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Report on Out come of viral hepatitis, chronic hepatitis, liver cirrhosis, liver carcinoma, and liver coma.

A. Chronic hepatitis – Its inflammation of the liver continuing without improvement for at least 6 months
or longer, classification if based on histology, there are 3 forms
1. Chronic persistent hepatitis (CPH) – There is marked expansion of the portal tracts with infiltration by
mono nuclear cells. Liver architecture is undisturbed and the limiting plate b/w hepatocytes is intact this
is often seen in HCV.
2. Chronic lobular hepatitis (CLH) – histologically resembles HAV with predominant intra ascinar
inflammation and necrosis. Its uncommon and presents with a hepatic picture. The course is more than 3
months with remissions and exacerbations. It can fallow HBV & HCV often coexistent with PCH.
Serum antibodies may be present and response to steroids is good. Usually does not progress to
cirrhosis.
3. Chronic active hepatitis (CAH) – Classified as Viral, autoimmune, drug induced or of unknown
etiology.
•10% Of acute hepatitis A fails to eliminate the virus 5% from these progress to chronic active hepatitis
with persistence of HBE ag and HBS ag in the serum and continues expression of both core and HBS ag in
the liver.
•CAH also occurs in paranteral HCV hepatitis.
•Drugs- methyledopa, Isoniazide, Ketoconazole, Nitrofurantine.
•Metabolic- alfa 1 anti tripsin deficiency.
•Autoimmune wilsons disease.
Pathological features
• CAH is manifest by continuing progressive inflammation with liver cell degeneration and bridging
necrosis.
• The diagnostic lesion is piecemeal necrosis- there is destruction of liver cells leading to erosion of the
limiting plates of hepatocytes and around portal tracts, an inflammatory infiltrates expands to the portal area
and infiltrates in to the liver, continuing with fibrosis leading to bridging necrosis.
Clinical features
• There are non specific symptoms of anorexia tenderness, arthralgia, upper abdominal pain and often
ammonorrhoea. There can be hepatomegaly and splenomegaly proceed the development of any portal
hypertension.
• Signs of jaundice, and of chronic liver disease eg-
1. SKIN- spider navi – found above the nipple line.
- palma erythema due to hyperdynamic circulation.
- Clubbing, Dupuytren’s contracture
- Xanthoma- cholesterol deposits in palma creases, above eyes knees and elbows.
2. Abdomen – Initial hepatomegaly fallowed by small liver in well established Cirrhosis.
-Splenomegally.
3. Endocrine – Gynocomastia, testicular atrophy, loss of body hair.
[1] Chronic hepatitis B and C
• In B only3% of acute HBV infection progresses in to CAH.
• Patients with poor cell mediated response to the virus develop chronic hepatitis if the response is very poor
they are healthy carriers.
•In chronic hepatitis C patients are asymptomatic in C most of the patients turn from acute to chronic compared
to B.
Investigations in case of B & C –
• HBV moderately ↑ serum bilirubin and ASAT
• ↑ slightly AP
• HBS Ag histologically seen as “ground glass”
•HBC most prominent is↑ing of aminotransferases in serum with marked flactuations over years.
•Serum bilirubin, PT, serum albumin - normal
•Liver histology- necrosis although it can progress to cirrhosis.
In both conditions final diagnosis depends on the finding of:
•HBs Ag and HBe Ag in HBV chronic state
•HCV RNA in hepatitis C chronic state
 (anti HCV usually not detected)

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Treatment
• The aim is to suppress the viral replication.
• patients with CAH & asymptomatic carriers who have Hbe Ag & HBV DNA in serum are treated with anti
viral agents such as INF-alpha 5-9 MU/3*wk/3-12 months (4-6 months) i.m/s.c, INF not only suppress the
viral replication it also stimulates the immunity.
• In chronic HBV- INF + Lamivudine can be used. Lamivudine also can be used as monotherapy.
• In chronic HCV – INF+Ribavarin can be used. Ribavarin alone is not effective.
Prognosis- In Chronic Hbv – slow progression and remission may occur. And may develop cirrhosis.
And prognosis is poor for ♂,↑age, excess alcohol, HBV or HIV patient, Cirrhosis patient.
[2] Chronic Autoimmune Hepatitis
•Mostly in young (10-20) and middle aged women.
•there is a association with other conditions of autoimmune origin. Eg. Pernicious anemia, thyroiditis.
*Cause is unknown ,but many immunological abnormalities seen.(1)there is defect of T suppressor cells which
may lead to production of auto immune antibodies to surface antigens of hepatocytes.
(2)Humoral disturbances are associated with a hyper gama globulinemia(mainly IgG).
(3)Nuclear,smooth muscle (actin),liver/kidney microsomal(LMK 1)antibodies are found in serum.
Clinics-*Pations can be asymptomatic for years
*Amenorrhoea is common.
*Signs of chronic liver disease ; hepatomegaly, splenomegaly, cutaneous striae, acne, hiruties, jaundice.
*Also features of autoimmune dis: -fever, migratory polyarthritis, glomerulonephritis, pleurisy,
pulmonary infiltration and fibrosing alveolitis.
Investigations-•positive autoantibodies (anti nuclear, liver/kidney microsomal, smooth muscles)
•serum bilirubin, globulins, aminotrancferace
•Mild nomocromic, nomocytic anemia, with thrombocytopenia & leucopenia.
•Histology of liver biopsy- CAH with piecemeal necrosis.
Treatment- •Prednisolone 30mg daily for 2weeks followed by maintenance dose of 10-15mg daily along with
azathioprine 1-2mg/kg/d
Prognosis-•50% of patients will die of liver failure within 5 years if no treatment is given.
•Remissions & exacerbations occur.

[3] Drug-induced chronic hepatitis-patients are usually women presents with jaundice, hepatomegaly,has ↑
serum trancaminases & globulin levels. Improves with drug withdrawal but exacerbates when drug is
reintroduced.

B. Cirrhosis
Definition- It’s a condition involving the entire liver in which the parenchyma is changed in to a large
number of nodules separated from one another by irregular branching and anastomosing sheets of fibrous
tissues.
Causes- •alcohol •HBV •HCV are the most common causes others - •Primary and secondary biliary cirrosis
•Autoimmune CAH •Heamochromatosis •Budd chiari syndrome •wilsons disease •drugs such as
methotrexate • alpa 1-anti tripsin deficiency •CF •Hepatic venous congestion • idiopathic.

Aquired- Alcohol, post viral, idiopathic, biliary cirrhosis.

Inherited- heamochromatosis, Budd chiari syndrome, Wilsons disease, Alpha 1-antitripsin deficiency.

Pathogenesis and pathological features

•cirrhosis results from long continued loss of liver cells, with persistent inflammatory reaction accompanied
by fibrosis and compensatory hyperplasia with nodular formation. The initial cause of the injury, hepatocyte
loss continues as a result of ischemia and changers become progressive leading to death from hepatocellular
failure and/or portal hypertension.
•Liver may be normal in size or enlarged if there is fatty changers or excessive development of hyperplastic
regenerating nodules. Usually the liver shrinks due to loss of liver cells. The colour varies- pale if there is
fatty changers, bile stained if cholestasis and red if congestion.
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Classification- 2 types
1. micronodular- regenerating nodules are usually ≤3 mm in size (Ø) and surrounded by fibrous septa.
Mostly by on going alcohol or biliary tract disease.
2. Macronodular cirrhosis - the nodules are variable in size and may range up to 1 cm (Ø) and also normal
ascini may be seen within large nodules.
3. Mixed type-both small and large nodules are seen. Mostly in end stage of cirrhosis.

Symptoms-
1. compensated stage- generalized weakness, anorexia, malaise, weight loss jaundice, spider nevi,
hepatomegaly fallowed by a small liver with cirrhosis, splenomegally, clubbing, Xanthoma,
Gynecomastia, testicular atrophy, palma erythema and dupuytrens contracture.
2. In decompansated stage- additional signs are seen jaundice ascitis with or without peripheral edema.
There can be also portosystemic encephalopathy with drowsiness, stuper, flapping tremor disorientation,
coma.
Investigations-
1. to assess severerity- •liver biochem(↑ Alkaline phosphate, ALAT and ASAT, ↓ Albumine) • serum
electrolytes (Na)↓ •Blood analysis-prolonged PT, •if alpfa feto protein + then hepato cellular carcinoma.
2. To assess type- • viral markers •Auto antibodies •serum Ig’s • Alpha 1 antitripsin • ferritin• serum iron
and total iron binding capacity.
3. imaging-US, CT, barium swallow, endoscopy, scintigraphy.
4. Liver biopsy
Management- • proper fallow up, •progression of disease can be prevented by correctly treating the underline
cause. •Bed rest, salt restriction depending on severity of ascitis, fluid restriction (<1-5l/day), Plasma creatinine
weight and urine output.• if hyponatremic give albumine i.v, diuretics(spirenolactone 100mg/24hrs p.o ↑ the
dose every 2 days up to 400mg/24 hrs).

Complications- portal hypertension, veriseal bleeding, acitis, encephalopathy, renal falure, hepatocellular
carcinoma.

Prognosis- Overall 5 year survival is 50%.

Childs grading for prognostic evaluation
grade Serum bilirubin Serum albumin Jaundice, ascitis, Operative
encephalopathy mortality
A NORMAL ≥35g/l none 5%
B 20-50µmol/l 30-35g/l mild 10%
C >50µmol/l <30g/l Severe/uncontrolled 50%
c. Liver carcinoma
•Liver tumors – Most common liver tumor is a secondary(metastatic) tumor. Particularly from the GIT, breast,
broncus (♂-stomach, lung, colon , ♀-breast, colon, stomach, uterus.) Primary tumors can be malignant or
benign. Most common malignant.

1.Hepatocellular carcinoma(HCC) – The most common.

Aetiology-
• Carriers of HBV and HCV have an extremely high risk of developing HCC.Cirrhosis is present in over 80%
of these patients.
•Primary liver cancer is associated with other forms of cirrhosis – eg.alcoholic cirrhosis and haemachromatosis.
•long standing ulcerative colitis ± primary sclerosing cholangitis.
•aflatoxins(metabolite of a fungus)
•androgenic steroids – contraceptive steroids >8 yrs may ↑ risk 4 fold.
Pathogenesis – Precisely unknown. When there is persistent viral replication (in HBV).Viral DNA eventually
becomes incorporated into the host genomic DNA. This leads to malignant transformation.(HCV
carcinogenesis mechanism unknown b/c HCV is an RNA virus and is not incorporated into the host genome)
Pathological features – Microscopically the tumor may form a single large mass with central necrosis,
haemorrhage and bile staining.And maybe multicentric. Extra hepatic metastasis occurs.

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Clinical featues- • Usually below 50yrs.•weight loss• anorexia•fever•pain in right hypochondrium• asites.On
examination irregular tender liver .
Investigations- 1.serum alpha feto protein is raised (usually disappears soon after birth) 2. US,CT,MRI,radio
isotopic scan. 3 liver biosy under US guidance.
Treatment-• if untreated most patients die within 3-6 months of diagnosis. •Surgical resection of single
tumors<3cm in Ø gives a 3 yr survival of 60%. • Other – hepatic artery embolization with chemotherapy,
alcohol ablation via US guided percutaneous injection. • Immunotherapy with monoclonal antibodies +
cytotoxic agents. • Gene therapy. Chemotherapy and radiotherapy are unhelpful.
2. Cholangiocarcinoma – Tumors arising from the biliary epithelium. Can be extrahepatic or intrahepatic.
Intrahepatic adenocarcinomas arising from the bile duct account for approximately 10% of primary tumors.
They are not associated with cirrhosis or hepatitis B. Maybe associated with Clonorchis sinesis
Predisposing factors maybe • some chronic hepatobiliary parasitic infestations • congenital anomalies with
ectactic ducts • sclerosing cholangitis and ulcerative colitis • occupational exposure to possible biliary
carcinogens.
Clinics – •Painless jaundice. •pruritus •weight loss •cholic stasis• acholic stools (patient may present with
biliary obstruction.) • a deep seated vaguely localized right upper quadrant pain •hepatomegally and a palpable,
distended gall bladder are frequent signs. •fever is unusual unless associated with ascending cholangitis.
Treatment – Hilar tumors rarely resectable, response to chemotherapy is poor. Palliative stenting of the biliary
tree(obstructed extrahepatic biliary tree) may improve the quality of life. Prognosis 4-6 months on average.
•other malignant tumors – Angiosarcoma, hepatoblastoma.
•Benign tumors – Hepatic adenoma (associated with oral contraceptives), haemangioma (commonest benign
tumor),focal nodular hyperplasia, fibroma.
D. Hepatic coma/ portal-systemic encephalopathy.
May occur in fulminant hepatitis caused by viruses, drugs or toxins but more commonly occurs in cirrhosis or
other chronic disorders when extensive portal- systemic collaterals have developed as a result of portal HT.
Pathogenesis - 1.Liver metabolizes and detoxifies digestive products brought from the intestine by the portal
vein. 2. In liver disease, these products escape into the systemic circulation if the function of these
parenchymal cells is severely impaired. 3. These toxic products passes to the brain via blood. 4. Toxic
substances are not precisely known. Ammonia a product of protein digestion plays the main role.(ammonia is
produced by the breakdown of protein by intestinal bacteria). 5. Alterations in cerebrovascular permeability is
seen. Brain appears abnormally sensitive to metabolic stresses. Interference with cerebral energy metabolism
and inhibition of neural impulse by toxic amines acting as false neurotransmitters may occur. And also gama-
aminobutyric acid/GABA (the principal cerebral inhibitory neurotransmitter) synthesis appears increased.
6. All these first leads to hepatic encephalopathy then hepatic coma is the final manifestation.
Clinical features – Acute onset is usually precipitated by factors such as high dietary proteins, GI
haemorrhages, constipation, infections, drugs, surgeries. Chronically- •disorders of personality, mood intellect.
•sleep rhythm disturbances. • patient is irritable, confused, disorientated, has slurred speech. General features-
nausea, vomiting, weakness. •Convulsions of coma occurs as the encephalopathy becomes more marked.
Hyperventilation and pyrexia are seen.
Signs - fetor hepaticus ( sweet smell to the breath) •when the hands are stretched they gives a flapping tremor
and wrists are hyperextended (asterixis) • construction apraxis & the patient cant write or draw as coma
progress these signs disappear and hyperreflexia develop with babinski response.
Diagnosis- 1. clinics 2. liver biochem 3. additional investigations-•EEG (diffuse slow wave activity)•blood
ammonia ↑.•PT
Complications – cerebral edema, bacterial infections, GI bleeding, renal failure.
Management- (in ICU)
•remove the possible precipitating cause eg-drugs
•Give purgation & enema to empty the bowels of nitrogenous substances-(lactulose 30 ml *3/day) is an osmotic
purgative that reduces the colonic PH & limits ammonia absorption.
•induce protein free diet •antibiotics- oral Neomycin 1g 6hrs, Metranidazole900mg 4*/day.
•stop or reduce diuretic therapy. •correct electrolyte imbalance. •give i.v fluids
•Flumazenil (benzodiazepine receptor antagonist) can induce a transient improvement.
Long term-•↑protein in diet as the encephalopathy improves •avoid constipation •give lactolase 10-30ml 3*/day
•avoid precipitating factors-narcotics, overdiuresis producing electrolyte disbalance.
Prognosis- in mild cases 2/3 survives, poor prognosis with HCV infection.
Report on Out come of viral hepatitis, chronic hepatitis, liver cirrhosis, liver carcinoma, and liver coma.

Report prepared by
1. Dr. Sajid Mahmood, MD (EU), Accident & Emergency Department, NHS Royal infirmary Liverpool United Kingdom.
2. Dr. Adnan Akram, MD (EU), Department of Infectious Diseases. University Hospital Riga Latvia.
3. Dr. Aftab Ahmed, MD (EU), Infection Control Department, Kaunas Medical University Clinic. Lithuania.

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