Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Bhanu K Bhakhri

"The Journal of Clinical and Diagnostic Research (JCDR) has been in operation since almost a decade. It has contributed a huge number of peer reviewed articles, across a spectrum of medical disciplines, to the medical literature.
Its wide based indexing and open access publications attracts many authors as well as readers
For authors, the manuscripts can be uploaded online through an easily navigable portal, on other hand, reviewers appreciate the systematic handling of all manuscripts. The way JCDR has emerged as an effective medium for publishing wide array of observations in Indian context, I wish the editorial team success in their endeavour"



Dr Bhanu K Bhakhri
Faculty, Pediatric Medicine
Super Speciality Paediatric Hospital and Post Graduate Teaching Institute, Noida
On Sep 2018




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Department of Dematolgy,
Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
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I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




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"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
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Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help ones reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journalsNo manuscriptsNo authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011

Important Notice

Reviews
Year : 2011 | Month : February | Volume : 5 | Issue : 1 | Page : 134 - 137

Subacute Hepatic Failure

KORA S A*, DODDAMANI G B**, DODDAMANI USHA***, BIRADAR SATISH****

*Asso. Professor, Department of Medicine; **Professor, Department of Medicine; ***Asst. Professor, Department of OBG; ****Asst. Professor, Department of Medicine

Correspondence Address :
Dr.Kora.S.A
‘Shailaja Nilaya’, Mahaveer Road
BAGALKOT- 587 101
(Karnataka-India)
e-mail: shreeramkora@yahoo.co.in

Abstract

Subacute hepatic failure (SAHF) had been recognized and reported from India in 1982, but until now, there has been no precise definition of the disease or the description of its nomenclature, clinical and pathological factors, aetiology, diagnosis and its management.
So, we have analyzed all the material which was available for over 30 years and have summarized a few points.
a) Poor regeneration of hepatocytes is the main pathogenesis of this disease.
b) Viral hepatitis, including hepatitis ‘E’, is the main aetiology of SAHF.
c) Ascites is the cardinal feature of this disease and it occurs in the 4th or 5th decade.
d) Liver biopsy shows submassive or bridging necrosis and plasma fibronectin levels are low.
e) The mortality is upto 70% when treated medically and the best available treatment is liver transplantation.
f) Renal failure indicates a bad prognosis.
It can be concluded that it requires further case studies and research to define the disease and to describe its nomenclature, aetiology, pathogenesis, clinical features, prognostic factors, investigation and management in the coming years.

Keywords

Subacute hepatic, onset hepatic, subfulminant hepatic failure.

Introduction
The liver is the largest organ of the body, weighing 1 to 1.5 kg and representing 1.5 to 2.5% of the lean body mass. A majority of the cells in the liver are hepatocytes, which constitute two-thirds of the mass of the liver. Inflammation of the hepatocytes leads to hepatitis. Hepatitis can be caused by drugs and toxic agents as well as by numerous viruses. Hepatitis can further be classified into acute and chronic hepatitis.

Hepatic failure is defined as the occurrence of the signs or symptoms of hepatic encephalopathy in a person with severe acute or chronic liver disease. In fulminant hepatic failure, encephalopathy occurs in less than 2 weeks of the onset of jaundice.

Sub acute hepatic failure (SAHF) had been recognized and reported from India in 1982 as a clinical entity which was distinct from fulminant and chronic hepatic failure and was characterized by progressive or persistent jaundice, 8 weeks after the onset of hepatitis, with unequivocal evidence of ascites in the absence of pre-existing liver diseases. Various western researchers, by using different names, have reported similar clinico-pathological entities.

Material and Methods

Definition and terminology
Tandon et al 1982 (1),(2) coined the term SAHF and proposed that its diagnosis was made on the basis of
1. Persistence or progressive jaundice, 10 weeks after the appearance of icterus in a patient with acute hepatitis.
2. Development of unequivocal ascites and or encephalopathy, 10 weeks after the appearance of the icterus.
3. Biochemical evidence of hepatocellular necrosis.
4. Sub-massive or bridging necrosis on liver biopsy whenever the tissue is obtained.
Within the next 4 years, various European, Asian and American workers proposed different terms for similar syndromes which occurred in patients with acute liver diseases.

Gimson et al (King’s College Group) (1),(3) used the term, Late Onset Hepatic Failure (LOHF), when encephalopathy and other evidences of hepatic decompensation occurred between 8 to 24 weeks after the first symptoms of illness.

According to O’Grady JG et al (4), LOHF is diagnosed when encephalopathy occurs later than 4 weeks after jaundice and when the cut off for encephalopathy(5) is 8 weeks.

Bernau et al (1),(6) preferred the term, Sub-Fulminant Hepatic Failure (SFHF), when acute liver failure was complicated by encephalopathy, 2 weeks to 3 months after the onset of jaundice. An American study (Peleman et al) (1),(7) considered the term SAHF when irreversible liver failure developed 8-28 weeks after the onset of symptoms in an individual without prior evidence of hepatic decompensation.

It is clear therefore, that there is an ongoing debate about the following points:
1. Nomenclature of the condition- subacute hepatic failure, late onset hepatic failure or sub-fulminant hepatic failure.
2. Which first symptom (Jaundice or any other non-specific symptom of acute illness) should be considered as the starting point of the original disease?
3. What should be the period between the onset of jaundice or hepatic illness and the onset of later symptoms which are suggestive of SAHF (2 to 12 weeks)?
4. Last, but not the least, whether ascites or encephalopathy should be the symptoms which are suggestive of SAHF.
According to the International symposium on SAHF, March 1993, there are several inclusion and exclusion criteria. (8),(9)

A) Inclusion Criteria:
I) Jaundice persisting for more than 8 weeks after its onset, with the development of unequivocal ascites with or without encephalopathy.
II) SGPT (ALT) levels twice the upper limit of the normal.
B) Exclusion Criteria:
I) Presence of dilated biliary radicals on sonography.
II) Evidence of varices larger than Grade-I on endoscopy.
III) Alcoholism.
IV) Chronic renal failure.
V) Kayser Fleischer ring or low ceruloplasmin level.
VI) Liver biopsy (either ante-mortem or post-mortem); histological evidence of established cirrhosis.

Aetiology
The most common aetiology of SAHF is viral hepatitis and its incidence ranges from 60 % to 90% of all hepatic diseases. In various series, the distribution of different viruses in cases of SAHF due to viral hepatitis (10),(11) is shown in (Table/Fig 1).


(Table/Fig 1): Distribution of different viruses in cases of SAHF due to viral hepatitis

The role of the hepatitis ‘E’ Virus is yet to be established because the prognosis of hepatitis ‘E’ Virus SAHF is very good (12) as compared to the prognosis of other viruses, drug toxicities (eg: troglitazone) (13) and autoimmune diseases (5) are other causes of SAHF. The history of herbal medicines is important, as these drugs are used routinely in the Asian sub-continent for the treatment of jaundice and it could be a possible aetiological factor.

Pathogenesis
In viral hepatitis, continuing liver cell necrosis with poor regeneration of the liver cells may lead to SAHF. (10) Impaired hepatic regeneration may probably be related to age, which explains the frequent occurrence of SAHF in the 4th and 5th decades.

In experimental liver injury which was produced by galactosamine, submassive hepatic necrosis was prevented by hepatopoietin (a low molecular weight peptide which promotes hepatic regenerations) in Wister rats. This probably explains the failure of the regeneration of hepatocytes as the main pathogenic event in SAHF.

Hepatopoietin has a trophic and an intiogenetic effect on hepatocytes and multiple cell lines. ( The levels of hepatopoietin, measured by ELISA, are elevated both in fulminant and chronic liver diseases as compared to those in the normal controls). No data on the hepatopoietin levels in SAHF is available as yet.

The mechanism of ascites (Lebree et al) (14) in case of SAHF, is the increased wedged hepatic venous pressure which is secondary to the collapse of the sinusoids, which means that the intrahepatic block is the cause of portal hypertension in SAHF which leads to ascites.

Pathology:
Submassive or bridging necrosis is characteristic of SAHF. Histology shows the features of viral hepatitis with bridging necrosis, which may be portal to portal, central to central, or portal to central. Regenerating activity is conspicuous by its absence. Necrotic areas contain a large amount of polymorphonuclear infiltration and a significant number of plasma cells.

Other features like the ballooning degeneration of the hepatocytes, lobular inflamation, cholestasis and the ductal proliferation of the bile ducts can be seen.

Clinical features
Age: SAHF is commonly encountered in the 4th and 5th decades; less than 2% patients were below the age of 20 years in a series of patients in Delhi. Other researchers who have described comparable entities under different terminologies as LOHF, SFHF, impaired regeneration syndrome and subacute hepatic necrosis, have observed a similar preponderance. The only exception was a report from USA where the mean age of the patients with SAHF, who underwent liver transplantation, was 28.7. A series from Vellore (TamilNadu) reported 32 cases with SAHF, with a mean age of 36  15 years.

Jaundice and ascites were the cardinal features and encephalopathy was the terminal event. (Table/Fig 2).


(Table/Fig 2): Distribution of Clinical features of Sub acute hepatic failure in various studies

The main clinical difference in FHF and SAHF was the slower tempo of the illness with ascites as a major manifestation in SAHF, in contrast to the rapid progression to encephalopathy in patients of FHF. Cerebral oedema was present in 80 to 100 % of the cases of FHF and was uncommon in SAHF (Gimson et al – 9%) (3)

Hepatomegaly was present in 40 to 60 % and splenomegaly was present in 10 to 30 % of the SAHF cases. Other clinical features like nausea, vomiting, abdominal pain, and fever have been reported in 20 to 80 % of the cases. Cerebral oedema was uncommon in patients with SAHF as compared to FHF and renal failure and SBP occurred more in SAHF cases. The incidence of bacteraemia, sepsis and GI bleeding was similar in acute and subacute hepatic failure cases. When these cases were treated medically, the mortality ranged from 70 to 90 %. Renal failure accounted for upto 50 % deaths, while GI bleeding and infection accounted for 30% of the deaths. All the survious developed chronic liver diseases within1 to 2 years. (Table/Fig 3).


(Table/Fig 3): Complications of Sub acute hepatic failure in various studies

Investigations
Liver function tests suggested hepatocellular necrosis. Predominantly, conjugated S.Bilirubin was elevated SGPT levels were increased, but they did not rise above 6 times the normal (8) . (Table/Fig 4).

(Table/Fig 4): Liver function tests Sub acute hepatic failure in various studies

 The prothrombin time was markedly prolonged (8)
 S. Albumin levels were also decreased mildly. (In the Naik et al series, the mean Albumin level was 3.0 gm / dl)
 Ascitic fluid was transudative in nature,
 The coagulation factors II, V, VII, IX and X were decreased below 50% of the normal. The estimation of the factor 5 levels was shown to have a diagnostic, prognostic and therapeutic role in SAHF according to some series (8).
 The plasma fibronectin concentration was significantly low in SAHF cases as compared to the normal and uncomplicated acute viral hepatitis cases. (10),(16). This may be the cause for impaired kupffer cell function and the consequent susceptibility to endotoxaemia and bacterial infections. The opsonisation activity was markedly impaired and it correlated well with secondary infections.
 Serum alpha fetoprotein levels were normal or low.
 Liver biopsy showed sub-massive or bridging necrosis.

Management
Aims of therapy
Logically, the therapeutic formulations should be based on pathogenesis. Based on the available information about the pathogenesis, the desired therapeutic aims of SAHF are (8):

I) Control of liver cell necrosis.
II) Acceleration of liver cell regeneration.
III) Replacement of necrosed liver tissue.
IV) Supportive therapy for liver failure.

I) Control of liver cell necrosis:
Today, at present, there are no standard drugs to prevent liver cell necrosis. Many controlled trials have shown that corticosteroids are not useful in FHF cases and that it is same for SAHF also. The role of other immunomodulators have not been studied in SAHF cases. The role of interferons was proved in case of chronic hepatitis and these did not show any good results in FHF. The role of these drugs in SAHF has to be studied. The role of antivirals like acyclovir, adenosine arabinose and interleukins is yet to be studied. The available studies do not (8),(18) show any good results with any of the drugs.

II) Therapy to accelerate liver cell regeneration:
There is no effective treatment for liver cell regeneration as yet. This is because we still do not know about the specific hepatocyte growth factors and the “Stem cells” which possibly repopulate the liver after massive hepatic necrosis.

Prostaglandins
In one series, Sinclair et al(19) treated 17 patients with FHF and SAHF by PGE-1 at a rate of 0.2 to 0.6 microgram / kg / h, for upto 28 days. Two of these patients underwent liver transplantation and 12 of the remainder (80%) survived. But the other two series failed to reproduce the same amount of results. These drugs acted by maintaining the integrity of the micro vascular circulation and cytoprotection. So, the role of prostaglandins is yet to be established (8).


Hepatocyte growth factors
Historically, there are two main theories for the growth factor control of hepatic regeneration. The first is that the reduction in the liver mass stimulated the production of positive growth factors and the second theory is that the normal liver mass decreases the local inhibitor and that the liver starts to regenerate until the normal inhibitor tone is restored. (17) Now, a recent theory has combined both these theories and has suggested that it is a complex interaction between stimulatory and inhibitor influences on growth.

Hepatocyte growth factors are capable of inducing hepatocyte replication by inducing the synthesis of DNA in hepatocytes. However, these are not organ specific. Epidermal growth factor (EGF), insulin, glucagon, norephinephrine, hepatocyte growth factor (HGF) and transforming growth factor (Alpha and Beta) are the known growth factors. EGF is the growth factor for several epithelial tissues and it induces DNA synthesis in hepatocytes. Its activity (in vivo) is markedly increased by the actions of Insulin and glucagon.

In one series, insulin and glucagon had promoted liver regeneration, but the results were not satisfactory in other series. So, the role of these hormones needs to be further evaluated in SAHF.

Transforming growth factor alpha and beta are stimulators and inhibitors respectively in the DNA synthesis of hepatocytes. TGF alpha has a 30 to 40 % sequence homology with EGF and can also bind to the EGF receptor and initiate hepatocyte replication. TGF alpha is more potent than EGF.

Recently, the hepatocyte growth factor (HGF) (hepatotrophin, probably identical with hepatopoietin A) was identified and it was found to be specific for hepatocytes. The non-parenchymal cells of the liver secrete it. So, further research on these factors can help us to treat SAHF by regenerating the liver cells.

(iii) Replacement of necrosed liver tissue:
(a) Liver support systems and bio-artificial liver (8):
Now- a -days – the ex vivo linear support which is generated by developing the bio-artificial liver, is becoming a reality. Now, two such devices are being used in clinical evaluation.
 One- this uses pig hepatocytes and is perfused with the plasma by a technique which is similar to plasmapheresis.
 Second - extra-corporeal liver assist device (EALD).

The EALD is still in the stages of early development and it may be useful. This device uses C-3A hepatoblastoma cells which are grown in hallow fiber cartridges. When EALD is used, blood passes through the porous channels between the cell chambers and the removal of bilirubin and the synthesis of S. albumin with the clotting factors is observed.

The device which is used currently contains 200 gm of hepatocytes as compared to 2000 gm of hepatocytes in normal adult liver. However, there are no accessory cells such as the bile duct epithelial cells, the kupffer cells and the endothelial cells which contribute substantially to the function of the liver. In recent reports from several, small, uncontrolled studies, these devices were found to improve encephalopathy, intracranial pressure and several biochemical measures. But controlled trails are needed and these will act as a bridge to transplantation in several patients.

(b) Liver transplantation:
The curative treatment for FHF is orthotopic liver transplantation and survival rates of 50 to 70 % have been reported. It may prove to be useful in SAHF, but some points have to be noted here. One exact status of viral replication is not known in SAHF and it is difficult to assess the chances of the recurrence of viral replication in transplanted livers.

Further, at least 20 to 30 % of the patients with SAHF do survive the illness. Until the prognostic factors are known, it would be difficult to predict as to which patient would die and which one would benefit from transplantation.

U.Zachriah et al(11), concluded from their study, that the worsening renal failure in hospitals could be used as markers for liver transplantation. In a study by Bruno et al (18) the survival rate after transplantation was found to be 75%. Selection criteria for liver transplantation is same as for fulminant hepatic failure, example the Kings or the Clichy criteria which are used in Berne for LOHF:

 Factor V < 20 % in patients who were less than 30 years old.
 Factor V < 30 % in patients who were more than 30 years old.

At some centers, auxiliary liver transplantation is suggested for FHF/LOHF, in which the native liver has to be left in place. Such patients have a survival rate of 65 %; in these series, the native liver was found to recover its function by 70 to 80 %, thus allowing the discontinuation of immunosuppression. The long-term effect of immunosuppression in these patients is not known. So, the available information indicates that liver transplantation is one of the best available treatments for SAHF and that it needs thorough evaluation.

(c) Hepatocyte transplantation:
This is one of the most important things that have emerged in the field of hepatology. Here, hepatocytes which were transplanted on the spleen were shown to survive for more than one year, they showed sinusoidal structures and bile canaliculli and possessed several liver specific enzymes. Thus, this procedure is a potential replacement for a more complex and expensive liver transplantation.

(iv) Supportive therapy:
The patients should be admitted to the ICU, with the maintenance of nutrition by either the oral or the parenteral route (about 1500 Kcal with low sodium diet). Fluid and electrolyte balance is a must. Diuretic therapy with spiralanolactone and frusemide may be useful. Complications like GI bleeding, infections and hepatorenal syndrome should be treated.

Conclusion

Further case studies and research regarding the definition, nomenclature, aetiology, pathogenesis, clinical features, prognostic factors, investigation and the management of this disease is essential in future.

References

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