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6 Gastroenterology
Prescribing in liver failure
HRS HRS
HRS
https://t.me/med1917
Avoid drugs that constipate (risk of encephalopathy), oral hypoglycaemics, and
IVIS
saline- containing
Paracetamol, methotrexate, isoniazid, azathioprine, phenothiazines, oestrogen,
6
- mercaptopurine, salicylates, tetracycline, mitomycin.
. Warfarin eects are enhanced. Hepatotoxic drugs include
Hepatic encephalopathy: letting loose some false neurotransmitters
As the liver fails, nitrogenous waste (as ammonia) builds up in the circulation and
passes to the brain, where astrocytes clear it (by processes involving the conversion of glutamate to glutamine). This excess glutamine causes an osmotic imbalance and a shift of fluid into these cells— hence cerebral oedema. Grading:
I Altered mood/ behaviour; sleep disturbance (eg reversed sleep pattern); dys-
praxia (‘Please copy this
II Increasing drowsiness, confusion, slurred speech ± liver flap, inappropriate
behaviour/ personality change (ask the family
III Incoherent; restless; liver flap; stupor.
IV Coma.
What else could be clouding consciousness? Hypoglycaemia; sepsis; trauma; postictal.
5
- pointed star’); poor arithmetic. No liver flap.
—
don’t be too tactful).
271
What is hepatorenal syndrome (
Cirrhosis + ascites + renal failure ≈
have been excluded. Abnormal haemodynamics causes splanchnic and systemic vasodilation, but renal vasoconstriction. Bacterial translocation, cytokines,
and mesenteric angiogenesis cause splanchnic vasodilation, and altered renal
autoregulation is involved in the renal vasoconstriction.
Types of
1 is a rapidly progressive deterioration in circulatory and renal
function (median survival <
ologies. Terlipressin resists hypovolaemia. Haemodialysis may be needed.
is a more steady deterioration (survival
portosystemic stent shunting may be required (
Other factors in cirrhosis may contribute to poor renal function (
Transplants Liver transplant may be required. After >8– 12wks of pre- transplant
dialysis, some may be considered for combined liver– kidney transplantation.
King’s College Hospital criteria in acute liver failure
Paracetamol- induced liver failure Non- paracetamol liver failure
• Arterial pH <
Or all of the following: Or
• Prothrombin time (
• Creatinine >
• Grade
7.3 24
h after ingestion. • PT >
PT
) >
300
µmol/ L.
III
or IV encephalopathy.
Fulfilling these criteria predicts poor outcome in acute liver failure and should
prompt consideration for transplantation (
Based on O'Grady J et al. ‘Early indicators of prognosis in fulminant hepatic failure.’
26
Neutrophilic leucocytosis need not mean a secondary infection: alcoholic hepatitis may be the cause.
27
Urea is synthesized in the liver, so is a poor test of renal function in liver failure; use creatinine instead.
HRS
)?
HRS
— if other causes of renal impairment
2
wks), often triggered by other deteriorating path-
~
6
months). Transjugular intrahepatic
TIPS
, p
252
).
p
272
100
s.
3
100
s.
out of 5 of the following:
1
Drug- induced liver failure.
2
Age <10 or >40yrs old.
3
>1wk from 1st jaundice to encephalopathy.
4
PT >50s.
5
Bilirubin ≥
300
µmol/ L.
p
273
).
Gastroenterology,
97(2):439– 45, 1989
2
).
.
6 Gastroenterology
Cirrhosis
HCC
MRI
SBP
https://t.me/med1917
272
Cirrhosis (Greek kirrhos = yellow) implies irreversible liver damage. Histologically,
there is loss of normal hepatic architecture with bridging fibrosis and nodular
regeneration.
Causes Most often fatty liver disease (chronic alcohol use and non- alcoholic),
HCV
infection. Others: see
or
Signs Leuconychia: white nails with lunulae undemarcated, from hypoalbuminaemia;
Te r ry ’ s n a i l s — white proximally but distal ⅓ reddened by telangiectasias; clubbing;
palmar erythema; hyperdynamic circulation; Dupuytren’s contracture; spider naevi (
6.30
); xanthelasma; gynaecomastia; atrophic testes; loss of body hair; parotid enlarge-
ment (alcohol); hepatomegaly, or small liver in late disease; ascites; splenomegaly.
Complications Hepatic failure Coagulopathy (failure of hepatic synthesis of clot-
ting factors); encephalopathy (
monia; septicaemia); spontaneous bacterial peritonitis (
hypertension
Ascites (fig
sophageal varices (± life- threatening upper
superficial periumbilical veins).
Te st s Blood
LFT
: or bilirubin,
function, look for albumin ±
the cause: ferritin, iron/ total iron- binding capacity (
immunoglobulins (
caeruloplasmin in patients <
+ duplex
p
286
May show a small liver or hepatomegaly, splenomegaly, focal liver lesion(s),
hepatic vein thrombus, reversed flow in the portal vein, or ascites.
size, smaller islands of regenerating nodules, and the presence of the right posterior
hepatic notch are more frequent in alcoholic cirrhosis than in virus- induced cirrhosis.
Ascitic tap Should be performed and fluid sent for urgent
3
indicates spontaneous bacterial peritonitis (see later in topic for treatment).
mm
Liver biopsy (See p
Management General Good nutrition is vital. Alcohol abstinence (p
NSAID
S, sedatives, and opiates. Colestyramine helps pruritus (
244
other drugs). Consider ultrasound ± - fetoprotein every
HCC
(p
282
) in those where this information will change management. Specific For
hepatitis- induced cirrhosis see
may improve
disease (
Give spironolactone
ters deranged renin– angiotensin– aldosterone (
for weight loss of
U&E
sion (
(
LFT
and improve transplant- free survival. Penicillamine for Wilson’s
p
281
). Ascites Fluid restriction (<1.5L/ d), low- salt diet (40–
≤½kg/ d. If response is poor, add furosemide ≤
(watch Na+ ) often. Therapeutic paracentesis with concomitant albumin infu-
6– 8
g/ L fluid removed) may be required. Spontaneous bacterial peritonitis
) Must be considered in any patient with ascites who deteriorates suddenly
(may be asymptomatic). Common organisms are E. coli, Klebsiella, and streptococci.
: eg piperacillin with tazobactam
prophylaxis for high- risk patients (albumin,
who have had a previous episode: eg ciprofloxacin
Recurrent episodes may be reduced in frequency with prophylactic lactulose and
p
270
rifaximin (
trapping in kidneys (
). Renal failure Hepatic clearance of immune complexes leads to
for hepatorenal syndrome
Prognosis Overall 5yr survival is ~50%. Poor prognostic indicators: encephalopathy;
+
<
110
serum Na
mmol/ L; serum albumin <25g/ L;
Liver transplantation The only definitive treatment for cirrhosis (p
Acute liver failure meeting King’s College criteria (see
dications
Hospital criteria in acute liver failure’,
of any cause; hepatocellular cancer (
BOX
‘Causes of cirrhosis’.
p
271
); hypoalbuminaemia (oedema); sepsis (pneu-
6.31
); splenomegaly; portosystemic shunt including oe-
PT/ INR
); autoantibodies (
40
yrs old (p
GI
risk.
AST
,
ALT
,
.
WCC &
platelets indicate hypersplenism. Find
ANA, AMA, SMA
281
); 1- antitrypsin (p
SBP
); hypoglycaemia. Portal
bleed) and caput medusae (enlarged
ALP
, GT. Later, with loss of synthetic
p
326
); hepatitis serology (p
, p
550
); - fetoprotein (p
286
). Liver ultrasound
MC&S
— neutrophils >
.) Confirms the clinical diagnosis.
4
g/ 12h PO, 1h after
6
months to screen for
p
274
. High- dose ursodeoxycholic acid in
100
mg/ 24h PO; dose as tolerated (max
RAA
) axis. Chart daily weight and aim
400
mg/ 24h)— it coun-
120
4.5
g/ 8h for 5d or until sensitivities known. Give
PT/ INR
, low ascitic albumin) or those
500
mg PO daily. Encephalopathy
IgA
nephropathy ± hepatic glomerulosclerosis). See also p
.
INR
.
p
271
) Chronic indications Advanced cirrhosis
1
nodule <5cm or ≤5 nodules <3cm).
BOX
HBV,
fig
274
282
Caudate lobe
250
276
). Avoid
PBC
(p
278
100
mmol/ d).
mg/ 24h PO; do
271
273
). Acute in-
‘King’s College
);
);
/
)
6 Gastroenterology
Fig 6.
https://t.me/med1917
30
Spider naevi: a central arteriole, from
which numerous vessels radiate (like the legs
of a spider). These fill from the centre unlike
telangiectasias that fill from the edge. They
occur most commonly in skin drained by the superior vena cava. ≤
Causes include liver disease,
(ie changes in oestrogen metabolism).
5
are normal (especially in ).
OCP
, and pregnancy
Fig 6.
31
Gross ascites. Note the umbilical
p
605
), gynaecomastia, and veins visible
hernia (
on the anterior abdominal wall.
273
Causes of cirrhosis
• Chronic alcohol use.
• Chronic
HBV
or
• Non- alcoholic steatohepatitis (
• Genetic disorders: haemochromatosis
p
284
(
HCV
); 1- antitrypsin deficiency (p
Wilson’s disease (
infection.
p
281
).
28
• Hepatic vein events (Budd– Chiari, p
• Autoimmunity: primary biliary cholangi-
NASH
).
p
278
); primary sclerosing cholangi tis
tis (
p
278
); autoimmune hepatitis (p
(
286
);
• Drugs: eg amiodarone, methyldopa,
methotrexate.
280
686
).
Is cirrhosis becoming decompensated? Prepare to make an arrest...
Cirrhosis may lie in wait for years before committing one of its three great crimes
against the person: jaundice, ascites, or encephalopathy. There are almost always
accomplices who, if arrested now, may stop a killing from unfolding. These usual
suspects are:
taneous peritonitis, see earlier in topic)
dehydration constipation covert alcohol use infection (eg spon-
opiate over- use— or an occult GI bleed. If
all have alibis, think of portal vein thrombosis, and call in the Chief Inspector.
Liver transplantation
The first liver transplant was in Denver,
UK
each year in the
(for indications see p
USA
, in
1963
. Now
800– 1000
271
). The limiting step for the procedure
are performed
is often the waiting list for a donor organ, which may be cadaveric (heart- beating
or non- heart- beating) or from live donors (right lobe). Contraindications include
extrahepatic malignancy; severe cardiorespiratory disease; systemic sepsis; expected non- compliance with drug therapy; ongoing alcohol consumption (in those
with alcohol- related liver disease). Refer earlier rather than later, eg when ascites
is refractory or after a
is based upon the
+
, creatinine, bilirubin, and
Na
Post- op 12– 48h on
monitoring of
mofetil (or azathioprine) + prednisolone. Hyperacute rejection is a result of
incompatibility. Acute rejection (
well with pyrexia and tender hepatomegaly— often managed by altering the immunosuppressives. Other complications: sepsis (esp. Gram −ve and
artery thrombosis, chronic rejection (at
rarely, graft- versus- host disease. Average patient survival at
60– 90
vival
%; depends on the pre- op disease).
1
st episode of bacterial peritonitis. Prioritization in the UK
UKELD (UK
end- stage liver disease) score, calculated from serum
29
INR
ITU,
LFT
. Immunosuppression examples: tacrolimus ± mycophenolate
.
with enteral feeding starting as soon as possible and close
T
- cell mediated, at 5– 10d): the patient feels un-
CMV
6– 9
months), disease recurrence, and,
1
), hepatic
yr is ~80% (5yr sur-
ABO
).
28
Clues as to which patients with chronic
bumin ratio ≥
1
, and
AST/ ALT
29
Online calculators available, eg at www.odt.nhs.uk.
ratio ≥1—
HCV
will get cirrhosis: platelet count ≤
100
% + ve predictive value but lower sensitivity (~30%).
140
×
109/ L, globulin/ al-
6 Gastroenterology
Viral hepatitis
https://t.me/med1917
274
Hepatitis A
America, so a problem for travellers. Most infections are in childhood.
2– 6
wks.
RNA
virus. Spread Faecal– oral or shellfish. Endemic in Africa and S
Symptoms Fever, malaise, anorexia, nausea, arthralgia— then: jaundice (rare in
Tests
AST
children), hepatosplenomegaly, and adenopathy.
after exposure (
from day
Avoid alcohol. Rarely, interferon alfa for fulminant hepatitis.
With inactivated viral protein. 1 IM dose gives immunity for 1yr (20yrs if further
booster is given at
ALT
may be >
25
and means recent infection. IgG is detectable for life. Supportive.
1000IU/ L), returning to normal over 5– 20wks.
6– 12
months). Prognosis Usually self- limiting. Fulminant hepa-
and
Active immunization
titis is rare. Chronicity doesn’t occur.
Hepatitis B virus (
sexual, direct contact.
HBV
, a
DNA
virus.) Spread Blood products, IV drug abusers (
Deaths 1 million/ yr. Risk groups IV drug users and their
sexual partners/ carers; health workers; haemophiliacs; men who have sex with
men; haemodialysis (and chronic renal failure); sexually promiscuous; foster carers;
close family members of a carrier or case; sta or residents of institutions/ prisons;
HBsA
babies of
East, Africa, Mediterranean.
but arthralgia and urticaria are commoner.
1– 6
months after exposure. HBeAg (e antigen) is present for 1½– 3 months after acute
illness and implies high infectivity.
status and occurs in
HBV DNA
HBsA
to
to therapy. See
(specific antihigh- risk exposure.
Complications Fulminant hepatic failure, cirrhosis,
g + ve mothers; adopted child from endemic area. Endemic in Far
Incubation 1– 6 months. Signs Resemble hepatitis A
Tests HBsAg (surface antigen) is present
HBsA
5– 10
<
2000IU/ mL. Antibodies to HBcAg (anti- HBc) imply past infection; antibodies
g (anti-
HBV
% of infections; biopsy may be indicated unless
HBS
) alone imply vaccination.
fig
6.32
and table
immunoglobulin) may be given to non- immune contacts after
g persisting for >6 months defines carrier
HBV PCR
6.11
. Vaccination See p
allows monitoring of response
283
. Passive immunization
HCC,
cholangiocarcinoma,
cryoglobulinaemia, membranous nephropathy, polyarteritis nodosa (
Avoid alcohol. Immunize sexual contacts. Refer all with chronic liver inflammation
ALT
30IU/ L), cirrhosis, or
(eg
ide analogues, eg tenofovir, entecavir are preferred
side eect profile and predictable ecacy than
PEG
) interferon alfa- 2a but are required long- term). The aim is to clear HBsAg and
(
prevent cirrhosis and
Hepatitis C virus (
sexual contact.
mild/ asymptomatic.
20
yrs— of these, 4% develop
higher viral load, use of alcohol,
p
272
velops,
UK
prevalence: ~80
), anti-
HCV
HCV) RNA
~
tion/ chronicity; liver biopsy or non- invasive elastography if
damage and need for treatment. Determine
triumph’; quit alcohol.
thyroiditis; autoimmune hepatitis;
HBV DNA
>
2000IU/ mL for antivirals (oral nucleos(t)
HCC
(risk is if HBsAg and HBeAg + ve).
1
st line based on their better
48
wks subcutaneous pegylated
flavivirus. Spread Blood: transfusion, IV drug abuse,
000
85
% develop silent chronic infection; ~25% get cirrhosis in
HCC
/ yr. Risk factors for progression Male, older,
HIV, HBV
. Te s t s
antibodies confirm exposure;
HCV
(and falling, see
BOX
). Early infection is often
LFT (AST:ALT
<1:1 until cirrhosis de-
HCV- PCR
confirms ongoing infec-
HCV- PCR
ge no typ e (1– 6).
+ ve to assess liver
BOX
Other complications Glomerulonephritis; cryoglobulinaemia;
PAN
; polymyositis; porphyria cutanea tarda.
Incubation
ALT
rise 22– 40d
IGM
rises
IVDU
ALT
and
p
554
).
‘The virologists’
),
cination prevents
cause acute liver failure/ cirrhosis.
As interferon alfa has limited success, liver transplantation may be needed.
+ ve).
Hepatitis E virus (
HDV
HEV
in older men and also commoner than hepatitis
nancy. It is associated with pigs. Epidemics occur (eg Africa). Vaccine is available in
China (not Europe).
Serology. Nil specific.
Other infective causes of hepatitis
ilis; yellow fever.
infection. 5% of
Tests Anti-
)
RNA
virus. Similar to
HBV
carriers have
HDV
HAV
EBV; CMV
; leptospirosis; malaria; Q fever; syph-
HDV
co- infection. It may
antibody (only ask for it if HBsAg
; common in Indochina (commoner
A
in UK); mortality is high in preg-
6 Gastroenterology
Table 6.
SERUM Liver (I.F. )
Weeks
https://t.me/med1917
LFT
HBsA
HBeA
AntiAntiAntiAnti-
Exposure
11
g
g
HB
s
HB
e
HBc IgM
HBc IgG
Serological markers of
HBV
infection
Incubation Acute Carrier Recovery Vaccinated
Normal Normal
+ + +
+ + + / −
+ +
+ / −
+ + / −
+ + +
HBcAg
HBsAg
275
HBeAg
DNAP
AST
08 20
Fig 6.
32
Viral events in hepatitis B in relation to
HB
s= hep. B surface; HBc= hep. B core; HBe= hep. B e antigen;
The virologists’ triumph: curing
Since the original isolation of
scare, less than three decades have elapsed. In this time, the comparatively
simple genome of
HCV
has undergone nothing less than a revolution to the point where many
of
HCV
has proven far easier than
common genotypes are considered curable.
All patients with sustained detectable
Options are evolving rapidly, but centre on the use of inhibitors of non- structural
viral proteins (eg ledipasvir + sofosbuvir) which are much better tolerated than
the previous mainstay of treatment, pegylated interferon. Interferon- free regimens therefore eliminate major barriers to compliance including treatment
duration and
regimens can now realistically achieve the complete absence of
virus in the blood
SE
, as well as achieving superior results: contemporary antiviral
6
months post- treatment in almost
tients, including patients with established cirrhosis. Ribavirin, a nucleoside analogue, can also increasingly be avoided in genotype
treatment for the harder- to- treat genotypes
sustained undetectable viral levels now routinely exceed
ment are high, but cost- eectiveness analysis is favourable given the cure rates
and the significant public health burden of
lent in lower- income countries and have received less attention but limited data
where resources do exist suggest similarly good response rates.
Meanwhile, the threat of
HIV
and >90% for IV transmission. Untreated
mitted
HCV
- induced liver fibrosis. All
of
combination antiviral therapy. Given the potential for toxicities and viral resistance
mutation, such therapies should be planned and delivered through expert services.
HBsAg
HIV
anti-HBe
anti-DANE PART ICLE
anti-HBc
AST
peak. IF= immunofluorescence; Ag= antigen;
DNAP= DNA
HCV
HCV
in the late
remains.
HIV/ HCV
1980
s, riding the wave of the
HIV
to combat and the treatment
HCV
should be considered for treatment.
2
and 3. Here, reported rates of
HCV
. Genotypes 4, 5, or 6 are preva-
HCV
prevalence is ~7% for sexually trans-
co- infected patients should be assessed for
anti-HBs
polymerase.
100
% of genotype 1 pa-
1
, though it remains a useful
90
%. The costs of treat-
HIV
may accelerate progress
PCR
- detectable
32
AIDS
6 Gastroenterology
Alcohol misuse
CAGE
C
G
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276
Alcohol use is the leading risk factor for death and disability among the global popula-
15– 50
tion aged
validated (eg
such as ‘How many times in the past year have you had five (four for ) or more drinks
in a day?’ (+ ve if >
questions for dependence: ever felt you ought to
years. Screening Several screening tools for hazardous use have been
AUDIT
) but for simplicity, a single- item question has much to recommend it,
0; 82
by criticizing your drinking? Ever felt
in the morning? ‘Yes’ to ≥
97
%). Those who refuse, or give unconvincing answers may have more to tell in their
blood: look for
GT, ALT, MCV, AST:ALT >2,
Withdrawal Star ts wi thi n 10h of last drink. Consider it in any new (3d) ward patient
with acute confusion.
ally visual, but sometimes tactile/ auditory); delirium tremens— occurs in
48
h after the last drink, hallucinations, disorientation, BP, HR. Management There
>
is almost no role for hospital inpatient ‘detox’ as a sole indication for admission however attractive the idea of a ‘quick fix’ may be— community- based services are much
better placed to support cessation. Admit only if complicating or coexisting medical
problems require inpatient treatment. Check
chlordiazepoxide, eg
regimen over
cephalopathy (
5– 7
d. Thiamine and glucose should be given to prevent Wernicke's en-
p
700
).
Chronic complications Don’t forget the risk of trauma while intoxicated.
The live r Normal in 50%; or
tion, eg fatty liver,
AIH
drinkers, occurs acutely but is rapidly reversible with abstinence. Inflammation
(steatohepatitis) may occur if drinking continues, and the risk of progression to cirrhosis is increased.
failure in
77
%). Biopsy: Mallory bodies ± neutrophils (can be indistinguishable from
Gut Obesity;
Alcoholic hepatitis See
10
%). Cirrhosis (See p
D&V
; gastric erosions; peptic ulcers; varices (p
or chronic); cancer (many types); oesophageal rupture ( vomiting against a closed
glottis; suspect if shock and surgical emphysema in the neck: Boerhaave’s syndrome).
Nervous system Memory/ cognition: high- potency vitamins IM or IV may re-
p
700
verse it (
wide- based gait; neuropathy; confabulation/ Korsako ’s (
cephalopathy (
Blood
folate deficiency, haemolysis; sideroblastic anaemia. See
Cardiovascular Arrhythmias; BP; cardiomyopathy; sudden death in binge drinkers.
); cortical/ cerebellar atrophy; retrobulbar neuropathy; seizure; falls;
p
700
MCV
). Symmetrical polyneuropathy; alcoholic myopathy.
anaemia from: marrow depression, GI bleeding, alcoholism- associated
Reproduction Testicular atrophy; testosterone/ progesterone; oestrogen; fetal
alcohol syndrome—
Alcohol dependence Problematic pattern of alcohol use leading to clinically
significant impairment or distress. Other addictions may coexist. Lifetime preva-
10
lence: ≈
Management Group therapy or self- help (eg Alcoholics Anonymous) may be
useful— especially if self- initiated and determined. Encourage the will to change.
Relapse 50% will relapse soon after starting treatment. Acamprosate (p
help intense anxiety, insomnia, and craving.
atinine >
65
<
continued for
% ( ≈ 4%). Denial is a leading feature, so be sure to question relatives.
120
µmol/ L.
yrs old. It should be started as soon as acute withdrawal is complete and
~
1
yr. Disulfiram can be used to treat chronic alcohol dependence.
It causes acetaldehyde build- up (like metronidazole) with extremely unpleasant effects to any alcohol ingestion— eg flushing, throbbing headache, palpitations. Care
must be taken to avoid alcohol (eg toiletries, food, medicines) since severe reactions can occur.
30
GT is in 52% of alcoholics; it is also in 50% of those with non- alcoholic fatty livers. Its best use is not in
diagnosing alcoholism but in seeing if a raised
Confer with experts if drugs are to be used.
% sensitive, 79% specific). This can be followed up with the
2
may predict dependency (sensitivity 43– 94%; specificity 70–
uilty about your drinking? Ever had an Eye- opener
ut down? Have people Annoyed you
2
urea, Mg
+
, platelets.
Signs Pulse; BP; tremor; confusion; seizures; hallucinosis (usu-
5
%, begins
BP
10– 50
mg/ 6h PO with additional doses
30
(p
IQ
SE: D&V
GT
280
),
HBV
. Fatt y l iv er ( st e at os i s) Present in 90% of heavy
272
.) 5yr survival is 48% if drinking continues (if not,
, short palpebral fissure, absent philtrum, and small eyes.
, or libido; dose example:
ALP
+ HR/ 4h. For the 1st 3d give generous
PRN
, then plan weaning
— but may be in any type of liver inflamma-
BOX
. 80% progress to cirrhosis (hepatic
NASH
445
, p
) may
252
); pancreatitis (acute
p
690
p
326
.
CI
: pregnancy, severe liver failure, cre-
666
mg/ 8h PO if >60kg and
is likely to be from liver, not bone.
) ± Wernicke’s en-
281
).
6 Gastroenterology
Addressing the behaviour of harmful drinking
https://t.me/med1917
The Green Fairy was an in congruou s nickname given to the bearer of social degradat ion in
would spill onto the boulevards at
19
th- century France. Parisians
('l'heure verte') to the nearest café for their
absinthe. Rather than the havoc it wreaked,
absinthe became symbolic of rebellious artistic enlightenment and bohemian lifestyle.
But Degas portrayed a grimly realistic view
of the behaviour induced by alcohol. Dans
fig
6.33
un café (
A couple, lethargic, dishevelled, and trapped
) depicts a desolate scene.
in vacant isolation despite their proximity,
sit before a murky yellow- green glass of absinthe. Why would this well- dressed woman
return to her cage of numbed misery and
loneliness every evening? How might we
help our patients similarly bound by entrenched behaviour from their Green Fairy?
Referral to specialist alcohol services is the only intervention of proven ecacy in
those who are alcohol dependent. But the 'brief intervention', a structured, motivational conversation about alcohol consumption, is eective in those drinking at
hazardous levels. Start by asking permission to talk about alcohol consumption
and normalize the discussion 'lots of people are concerned about their drinking patterns . . . '. Ascertain their level of motivation to change, and explain the health benefits or risks (depending on their responses). Follow this with open- ended questions
asking what they think of these benefits/ risks and their alcohol use. Emphasize that
they have the responsibility for changing this and establish goals (cutting down
or abstinence) and strategies to achieve these (eg not having alcohol at home, or
avoiding friends who drink too much).
Managing alcoholic hepatitis
The patient Usually an acute onset of symptomatic hepatitis in those with long-
standing heavy drinking, possibly with a recent intake. Malaise; anorexia; fever;
D&V
; tender hepatomegaly; jaundice; ascites. Blood
or hypersplenism); albumin (malnutrition or synthesis);
erately raised, usually <
≈
severe hepatitis. Rule out other causes of acute hepatitis; infectious screen,
transabdominal ultrasound, ± ascitic tap and treat for
• Most need hospitalizing; fluid resuscitation (albumin ideally), urinary catheter and
CVP
mon itori ng may b e need ed.
• Determine severity; the Maddrey discriminant function (DF) = (4.6 ≈ PT – control
PT
) + (bilirubin(µmol/ L)/ 17.1) reflects mortality.
• Stop alcohol consumption (many have stopped due to symptoms), treat withdrawal.
• Vitamins: vit K: 10mg/ d IV for 3d. Thiamine
also be given
• Optimize nutrition (35– 40kcal/ kg/ d non- protein energy). Use ideal body weight for
calculations, eg if malnourished. Don’t use low- protein diets.
• Daily weight;
• Steroids may confer benefit in those with severe disease. If DF >31 then consider
prednisolone
largest study to date (
• Pent oxifyl line
with steroid
IV
as Pa brinex ®— 1 pai r of ampou les in 50mL 0.9% saline
LFT; U&E; INR.
40
mg/ d for 5d tapered over 3wks.
STOPAH
400
mg
TDS
CI
, but data are also inconsistent.
Prognosis Mild episodes hardly aect mortality; if severe, mortality ≈50
1
yr after admission for alcoholic hepatitis, 40% are dead... a sobering thought.
5
pm
Fig 6.
33
Dans un cafe, Degas.
Peter Barritt/ Alamy Stock Photo.
WCC
; platelets (toxic eect
INR
;
AST
300
IU/ L
). Jaundice, encephalopathy, or coagulopathy
SBP
(p
272
).
100
mg/ d PO (high- dose B vitamins can
If c reatin ine , get help with this—
HRS (
CI:
sepsis; variceal bleeding. The
(mod-
IVI
over ½h).
p
271).
) showed only a non- significant trend towards benefit.
(lower dose in renal dysfunction) is an alternative in those
% at 30d.
277
6 Gastroenterology
Primary biliary cholangitis (
PBC
PSC
ERCP
MRCP
https://t.me/med1917
278
Interlobular bile ducts are damaged by chronic autoimmune granulomatous31
inflammation causing cholestasis which may lead to fibrosis, cirrhosis, and portal
hypertension.
Cause Unknown environmental triggers (?pollutants, xenobiotics, non- pathogenic
bacteria) + genetic predisposition (eg
ance to self- mitochondrial proteins.
Antimitochondrial antibodies (
Prevalence 4/
100 000
Risk if: + ve family history (seen in 1– 6%); many
other autoimmune diseases; use of nail polish/ hair dye.
Typical age at presentation ~50yrs.
The patient Often asymptomatic and diagnosed after incidental finding
Lethargy, sleepiness, and pruritus may precede jaundice by years.
skin pigmentation; xanthelasma (
Complications
Those of cirrhosis (p
fat- soluble vitamins (
in osteomalacia and coagulopathy;
Tests Blood
prothrombin time.
topic). Other autoantibodies (
(esp.
Biopsy Not usually needed (unless drug- induced cholestasis or hepatic sarcoidosis
ALP
, GT, and mildly
98
IgM
).
TSH &
cholesterol or . Ultrasound Excludes extrahepatic cholestasis.
need excluding); look for granulomas around bile ducts ± cirrhosis.
Treatment Symptomatic Pruritus: try colestyramine 4– 8g/ 24h
and rifampicin may also help. Diarrhoea: codeine phosphate, eg
Osteoporosis prevention:
K
. High- dose ursodeoxycholic acid (
and
recommended medication aimed at the condition itself; it may improve survival and
delay transplantation.
deemed inadequate.
Liver transplantation (See p
rhotic.
itus. Histological recurrence in the graft:
occur as a result of recurrence, it is rare and unpredictable.
Prognosis Highly variable. The Mayo survival model is a validated predictor of sur-
vival that combines age, bilirubin, albumin,
Primary sclerosing cholangitis (
Progressive cholestasis with bile duct inflammation and strictures (figs
Symptoms/ signs Pruritus ± fatigue; if advanced: ascending cholangitis, cirrhosis,
and hepatic failure.
Northern European patients also have
with risk of colorectal malignancy.
Cancers Bile duct, gallbladder, liver, and colon cancers are more common, so do
yearly colonoscopy + ultrasound; consider cholecystectomy for gallbladder polyps.
Te st s
ALP
, then bilirubin; hypergammaglobulinaemia and/ or IgM;
SMA,
and
ANCA
duct anatomy and damage. Liver biopsy shows a fibrous, obliterative cholangitis.
Tre at me nt Liver transplant is the mainstay for end- stage disease; recurrence occurs
in up to
develop colorectal cancer post- transplant. Endoscopic therapy to dilate/ stent strictures.
Ursodeoxycholic acid may improve
High doses, eg
(naltrexone and rifampicin may also help). Antibiotics for bacterial cholangitis.
may be + ve; see
30
%; 5yr graft survival is >60%. Prognosis is worse for those with
25– 30
mg/ kg/ d, may be harmful. Colestyramine 4– 8g/ 24h PO for pruritus
)
IL12A
locus) leading to loss of immune toler-
AMA
. :
) These are the hallmark of
≈
9:1
.
UTI
PBC
.
S; smoking; past pregnancy;
Signs Jaundice;
fig
14.12, p683
A, D, E, K
272
) due to cholestasis and bilirubin in the gut lumen results
HCC
% are
AMA M2
p
550
) may occur in low titres. Immunoglobulins are
); xanthomata; hepatosplenomegaly.
); osteoporosis is common. Malabsorption of
(p
282
).
AST & ALT
; late disease: bilirubin, albumin,
subtype + ve, eg in a titre of 1:40 (see earlier in
31
PO;
naltrexone
30
p
674
. Specific Fat- soluble vitamin prophylaxis: vitamin
UDCA
) with meals and at bedtime— the only
SE
: weight. Obeticholic acid can be added if the response is
Monitoring Regular
Associations • sex. •
LFT
; ultrasound ±
273
.) For end- stage disease or intractable prur-
~
17
% after 5yrs; although graft failure can
PT
time, oedema, and need for diuretics.
HLA- A1; B8; DR3.
IBD
, usually
BOX
and p
550
.
LFT
but has not shown evidence of survival benefit.
AFP
twice- yearly if cir-
)
•
AIH
(p
) or
AMA
(fig
280
−ve, but
IBD
UC;
this combination is associated
(fig
6.34
); >80% of
ALP
mg/ 8h PO.
A, D,
6.34, 6.35
).
ANA
6.35
) reveal
, as 5– 10%
.
32
,
6 Gastroenterology
Testing for autoantibodies— the anguish of partial understanding
https://t.me/med1917
The diagnostic approach to several inflammatory conditions includes the measurement of autoantibodies. Consequently, and all too often, attempts to acquire
(and test) medical knowledge may promote these antibody panels to a position
as the final arbiter of disease diagnosis which, with their varying sensitivities
and specificities, they are quite unfit to assume. Indeed, often just such a workup
shows strange overlap conditions between apparently dierent diseases: strange
until we realize that these markers are just surrogates for processes that we lack
a complete aetiological explanation for and in which the antibodies themselves
may just be bystanders. Process that we lack the tools to visualize, as cells of the
immune system continue their onslaught against their perceived enemies, driven
by reasons that none present seem willing to reveal to our crude probing with
blood tests,
death, our minds attempt to impose a unitary disease on unsuspecting and sometimes innocent cells.
overlaps with
stand the dominant process, but equally may mystify matters still further if we
attempt to apply our inadequate classifiers (‘But why is the
cries the student, enraged at the failure of the miserable patient’s
X
- rays, and biopsies. While the body knows no diseases, only pain and
For example, clinically we observe that autoimmune hepatitis (
PSC
and
IBD
. A battery of antibody tests may sometimes help under-
ANCA
AIH
) frequently
not positive?’
B
lymphocytes
to do the honourable thing). As ever, management should be individualized dependent on liver and bowel histology, serum immunoglobulin levels, the degree of
biochemical cholestasis, cholangiography, and, yes, autoantibodies.
279
Fig 6.
34
ERCP
tures in the biliary tree with a characteristic ‘beaded’ appearance.
31
Other causes of liver granulomas: TB, sarcoid, infections with
PAN, SLE
inol. Signs:
32
Usually gallbladder polyps are an incidental finding on ultrasound, and they can often be left if <1cm
diameter, but in
showing many stric-
© Dr Anthony Mee.
, granulomatosis with polyangiitis, lymphoma, syphilis, isoniazid, quinidine, carbamazepine, allopur-
PUO
;
LFT
.
PSC
they are much more likely to become malignant.
Fig 6.
35
MRCP
patic ducts show multifocal strictures. Strictures can
be hard to dierentiate from cholangiocarcinoma
(coexistence of
Stenting may be needed.
showing features of
UC
may promote this development).
© Norwich Radiology Department.
HIV
(eg toxoplasmosis,
PSC
. The intrahe-
CMV
, mycobacteria),
6 Gastroenterology
Autoimmune hepatitis (
AIH
MRCP
https://t.me/med1917
280
)
An inflammatory liver disease of unknown cause33 characterized by abnormal Tcell function and autoantibodies directed against hepatocyte surface antigens.
Classification is by autoantibodies (
or middle- aged women (bimodal, ie
table
6.12
).
AIH
10– 30
predominantly aects young
yrs— or >40yrs old). Up to 40% present
with acute hepatitis and signs of autoimmune disease, eg fever, malaise, urticarial
rash, polyarthritis, pleurisy, pulmonary infiltration, or glomerulonephritis. The remainder present with gradual jaundice or are asymptomatic and diagnosed incidentally with signs of chronic liver disease. Amenorrhoea is common and disease
tends to attenuate during pregnancy.
Complications Those associated with cirrhosis (p
Tests Serum bilirubin,
IgG
), + ve autoantibodies (table
(esp.
cate hypersplenism.
periportal areas and piecemeal necrosis ± fibrosis; cirrhosis ≈ worse prognosis.
(See p
726
AST, ALT
Liver biopsy (See p
.) Helps exclude
, and
PSC
ALP
if
ALP
272
) and drug therapy.
all usually , hypergammaglobulinaemia
6.12
). Anaemia,
244
.) Mononuclear infiltrate of portal and
WCC
, and platelets indi-
disproportionately.
Diagnosis Depends on excluding other diseases (no lab test is pathognomonic).
IgG
Diagnostic criteria based on
of viral disease are helpful. Sometimes diagnosis is a challenge— there is overlap
with other chronic liver disease: eg
Table 6.
12
Classifying autoimmune hepatitis: types I–
I
Seen in 80%. Typical patient: <40yrs. :
≈
70
% with titres >1:
+ ve in
90
% but are poorly specific. IgG in 97%. Good response to immunosuppression
80
%. 25% have cirrhosis at presentation.
in
II
Commoner in Europe than
commonly progresses to cirrhosis and less treatable. Typically anti- liver/ kidney
microsomal type
levels, autoantibodies, and histology in the absence
PBC
(p
278
),
PSC
(p
278
), and chronic viral hepatitis.
II
≈
4:1
Antinuclear antibody (
10:1
. More often seen in children, and more
ASMA
and
ANA
typically −ve.
1
(
LKM1
) antibodies + ve.
160
. Antismooth muscle antibodies (
≈
USA
. :
ASMA
Management Immunosuppressant therapy Prednisolone 30mg/ d PO for 1 month;
5
mg a month to a maintenance dose of 5– 10mg/ d PO. Corticosteroids can some-
by
times be stopped after
PO
) may be used as a steroid- sparing agent to maintain remission. Remission is
achievable in
SE
are a big problem (p
non- cirrhotic
cirrhosis or if there is failure to respond to medical therapy, but recurrence may
occur. It is eective (actuarial
2
yrs but relapse occurs in 50– 86%. Azathioprine (50–
80
% of patients within 3yrs. 10- and 20yr survival rates are >80%.
373
AIH
)— partly ameliorated by a switch to budesonide, eg in
. Liver transplantation (See p
10
yr survival is 75%).
273
.) Indicated for decompensated
Prognosis Appears not to matter whether symptomatic or asymptomatic at pres-
10
entation (
reduces
cholangitis) overlap is worse than
yr survival ~80% for both). The presence of cirrhosis at presentation
10
yr survival from 94% to 62%. Overlap syndromes:
AIH- AIC
(autoimmune cholangitis).
AIH- PBC
ANA
) is
) + ve in up to
100
mg/ d
(primary biliary
Associations of autoimmune hepatitis
• Pernicious anaemia. • Autoimmune haemolysis.
• Ulcerative colitis. • Diabetes mellitus.
• Glomerulonephritis. •
• Autoimmune thyroiditis. •
33
Hepatotropic viruses (eg measles, herpes viruses) and some drugs appear to trigger
predisposed individuals exposed to a hepatotoxic milieu intérieur. Viral interferon can inactivate cytochrome
P450
enzymes ( metabolism of ex- or endogenous hepatotoxins). Resulting modifications to proteins may
generate autoantigens driving
CD4 T
- helper cell activation.
PSC
(p
278
HLA A1, B8
).
, and
DR3
haplotype.
AIH
in genetically
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