Panel consisted of Dr Ehsan Asad, Dr Arshad Javaid Sh, Dr Mehboob Asraf, Dr
Liaqat Ali Ch and Dr Saleem Akhtar Rana.
It was decided to divide questions on Hepatology in two parts. Part one is to
concentrate on clinical problems related with liver as a whole and Part two will
consist of purely viral hepatitis. This scheme has been devised to highlight
those areas of hepatology, which are usually ignored under the umbrella of part
two. Following text has been prepared from the answers given to the questions.
As questions were the privilge of panel so choice of topics discussed belong to
the panel.
Main Symptoms associated with liver diseases.
v Anorexia
v Nausea/Vomiting
v Change of colour of urine
v Jaundice
v Pruritis
v Pain right hypochondrium
v Weight loss
v Lethargy,fatigue
v Aches,pains ,Arthralgias
v Scanty hair in males.
v Execessive hair on face in women.
v
v Hematemesis & Melena
v Distended abdomen
v Swelling of face and legs.
v Menstrual disorders.
v Breast changes,atrophy or Gynaecomastia.
Signs associated with Liver diseases.
v Jaundice
v Oedema
v Ascites
v Distended veins(Collaterals) over abdomen.
v Loss of male hair pattern in males.
v Testicular Atrophy
v Gyaenocamastia
Diseases of Liver, other than Viral Hepatitis, which are not uncommon
in our countery.
q Drugs & Toxins induced Liver disease.
q Alcohalic Liver Disease.
q Infections.
q Autoimmune Hepatitis.
q Malignancy
q Associated liver involvement in systemic and other organ diseases.
Main Emergencies in Hepatology and their management.
1. Hemetemisis
2. Encephalopathy.
3. Persistent vomiting in Ac.Hepatitis.
Hemetemisis.
Resuscitation and first step treatment should be started by family physicians.
Maintain cardiac output. By fluids, blood, and by drugs like dopamine. Ideal systolic pressure shall be 90 mm. This is enough to maintain circulation to vital organs.
Start Homeostasis. 1) Give Transamin injection immediately. Repeat 8 hourly.
2) Start Sandostatin.Give bolus dose of 50-100 microgram. And start sandostatin infusion at the rate of 25-100 microgram/hour.
(Sandostatin is fairly safe drug. Do not hesitate to start it)
3) Give Inj Vit K 10 mgs. One daily for 3 days. One injection shall restore 10 % of primary store.30 % of normal levels is good enough to maintain homeostasis.
H2 Antagonists. Start H2 antagonists. Give intravenous Ranatidine/Cimetedine.
No Antiemetics avoid these. Empty stomach is a requirement.
Further Disposal Ideally patient should be refered to secondary or tertiary care centres to establish the diagnosis. Bleeding may not stop. This needs repeated transfusions and other managements. Endoscopy has to be done as soon as patient is stable. If patient can not be refered immediately then watch for following complications of excessive bleeding and maintain on above mentioned routine.
Complications of continued bleeding.
Ø Shock may hamper flow to vital organs and produce all known complications. Blood pressure, pulse pressure, and pulse rate should be monitored.
Ø Patient may aspirate blood during vomiting or otherwise.
Ø Blood collected in intestine predisposes to encephlopathy. Colour of stools shall indicate continued bleeding.
Ø Infection may develop like SBP (Spontaneous Bacterial Peritonitis) or somewhere else.
Drowsiness, confusion, lethargy, incoherent talk, disorientation are the behaviour changes which shall be looked for in situations where encephalopathy is possible. This is pre-encephalopathy before patient looses consciousness.
Precipitating factors.
· Large amounts of blood retained in the intestine.
· High protein diet
· Systemic or hepatic infections.
· Drugs.(Diuretics,Sedatives,Narcotics,Hypnotics etc)
· Dehydration
· Electrolyte imbalance,Hypokalemia
· Constipation
· Alkalosis
· Paracentesis with attendant hypovolumia
· Portosystemic shunts.
· Start Lactulose, 30-60 ml/hour oraly through NG tube or retension enema.300 mls in 700 mls of N/Saline.
· Stop diuretics.
· Correct the underlying cause and precipitating factors.
· Maintain caloric intake and fluid/electrolite balance.
· Sterlize the gut with flagyl and/or Kanacin.
· Regular enemas.(e.g Kleen enema)
· For sedation use Oxazepam or Temazepam.
Persistent vomiting in Acute Hepatitis.
· Nothing much has to be done.
· Intravenous fluids relieve the symptoms and discomfort to large extent. Dextrose containng fluids in otherwise normal healthy person do not do any harm. These help to restore glycogen stores and fullfill the daily need of calories and fluid.
· Essential fatty acids and aminoacids may help liver to some extent to face the problem.
· Antacids and H2 antagonists can help.
Drug Induced Liver Disease.
Following drugs affect liver adversely. These are mentioned in the order of incidence.
Antituberculous Therapy.
All components of ATT are hepatotoxic. Pyrazinamide is most hepatotoxic, followed by Rifampicin and INH and then Ethumbutol.Whenever there is a problem, drugs should be drawn.If some drug has to be used then it can be introduced later on (once the hepatitis is resolved) in small doses. Dose can be increased slowly.
This is the second commonest cause of admissions in the hospital for drug induced liver disease.
Locally made Alcohalic drinks.
Here it is methyl alcohal instead of ethyl alcohal. It can cause severe fulminant hepatitis.
NSAIDS.
All are hepatotoxic and can cause acute on chronic hepatitis.
It can cause hepatitis and progress to Cirrhosis of Liver, if continued.
Other commonly used hepatotoxic drugs include antibiotics,steroids,oral contraceptive and anticonvulsants.
Alcohlic Liver Disease.
Regular consumption of more than 50 gms for 10 –15 years can lead to Cirrhosis of liver. Earliest disturbance in LFT is gamma GT.This test is useful and specific only in the earlier stages when all other enzymes are normal. But once the whole spectrum is disturbed due to any cause, it will also be raised. But this rise will not be specific for alcoholism.
Infections affacting Liver
Other than specific viruses many more organisms, including bacteria, parasites and fungi can invade liver. Many systemic infections can affect liver.
Amoebic Liver abcess.
Patient presents with fever, pain Rt hyopochondrium, toxic symptoms and the diagnosis is confirmed on ultrasound. Liver profile is usually not disturbed. Metronidazole or tinidazole are still drugs of choice. Chloroquin can be added. If abcess is larger than 7 cms then it has to be drained. If there are multiple abcesses then you may decide to add cover for multiple bacteria. Monitoring size of abcess with repeated ultrasound examination is not helpful as abnormality keeps on appearing on scan for many months. Symptomatic improvement provides the monitoring tool for success of therapy.
This can be diagnosed on ultrasound and relevant laboratory tests. Albendazole 800 mgs daily or Mebendazole 500 mgs daily for 3 weeks, with interruption for one week and then again same therapy for 3 weeks, in 3 courses is effective.
Only granulmatous lesions. No abcess. Only Biopsy can confirm the suspision. This diagnosis is suspected when there are other sites involved by tuberculosis and enlarged tender liver is an additional finding.
These infections involve liver and disturb liver profile. Mild jaundice is common. Differentiation between typhoid and acute viral hepatitis is very simple. Peak of rise in enzymes in viral hepatitis is at the time when fever has subsided. While in typhoid peak in rise of enzymes corresponds to the temperature? Patient is still running fever when enzymes are disturbed. Actual figures of ALT and AST can be in hundrads and can even go to thousands.
Cholangitis.
In 70-80 % of cases it is secondary to biliary obstruction. Fever, chills, rigours, severe pain in right upper quadrant and toxic symptoms should raise the suspicion.
Whatever is the cause following are the symptoms of portal hypertension.
q Dilated veins on abdomen. Caput medusae. Collaterals.
q Varices in the gut. Oesophageal varices and haemorrhoids. Mucosal congestion.
· Hemetemisis
· Melena
· Fresh copious bleeding per rectum.
q Ascites
q Splenomegaly.
Diagnosis is based upon symptoms, sign and investigations. Normal diameter of portal vein is 11 mms. Ultrasound may report diameter larger than this. Actual measurement of pressure or venography is not needed as symptoms and signs are sufficient to make this diagnosis.
· Simple dietary measurements like salt restriction.
· Addition of spironolactone
· Late on loop diuretics like frusamide
· Beta-Blockers for prophylaxis against bleeding.
· Propranolol and Nadolol (Corgard) have been studied for this purpose. These are helpful. Nadolol is prefered as it is more selective. Blood pressure and pulse rate shall be monitored. Pulse rate shall not drop to less than 75 % of pretreatment figure. These agents can be started even when there is no history of bleeding but diagnosis is fairly established.
Ascites.
· Cirrhosis of liver
· Tuberculosis
· Malignancy.
· Systemic diseases like Nephrotic syndrome,CCF.
A small amount of fluid should be always aspirated and sent for laboratory examination to establish diagnosis. This is essential step for Tuberculosis and malignancy.
Pathophysiological factors In-Patients of Cirrhosis.
· Low serum albumin
· Portal hypertension
· Salt retension due to distrubed metabolism of aldosterone and related hormones.
· Disturbed lymphatic flow.
Management.
Stepwise approach shall be used to manage patients on long term basis.
· Salt restriction.
· Spironolactone upto 100-300 mgs daily
· Addition of loop diuretics likes frusamide.
These measures may fail and ascites may be producing symptoms like respiratory distress. Such refractory ascities can be managed by following measures.
Rule out infections. Cytological examination of peritoneal fluid should decide this factor. Cell count of 250 in sympptomatic patients (low-grade fever, tenderness, and pain) and 500 in asymtomatic patients shall be taken as evidence of infections. Ciproxin and third generation cephalsporins are athe antibiotics of choice.
Paracentesis: Now paracentesis is accepted as therapeutic measure.
Shunts: Shunt for ascites is simple measure. Tube from peritoneal cavity to jugular vein. This is available easily. But shunts for portal hypertension (ITP) are not easily available.
Albumin: This is only a temporary measure. Half-life of this albumin is only 1-2 weeks.
When all features of hepatitis are present in a young female patient, accompanied by
Disturbed liver profile but negative serology for viruses then this is the diagnosis which
Should appear in our list of DD.Pruritis and severe aches pains are typical of this type of hepatitis. These appear early and are quite severe.This condition is also associated systemic manifestations. It follows slow downhill course to cirrhosis. Steroids and immunosuppressive therapy can modify the response and may delay the progress.
ESR is raised.Biopsy will clinch the diagnosis. Disturbed lipid profile and presence of ANA, ASA, and AMA characterize it.
Immunological complaints due to chronic infections.
(e.g Chronic Viral Hepatitis)
(More and more patients with complaints of artheralgias and joint pains, after receiving antirheumatic treatment (NSAIDS) for months or even years end up with the diagnosis of chronic hepatitis presenting with immunologic symptoms. Some patients are diagnosed after the first episode of hemetemisis due to NSAIDS.In this background panel was interested to know the views of our expert on this aspect.)
In all chronic infections immune system is loaded up with the products of antigen antibody reaction. These products cross react with many tissues, especially basement membrane. Many chemicals are released. Serotonin is one of these. This is especially blamed for fatigue and prurtitis. Manifestations from these secondary effects of all chronic infections including chronic viral hepatitis are usually systemic, affecting all systems.
Kidney: Membranous glomerulonepheritis ending up in nephrotic syndrome.
Skin: Pruritis, Vasculitis.Porphyria,
Blood Purpura (petechiae),Haemophilic anaemia.
Eye fundal haemorrhages
Musculo-
Skeletal System: Hepatitis B is especially notorius to produce artheritis. Fatigue, Myalgia, artheralgias are frequent complaints. Significane is use of NSAIDS, which are severely contraindicated in chronic viral hepatitis as for effects on liver and stomach are concerned.
Association with Systemic Diseases.
CCF, condition affacting lungs, and pericardial effusions, Tuberculosis, Diabetes Mellitus and almost all other systemic diseases or their treatment can affact liver adversely. Enlargement of liver and appearance of jaundice shall always call for analysis of these factors.
Estimation of liver function in liver failure. (Degree of decompensation)
Childpugh Classification Table.
Following table is helpful to decide the degree of loss of function.
Criteria A B C
Minimal Moderate Advanced.
Serum Bilirubin < than 2.0 mgs 2-3 mgs > 3 mgs
mg/dl
Serum Albumin > 3.5 3-3.5 < 3
gms/dl
Ascites. None Easily poorly
Controlled Controlled
Encephlalopathy None minimal Advanced
Coma
Nutrition Excellent Good Poor
Wasting.