained stable.
Variceal bleeding rate was considerably reduced. There were no clinical and
laboratory signs of deterioration of liver function in any patient.
We conclude
that elective subtotal spleen resection combined with shunt surgery may become
method of choice in treating patients with severe hyperspenism associated with
portal hypertension and massive
splenomegaly.
Key
words:liver cirrhosis,portal hypertension,hypersplenismus.
Sažetak
Kliničke manifestacije
portne hipertenzije (PH) prvenstveno nastaju zbog razvoja
kolateralnog krvotoka i pasivne kongestije slezine. Parcijalna
resekcija slezine i dekompresivni
portosistemski šant prestavljavju jedan od načina da se reši problem PH
sa hiperpslenizma. i variksima.
U našoj studiji koja je trajala od sredine 1995. godine do kraja oktobra 2002. godine pratili smo 63 bolesnika sa
kompenzovanom cirozom jetre, masivnom splenomegalijom i simptomatskim znacima
hipersplenizma. Kod njih su uglavnom uradjene dvotrećinske reskcije slezine uz
latero-lataralni splenorenalni (L-L
SR-H), mezocavalni (M-C-H) ili selektivni distalni splenorenalni (SDSR)
Waren-ov šant. Kod većine pacijenata 45 (71%) došlo je do statistički značajnog
povećanja broja krvnih elemenata svih
loza. Vreme praćenja ovih bolesnika bilo je u proseku 4.3 godine. Tokom ovog
perioda broj krvnih elemenata se nije značajnije menjao u odnosu na vrednosti istih u neposrednom postoperativnom periodu.
Funkcija jetre ostala je nepromenjena. Veličina variksa i broj recidivantnih
krvarenja iz variksa su znatno redukovani.
Zaključujemo da ovakav način lečenja bolesnika sa
kompenzovanom cirozom jetre i njenim
komplikacijama kao što su PH, masivna splenomegalija i simptomatski
hipersplenizam je metoda izbora.
Ključne
reči:ciroza jetre, portna hipertenzija, hipersplenizam.
In patients
with liver cirrhosis secondary hypersplenism is a common complication of
massive congestive splenomegaly due to portal hypertension (PH). This lead to
decrease of all blood elements (1,2). Several aetiological factors additionally
act in decreasing all corpuscular blood elements such as recurrent
gastrointestinal bleeding, nutritional deficits, bone marrow alchohol toxicity,
and protein deficiency.
Low
platelet count is the most essential abnormality in hypersplenism. This is to
occur in 14% to 70% patients depending of the reported series, definition of
the stage of liver disease and lower cutt off trombocyte value (3).
Thrombocytopenia mostly develops because of platelet pooling within enlarged
spleen (1). In liver cirrhosis decreased hepatic thrombopoetin synthesis
additionally contributes to the development of trombocytopenia (4).
Granulocyte
and lymphocyte celullar kinetic in normal and enlarged spleen has been
insufficiently studied. It seems that splenic leukocyte pooling and their
sequestration is responsible for leukopenia in hypersplenism (1,5). Neutropenia
in PH-related hypersplenism is mild with average leukocyte number between 2-4 x
109 /L. It is recorded in 11% to 41% of patients with liver
cirrhosis. Mild leukopenia is without any clinical significance. The most
common abnormality in chronic liver disease seems to be absolute lymphopenia,
even in the absence of overall leukopenia.
Anemia in
chronic liver diseases is almost constant finding and develops in
aproximatelly 50% of patients. It does
not correlate with the degree of liver diseases. Anemia due to hypersplenism is
mild and normochromic with hemoglobin between 100-120 g/L and normal
reticulocyte count. Beside sequestration of erythrocytes by the spleen, other
aetiological factors are operable (1,2,5).
There is an
evidence that in patients with portal hypertension and massive splenomegaly,
successfully performed shunt operation do not correct haematological
abnormalities of hypersplenism. In this
case shunt decompression and variceal disengagement is not paralelled with
haematological reconstruction. It seems that shunt operation combined partial
spleen resection is necessary surgical intervention in hypersplenism associated
with symptomatic cytopenia (6).
Here we
report our approach to the management of portal hypertensive patients with massive splenomegaly and pronounced
haematological abnormalities of hypersplenism.
From 1995
until 2002, 63 patients diagnosed as having liver cirrhosis and symptomatic
signs of hypersplenism, with or without gastroesophageal varices, underwent
subtotal splenic resection combined with Warren selective distal splenorenal
shunt (S-D SR), latero-lateral splenorenal shunt (L-L SR) H shunt or mesocaval
H shunt (MC H shunt). Patients were examined at the Clinic for Gastroenterology
and Hepatology, Clinical Center of Serbia, while surgical interventions were
performed at the Institute of Cardiovascular Diseases “Dedinje” by one of us (
BR). The hepatic function was graded as Child B in 47 (74.7%), and Child C in
15 (25.3%) patients. Liver function tests and hematological analyses were
performed before operation, one month, one year, and 3 years after splenic
surgery.
RESULTS
Preoperatively 28 (44.4%) patients bled from oesophageal varices. After shunt surgery combined with subtotal splenic resection variceal haemorrhage recurred only in one patient; the volume of varices was reduced in 35 (66.6%) cases, while remained same in 28 (33.4%) patients. Three patients died postoperatively during the first month. In the remaining 60 patients liver function tests remained unchanged during the follow up period.The number of blood elements considerably increased. The peak was reached on day 14 after the operation, and satisfactory values remained stable until the completion of this study.
Table 1.
Clinical picture of operated patients with liver cirrhosis and hypersplenism
|
Feature |
before |
after shunt and spleen resection 1
year 3 years |
|
Age Males/females Child s grading (B/C) AST (IU/L) ALT (IU/L) Serum albumin (g/dL) Total bilirubin (mg/dL) Prothrombin time (%) |
43.3 34/29 47/15 47.3 ± 31.2 61.6 ± 51.8 3.4 ± 0.5 1.2 ± 1.0 67.0 ± 18.1 |
52.3 61.7
72.3 76.4
3.3 3.3
1.1 1.2
63.4 62.3 |
|
|
|
|
Table 2.
Changes of white cell and platelet count before and after shunt and
partial spleen
resection
|
|
before
therapy |
after 1
month |
after 1
year |
after 3
years |
|
WBC/mL Platelets/mL |
2718 57 |
3012 191 |
3017 167 |
3974 113 |
|
|
|
|
|
|
White blood
cell and platelet count increased immediately after the operation, and remained
stable throughout the whole study. There was no significant difference between
AST, ALT, albumin and bilirubin levels before and after one month, a year and 3
years of the splenectomy.
The
follow-up of these patients was approximately 4 years and 3 months, while liver
function tests and the number of blood elements remained unchanged.
DISCUSSION
In the adult population portal hypertension is usally caused by chronic liver disease. Splenomegaly is an important sign of PH. Its size does not corelate with degree of increased portal pressure (7). Massive splenomegaly is usually accompanied with hypersplenism, but the majority of patients with splenomegaly has no hypersplenism. Oppositelly in alcoholic hepatitis, some authors noted blood changes due to hyposplenism (8).
Passive
spleen congestion in PH causes haematological abnormalities of hypersplenism
because of increased splenic pooling and/or destruction of corpuscular blood
elements (9.10). Bone marrow is usually hypercellular. In 1996, Shah et Jalani
studied the relation of splenic size, degree of hypersplenism, and portal
hemodynamics in liver cirrhosis (9,11). They found negative correlation between
splenic size and white blood cell count. There were no correlation between
spleen size, red cell and platelet count (9,11).
Decompressive
shunt surgery is very effective means of lowering portal pressure and variceal
disengagement. Conversely shunt procedures itself do not ultimatelly correct
blood changes of hypersplenism; the increase of blood elements may occur in
approximately 50% of patients (6,11). To
correct blood dyscrasia caused by
hypersplenism and upregulate splenic reduction procedures are neccessary.
Multiple
therapeutic options have been used for treatment of hypersplenism including splenectomy,
partial splenectomy, partial splenic embolization, decompressive shunt, TIPS,
etc. It seems that elective decompressive shunt surgery combined with subtotal
splenic resection is an advantageous option for variceal decompressing and
relieving blood dyscrasia due to hypersplenism. Our study confirms that after
partial resection of the spleen and decompressive shunt surgery, an improvement
of thrombocytopenia, leukopenia parallel decreased incidence of variceal
bleeding (14).
David and
associates reported that following spleenic resection all their patients
experienced splenic regeneration, but the degree of splenic regeneration was
not in correlation with recurring hypersplenism (12). In our series after
surgical resection there was no evidence of increased regeneration of splenic
tissue or signs of more pronounced recurrent hypersplenism. Hypersplenism
appeared to repeat in those patients who had the resection of splenic tissue
less than 60% (13).
There is
plenty of evidence that thrombocytopenia occur after transjugular intrahepatic
portosystemic shunt (TIPS) placement. Only one study demonstrated some increase
of platelet count at 1 month and 1 year TIPS but full normalization of platelet
count was not noted (15).
Since
recently, there are some reports about improvement of liver function after
partial splenic embolization making 60% to 75% splenic tissue disfunctional
(16). Likewise, several earlier studies showed that hepatic regeneration after
partial hepatic resection was accelerated over time once a splenectomy was
performed. However, the effects of splenectomy to cirrhotic patients have not
been fully clarified. Splenectomy may improve hypersplenism in cirrhotic
patients and is assumed to benefit such patients by promoting hepatocytes regeneration
(14,17,18). In our study we had no evidence of liver function improvement after
subtotal splenic resection, but there was no aggravation in relation to
preoperative liver status.
In the
intractable portal hypertension with severe blood dyscrasia liver
transplantation is indicated. Hypersplenism is usually improves after liver
transplantation. After several years of successful liver transplantation, the
spleen becomes smaller and the number of blood cells increases; it seems that
liver transplantation is an optimal treatment for patients with advanced liver
disease and hypersplenism (19,20). This combined with hematopoetic growth
factors may further improve the prospect of such patients. Administering
granulocyte-macrophage colony-stimulating factor (GM-CSF) for 7 days, may increase white blood cell count in patients
with end-stage cirrhosis and neutropenia (22). Cytokine therapy using
thrombopoietin and granulocyte-macrophage colony-stimulating factor (GM-CSF)
may be promising in the future.
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