This document discusses pyogenic liver abscess, including epidemiology, risk factors, pathogenesis, microbiology, and relationships to hepatocellular carcinoma and colorectal cancer. Some key points:
- Klebsiella pneumoniae is the most common causative organism, especially in Asia.
- Risk factors include diabetes, liver cirrhosis, hepatitis B/C infection, and older age.
- Pathogenesis can involve biliary tract infection, hematogenous spread, or direct invasion.
- In some cases, liver abscess may be an initial manifestation of underlying hepatocellular carcinoma or metastasis from colorectal cancer.
4. 肝膿瘍はHCCの初症状かも?
台湾における1997-2008年に報告された肝膿瘍32454例の解析
平均年齢61歳. 18-106歳まで分布. 男性例が61.3%
糖尿病41.3%, 肝硬変7.2%, 胆石症23.7%, 慢性肺疾患6.9%
HCCの初発症状として肝膿瘍を認めた例が2.15%あり,
特に>65y, HBV, HCV陽性, 肝硬変(+)群ではhigh risk.
60d死亡率はHCC群で14.5%, 非HCC群で8.1%と予後にも関わる.
治療方針にも関わるため, HCCの関与の有無を評価するのは大事.
The American Journal of Medicine (2011) 124, 1158-1164
5. genic liver abscess as the initial manifestation of underlying
hepatocellular carcinoma has been reported only in a small
case series from east Asia.12-14
To our knowledge, this is the
first attempt to investigate the frequency of, risk factors for,
cellular carcinoma was already present in our patients at the
time pyogenic liver abscess was diagnosed. We found that
liver cirrhosis, hepatitis B virus infection, hepatitis virus C
virus infection, and advanced age were independent risk
Characteristics
Pyogenic Liver Abscess as
the Initial Manifestation
of Underlying
Hepatocellular Carcinoma
(n ϭ 698)
Pyogenic Liver Abscess
without Hepatocellular
Carcinoma (n ϭ 31,756)
P ValueNumber % Number %
Sex
Male 463 66.3 19,429 61.2 .006
Female 235 33.7 12,327 38.8
Age, years Ͻ.001
Ͻ65 319 45.7 17,292 54.5
Ն65 379 54.3 14,464 45.5
Comorbidity
Diabetes mellitus 184 26.4 13,231 41.7 Ͻ.001
Chronic renal failure 54 7.7 2554 8.0 .826
Autoimmune diseases 5 0.7 174 0.5 .441
Chronic pulmonary disease 69 9.9 2173 6.8 .002
Liver cirrhosis 247 35.4 2085 6.6 Ͻ.001
Cholelithiasis 172 24.6 7522 23.7 .561
Hepatitis B virus infection 136 19.5 1106 3.5 Ͻ.001
Hepatitis C virus infection 100 14.3 647 2.0 Ͻ.001
Septic metastasis* 1 0.1 606 1.9 Ͻ.001
Management
Abscess drainage 128 18.3 9972 31.4 Ͻ.001
Surgical intervention 193 27.7 4497 14.2 Ͻ.001
60-day mortality 101 14.5 2574 8.1 Ͻ.001
*Including endophthalmitis or meningitis.
HCCの初症状としての肝膿瘍 vs HCCに関係しない肝膿瘍
DMが無く, 肝硬変, HBV, HCV(+)の患者での肝膿瘍ではHCCの関与を疑う
6. 大腸癌関連の肝膿瘍96例の報告例の解析.
報告例の大半が東アジアから. 特に日本からは40例と多い.
中国 26例, 韓国 8例.
報告例の平均年齢 64.4±10.1y
男女比は1.5:1と男性で多い.
大腸癌→肝膿瘍のパターンも増加中
World J Gastroenterol 2012 June 21; 18(23): 2948-2955
Country/region No. of cases No. of articles
Eastern Asia
Japan 40 36[6-10]1
China 26 6[4,5,11-14]
Korea 8 1[15]
Singapore 3 1[16]
Middle East and Europe
Israel 3 3[17-19]
Italy 2 2[20,21]
Spain 2 2[22,23]
Portugal 1 1[24]
France 1 1[25]
United Kingdom 1 1[26]
North and Central America
United States 7 7[2,27-32]
Canada 1 1[33]
Netherlands Antilles 1 1[34]
Total 96 63
Table 1 Documented cases collected from the international
literature
Qu K et al. Liver abscess complicated with colorectal can
o. of cases No. of articles
40 36[6-10]1
26 6[4,5,11-14]
8 1[15]
3 1[16]
3 3[17-19]
2 2[20,21]
2 2[22,23]
1 1[24]
1 1[25]
1 1[26]
7 7[2,27-32]
1 1[33]
1 1[34]
96 63
ted from the international
cle reference were included[8]
.
Pathogens
Eastern Asia Non-Eastern Asia Total
(n = 49) (n = 9) (n = 58)
Bacteria
Gram negative bacteria
Klebsiella pneumoniae 28 (57.14) 1 (11.1) 29 (50.0)
Fusobacterium species 4 (8.16) 0 4 (6.90)
Bacteroides species 2 (4.08) 1 (11.1) 3 (5.17)
Escherichia coli 0 1 (11.1) 1 (1.72)
Pseudomonas aeruginosa 1 (2.04) 0 1 (1.72)
Gram positive bacteria
Streptococcus species 1 (2.04) 3 (33.3) 4 (6.90)
Enterococcus faecium 2 (4.08) 0 2 (3.44)
Polymicrobial 0 2 (22.2)1
2 (3.44)
Amoebae 2 (4.08) 0 2 (3.44)
Negative 9 (18.37) 1 (11.1) 10 (17.24)
Table 2 Constituent ratio of pus bacterial cultures n (%)
1
Pus cultures showed mixed infection in two patients: E. corrodens, Candida
albicans and Candida glabrata; Peptostreptococcus anaerobius, Bacteroides mela-
ninogenicus and Peptostreptococcus spp.
y/region
ountry/region
990 1991-2000 2001-2011
(yr)
Eastern Asian country/region
Non-Eastern Asian country/region
41-50 51-60 61-70 71-80 > 80
Age (yr)
No.ofcases
30
20
10
0
Figure 2 Age distribution of reported cases in different countries/regions.
plicated with colorectal cancers
7. 原因菌;
アジアでは, GNRが多く, 特にKlebsiella pneumoniae.
海外はGP, GNが同等程度
No. of cases No. of articles
40 36[6-10]1
26 6[4,5,11-14]
8 1[15]
3 1[16]
urope
3 3[17-19]
2 2[20,21]
2 2[22,23]
1 1[24]
1 1[25]
1 1[26]
America
7 7[2,27-32]
1 1[33]
lles 1 1[34]
96 63
mented cases collected from the international
Pathogens
Eastern Asia Non-Eastern Asia Total
(n = 49) (n = 9) (n = 58)
Bacteria
Gram negative bacteria
Klebsiella pneumoniae 28 (57.14) 1 (11.1) 29 (50.0)
Fusobacterium species 4 (8.16) 0 4 (6.90)
Bacteroides species 2 (4.08) 1 (11.1) 3 (5.17)
Escherichia coli 0 1 (11.1) 1 (1.72)
Pseudomonas aeruginosa 1 (2.04) 0 1 (1.72)
Gram positive bacteria
Streptococcus species 1 (2.04) 3 (33.3) 4 (6.90)
Enterococcus faecium 2 (4.08) 0 2 (3.44)
Polymicrobial 0 2 (22.2)1
2 (3.44)
Amoebae 2 (4.08) 0 2 (3.44)
Negative 9 (18.37) 1 (11.1) 10 (17.24)
Table 2 Constituent ratio of pus bacterial cultures n (%)
1
Pus cultures showed mixed infection in two patients: E. corrodens, Candida
albicans and Candida glabrata; Peptostreptococcus anaerobius, Bacteroides mela-
ninogenicus and Peptostreptococcus spp.
ver abscess complicated with colorectal cancers
World J Gastroenterol 2012 June 21; 18(23): 2948-2955
8. 肝膿瘍の部位は右葉が2/3.
両側性のこともある.
大腸癌の部位は,
直腸, S状結腸が最多.
ただし, 何処でもありえる.
Liver
Stomach
Abscess
locatioin
7.6%
Transverse colon
18.2%
6.0%
Tumor
40.9%
27.3% Sigmoid colon
Right lobe
66.7%
Both lobes
12.1%
Left lobe
18.2%
Rectum
Descendingcolon
Ascendingcolon
Figure 4 Distribution of colorectal cancer and liver abscesses.
World J Gastroenterol 2012 June 21; 18(23): 2948-2955
GNRでも遠隔転移の可能性がある
また, 肝膿瘍は肝癌, 大腸癌に
由来するものの可能性もあり,
リスクがある場合はチェックが必要.
12. ムコイドタイプのK.P.
Capsular serotype K1, K2がムコイドK.P.に関与.
遺伝子検査は研究室レベルでないと不可能だが,
ムコイドタイプのK pneumoniaeの検出にはString signで分かる.
コロニーをすくって, 粘液糸(>5mm)を認めれば
ムコイドタイプである可能性.
その場合, 眼内炎やCNS播種のリスクが高いため,
眼窩診察が必要となる.
Clinical Infectious Diseases 2012;54(2):303–4
abscess. However, Echinococcus granulosis is not endemic in the
Philippines [1], and radiographic features considered pathogno-
monic for hydatid cysts (such as the presence of a laminar layer or
of daughter cysts that contain fluid of lower density than the
surrounding mother cyst fluid [2]) were absent.
In this case, epidemiologic, historic, and imaging characteristics
(seeFigure 1) pointed toward a diagnosis of pyogenic liver abscess,
while growth of bacterial colonies with features characteristic of
K. pneumoniae on blood agar (see Figure 2) confirmed the
diagnosis. In recent series, pyogenic liver abscess has been incre-
asingly common in patients of Asian descent [3, 4]. A previous
history of biliary disease, as in this case, is an important risk
factor for pyogenic liver abscess [4]. Further, the most common
radiographic finding in amoebic liver abscess (ALA) is a single,
common finding is that of a single, right-sided lesion [3].
Over the past few decades, a clinically distinct syndrome o
community-acquired K. pneumoniae liver abscess (KLA) has bee
described by researchers in Taiwan and other areas. This syn
drome affects relatively healthy hosts, has been variably associate
with the presence of diabetes mellitus as an underlying risk facto
and causes a high rate of metastatic spread. K. pneumoniae isolat
from these patients have reliably been linked to the hyperprodu
tion of capsular, or slime, polysaccharide (ie, hypermucoviscosity
which forms a ‘‘string’’ when the colony is touched by a loop (se
Figure 2). The pathogenesis of this syndrome is under study, bu
the presence of capsular serotype K1, and to a lesser extent K
appears to play a role in the virulence of the organism [7, 8].
Management of pyogenic liver abscess includes effective ant
microbial therapy, in combination with surgical or percutaneou
drainage in most cases. Curative medical management alone
possible, but is associated with a higher risk of complications suc
asabscessruptureorrelapse.Bacteremiaisverycommonincases
KLA, and metastatic or extrahepatic abscesses have been reporte
14. Subtypeと毒性の関係
magA, rmpAは
肝膿瘍に関連する
rmpA Aerobactin Resistance Virulence*
Phagocytic Serum
K118
+ + + + +++
K118
+ + + − V(+++,+)
K118
+ + − − +
K118
+ − + + +
K118
+ − + − +
K142
+ + ND ND V(+++,+)
K142
− − ND ND −
K2* + + + + +++
K2* + + + − V(+++,+)
K2* + + − + V(+++,+)
K2* + − + − +
K142
+ + ND ND V(+++,+)
K142
− − ND ND V(+,−)
Non K1 or K242
+ + ND ND V(+++,+)
Non K1 or K242
− − ND ND −
+=virulent strains with a 50% lethal dose (LD50) of ≥1×10³ colony-forming units
(CFU) and >1×10⁶ CFU are less likely to induce complications in mice.
+++=hypervirulent strains with an LD50 of less than 1×10³ CFU are more likely to
induce complications in mice. −=non-virulent strains with an LD50 of 1×10⁶ CFU of
greater (do not cause complications). ND=no data. V=variable. *Chang F-Y,
unpublished data.
Table 2: Microbiological features of Klebsiella pneumoniae associated
with virulence, by serotypeLancetInfectDis2012; 12: 881–87
15. ムコイドタイプのK.P.
(K1,K2)
Wild typeでは粘糸を認めるが
magA, rfbPm rmpA欠損例では
粘糸が認められない.
(Δ; deletion)
function is restricted to the capsular gene cluster of
serotype K1 only.48,49
Silencing of genes surrounding
magA (figure) in the same cluster of genes needed for
capsular polysaccharide synthesis resulted in
hypermucoviscosity and virulence.23
In 2006, rmpA was proposed as a virulent factor in
addition to magA and capsular serotypes K1/K2.50
rmpA is
not an independent factor contributing to liver abscess
but aids capsule synthesis.7
One report showed that all
rmpA Aerobactin Resistance Virulence*
Phagocytic Serum
K118
+ + + + +++
K118
+ + + − V(+++,+)
K118
+ + − − +
K118
+ − + + +
K118
+ − + − +
K142
+ + ND ND V(+++,+)
K142
− − ND ND −
K2* + + + + +++
K2* + + + − V(+++,+)
K2* + + − + V(+++,+)
K2* + − + − +
K142
+ + ND ND V(+++,+)
K142
− − ND ND V(+,−)
Non K1 or K242
+ + ND ND V(+++,+)
Non K1 or K242
− − ND ND −
+=virulent strains with a 50% lethal dose (LD50) of ≥1×10³ colony-forming units
(CFU) and >1×10⁶ CFU are less likely to induce complications in mice.
+++=hypervirulent strains with an LD50 of less than 1×10³ CFU are more likely to
induce complications in mice. −=non-virulent strains with an LD50 of 1×10⁶ CFU of
greater (do not cause complications). ND=no data. V=variable. *Chang F-Y,
unpublished data.
Table 2: Microbiological features of Klebsiella pneumoniae associated
with virulence, by serotype
Wild-type
Δwzy(magA)
ΔrfbP
ΔrmpA
Serotype K1 Serotype K2
LancetInfectDis2012; 12: 881–87
22. 原因菌頻度
最も多いのはKlebsiella spp.
特にアジア人で多い.
単一菌のみ検出は44%.
検出できなかったのが31%
それ以外の25%は
複数菌による感染症.
Clinical Infectious Diseases 2004;39:1654–9
Figure 3. Identity of organisms recovered from patients with pyogenic
liver abscesses.
only bacterial isolate. The number of bacterial species isolated
from the abscess cavity for each case is shown in figure 2. Most
often, only a single organism was identified (44.2% of cases).
The species of bacteria that were isolated are summarized in
figure 3. K. pneumoniae was the species most commonly iso-
lated and was found in 41% of the 54 cases in which an or-
ganism was recovered. E. coli and Enterococcus species were tied
as the second most commonly isolated organisms (11 cases
each). Klebsiella isolates were more common among Asian pa-
ganism was recovered. E. coli and Enterococcus species were tied
s the second most commonly isolated organisms (11 cases
ach). Klebsiella isolates were more common among Asian pa-
ients than other patients, and they were only isolated from
Asian and Hispanic patients (figure 4). Eighteen (50%) of 36
Asian patients had K. pneumoniae isolated, in contrast with 6
27%) of 22 non-Asian patients, a difference that was not sta-
istically significant ( ).P p .075
In the 23 cases in which K. pneumoniae was recovered, it
was most often the only pathogen. Only 5 of the 23 infections
were polymicrobial. K. pneumoniae was recovered in 22 (46.8%)
of 47 cases in which there was no extrahepatic intra-abdominal
nfection, but it was recovered in only 1 of 11 cases in which
uch an infection was present. The percentage of K. pneumoniae
solates recovered was similar in cases from Bellevue Hospital
nd NYU Downtown Hospital (42.4% and 40.0%, respectively).
Twenty-one of the 23 K. pneumoniae isolates were tested for
ntimicrobial susceptibility. Almost all of the isolates were
highly susceptible, with only 3 isolates showing resistance to
ny drug tested other than ampicillin. Only 1 isolate was an
xtended-spectrum b-lactamase (ESBL) producer.
There was no significant difference in the number of febrile
days or days hospitalized between patients with and patients
without K. pneumoniae isolates, nor was there any significant
difference between K. pneumoniae and non–K. pneumoniae
ases in terms of the initial laboratory parameters. Only 1 pa-
ient was noted to have a Klebsiella species isolated other than
K. pneumoniae (Klebsiella oxytoca), but it was found in con-
unction with K. pneumoniae.
abdominal ultrasound examination.
The most common primary treatment modality was percu-
taneous drainage, which was done in 44 patients (55.7%). Twenty
patients (25.3%) were treated surgically, and 14 (17.7%) were
treated medically. Treatment patterns differed significantly be-
tween the 2 hospitals. At Bellevue Hospital, 67.4% of the patients
were treated primarily with percutaneous drainage, 19.6% re-
ceived medical management, and 13.0% received surgical man-
agement. At NYU Downtown Hospital, 43.8% were treated
surgically, 40.6% were treated with percutaneous drainage, and
15.6% received medical management ( ; ;2
x p 9.50 df p 2 P p
). This difference was attributed to the lack of on-site in-.009
terventional radiology at NYU Downtown Hospital.
ess.
or-
en-
on
es-
xcel
11
s of
x2
bles
YU
age
ale.
ite,
pa-
re-
wn
nts
ion
ere
The
ue,
rast
was present in 32 (43%) of 74 patients who had data recorded
for all 3 findings, and 86% had у2 of these symptoms and
signs on initial evaluation.
Sixty (77%) of 78 evaluable abscesses were solitary. Fifty-
four (70.5%) were right sided, 11 (14.1%) were left sided, and
4 (5.1%) were bilateral. In 9 patients, the location of the abscess
was not documented.
The most common underlying or concomitant conditions
were biliary disease (in 34 [43%] of the patients), hypertension
(14 [17.7%]), intra-abdominal infection (14 [17.7%]), and di-
abetes (12 [15.2%]). Other underlying diseases included ma-
lignancy (12.7%), cardiovascular disease (12.7%), alcohol abuse
(2.5%), and cirrhosis, diverticulitis, and inflammatory disease
(1.3% each).
Fifty-four patients had у1 organism recovered from the ab-
scess. Eighteen (33.3%) of the infections were polymicrobial;
6 of these included anaerobes. In 2 cases, anerobes were the
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