HOW TO DIFFERENTIATE ALCOHOLIC HEPATITIS FROM ALCOHOLIC CIRRHOSIS AND IS THE DIFFERENTIATION IMPORTANT?

HOW TO DIFFERENTIATE ALCOHOLIC HEPATITIS FROM ALCOHOLIC CIRRHOSIS AND IS THE DIFFERENTIATION IMPORTANT?

Sundeep S Shah*, Sharad C Shah**
*Dept of Gastroenterology, Jaslok Hospital and Research Centre, Mumbai - 400 026; **Honorary Consultant in Gastroenterology, HN Hospital and Medical Research Centre, Jaslok Hospital and Research Centre, Mumbai - 400 026.

INTRODUCTION

The association of alcohol abuse and liver damage is known since the times of ancient Greeks and is also recognised in Ayurveda. [1] The clinical spectrum of alcoholic liver injury varies from asymptomatic hepatomegaly to profound hepatocellular failure with portal hypertension. The clinical picture tends to be more florid in individuals with more advanced liver injury. [1] Alcoholic liver injury appears to progress from fatty changes through alcoholic hepatitis to cirrhosis. [2] Majority of the individuals who abuse alcohol will develop fatty changes in their liver at some stage of their drinking career. However only 20% of such individuals will develop cirrhosis. [3] The apparent predisposition of certain people to develop alcoholic cirrhosis is unknown. Fatty liver, though indicating a profound metabolic disturbance within the liver, is not necessarily harmful. Certainly, cirrhosis may develop in an alcoholic who has never had fatty change and isolated fatty change has not been shown to proceed directly to cirrhosis. [4] Alcoholic hepatitis develops in only a proportion of drinkers even after decades of abuse and is assumed to be a precirrhotic lesion, although its natural history is not well understood. [5] Thus in approximately 50% of individuals alcoholic hepatitis may persist for several years and in 10% of individuals the lesion may heal despite continued alcohol abuse. [6] It has therefore been suggested that although alcoholic hepatitis may contribute, when present, to the evolution towards cirrhosis, it is not a sine qua non of such progression. [7] Though most of the alcoholics may have a combination of alcoholic hepatitis and cirrhosis on biopsy and more or less similar clinical and biochemical features, there are certain features which may help in differentiating the two conditions as given in the Table 1 below.

Since alcoholic hepatitis is reversible and hepatic function improves over a period of time with abstinence, management consists predominantly of abstinence from alcohol and supportive care; whereas alcoholic cirrhosis once established is irreversible and hepatic function may not improve over time, management consists of abstinence from alcohol, treatment of complications and liver transplantation may be a viable option in carefully selected patients. Liver transplantation should not be done in patients with pure alcoholic hepatitis. Hence it is very essential to differentiate a patient having alcoholic from the one having alcoholic cirrhosis as the management and prognosis is different.

TABLE 1 Differentiation between alcoholic hepatitis and alcoholic cirrhosis
Alcoholic hepatitis	Alcoholic Cirrhosis
Symptomatology	Symptomatology
• Patients with alcoholic hepatitis have been abusing alcohol till the time of presentation; they look more ill and being symptomatic present to a physician.	• Patients with alcoholic cirrhosis may not have abused alcohol for many years prior to presentation; most of them are well compensated, with only one-third being symptomatic.
• Jaundice is usually one of the most common symptom. Some common mode of presentations are: jaundice - 50% of the patients, ascites in 30 - 60% and splenomegaly - 15% of the patients.	Ascites is usually the common symptom. Some common mode of presentations are: 40%, dilated abdominal wall veins - 60% and splenomegaly - 25% of the patients.
• Fever (even high grade) is seen in upto 50% of the subjects.	• High grade fever is not seen (unless there is superadded infection).
• Symptoms of variceal bleeding and hepatic encephalopathy are uncommon.	• Variceal bleeding and hepatic encephalopathy are quite common.
Clinical Signs	Clinical Signs
• Spider naevi and palmar erythema may be florid.8	• Spider naevi and palmar erythema though seen, may not be florid.
• Features of portal hypertension - Ascites, dilated abdominal wall veins, splenomegaly and oesophageal varices are not a prominent features of pure alcoholic hepatitis.	• Features of portal hypertension are a prominent feature of alcoholic cirrhosis.
• Liver is very large and tender on palpation; its surface is smooth and consistency is soft to firm.	• Liver is mild to moderately enlarged or may not be palpable in advance cirrhosis and when palpable it is nontender, irregular with palpable nodules and firm in consistency.
• Arterial bruit may be heard over the liver area.	• Unless there is superadded hepatocellular Unless there is superadded hepatocellular
Investigations	Investigations
• Polymorphonuclear leucocytosis (upto) 20,000/mm3) is quite common.	• Polymorphonuclear leucocytosis though seen may not be as high as in alcoholic hepatitis.
• Platelet function is depressed, but there may not be thrombocytopenia. There is no evidence of hypersplenism.	• Both platelet function and number are reduced and there is evidence of hypersplenism.
• SGOT and SGPT are elevated upto 300 to 400 IU with SGOT/SGPT ratio > 2.	• SGOT and SGPT are usually normal.
• Highest levels of rise of gamma glutamyl transpeptidase, glutamate dehydrogenase and tumour necrosis factor are seen in alcoholic hepatitis.	• There is mild to moderate rise of gamma glutamyl transpeptidase and glutamate dehydrogenase in alcoholic cirrhosis.
• Most of the elevated enzymes fall back to normal level within 1 week of abstinence.	• No significant fall in enzyme levels are seen over a period of time, even if abstinent.
• Isotope liver scan may show total absence of radiotracer uptake by the hepatic parenchyma ("Medical hepatectomy") with avid uptake by the spleen and the bone marrow of vertebrae and the ribs. After a period of recovery, the liver scan may show normal tracer uptake.	• Isotope liver scan show inhomogeneous tracer distribution in the liver, with left lobe uptake greater than the right lobe, colloid shift to the spleen ("Hot spleen") and visualisation of the bone marrow of the vertebrae. Liver scan picture does not show improvement over time.
• Liver biopsy histology:	• Liver biopsy histology:
Three obligatory features for the histologic diagnosis are -	On liver biopsy the following features are seen-
......- ballooning degeneration of hepatocytes, with areas of necrosis.	......- parenchymal necrosis
......- inflammatory cell infiltrates, predominantly	......- regeneration
	......- scarring
......polymorphonuclear leucocytes
........- fibrosis, both pericellular (producing a lattice-like or chicken wire appearance) and perivenular (centrolobular).
• 20% of alcoholics show features of hepatitis on 18.3% of alcoholics show features of cirrhosis (6.7%) or in combination with cirrhosis (13.4%).8 Alcoholic hepatitis rarely is seen as an isolated pathology on liver biopsy. On most occasions it is seen in combination with either fatty liver or cirrhosis.	• 18.3% of alcoholics show features of cirrhosis on biopsy; 5% as only cirrhosis and 13.4% in combination with alcoholic hepatitis. Thus alcoholic cirrhosis may be the only pathology alcoholic cirrhosis may be the only pathology
Management	Management
• Alcoholic hepatitis is usually reversible on Alcoholic cirrhosis is generally considered to	• Alcoholic cirrhosis is generally considered to be an irreversible lesion once it is established.
• Treatment consists of abstinence and proper nutritional support. Liver transplantation is not recommended at this stage.	• Apart from abstinence and treatment of complications, liver transplantation may be a viable option.
Prognosis	Prognosis
• Though high initial in hospital mortality of about 50%, long term prognosis of those who abstain from alcohol is very good.	• Though initial in hospital mortality may not be high (but depends on the mode of decompensation), long term prognosis is presentation and degree of hepatic dismal with nearly 50% 5 year mortality
• The Maddrey discrimination function is a simple equation in which the serum bilirubin and prothrombin time are used to indicate the presence of severe alcoholic hepatitis (4.6 x (PT in secs - control time) + serum bilirubin in mg/dl). A score greater than 32 indicates severe alcoholic hepatitis with poor prognosis. [10]	• Child-Pugh score is used to determine the prognosis using the following parameters - ascites, encephalopathy, bilirubin, albumin and prothrombin time. Child class A has the best prognosis and child class C has the worst.

SUMMARY

Alcoholic hepatitis	Alcoholic Cirrhosis
• Acute debauch, continued alcohol consumption	• Probably a past drinker
• Ill patient (may be febrile)	• Relatively well preserved (unless severely decompensated)
• Presents usually with jaundice which may be deep (Cholestatic!)	• Presents usually with ascites or GI bleeding
• Tender, large and smooth hepatomegaly	• Non tender, firm, irregular and nodular liver
• Florid spider angioma and palmar erythema	• Spider angioma and palmar erythema present
• No major signs of portal hypertension	• Signs of portal hypertension present
• ? Arterial bruit over the liver	• Arterial bruit over liver only with hepatoma
• Polymorphonuclear leucocytosis	• Minimal polymorphonuclear leucocytosis
• GGT, SGOT and SGPT elevated - usually upto 300 IU/L	• Liver enzymes usually in normal range
• Gold standard for diagnosis is liver biopsy	• Gold standard for diagnosis is liver biopsy
• Poor prognosis for Maddrey’s score > 32.	• Poor prognosis for Child class C.

REFERENCES