Unani Treatment Improved Fibrosis in Decompensated Cirrhosis of Liver : A Case Series

Introduction At present, liver transplantation remains the only curative option for the patients with cirrhosis and end-stage liver diseases. The survival rate and recurrent diseases remains the major issue in the patient post-transplantation. Unani medicine is one of the oldest traditional system of medicine, has been treating chronic liver diseases and cirrhosis [Talayyaful-Kabid] since centuries. The purpose of our study was to assess the impact of Unani treatment in decompensated cirrhosis and collect data to warrant further clinical trials. Case presentation We have conducted a case series with three patients of decompensated cirrhosis and portal hypertension. Cases were confirmed by fibroscan and ultrasound and treated with Unani treatment orally for 3 months. Results were evaluated based on fibroscan, liver function test, EQ5D and TTO-TIME [tradeoff question]. Conclusions Significant improvement in liver function test, fibrosis and quality of life were achieved in the patients. We reviewed the literature related to the herbal constituents of chief medicines used for the treatment in this case. The herbs have been proved for its potential anti-oxidative, anti-inflammatory, hepatoprotective, immuno-modulator and antiviral activities, suggesting plausible mechanisms of action in these cases. The preliminary findings indicate the potential therapeutic role of Unani treatment in decompensated cirrhosis. Clinical trials should be conducted to explore the further therapeutic potential of Unani treatment in decompensated cirrhosis. DOI Name http://dx.doi.org/10.3126/jaim.v4i2.16898


INTRODUCTION
Cirrhosis is defined as the histological development of regenerative nodules surrounded by fibrous bands in response to chronic persistent liver injury, which leads to portal hypertension, ascites and end-stage liver disease.2][3][4][5] Progresses of fibrosis occurs at variable rates, depending on the cause of liver disease, environmental and host factors. 1 The major clinical consequences of cirrhosis are impaired hepatocyte [liver] function, an increased intrahepatic resistance [portal hypertension], ascites and the development of hepatocellular carcinoma [HCC]. 1,2,5coholic liver disease and hepatitis C are the most common etiologies of liver fibrosis in the Western world, while hepatitis B prevails in most parts of Asia and sub-Saharan Africa. 1 Alcohol consumption is estimated to cause from 20% to 50% of cirrhosis of the liver. 3After the identification of the hepatitis C virus in 1989 and of non-alcoholic steatohepatitis [NASH]  in obese and diabetic subjects, the diagnosis of cirrhosis without an apparent cause [cryptogenic cirrhosis] is rarely made.Epidemiological studies shows that identified regular [moderate] alcohol consumption, age above 50 years, and male gender as risk factors in chronic hepatitis C, or older age obesity, insulin resistance/type 2 diabetes, hypertension and hyperlipidemia [all features of the metabolic syndrome] in NASH.Approximately 10-20% of patients with chronic HBV or HCV infection have cirrhosis at first clinical presentation, and as many as 20-30% of those who do not have cirrhosis will eventually develop this condition and its complications within one or more decades. 2ver cirrhosis is a significant cause of global health burden, with more than one million deaths in 2010.Mortality from liver cirrhosis was also comparatively high in countries of Central Asia, particularly Mongolia, Uzbekistan and Kyrgyzstan, and in parts of sub-Saharan Africa. 4e physicians of Unani system of Medicine have been treating cirrhosis of liver and its consequences since centuries.The entity "Warm-e-Jigar Barid Saudawi"/ "Taleef-ul-Kabid" in Unani literature, mimic liver cirrhosis and associated constellation of symptoms.A large number of single and compound drug preparation have been documented in the treatment of Taleef-ul-Kabid.These scientific studies have validated the antioxidant, anti-inflammatory, antiviral, immuno-modulatory, and hepatoprotective nature of plant-based medicines, and their bioactive principle has been isolated and characterized.The cases who were treated in the present series includes only those who were advised for liver transplantation.Due to nonavailability of donor and certain factors such as restricted and costlier resources in overpopulated India, Unani treatment has been given in these cases as per Unani paradigms documented in Unani literature for cirrhosis of liver.Unani treatment, given in this case series comprised of multiple poly-herbal or compound preparation of Unani medicine.

OBJECTIVE
Present case series was performed, primarily aimed to explore the antifibrotic and liver regenerating effect of Unani treatment in the three cases of liver cirrhosis.

Consent
Informed consent was taken from the patients.The human data's, included in this case series were obtained in compliance with the Declaration of Helsinki.

Outcome measures
Results were evaluated based on clinical manifestation and investigation such as fibroscan, liver function test and findings of ultrasonography of abdomen.Assessment of quality of life was also done using EQ5D and TTO-TIME [trade-off question] section 37 of physical health version 2, October 2005, pre and post-Unani treatment.
Case 1: S.J 40 years Indian male admitted to the in-patient department of Majeedia Unani Hospital [MUH]

DISCUSSION
The ultimate therapy for cirrhosis and end stage liver disease is liver transplantation.The major issues that remain in the care of the patient post liver transplantation are recurrent disease in the transplant, particularly HCV, and long term consequences of immunosuppressive agents such as hypertension, hyperlipidemia and renal disease. 1 Even in the developed world, however, the number of donor organs available but the condition of the potential recipients limit the applicability of this transplantation, and thus validation of traditional therapies to halt or reverse fibrosis are urgently needed.
In in single and poly-herbal form for chronic liver diseases since decades in Unani system of medicine.
The immune system [both the innate and the adaptive immune cells] plays an important role in fibrosis, since persistent inflammation almost always accompanies fibrosis.In our cases, reduction in fibrosis could be due to immunomodulatory effect of the constituents in above mentioned Unani treatment, proven in various animal models. 11,21,22nce chronic inflammation almost always precedes and accompanies fibrotic changes and the medicines that target the inflammatory cascade typically have antifibrotic activity.Moreover, because the vicious cycle of scar formation is initiated by oxidative stress, targeting ROS generation also reduces the inflammatory response, which will attenuate HSC activation and fibrogenesis.Antioxidants can attenuate ROS effects and hold promise as potential antifibrotic therapies, provided that sufficient antioxidant activity can be delivered to the sites of injury within the liver.
][19][20]24 Moreover these drugs have also been proved for their hepatoprotective and anti-inflammatory activity [13][14][15][16]24 and persistent inflammation almost always precedes and accompanies fibrosis. So edicines that target the inflammatory cascade and mitigate further liver injury [hepatoprotective] typically designated to possess antifibrotic activity, highlights the antifibrotic effect of Unani treatment.6[ Return of liver function test toward normal and reduction in inflammation, could be due to hepato-protective and antiinflammatory effect of Unani treatment.HBV DNA became undetectable in case 2, could be due to anti-hepatitis B properties of constituents such as Swertia chiraita.23,24 Jigreen, has been proven for its effects on anorexia, pain in abdomen, nausea and vomiting, probably the cause for symptomatic relief in our cases.Jigreen has also reduced bilirubin levels and improved other liver biochemical markers.8,,9 Chicory [kasni] has exhibited analgetic activity in mice in hot plate and tail-flick tests.7,9 Majoon Dabeed-ulward, is a compound formulation of Unani medicine, which contain Rosa damescene [Rose] as main drug, proven as hepatoprotective in various studies.24,25

CONCLUSION
This case report provides a novel direction in which above mentioned Unani treatment can be used for regeneration of liver and halting progression of fibrosis in cirrhosis and for alleviation of constellation of symptoms.Unani treatment also improved quality of life in these three cases.Therefore further studies should be performed to warrant the antifibrotic and regenerative effect along with elucidation of mechanism of action of Unani treatment in cirrhosis of liver.

CONFLICTS OF INTEREST
None declared

Table 2
is summary of quality of life assessment in these 3 cases.