Liver 2017

1. Alcoholic hepatitis
acute heaptic decompensation in a background of chronic alcohol
abuse . rapidly progrsssing jaundice, fever, SIRS, signs of liver
cirrhosis, ast-alt ratio more than 2 . plan 1. Assess severity using
MELD score, Madrey score . Always do screen for infection on
admission blood, urine , ascites cultures, cxr.start protocol alcohol
withdrawal .void iv fluids, stop nephrotoxic drugs, avoid iv contrast if
possible, do US doppler abd. Treat complications of cirrhosis if present
. Remenber than 7 % develop hepatorenal syn, try to avoid it.
Presence of systemic inflammatory response syndrome (SIRS) on
admission is associated with an increased risk of multi-organ failure
(MOF) syndrome. Development of MOF, usually due to infections
developing after initial diagnosis of AH, is associated with a very high
mortality rate.
2. Serial MELD scores though the hospital stay , if MELD score increases
in 2 points in the first week, the hospital mortality is higher and may
need referral for transplant
3. if mildmod MELD less than 20 refer to alcohol specialist , psych and
strt a high protein diet, folic acid, vit b group
4. Because of malabsortion from jaundice Vit K may be given sc or iv for
3 days

5. Liver biopsy is not necessary for diagnosis but consider if diagnosis

unclear or no good response

6. Nutrition is very important always give 30 -40 cacl-kg-day , 1 to 1.5 g

protein, refrral to nutritionist, put an NG if needed , consider night
enteral nutrition

7. If MELD more than 20 , Maddrey more than 32 severe AH start

corticoides prednisolone 40 mgr-day or if prednisolone unavailable
prednisone or methylprednisolone iv 32 mgr-day. Do Lille socre after 1
week of tx to know if pt is responding to cortis or not. Cortis improve
the mortality at 28 days but not on the long term. If Lille score less
than 56 , continue cortis for 4 weeks , if more, stop them, they are not
working, consider referral for transplant

8. Contraindica to cortis are TB, hepatitis B , active uncontrolled

infection, acute kidney injury, git bleeding, acute pancreatitis. If
cultures reveal infection stop cortis but consider re stating after 48 h
of proper antibiotics tx. Is suspition for infection is low and cultures
are neg in 24 to 48 h start cortis .Only cortis improve mortality, the
data in pentoxifilline is conflicting but if contraind to cortis , start
pentoxyfiline 400 mg oral 8h x 4 weeks

9. Along with cortis start Nacetyl cystein ) same dose as paracetamol od

for 5 days
10.Watch for hepatorenal synd and if so start albumin 25 % 1 gr- kg- day
x 2 days max 100 mg . in the 25 % solution each ml has 0.25
grams , see hepatorenal synd for details.

11.VARICEAL BLEEDING . PORTAL HYPERTYENSION

12.Primary prophylaxis screening endoscopy Increased risk of a variceal
hemorrhageif Child B or C ,larger varices, and those with red signs
on the varices. Indefinite use of nonselective -blockers to reduce
resting heart rate by 25%, with a heart rate no lower than 55
beats/min. Nadolol 40 mg once a day adjusting renally or propanolol
20 mg twice daily. If a patient cannot tolerate -blockers esophageal
variceal ligation .
Risk increased if severe portal hypertension, gradient more than 20, ,
large varices with red wale markings and/or in Child C Bleeding
usually occurs at the GE junction . Approximately 50% of the acute
variceal bleeding ceases spontaneously8. After an index bleeding
episode, most of the episodes of rebleeding occurs in the first 6
weeks and over 50% of such rebleeding episodes occur within 3 to 4
days from the time of admission for the initial bleeding.
1 risk factors for early rebleeding severe initial bleeding with
hemoglobin less than 8 g/dL, gastric variceal bleeding,
thrombocytopenia, encephalopathy, alcohol-related cirrhosis, large
varices, active bleeding during endoscopy, and a high gradient .In
the the long-term, approximately 70% of subjects experience
further variceal bleeding Age greater than 60 years, large
esophageal varices, severity of liver disease, continued
alcoholism, renal failure, and presence of a hepatoma increase the
risk of rebleeding
Up to 40% of patients still die from exsanguinating bleeding. Of note,
most deaths are unrelated to bleeding per se and are rather caused
by complications of bleeding such as liver failure, infections and
hepatorenal syndrome
2 Resucitation with crystalloids and packed red blood cells to keep
systolic blood pressure at least at 90100 mmHg, hemoglobin around
78 g/dL. Avoid overtransfusion as this can cause a rebound increase
in portal pressure and precipitate early rebleeding . May need
platelets and FFP if massive bleeding protocol but avoid overload
Very high risk for aspiration pneumonia, protect airway.
Prophylactic antibiotics for 7 days 30% to 40% will have bacterial
infection on admission or within the first week after variceal
bleeding ,most common spontaneous bacterial peritonitis,,
bacteremia, followed by urinary tract infections and pneumonia. Most
infections are due to enterobacteria.Quinolones in uncomplicated
patients and Ceftriaxone in high-risk patients with advanced liver
disease (ascites, encephalopathy, jaundice, and malnutrition) or
previous therapy with quinolones
Hepatic encephalopathy is common Start aggressive therapy with
Lactulose orally or NG once bleeding is controlled . Combination
 therapy of Lactulose with Rifaximin may be more useful. Patients with
persistent hepatic encephalopathy without improvement despite
withdrawal of sedation and aggressive use of lactulose, need an
imaging study of the head (CT scan or MRI) and
electroencephalogram
3. Endoscopic sclerotherapy, and variceal ligation. If failing standard
measures consider rescue therapy such as balloon tamponade,
placement of esophageal covered metal stent, TIPS, BRTO
4. pharmacological tx with the idea to cause splanchnic
vasoconstriction leading to a reduction in portal venous inflow and
consequently to a decrease in portal pressure.
Octreotide initial bolus of 50 g, followed by an infusion of 50
g/h
Terlipressin every 4 hours .caution as is a potent coronary and
crebral vasoconstrictor 5. Transjugular intrahepatic portosystemic
shunt (TIPS)
HEPATIC ENCEPHALOPATHY
30% to 45% of patients with decompensated cirrhosis
West Haven Criteria for altered mental state in hepatic encephalopathy
StAGe DeSCRiPtion Grade I Trivial lack of awareness Euphoria or anxiety
Shortened attention span Impairment of addition or subtraction Altered
sleep rhythm Grade II Lethargy or apathy Disorientation for time
Obvious personality change Inappropriate behaviour Dyspraxia
Asterixis Grade III Somnolence or semistupor Responsive to stimuli
Confused Gross disorientation Bizarre behaviour Grade IV Coma
Ammonia is the toxin most often implicated in the pathogenesis of HE.
However, an elevated serum ammonia level is not required to make a
diagnosis of HE .If a patient with HE has an elevated ammonia level, it does
not rule out .coexistent medical conditions that might explain abnormal
mental status, rendering HE a diagnosis of exclusion.
Tx 1. Assess for precipitants such as infections, gastrointestinal bleeding,
electrolyte disorders, hypovolemia, constipation, and psychotropic
medications.
lactulose 30-Ml EVERY 12H titrated up with the aim of having 2 to 3 soft
stools per day. Lactulose can also be administered via nasogastric tube or as
a rectal enema (300 mL in 1 L of water retained for 1 hour with the patient
in the Trendelenburg position). Common side effects include diarrhea,
bloating, and abdominal cramps
Rifaximin oral 550 mg twice daily ,has minimal systemic
absorption ,few side effects and when added to lactulose
decreases recurrence of HE
Many patients with ESLD have protein-calorie malnutrition, protein
restriction is generally not recommended.

Spontaneous bacterial peritonitis

diagnostic paracentesis is recommended in all cirrhotic with ascites at the
time of admission and/or in case of gastrointestinal (GI) bleeding, shock,
signs of inflammation, hepatic encephalopathy, worsening of liver or renal
function
The hospital mortality for SBP ranges from 10%-50%. overall one-year
mortality rate after a first episode of SBP are 30%-93% regardless of its
recurrence
Predictors for poor prognosis in SBP include older age, higher Child-Pugh
scores, nosocomial origin, encephalopathy, elevated serum creatinine and
bilirubin, ascites culture positivity, presence of bacteremia, and infections
with resistant organisms
Diagnosis fluid infection PMN count of 250 cell/mm3 or greater and an
ascitic fluid culture positive for bacteria, in the absence of a surgically
treatable source.
Primary prophylaxis of SBP only if advanced cirrhosis, history of variceal
bleeding or ascites fluid protein levels below 1.5g/dL. Use 400 mg of
norfloxacin daily .
Start empiric therapy when 1 or more of the following findings are present:
a temperature greater than 37.8C (100F), abdominal pain or tenderness, a
change in mental status, or an ascitic fluid polymorphonuclear cell count of
250 cells/mm3 or greater Most coomon are Gram-negative, single-species
Escherichia coli bacteria or Klebsiella species .
treatmen third-generation : 2 g of cefotaxime intravenously every 8 hours
or 1 g of ceftriaxone intravenously or intramuscularly twice daily is an
alternative.. In countries with low rate of quinolone-resistant
Enterobacteriaceae, oral quinolones may be used for uncomplicated SBP, as
defined by cases without shock, ileus, GI bleeding, hepatic encephalopathy
( grade II) or renal impairment (creatinine > 3 mg/dL)
In nosocomial SBP, use of the antibiotics recommended above can be
associated with unacceptable failure rates because resistance to third-
generation cephalosporins (23%-44%) and quinolones (38%-50%) are
increasingly reported. Consider carbapemen ].
Use of non-selective -blockers in patients who develop SBP is associated
with worse outcomes, including increased mortality, and these should be
permanently discontinued.
After the first episode of SBP, the rate of recurrence is up to 70%, and
secondary prophylaxis is indicated in all patients. Quinolones (400 mg of
norfloxacin daily and alternatively 1 double-strength tablet of
trimethoprimsulfamethoxazole daily) decrease the risk of SBP recurrence
from 70% to 20%.
In cases with questionable diagnosis or in those who did not satisfactorily
improve with ATB, repeated paracentesis If the PMN count does not reduce
by at least 25% after 2 d of ATB, changing treatment and/or reevaluation for
other possible causes
Renal impairment develops in 30%-40% of SBP cases Use of intravenous
albumin (1.5 g/kg within 6 h of SBP diagnosis followed by 1 g/kg on day 3)
decreases renal faliure and mortality. Notably, albumin infusion was
particularly effective in patients with baseline serum creatinine 1 mg/dL,
blood urea nitrogen 30 mg/dL or bilirubin 4 mg/dL[

Common
Types of Suggested empirical antibiotic
responsible bacteria
infection
SBP,
spontaneous Enterobacteriaceae 1st line: Cefotaxime or ceftriaxone or BL-BI IV
bacteremia, SBE
Options: Ciprofloxacin PO for uncomplicated
S. pneumoniae
SBP1; carbapenems IV for nosocomial
infections in areas with a high prevalence of
S. viridans
ESBL
BL-BI may prefer in those with suspicious for
enterococcal infection2
Community-acquired: ceftriaxone or BL-BI IV
Pneumonia Enterococci
+ macrolide or levofloxacin IV/PO
 Common
Types of Suggested empirical antibiotic
responsible bacteria
infection
Nosocomial and health care-associated
S. pneumoniae
infections: Meropenem or cetazidime IV +
ciprofloxacin IV (IV vancomycin or linezolid
H. infuenzae
should be added in patients with risk
M. pneumoniae factors for MRSA3)
Legionella spp.
Enterobacteriaceae
P. aeruginosa
S. aureus
Urinary tract 1st line: Ceftriaxone or BL-BI IV in patients
Enterobacteriaceae
infection with sepsis. Ciprofloxacin or
E. faecalis cotrimoxazole PO in uncomplicated infections
Options: In areas with a high prevalence of
ESBL, IV carbapenems for nosocomial
E. faecium infections and sepsis (+ IV glycopeptides for
severe sepsis); and nitrofurantoin PO for
uncomplicated cases
Skin and soft Community-acquired: Ceftriaxone +
S. aureus
tissue infections cloxacillin IV or BL-BI IV
Nosocomial: Meropenem or cetazidime IV +
S. pyogenes
glycopeptides IV
Enterobacteriaceae
P. aeruginosa
Vibrio vulnificus
Aeromonas spp.
Community-acquired: Cefotaxime or
Meningitis S. pneumoniae
ceftriaxone IV + vancomycin IV
Ampicillin IV should be added if L.
Enterobacteriaceae
monocytogenes is suspected4
L. monocytogenes Nosocomial: Meropenem + vancomycin IV
N. meningitidis
1
Quinolones should not be used in patients submitted to long-term norfloxacin
prophylaxis or in geographical areas with a high prevalence of quinolone-resistant
Enterobacteriaceae;
2
Risk factors for Enterococci: Quinolone prophylaxis, hospital-acquired infection;
3
Risk factors for MRSA: Ventilator-associated pneumonia, previous antibiotic therapy,
nasal MRSA carriage;
4
Risk factors for L monocytogenes: Hemochromatosis, detection of gram-positive
bacilli/coccobacilli in cerebrospinal fluid..
Table 3 Common manifestations and risk factors of bacterial pathogens in patients with
cirrhosis.
Common
Pathogens clinical Risk factors Remarks
syndrome
Contaminated
Increased incidence
food and water
SBP, High mortality
Aeromonas spp. (A.
bacteremia, Diabetes (20%-60%),
hydrophila, A. sobria, A.
SSTI, especially when
aquariorum)[120-126]
enterocolitis presence of
Most reports were
hypotension on
from East Asia
admission
Increased incidence
Bacteremia, High mortality
Campylobacter spp.[127,128] Alcoholic
SBP (10% in
bacteremia)
Clostridium spp. (C. Increased incidence
perfringens, C. bifermentans, SSTI Diabetes Very high mortality
C. septicum)[4,129,130] (54%-65%)
Broad-spectrum
Increased incidence
ATB
Higher mortality
ATB-associated (14%) when
Clostridium difficile[108,131- Hospitalization
diarrhea and compare to non-
133]
colitis cirrhotics
Increased cost and
PPIs length of hospital
stay
Healthcare-
associated Increased incidence
infection
SBP, High mortality
bacteremia, Quinolone (30% in
Enterococcus spp. (E. faecium,
UTI, prophylaxis bacteremia; 60% in
E. faecalis, E. galinarum)
endocarditis, SBP)
[134-136]
biliary tract Increased incidence
infection of VRE
colonization and
infection in liver
transplant setting
SBP,
Listeria
bacteremia, Hemochromatosis Increased incidence
monocytogenes[137,138]
meningitis
Mycobacterium TB[2,139,140] Pulmonary TB, Alcoholic Increased
 Common
Pathogens clinical Risk factors Remarks
syndrome
incidence,
especially
extrapulmonary
forms (>
50% of TB
TB peritonitis, Developing peritonitis cases in
TB countries the United States
lymphadenitis, had
disseminated Exposed to TB underlying
TB case cirrhosis)
High mortality
(22%-48%)
Increased risk for
multi-drug resistant
TB
Increased risk for
anti-TB-induced
hepatotoxicity
Presence of ascites
SBP, Increased incidence
(TB peritonitis)
Pasteurella multocida[141- bacteremia
143] septic arthritis, Domestic animal High mortality
meningitis (cats or dogs) bites (10%-40% in
or scratches bacteremia)
Increased incidence
Alcoholic of MRSA carriage
and infection
SSTI, UTI,
High mortality
Staphylococcus SBP, Invasive
(30% in
aureus[45,144,145] bacteremia, procedures
bacteremia)
endocarditis
Removal of the
Hospitalization eradicable focus
was associated with
decreased mortality
Streptococcus bovis[146,147] Bacteremia, Quinolone
Increased incidence
SBP prophylaxis
meningitis, High mortality (up
endocarditis, Colonic lesion(s):
to 40% in
septic arthritis Adenoma or
bacteremia with
adenocarcinoma
advanced cirrhosis)
(presence in
18%-40% of Colonic lesion(s)
 Common
Pathogens clinical Risk factors Remarks
syndrome
was present in
cases)
18%-40% of cases
Alcoholic
SSTI, Increased incidence
bacteremia, Post endoscopic
Streptococcus group B[148-
SBP, sclerotherapy and High mortality
150]
meningitis, banding ligation (10%-25% in SBP
pneumonia and bacteremia;
45% in meningitis)
Increased incidence
Pneumonia, of invasive
Alcoholic
SBP pneumococcal
Streptococcus pneumoniae[89- disease
bacteremia,
92]
SSTI, High mortality
Post-splenectomy
meningitis (10%-20%)
Not vaccinated
Hemochromatosis Increased incidence
Exposed to Very high mortality
SSTI,
Vibrio spp. (V. vulnificus, non- seawater and (50%-60% in
bacteremia,
o1 V. cholera, V. undercooked bacteremia; 24% in
gastroenteritis,
parahemolyticus)[151-153] seafoods SSTI)
diarrhea, SBP
Most reports were
from East Asia
Increased incidence
Hemochromatosis (in
Bacteremia, hemochromatosis)
Yersinia spp. (Y. enterocolitica,
SBP, High mortality
Y. pseudotuberculosis) Exposed to
hepatosplenic (50% in
[154,155] animals and
abscesses bacteremia)
contaminated
foods

secondary prophylaxis of SBP should be given indefinitely or until LT[37,40,61,64].

Intermittent dosing of prophylactic ATB may select resistant flora, thus daily dosing is
preferred[37,40] (Table 4).

Table 4 Vaccinations and other preventive measures for bacterial infections in patients
with cirrhosis.
Avoidance
Raw/uncooked foods, especially seafood
Close contact to at-risk animals or sick people
Wound exposure to flood or seawater
Vaccination[87]
Recommended yearly for all patients with chronic liver
Influenza
disease
Pneumococcal Recommended for all cirrhotic patient
(polysaccharide) Booster dose after 3-5 yr
Recommended for all non-immune, cirrhotic patient, 2
Hepatitis A injections 6-12 mo apart
Anti-HAV should be checked 1-2 mo after the second dose
Recommended for all cirrhotic patient without serological
markers of HBV (e.g., negative HBsAg, anti-HBs, and anti-
HBc antibodies)
3 injections (at month 0, 1 and 6)
Hepatitis B Anti-HBs should be checked 1-2 mo after the last dose
Patients with advanced cirrhosis should receive 1 dose of 40
g/mL (Recombivax HB) administered on a 3-dose schedule
or 2 doses of 20 g/mL (Engerix-B) administered
simultaneously on a 4-dose schedule at 0, 1, 2 and 6 mo
Other vaccines, e.g., Td,
Recommendations are as same as general adult population
Tdap, MMR, varicella
Prophylactic antibiotics
Secondary prophylaxis Recommended for all cirrhotic patients who recovered from
for SBP[32,41] SBP
Norfloxacin 400 mg PO daily
Alternatives: TMP/SMX 1 double-strength tablet or
ciprofloxacin 500 mg PO daily
Primary prophylaxis in
Recommended for all cirrhotic patients with GI hemorrhage
GI bleeding[32,41]
Norfloxacin 400 mg PO twice daily or ceftriaxone 1 g IV
daily for 7 d
IV ceftriaxone is preferred, in patients with advanced
cirrhosis as defined by the presence of at least two of the
following: Ascites, severe malnutrition, encephalopathy or
bilirubin > 3 mg/dL
Recommended for cirrhotic patients with ascitic fluid protein
Primary prophylaxis in < 1.5 g/dL and at least one of the following is present:
patients with low ascitic Serum creatinine > 1.2 mg/dL, blood urea nitrogen > 25
fluid protein[32,41] mg/dL, serum sodium < 130 mEq/L or Child-Pugh > 9
points with bilirubin > 3 mg/dL
Prophylaxis before Prophylactic antiobiotics are recommended for the
undergoing endoscopic moderate-high risk invasive endoscopic or surgical
and surgical procedures procedures (choice of antibiotics should be individualized)
Prophylactic antibiotics are not routinely recommended for
 diagnostic endoscopy, elective variceal band ligation or
sclerotherapy, and abdominal paracentesis

ASCITES