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REVIEW OF LITERATURE

Sao Paulo Med. J. vol.112 no.2 So Paulo (Apr./June 1994)

In his term Alcohol-induced Hepatic Diseases [ALD] we refer to the hepatopathy induced by ethanol and/or its
metabolites. The study of this subject is of great importance since it represents a prototype of disease in which
biological, clinical, epidemiological, sociological and psychological factors converge.

Unlike many other diseases. ALD can be avoided, as long as the ingestion of ethanol does not exceed certain limits,
and it remains static or even regresses after alcoholic abstinence .

ALD is very common, [it is often the most common type of chronic liver disease] in almost every country. including
Brazil. This fact is related to the high consumption of ethanol, the lack of effective therapies. and the difficulty the
majority of alcoholics have remaining abstinent.

Up until about 30 years ago, it was still thought that hepatic diseases and other important pathological conditions
observed in alcoholics were exclusively consequences of the associated nutritional deficiencies and not to the toxic
effects of alcohol. This theory was based mainly on the work of Best et al. The authors concluded that ethanol was
as damaging to hepatic cells as sugar was, in other words, that it was not hepatotoxic .

The hepatic alterations so frequently found in alcoholics were considered to be principally due to the deficiency of
lipotropic substances, such as choline and methionine, in spite of the fact that in this research, done on rats, the
ethanol consumed was only 10-20% of the total calories of their diet. This dosage resulted in very low levels of
ethanolemia [thus not representing the habitual ethanol consumption of alcoholic patients] Studies developed over
recent years made it possible to show that even with an adequate diet, and without nutritional deficiency, ethanol can
produce steatosis. ultrastructural alterations [in the mitochondrion, endoplasmatic reticulum, and plasmatic
membranes] and discrete fibrosis in rats , fibrosis and cirrhosis in baboon monkeys and steatosis in man.
Epidemiological data also reinforce the arguments as to the hepatotoxity of ethanol. A marked reduction occurred in
the mortality rate of cirrhosis in the United States during the Prohibition, when alcohol consumption was outlawed,
and in France, during the Second World War, when there was wine rationing. These indexes began to climb after the
liberation of alcoholic sales. In a recent epidemiological study it was observed that the reduction of the mortality
rates due to cirrhosis was related to the reduction in the per capita consumption of alcohol and the increase in the
number of members of Alcoholics Anonymous . The death rate for cirrhosis in the United States has diminished in
the last decade, partially due to the treatment of alcoholism and the important work done by Alcoholics Anonymous.
A recent study on the population of the United States noted that the percentage of cirrhotics was significantly greater
in those that had three drinks per day than in those that abstained. The results of all these studies, considered
together, allow us to confirm that ethanol is truly a hepatotoxic substance. There are, nonetheless, rare differing
opinions. Derr et al. deny the toxic nature of ethanol and affirm that "experimental data do not demonstrate, to this
day, that ethanol is, in itself, a hepatotoxic". And they even assure that ethanol "allows or favors recovery from
hepatic disease". This concept has no scientific basis, is based on incomplete and distorted analysis of clinical and
experimental studies, and besides this, constitutes a disservice to those who, at the cost of great sacrifice, are in
abstinence .

In the study on rats done by Derr et al. the quantity of ethanol administered represented only 26% of the total
energy consumed and the levels of ethanolemia were low.

Ethyl alcohol, being a liposoluble substance, can compromise the structure and function of membranes, modifying
the resistance of the cell and the organelles to aggressions and physiological signalling. The pathogenesis of AHD is
intimately related to the metabolism of ethanol, which is processed predominantly in the liver, the organ which
contains the greatest quantity of enzymes capable of metabolizing that substance. It has been demonstrated that a
significant fraction of alcohol ingested in "social" doses is oxidated in the stomach as well, which possesses the
enzyme alcohol dehydrogenase (ADH). The magnitude of this process of oxidation in the stomach can influence the
bioavailability of the ethanol and modulate its potential toxicity. The gastric activity of ADH is less in women than
in men. This factor could contribute to a greater vulnerability to the effects of ethanol in females. Recently various
isoenzymes of gastric ADH were identified as well as genes that corresponded to the different kinetic properties of
those same enzymes. An interesting aspect observed in 80% of Japanese patients was the absence of an ADH gastric
isoenzyme

Mamun-Al-Mahtab, Department of Hepatology, Bangabandhu Sheikh Mujib Medical


University, Dhaka, Bangladesh

In their study being recognized rather late non-alcoholic fatty liver disease (NAFLD) appears to be major
cause of liver related mortality and morbidity globally. Data source: Review of published literature on
NAFLD. Review of literature suggests that we now have broad based understanding about different aspects of
NAFLD ranging from aetiology to pathogenesis and prognosis to treatment. A lot still needs to be done
specially to diagnose non-alcoholic steatohepatitis (NASH) non-invasively as well as to develop specific
pathogenesis directed therapy for this apparently benign, but deadly disease.

He constructed a simple model utilizing routine laboratory data. The authors devised a novel index, termed the
AST to platelet ratio index, or APRI, which is the AST level/upper limit of normal (ULN) divided by the
platelet count (109/L) multiplied by 100. The sensitivity and specificity for fibrosis of the APRI value
depended on the cut-offs used. Using an APRI value of 1.50, the positive and negative predictive values for
significant fibrosis (Ishak score=3) were 91% and 65%, respectively, whereas for cirrhosis and an APRI of
2.00, the positive and negative predictive values were 65% and 95%, respectively. Although the APRI is
attractive because of its simplicity, it can neither definitively diagnose nor exclude cirrhosis and it will not
identify patients with early fibrosis.

A combination test including hyaluronic acid, TIMP1, and 2- macroglobulin was examined in a cohort of 294
patients with HCV infection and subsequently validated in a second cohort of 402 patients[29]. This had a
combined AUROC of 0.831 for METAVIR F2-F4 fibrosis. The positive and negative predictive values were
74.3% and 75.8% respectively, with an accuracy of 75%. This three-marker panel thus may help differentiate
patients with HCV infection with moderate/severe fibrosis from those with no/mild fibrosis, although it was
not possible to differentiate specific stages accurately.

Another combination test was developed by the European Liver Fibrosis (ELF) Study Group[30]. This
group examined collagen IV, collagen VI, PIIINP, matrix metalloproteinase 2 (MMP-2), matrix
metalloproteinase 9 (MMP-9), TIMP-1, tenascin, laminin and hyaluronic acid (HA). The study was unique in
that it examined patients with a wide variety of liver diseases, including those with chronic hepatitis C virus
infection (n=496), alcoholic liver disease (n=64), non-alcoholic fatty liver disease (n=61), chronic hepatitis B
virus infection (n=61), primary biliary cirrhosis or primary sclerosing cholangitis (n=53), recurrent liver
disease post-orthotopic liver transplantation (n=48), autoimmune hepatitis (n=45), hemochromatosis (n=32),
cryptogenic cirrhosis (n=19), both hepatitis B and C (n=4) and other or no known diagnosis (n=138); the
cohort also had a wide distribution of fibrosis stages (Scheuer fibrosis stages were as follows: stage 0=24.6%;
stage 1=35.5%; stage 2=13.4%; stage 3=14.9%; and stage 4=1.8%). An algorithm was developed that detected
the upper third of fibrosis groups (Scheuer stages 2, 3, and 4) with a sensitivity of 90% and accurately detected
the absence of fibrosis (Scheuer stages 0, 1), with a negative predictive value for this level of fibrosis of 92%.
The AUC of a receiver operating characteristic (ROC) plot was 0.804. Interestingly, the addition of clinical
chemistry tests including liver function tests, or hematological indices including platelet count and
prothrombin time, did not improve test performance. The test appeared to be best in patients with hepatitis C,
NAFLD and alcoholic liver disease. The inclusion of patients with multiple etiologies of liver disease,
although appealing, has the potential to limit the accuracy of these and other panels, as the characteristics of
specific assays may be disease specific. Another model, including AST, cholesterol and insulin resistance (as
well as age and an estimate of past alcohol intake) in patients with HCV, found that the sensitivity for detection
of advanced fibrosis depended on the index value used. At a low probability index, the sensitivity for
predicting significant fibrosis was high, but specificity was low, while at a high probability index, sensitivity
for significant fibrosis was low, but specificity was high.
Marsano et al., 2003,

Alcoholic liver disease (ALD) is a serious and potentially fatal outcome caused due to alcohol usage.
ALD encompasses three conditions mainly fatty liver, alcoholic hepatitis and cirrhosis. The diagnosis
and management of this disease is important for decreasing the mortality. For accurate diagnosis of
ALD new bio marker or identifier proteins are being investigated. There is no specific therapy for
ALD hence lifestyle changes, nutritional support and other therapies to improve the outcome are only
there. The new therapies are mainly aimed to improve the quality of life and to reduce the mortality
rates. Most of the alcoholic liver damage is caused due to the direct toxicity of the metabolic by-
products formed during alcohol metabolism. These by-products leads to inflammation expose liver
cells to bacterial toxins and cause liver diseases. This can contribute to fibrosis and ultimately
cirrhosis. Increased understanding of the mechanism of tissue injury has led to new treatments like
corticosteroids, antioxidants, antibiotics. By understanding the biological mechanisms underlying
liver injury it is possible to find new treatment approaches for alcoholic liver disease.

Medical nutrition therapy in non-alcoholic fatty liver disease a review of


literature

D Mischianu,* and G Radulian


In their study described Non-alcoholic fatty liver (NAFL) is a part of the spectrum of liver
disease called non-alcoholic fatty liver disease (NAFLD) . The NAFLD includes steatohepatitis
(NASH), fibrosis, cirrhosis and hepatocarcinoma (HCC).

NAFLD is the most common cause of liver disease worldwide, with a prevalence of 20%-40% in
Western populations . In Europe, the prevalence of NAFLD varies between 20-30% . The
prevalence increases to 58% in overweight individuals and can be as high as 98% in non-diabetic
obese individuals There is no consensus as to what diet or lifestyle approach is the best for
NAFLD patients. However, patients with NAFLD may benefit from a moderate- to low-
carbohydrate (40%45% of total calories) diet, coupled with increased dietary MUFA and n-
3 PUFAs, reduced SFAs. More CRT are needed to clarify the specific effects of different diets
and dietary components on the health of NAFLD patients.

Sheldon L Kaplan, MD
Rafael Esteban, MD

Hepatitis B virus (HBV) infection is a global public health problem. It is estimated that there are
248 million HBV carriers in the world, of whom roughly 600,000 die annually from HBV-related
liver disease . The implementation of effective vaccination programs in many countries has
resulted in a significant decrease in the incidence of new hepatitis B infection. Nevertheless,
HBV infection remains an important cause of morbidity and mortality.

The spectrum of clinical manifestations of HBV infection varies in both acute and chronic
disease. During the acute phase, manifestations range from subclinical or anicteric hepatitis to
icteric hepatitis and, in some cases, fulminant hepatitis. During the chronic phase, manifestations
range from an asymptomatic carrier state to chronic hepatitis, cirrhosis, and hepatocellular
carcinoma. Extrahepatic manifestations also can occur with both acute and chronic infection.
This topic review will discuss the epidemiology, modes of transmission, and prevention of HBV
infection. The clinical manifestations and natural history of HBV infection as well as hepatitis B
vaccination are discussed in detail separately.