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7/31/2019 Pentoxiphylline in severe alcoholic hepatitis, Capsule endoscopy, Methotrexate toxicity
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Pentoxifylline in Severe AlcoholicHepatitis: A
Prospective, Randomised Trial
Sandeep Singh Sidhu, Omesh Goyal,
Monika Singla, KL Bhatia, Rajoo Singh
Chhina, Ajit Sood
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INTRODUCTION
Severe Alcoholic hepatitis (SAH), defined by modified
Maddreys Discriminant Function (DF) 32, is associated with
significant morbidity and mortality.
Of the various treatment modalities evaluated for treatment
of SAH, corticosteroids have been the most extensively
studied.
Five out of 13 RCTs, and four out of 5 meta-analysis have
shown a survival benefit with corticosteroids, especially in
patients with DF 32 and/or encephalopathy.
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However, the role of corticosteroids in SAH still remains
somewhat controversial.
Corticosteroid therapy is not considered the ideal option by all
authors because their beneficial effect seems to be confined
to a highly selected minority group in which the inhibitory
effect of corticosteroids on liver inflammation is NOT
outweighed by side effects such as weakened defence against
infections, anti-anabolic effects, and possible ulcer promoting
effects.
Also corticosteroids are contraindicated in patients with renal
failure, gastro-intestinal (GI) bleed, pancreatitis and active
sepsis.
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Pentoxifylline (PTX), a non-selective phosphodiesterase
inhibitor, also decreases the production ofTNF-, IL-5, IL-10
and IL-12.
A prospective, randomised trial showed significantly lower
mortality in SAH patients who received PTX compared to
controls (24.5% versus 46.1%).
The survival benefit of PTX seemed to result from a decrease in
risk of hepato-renal syndrome, unlike corticosteroids which
seem to lead to an improvement in hepatic function.
Unlike corticosteroids, clinical trials to assess the efficacy of PTX
in SAH are scarce.
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METHODOLOGY Prospective,Randomised Trial conducted in a tertiary care
institute of northern India.
INCLUSION CRITERIA :
1) Patients with clinical features suggestive of alcoholic
hepatitis i.e. History of chronic alcoholism,
recent onset of jaundice, fever, tender hepatomegaly2) Patients with DF > 32
EXCLUSION CRITERIA :
1) Positive viral serology2) Concomitant infections
3) Active GI haemorrhage
4) Severe cardiovascular or pulmonary diseases
5) A decline in DF < 32 with symptomatic treatment for
5-7 days
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Routine investigations including biochemical liver tests,
prothrombin time index and markers for hepatitis A, B, C and
E viruses were done.
Patients were randomised into 2 groups using sequentially
numbered (table of random numbers), sealed, opaque
envelopes.
PTX group received tablet PTX 400 mg thrice daily for 28
days.
Control group received placebo (vitamin tablets) for 28 days.
Patients were recommended a diet constituting 2500-3000
calories, and 1 g/kg proteins.
All investigations were repeated twice weekly or earlier if
required.
Serum TNF levels were done at initiation and end of therapy.
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Statistical analysis was done using Fischers exact test for
qualitative variables, and Mann Whitney test for quantitative
variables. Multiple logistic regression analysis was used for differences
between survivors and non-survivors.
P-value of
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RESULTSMOTRALITY & MORBIDITY :
At 4 weeks, mortality in PTX group was 20% (5/25), and that in
controls was 40% (10/25) (p=0.216; RR 0.5; 95% CI 0.19-1.25).
All deaths occurred due to progressive hepatic failure, either
alone or in combination with other terminal events.
In PTX group, GI bleed was pre-terminal event in two patients,
septicemia in two, and renal failure in one patient.
Among controls, GI bleed was pre-terminal event in three,
and renal failure in seven patients.
Renal failure was the cause of mortality in 20% (1/5) patients
in PTX group, and 70% (7/10) patients in controls (p=0.11).
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CHANGE IN RENAL FUNCTIONS :
At 4 weeks, there was a significant reduction in urea and
creatinine in PTX group but not in controls. At the end of therapy, PTX group showed a significant
reduction in the number of patients having renal dysfunction
as compared to controls.
CHANGE IN HEPATIC FUNCTIONS :
A significant decrease in DF was noted in PTX group at end of
therapy (p=0.00) while controls showed an increase in DF.
Also, number of patients showing improvement in DF by >50%of baseline was significantly more in PTX group {66.7% (12/18)
versus 7.1% (1/14), (p= 0.0009)}
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TNF & OTHER LAB PARAMETERS :
PTX group showed a significant decrease in TNF, bilirubin, PTI
and AST levels; and a significant increase in serum albumin.
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THUS ..
The present study confirmed the beneficial effect of PTX on
renal functions and on reduction in short-term mortality in
SAH.
In addition, significant improvement in hepatic functions in
PTX group was an important finding.
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CONCLUSION
PTX leads to a significant improvement in hepatic and renal
functions in patients with SAH.
PTX leads to a trend towards decreased mortality.
Thus, PTX is a useful treatment option for patients with SAH.
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END OF ORIGINAL ARTICLE
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Advances in Small Bowel Imaging -
Capsule Endoscopy
- Praveen Sharma
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INTRODUCTION The small bowel has been a difficult area to examine due to its
anatomy, location and relative tortuosity.
Capsule endoscopy technology has revolutionized the imagingof small bowel.
Capsule endoscopy (CE) was launched at the beginning of this
millennium. Small bowel CE, therefore, represents a major advance as it is
a safe, non-invasive procedure and it is cost-effective in avariety of clinical situations.
This technique evaluates endoscopically, with high resolutionimages, the whole small bowel, avoiding any sedation, surgeryor radiation exposure.
Currently, CE is recommended, after a negative gastroscopyand colonoscopy in patients with obscure gastrointestinal
bleeding.
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CE is also useful in other clinical situations, such as detection
of small bowel lesions in Crohns disease, non steroidal anti-
inflammatory drug enteropathies, celiac disease, small
bowel polyposis syndromes and small bowel tumours.
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What is Capsule Endoscopy? CE is performed by ingestion of a small (2611 mm)
disposable battery powered pill containing a complementarymetal oxide semiconductor camera which provides a field ofview of 156, a variable depth of view (1-30 mm), and aresolution of 0.1 mm.
Four light emitting diodes illuminate the lumen of the bowel.
PROCEDURE :
Patient need to remain following 8-10 hours fasting when the
capsule is swallowed. Eight skin leads are placed to the patients anterior abdominal
wall and connected to the hard drive.
The camera is activated by removal of the capsule from itsmagnetic holder.
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Camera takes 2 3 images per second and transmits these by
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Camera takes 2-3 images per second and transmits these bymeans ofradio frequency to a sensor array placed on thepatients abdomen and from here to a recording device in abelt that the patient wears for the duration of the battery life
(8-10 h). Now the patient swallows the capsule with a few sips of
water, then the capsule is passively moved along byperistalsis.
Two hours after ingestion, the patient is allowed to drink,
while eating is allowed after 4 h.
After the 10-12 hours recording device is removed and therecorded images are downloaded to the computer.
It takes an average 40-60 min to read these images.
Since its development, additional support systems have beenadded to the software to assist the reader, such as localizationcapability, suspected blood indicator, a multiviewing featureand quick view modality.
The capsule is excreted with the feces, usually within 24 to
48hrs.
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Indications for Capsule Endoscopy
Obscure gastrointestinal bleeding
Small bowel Crohns disease
Assessment of coeliac disease
Screening and surveillance for polyps in familial polyposis
syndromes
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Contraindication for
Capsule Endoscopy
Patients with known or suspected GI obstruction, strictures,
or fistulas based on the clinical picture or pre-procedure
testing
Patients with cardiac pacemakers or other implanted
electromedical devices
Patients with swallowing disorders
Pregnancy
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ADVANTAGES
CE now has an established role in patients with persistent
obscure gastrointestinal bleeding (OGB) who have had anegative gastroscopy and colonoscopy.
The diagnostic yield of capsule endoscopy, with other
procedures, in patients with OGB confirmed the superiority ofCE over other procedures for imaging the small bowel.
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DISADVANTAGES
The retention of the device is the main complication of theprocedure and is defined when CE remains in the digestive
tract for a minimum of 2 wk.
A plain abdominal radiograph should be obtained to confirmexcretion of capsule if the video fails to show that it enters the
colon.
Patient should not undergo magnetic resonance imaging afterCE until the capsule as passed out.
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Esophageal Capsule Endoscopy
The oesophageal capsule measures 1126 mm and acquires
video images from both ends of the device (14 frames/s).
Moderately high sensitivity and accuracy in the diagnosis and
surveillance ofBarrett esophagus in patients with
gastroesophageal reflux disease.
In patients with portal hypertension, ECE has a sensitivity of
63% to 100% for screening ofesophageal varices.
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Colon Capsule Endoscopy Useful in the diagnosis ofcolorectal cancer when colonoscopy
is incomplete or contraindicated.
The reported sensitivity varied from 50% to 70%, and
specificity from 73% to 100% , when comparing colon capsule
with colonoscopy for the detection of polyps.
CCE has also been shown to detect a variety of lesions such as
diverticulosis, proctitis, angiomas and melanosis coli.
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Conclusion Capsule endoscopy is a reliable, well accepted and tolerated
by the patients, which allows complete exploration of the
small intestine.
CE offers the advantages oftotal bowel visualization during a
single examination, and helps the endoscopist in deciding the
rout for doing deep enteroscopy.
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END OF REVIEW ARTICLE
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CASE REPORT
A k/c/o PSORIASIS PRESENTING WITH
ABDOMINAL DISTENSION & LEG SWELLING
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HISTORY
A 67 yr old male with
c/c abdominal distension since 3 months
c/o B/L leg swelling
c/o loss of apetite
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NEGATIVE HISTORY :
No h/o decrease in urine output
No h/o chest pain / palpitations
No h/o jaundice
No h/o TB / tuberculosis contacts
No h/o haematemesis / malena
No h/o abdominal distension in past
No h/o smoking / alcohol useNo h/o DM / HT
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Past history
k/c/o Psoriasis for last 35 years, on weekly methotrexate
therapy (7.5 mg) since last 15 yrs
On topical therapy initially, but later shifted to methotrexate
by treating physician
Psoriatic lesions within control with weekly mtx therapy
Liver function monitored periodically which were essentially
normal except once when SGPT was raised less than twice the
upper limit of normal
Not taking NSAIDs, PUVA therapy or any other hepatotoxic
drug
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EXAMINATION
Alert, stable vitals
Mild pallor
Spider angiomata over upper trunk
Pitting pedal edema Psoriatic plaques over the extensor surface of legs & forearms
& over the back of chest
Abdominal distension with shifting dullness
Liver span 9 cm , moderately enlarged spleen
Rest of general & systemic examinations were essentially
normal
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INVESTIGATIONS
Hb = 9.5 gm/dl
TLC = 8300 / cu. mm
Platelets = 1.2 lakh/ cu. mm
PCV = 29 %MCV = 84 %
SGOT = 44 IU/L
SGPT = 33 IU/L
ALP = 114 IU/LBilirubin : T = 1.3 mg/dl, D = 0.7 mg/dl
INR = 1.44
SAAG = 2.2
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USG Abdomen - normal sized liver with coarse parenchymal
echo texture and nodular surface outline.
Portal vein diameter was 13 mm at porta.
Spleen was enlarged with a span of 14.8 cms, splenic vein
diameter was 8 mm at porta.
Moderate amount offree fluid was seen in pelvis and
paracolic gutters.
UPPER GI ENDOSCOPY - 2 oesophageal varices of grade III.
DIAGNOSIS : k/c/o Psoriasis /w cirrhosis of liver /w portalhypertension /w ascitis /w oesophageal varices
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DISCUSSION
There have often been doubts to the possibility of psoriasisper se being the cause of cirrhosis, but unfortunately, notenough or recent studies are there to clear the air on this.
This patient was on weekly oral methotrexate therapy, taking7.5 mg tablet every week for the past 15 years, amounting to
total cumulative dose of 5.85 g till the presentation ofsymptoms related to cirrhosis.
The long duration of therapy is the risk factor in this patient.
The duration of methotrexate therapy, age, daily oralmethotrexate dosage schedule, risk factors for non-alcoholic
steatohepatitis (obesity, diabetes mellitus, and glucoseintolerance) and concurrent alcohol ingestion have beenidentified as significant risk factors in the evolution of hepaticfibrosis in patients taking methotrexate.
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Concurrent PUVA therapy has also been suggested to cause
derangements in liver function, but this patient was not on
topical therapy for psoriasis for last more than 15 years.
Many studies have found that abnormal liver function testsare often encountered during the treatment of psoriasis with
methotrexate.
But studies as early as in 70s have found that clinical signs of
serious hepatic damage may be the first indication of cirrhosisand that liver function studies might not be reliable indicators
of pathologic changes found on liver biopsy.
This underlines the need of proper selection of patients and
monitoring of therapy based on periodic liver biopsy, withoutbanking solely on liver function tests.
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Not all cases of methotrexate-induced hepatotoxicity may be
detected by liver function tests, and liver biopsy is still
considered the most reliable method of detecting
hepatotoxicity in patients treated with methotrexate.
The American Academy of Dermatology recommends that
sequential liver biopsies should be performed at a cumulative
dose of 1-1.5 g and repeated at cumulative dose intervals of15 g thereafter.
The presence of pathological changes detected by the liver
biopsy should direct the decision of whether or not tocontinue methotrexate therapy.
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Patients with grade I or II histological changes (without
fibrosis) can continue methotrexate; patients with grade IIIA
changes (mild fibrosis) can continue methotrexate with a
repeat liver biopsy after 6 months; patients with grade IIIBchanges (moderate to severe fibrosis) or grade IV changes
(cirrhosis) should discontinue methotrexate.
There is a need to guard against the false sense of securityrendered by normal results of liver function tests and to
perform serial liver biopsies starting at cumulative dose of
1.5g in patients on methotrexate therapy.
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TREATMENT
Haematinics, Diuretics
Band ligation for oesophageal varices
Tapering off of methotrexate & topical therapy
for psoriasis
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THANK YOU