A Comprehensive Review of Hepatoprotective Properties of Medicinal Plants with Special Emphasis on Cosmostigma Racemosum

Anatomy of the Liver

The liver is a vital, cone-shaped organ situated in the upper right quadrant of the abdominal cavity, positioned just below the diaphragm and above the stomach, right kidney, and intestines. It appears dark reddish-brown in color and typically weighs approximately 1.4 kilograms (3 pounds).

Blood supply to the liver is derived from two primary sources:

1.Hepatic artery, which delivers oxygen-rich blood.

2.Hepatic portal vein, which carries nutrient-rich blood from the gastrointestinal tract.

At any given time, the liver contains approximately 13% (around one pint) of the body’s total blood volume. Anatomically, the liver comprises two major lobes, subdivided into eight functional segments. These segments further divide into roughly a thousand smaller units called lobules. Each lobule is associated with tiny ducts that progressively merge into larger ducts, ultimately forming the common hepatic duct. This duct carries bile produced by hepatocytes (liver cells) to the gallbladder and the duodenum (the initial section of the small intestine) through the common bile duct. (Boyer and Le Rousseau, 2014; Yale et al., 2024)

Figure 1: Anatomy of liver

The liver plays a pivotal role in regulating numerous chemical concentrations within the bloodstream and secretes an essential substance known as bile. Bile facilitates the elimination of metabolic wastes and aids the digestion and absorption of fats in the small intestine. All blood exiting the stomach and intestines passes through the liver, where it undergoes meticulous processing. Hepatic cells (hepatocytes) metabolize nutrients, maintain their optimal balance, and convert them into usable forms for various tissues throughout the body. Additionally, the liver metabolizes drugs and other xenobiotics, converting them into safer, less toxic forms suitable for elimination. Over 500 distinct functions have been attributed to the liver, underscoring its centrality in human physiology. Prominent among these roles include the synthesis of proteins essential for blood plasma, such as albumin and clotting factors, which are crucial for maintaining fluid balance and preventing hemorrhage. The liver synthesizes cholesterol and specialized lipoproteins to transport lipids throughout the body, contributing significantly to lipid metabolism and homeostasis. It serves as a vital energy regulator by converting excess glucose into glycogen for storage and later reconverting glycogen to glucose when energy demands increase. Furthermore, the liver regulates blood concentrations of amino acids, the fundamental building blocks for protein synthesis. It also facilitates hemoglobin metabolism, effectively recycling iron from senescent red blood cells and storing it for future erythropoiesis. A critical detoxification function involves transforming toxic ammonia, a byproduct of protein catabolism, into less harmful urea, which is subsequently eliminated via renal excretion. Another vital function is the detoxification and clearance of various drugs, environmental toxins, and other harmful compounds, safeguarding the body against potential toxicity. The liver plays a crucial immunological role by synthesizing immune mediators and by actively removing pathogens from circulation through specialized macrophages known as Kupffer cells. Additionally, hepatic clearance of bilirubin—produced from the breakdown of aged red blood cells—is essential. Disruption in bilirubin metabolism often leads to jaundice, characterized by yellow discoloration of the skin and sclera. The liver also serves as a major reservoir for fat-soluble vitamins (A, D, E, and K) and trace minerals like copper and zinc, ensuring their adequate availability when dietary intake is compromised. Moreover, it is involved in hormone metabolism, specifically regulating the levels and activities of hormones such as insulin, glucagon, cortisol, and estrogen. Collectively, these myriad functions highlight the indispensable role of the liver in maintaining systemic metabolic balance and physiological health.  (Boyer and Le Rousseau, 2014; Hundt et al., n.d.)

Liver Disease

The liver, owing to its structural and functional complexity, is vulnerable to a wide array of pathological insults that can lead to hepatic dysfunction, broadly classified as acute or chronic liver disease. Acute liver disease typically arises from a sudden episode of hepatocellular injury, which is often self-limiting and reversible. However, in certain instances, it can progress to acute liver failure (ALF)—a rare but life-threatening condition characterized by rapid hepatic deterioration, coagulopathy, jaundice, and hepatic encephalopathy. ALF is associatewith high morbidity and mortality, particularly in the absence of timely intervention or liver transplantation. In contrast, chronic liver disease (CLD) results from persistent or repetitive hepatic injury leading to progressive architectural distortion. Long-standing damage induces hepatocyte death, chronic inflammation, and fibrogenesis, culminating in cirrhosis—a condition marked by the replacement of functional liver parenchyma with fibrotic tissue and regenerative nodules. Cirrhosis significantly impairs hepatic function and increases the risk of complications such as portal hypertension, liver failure, and hepatocellular carcinoma. Traditionally, cirrhosis was considered an irreversible endpoint of chronic liver injury. However, emerging evidence suggests that fibrosis regression is possible, particularly with the removal of the underlying cause. Notably, antiviral therapies for chronic viral hepatitis B and C have demonstrated the potential to halt disease progression and even reverse cirrhotic changes, indicating a degree of hepatic plasticity and regenerative capacity under favorable therapeutic conditions.  (Dixon et al., 2013; Liki?-La?evi? et al., 2024; Osna et al., 2017; Walker and Edwards, 1995)

Definition

Hepatotoxicity refers to the medical condition characterised by liver damage caused by the use of medications, chemicals, or herbal and dietary supplements. Certain medicinal agents, when taken in overdoses and sometimes even when introduced within therapeutic ranges, may injure the organ.

Types of Hepatotoxicity

? Drug-Induced Hepatotoxicity: Caused by certain medications and drugs that have adverse effects on the liver. Examples include acetaminophen, certain antibiotics, statins, and antifungal drugs. (Osna et al., 2017)

? Alcohol-Induced Hepatotoxicity: Resulting from chronic alcohol consumption, which can lead to conditions such as alcoholic fatty liver disease, alcoholic hepatitis, and alcoholic cirrhosis. (Sarkar et al., 2021)

?Viral Hepatotoxicity: Caused by viral infections affecting the liver, such as hepatitis viruses (e.g., hepatitis A, B, C, D, and E). (Ciobanu and Gherasim, 2018; Mehendale et al., 1994)

?Herbal and Dietary Supplement-Induced Hepatotoxicity: Some herbal remedies and dietary supplements may lead to liver damage. Certain plants and natural products can have hepatotoxic effects, especially when taken in excessive amounts or in combination with other substances. (de Boer and Sherker, 2017)

?Chemical-Induced Hepatotoxicity: Exposure to certain industrial chemicals, environmental toxins, or pollutants can contribute to liver damage. (Hussain et al., 2021)

?Ischemic Hepatotoxicity: Occurs when there is a lack of blood supply to the liver, leading to tissue damage. This can happen in conditions like shock, severe dehydration, or vascular disorders. (Ciobanu and Gherasim, 2018)

?Autoimmune Hepatotoxicity: Involves the immune system mistakenly attacking the liver cells, leading to inflammation and damage. Conditions like autoimmune hepatitis fall into this category. (Ciobanu and Gherasim, 2018; Mehendale et al., 1994)

?Metabolic Hepatotoxicity: Linked to metabolic disorders that affect the liver, such as non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). (Hussain et al., 2021; Ioniuc et al., 2024)

Figure 3: Types of the Hepatotoxicity

India bears a substantial liver disease burden, reflecting its large population and epidemiological transition. In fact, India reports one of the highest absolute numbers of liver disease deaths globally. The Indian Council of Medical Research (ICMR) and Global Burden of Disease studies estimated that in 2017, about 220,000 Indians died due to cirrhosis and other chronic liver diseases, accounting for roughly 2.8–3% of all deaths in the country. This means liver diseases are responsible for roughly 1 in 35 deaths in India, a proportion comparable to or higher than many Western nations. By 2019, WHO data indicated liver disease deaths in India had risen to ~259,000 (≈2.95% of total deaths), suggesting a growing toll. The age-standardized mortality rate from cirrhosis in India was reported at ~199.5 per million population in 2016 – a high rate reflective of ongoing viral, alcohol, and metabolic liver damage in the populace. Chronic viral hepatitis is a major public health problem in India. The country has an intermediate endemicity of HBV: 3–4% of Indians are HBsAg positive, translating to approximately 40 million chronic hepatitis B carriers nationally. This represents about 10–15% of the world’s HBV carriers by some estimates. Each year, HBV and its complications (cirrhosis, liver cancer) cause an estimated ~100,000+ deaths in India. Hepatitis C prevalence in India is lower but non-trivial – estimated anti-HCV positivity around 0.5–1% of the population – which corresponds to ~6 to 12 million people chronically infected with HCV nationwide. Importantly, these infections are unevenly distributed: certain regions and risk groups have much higher prevalence (discussed in the next section). India launched a National Viral Hepatitis Control Programme (NVHCP) in 2018 aiming to diagnose and treat these millions of viral hepatitis patients. As of early 2023, over 5.8 crore (58 million) people have been screened for hepatitis B/C and 174,000+ patients started on treatment under this program. Non-alcoholic fatty liver disease has become astonishingly common in India, paralleling rising obesity and type 2 diabetes rates. NAFLD is now considered the leading cause of liver failure in India (as in the world). Because India’s population is so large and metabolically at-risk, even moderate prevalence translates to huge patient numbers. Various epidemiological studies indicate NAFLD prevalence in Indian adults ranges roughly 9% to 32%, with urban and high-risk groups approaching 40%. Indeed, a recent hospital study in New Delhi found around 38% of the Indian subjects had NAFLD – suggesting nearly 1 in 3 Indians may have fatty liver disease. Even using conservative estimates (~25% prevalence), over 250 million Indians could be affected by NAFLD. Consequently, NAFLD and its progressive form NASH are contributing to an ever-greater share of cirrhosis, end-stage liver disease, and liver cancer in the country. Alcoholic liver disease is another key contributor to India’s liver disease burden. India has seen an increase in per-capita alcohol consumption over past decades, and heavy drinking is prevalent among certain demographics. Epidemiological data now show alcohol is the single most common cause of cirrhosis in India, responsible for roughly 34–43% of cirrhosis cases in adults. A comprehensive 2023 meta-analysis of Indian cirrhosis patients found 43.2% were attributable to alcohol, far exceeding other etiologies. This reflects the large number of patients with alcohol-use disorders; one liver specialist noted that about 20% of all liver disease patients in India are actively consuming alcohol at the time of evaluation. Alcoholic hepatitis and acute-on-chronic liver failure due to alcohol are commonly seen in Indian hospitals, often with high fatality rates. Alarmingly, clinicians report alcohol is driving most severe liver failure cases (acute decompensations) presenting to tertiary centers. This alcohol-related burden is compounded by high relapse rates among survivors and lack of any definitive therapy for alcoholic hepatitis aside from abstinence. Drug-induced liver injury (DILI) also constitutes a significant and under-recognized burden in India. With a high prevalence of tuberculosis and widespread use of medications, India sees many cases of hepatic injury from drugs – both prescription and over-the-counter. Notably, anti-tuberculosis therapy is highly hepatotoxic: an AIIMS study reported 67% mortality among patients who developed acute liver failure from anti-TB drugs. In that cohort, many (60%) had been started empirically on TB therapy without confirmed TB, highlighting the risk of injudicious use of hepatotoxic drugs. Aside from TB medications, commonly used drugs like paracetamol (acetaminophen), certain antibiotics and antiepileptics, cancer chemotherapy agents, and various herbal/traditional remedies all contribute to DILI cases. Taken together, DILI cases form a portion of acute liver failure and acute hepatitis hospitalizations in India – a proportion that appears to be increasing as more people use medications. (Globally too, DILI is now implicated in a growing share of acute hepatitis cases.) Finally, acute viral hepatitis A and E continue to cause periodic outbreaks and severe acute liver disease in India. Hepatitis A virus is endemic; most Indians are exposed in childhood, and symptomatic HAV in adults is less common. Hepatitis E, however, frequently causes water-borne epidemics of jaundice. It is the leading cause of acute viral hepatitis outbreaks in India, and a major cause of acute liver failure. An AIIMS study found hepatitis A and E together accounted for ~30% of acute liver failure cases seen, with over 50% mortality in those cases. Pregnant women are especially vulnerable to fulminant hepatitis E. These statistics underscore that, despite economic progress, unsafe water and sanitation still exact a toll via hepatitis A/E in parts of India.(Abdulkarim et al., 2011; Björnsson, 2019; Devarbhavi et al., 2023; Goodman, 2007; Jain et al., 2023; Jurczak, n.d.; Krishna, 2017; Mohi-Ud-Din et al., 2019; Mondal et al., 2022; Nassir et al., 2015; Younossi et al., 2023)

Stages of Liver Disease (Jurczak, n.d.; Krishna, 2017; Mohi-Ud-Din et al., 2019; Mondal et al., 2022)

Liver disease progresses through a well-recognized sequence of pathological stages, each reflecting escalating damage and declining hepatic function. The initial phase, Stage 1: Inflammation, involves hepatocellular injury caused by factors such as viral infections, alcohol consumption, metabolic disorders, or toxins. In this stage, liver cells become inflamed and swollen, often resulting in hepatomegaly and mild right upper quadrant pain. Although symptoms may be minimal or absent, especially in conditions like non-alcoholic fatty liver disease (NAFLD), liver enzyme levels such as ALT and AST may be elevated. Early detection through routine liver function tests during annual health check-ups is crucial for timely intervention. If the inflammatory insult remains unaddressed, it progresses to Stage 2: Fibrosis, characterized by the deposition of scar tissue (collagen and extracellular matrix proteins) as part of the wound-healing response. Fibrosis begins to disrupt normal liver architecture and intrahepatic blood flow, although the liver may still maintain adequate function. This stage is often silent but reversible if the underlying cause is removed. Pharmacological intervention, combined with dietary and lifestyle modifications—such as cessation of alcohol, control of metabolic syndrome, and antiviral therapy—can significantly halt or even regress fibrosis in its early stages.

Advancing to Stage 3: Cirrhosis, the liver undergoes extensive scarring and nodular regeneration, leading to architectural distortion, impaired liver function, and complications such as portal hypertension, ascites, and hepatic encephalopathy. Cirrhosis is considered largely irreversible and represents a critical turning point in disease progression. Symptoms typically become more apparent, including fatigue, anorexia, abdominal distension, jaundice, pruritus, and muscle wasting. Management at this stage focuses on controlling complications and preventing decompensation, though liver transplantation remains the definitive treatment in advanced cases. It is noteworthy that cirrhosis may take several decades to manifest, emphasizing the importance of early-stage detection.

Stage 4: End-Stage Liver Disease (ESLD) encompasses complete hepatic decompensation and liver failure. This may arise acutely (acute liver failure) due to drug-induced hepatotoxicity, viral hepatitis, or autoimmune conditions, or chronically due to long-standing cirrhosis, particularly from chronic alcohol abuse or untreated viral hepatitis. Clinical manifestations include nausea, vomiting, diarrhea, weight loss, hypoalbuminemia, coagulopathy, hepatic encephalopathy, and multiorgan dysfunction. Without prompt liver transplantation, ESLD is typically fatal, and transplant eligibility depends on factors such as MELD score and absence of contraindications. Though sometimes excluded from the staged progression, Stage 5: Liver Cancer, particularly hepatocellular carcinoma (HCC), may arise at any point during chronic liver disease, particularly in the context of cirrhosis. HCC may be primary—originating from hepatocytes—or secondary (metastatic), originating from malignancies elsewhere in the body. Risk factors include chronic hepatitis B or C infection, aflatoxin exposure, and advanced fibrosis. Liver cancer is frequently asymptomatic in its early stages, making surveillance in high-risk populations essential. Prognosis is poor without intervention, but early detection combined with resection, ablation, or liver transplantation significantly improves survival outcomes.

Forms of liver Toxicity

1. Zonal Necrosis
2. Cholestasis
3. Steatosis
4. Granuloma
5. Vascular lesions
6. Neoplasm

Zonal Necrosis

Zonal Necrosis Zonal necrosis represents one of the most frequently observed histopathological patterns of hepatocellular injury, particularly in cases of drug-induced liver injury (DILI). This form of liver damage is characterized by localized necrosis within specific zones of the hepatic lobule, typically classified using the acinar model into Zone 1 (periportal), Zone 2 (midzonal), and Zone 3 (centrilobular) regions. Among these, centrilobular (Zone 3) necrosis is the most common, primarily due to the high concentration of cytochrome P450 enzymes and relatively low oxygen tension in this area, rendering it more susceptible to metabolic activation of hepatotoxins and hypoxic injury. Necrosis, or regulated cell death, is a physiological response to cellular stress; however, when excessive or uncontrolled, it becomes pathological, contributing to acute liver damage and triggering chronic fibrogenic cascades. In the context of toxicological liver injury, zonal necrosis provides valuable diagnostic insights. Liver biopsy remains a critical tool for assessing the extent, pattern, and zonal distribution of necrotic lesions, often accompanied by varying degrees of inflammation. These histological findings are essential not only for identifying the etiological agent but also for determining disease severity and guiding therapeutic interventions. Zonal necrosis is also frequently observed in viral, autoimmune, and ischemic hepatitis, as well as in exposure to hepatotoxic agents such as acetaminophen, carbon tetrachloride, and halothane. The degree of necrosis, when assessed alongside hepatic inflammation, provides staging and grading for liver diseases. Over time, chronic or extensive necrosis can contribute to progressive fibrosis and ultimately to cirrhosis if left unaddressed. It is also important to distinguish hepatitis, which broadly refers to inflammation of the liver, from zonal necrosis, which specifically denotes cell death localized to defined regions of the liver lobule. However, the two processes are often interrelated, as inflammatory mechanisms frequently precede or accompany necrotic injury in hepatopathology. (Goodman, 2007; Jain et al., 2023; Li et al., 2022)

Cholestasis

Cholestasis is a pathological condition characterized by impaired bile formation or flow from the liver to the duodenum, resulting in the accumulation of bile constituents within the liver and systemic circulation. This disruption may arise from defective hepatocellular secretion (intrahepatic cholestasis) or from mechanical obstruction of the biliary tract (extrahepatic cholestasis). Regardless of the origin, cholestasis leads to the retention of substances that are normally excreted in bile, including conjugated bilirubin, bile acids, and cholesterol, which may exert toxic effects on hepatocytes and contribute to progressive liver damage. Clinically, cholestasis is evaluated by elevated levels of serum conjugated bilirubin, alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT). These laboratory parameters help identify cholestatic patterns of liver injury, although diagnostic interpretation can be complex due to variations in retention patterns across different cholestatic disorders. For instance, in Dubin–Johnson syndrome, a rare inherited condition, isolated elevation of conjugated bilirubin may occur without significant hepatocellular injury, reflecting a defect in the hepatic excretion of bilirubin glucuronides. From a histopathological perspective, cholestasis is identified by the presence of bile plugs within hepatocytes and canaliculi, often accompanied by ballooning degeneration, hepatocellular apoptosis, and Kupffer cell activation. Prolonged cholestasis can lead to bile infarcts, ductular reaction, and periportal fibrosis, eventually progressing to biliary cirrhosis if unresolved. The condition may also provoke pruritus, jaundice, dark urine, and pale stools, reflecting systemic manifestations of retained bile constituents. Understanding the etiology and pathogenesis of cholestasis is crucial for effective management, which often involves identifying and eliminating the causative agent, relieving mechanical obstruction, or modulating bile acid synthesis and transport pharmacologically using agents like ursodeoxycholic acid. In complex or genetic cases, advanced diagnostics including liver biopsy, molecular testing, and imaging modalities may be necessary to establish a definitive diagnosis and guide treatment. (Arman et al., 2022; Gupta and Lewis, 2008)

Steatosis

Hepatic steatosis, commonly referred to as fatty liver, is a condition characterized by the abnormal accumulation of lipids, particularly triacylglycerols (TAG), within hepatocytes. While small amounts of lipid deposition may serve a transient protective function, excessive fat accumulation disrupts hepatic homeostasis and can initiate a cascade of metabolic and inflammatory changes. Nonalcoholic hepatic steatosis, the most common form, affects approximately one-third of the adult population in the United States. It is diagnosed when intrahepatic TAG content exceeds 5% of liver weight or when ≥5% of hepatocytes exhibit cytoplasmic lipid vacuoles, in the absence of significant alcohol consumption or secondary causes. The severity of steatosis is histologically graded on a scale from 0 to 3, depending on the proportion of hepatocytes affected. Initially considered a benign, hepatoprotective adaptation, excessive and prolonged lipid deposition can transition into a pathogenic state, increasing the risk of progression to more severe liver diseases. Nonalcoholic fatty liver disease (NAFLD) represents a broad clinical spectrum that begins with simple steatosis and can advance to nonalcoholic steatohepatitis (NASH)—a state of hepatic inflammation and injury—followed by fibrosis, cirrhosis, and even hepatocellular carcinoma (HCC). The pathogenesis of NAFLD is closely linked to metabolic syndrome, with insulin resistance, obesity, type 2 diabetes mellitus, dyslipidemia, and hypertension serving as major contributing factors. The rising global prevalence of NAFLD is largely attributed to excess caloric intake, sedentary lifestyles, and an increasing burden of obesity and metabolic disorders. Notably, NAFLD is not confined to obese individuals; it is also observed in lean individuals and children, suggesting that early-life exposures and genetic predispositions may play a significant role in disease development. Despite its increasing prevalence, simple steatosis remains reversible, especially in its early stages, through targeted lifestyle modifications including caloric restriction, weight loss, increased physical activity, and control of comorbid metabolic conditions. Early diagnosis and intervention are critical to halting disease progression and preventing long-term hepatic complications. As NAFLD has emerged as the leading cause of chronic liver disease worldwide, it represents a growing public health concern and an active area of clinical and translational research. (Murray et al., 2008; Pandit et al., 2012)

Granuloma

A granuloma is a structured aggregate of immune cells, typically representing a localized nodular form of chronic inflammation within tissue. When such granulomas are identified in the liver, the condition is termed granulomatous hepatitis. This hepatic pathology can result from a diverse array of infectious, autoimmune, neoplastic, and drug-induced causes. Among the most common etiologies in the United States are sarcoidosis and primary biliary cholangitis (PBC), whereas tuberculosis remains a leading cause globally, particularly in regions where Mycobacterium tuberculosis infection is endemic. Granulomas may be identified incidentally during imaging studies, such as computed tomography (CT) or magnetic resonance imaging (MRI), as the use of advanced imaging modalities increases. However, their presence often signals an underlying systemic or hepatic disorder. Histologically, hepatic granulomas are typically composed of epithelioid macrophages, often surrounded by lymphocytes, and may contain multinucleated giant cells. Some may exhibit caseation necrosis, which can aid in distinguishing infectious etiologies like tuberculosis from non-infectious causes. Clinically, granulomatous hepatitis may present with non-specific symptoms, including right upper quadrant abdominal pain, tender hepatomegaly, fever, or fatigue. Laboratory abnormalities often include elevated alkaline phosphatase, aminotransferases (ALT, AST), and sometimes hyperbilirubinemia and jaundice, depending on the extent of hepatic involvement. Diagnosis typically requires a combination of serological testing, imaging, and liver biopsy, the latter being essential for confirming granulomatous inflammation and aiding in the exclusion of malignancy or infectious agents. Management is centered on the identification and treatment of the underlying cause. In autoimmune-related cases, such as sarcoidosis or PBC, immunosuppressive therapy (e.g., corticosteroids or ursodeoxycholic acid) may be indicated. For infectious causes, antimicrobial therapy tailored to the specific pathogen is essential. In some cases, especially when granulomas are incidental and asymptomatic, clinical observation with regular follow-up may suffice. (Murray et al., 2008; Nathwani and Kaplowitz, 2006; Pandit et al., 2012)

Vascular lesions

Vascular lesions of the liver represent a diverse group of abnormalities arising from injury to the vascular endothelium, leading to aberrant growth or remodeling of hepatic blood vessels. While liver tumors commonly originate from hepatocytes or cholangiocytes, a subset arises from endothelial cells, giving rise to vascular neoplasms. These lesions present significant diagnostic and therapeutic challenges due to their histological diversity, variable biological behavior, and low prevalence. The rarity of these entities often results in limited clinical awareness and contributes to ongoing controversies regarding their classification, diagnosis, and optimal treatment strategies. Benign vascular lesions, such as cavernous hemangiomas, are typically asymptomatic and incidentally detected on imaging. However, infantile hemangioendothelioma, a vascular tumor seen in neonates and infants, may present with life-threatening complications like cardiac failure or coagulopathy, warranting prompt medical or surgical intervention. Other entities, including nodular regenerative hyperplasia (NRH) and hepatic small vessel neoplasms (HSVN), may pose diagnostic difficulties due to overlapping imaging features and non-specific clinical presentations. Malignant vascular tumors—notably epithelioid hemangioendothelioma (EHE) and hepatic angiosarcoma—are exceptionally rare but clinically significant. These tumors are often aggressive, with a propensity for multifocal hepatic involvement and, in some cases, extrahepatic spread. Their variable progression, resistance to conventional therapies, and unclear molecular underpinnings make management highly individualized. Recent insights from the European Liver Registry and other multicenter studies have helped refine the diagnostic criteria and identify potential prognostic markers for these rare tumors. In select patients with unresectable or multifocal disease, particularly in the case of EHE without distant metastasis, liver transplantation has been explored as a potentially curative option. Nevertheless, careful patient selection and long-term surveillance remain essential due to risks of recurrence and post-transplant complications. As research advances, integration of molecular diagnostics, angiogenic profiling, and targeted therapies may offer more precise treatment options and improved outcomes for individuals with vascular liver lesions.  (Lerut and Iesari, 2018)

Neoplasm

Neoplasms, commonly referred to as tumors, are abnormal growths of tissue resulting from uncontrolled cellular proliferation. In the liver, primary neoplasms originate from hepatocytes, cholangiocytes, or other hepatic cell types and may be benign or malignant. Hepatocellular carcinoma (HCC) is the most prevalent primary malignant tumor of the liver and typically arises in the context of chronic liver disease, particularly chronic hepatitis B or C infection, and cirrhosis. HCC may present as a solitary lesion or with multifocal nodules and often exhibits vascular invasion, contributing to its aggressive clinical course. Benign hepatic tumors, such as hepatocellular adenomas, focal nodular hyperplasia, and dysplastic nodules, can mimic well-differentiated HCC, especially in cirrhotic livers, making accurate histopathological differentiation critical for guiding management. Hepatocellular adenomas are more commonly seen in young women, often associated with oral contraceptive use or metabolic disorders, and may carry a risk of hemorrhage or malignant transformation in select subtypes. Cholangiocarcinoma, the second most common primary hepatic malignancy, is an adenocarcinoma arising from the epithelial lining of the intrahepatic or extrahepatic bile ducts. It is often associated with chronic inflammatory conditions such as primary sclerosing cholangitis, hepatolithiasis, or biliary parasitic infections, although its etiology remains idiopathic in many cases. Cholangiocarcinoma typically presents with nonspecific symptoms such as jaundice, weight loss, and abdominal discomfort, and is often diagnosed at an advanced stage. Accurate diagnosis of hepatic neoplasms necessitates exclusion of metastatic disease—as the liver is a common site for metastases from gastrointestinal, breast, and lung primaries—and careful distinction from benign biliary lesions or regenerative nodules. A multidisciplinary approach combining imaging, serological markers (e.g., AFP for HCC, CA 19-9 for cholangiocarcinoma), histology, and immunohistochemistry is essential to establish a definitive diagnosis and guide appropriate therapeutic strategies. (Lerut and Iesari, 2018; Makhlouf et al., 2008)

Symptom

1. A tendency to bruise easily,
2. Abdominal stomach pain & swelling
3.  Swelling in the legs & ankles Jaundice
4. Dark urine color
5.  Nausea or vomiting
6. Loss of appetite
7. Pale stool color
8. Chronic fatigue
9. Itchy skin

Plant Profile

Biological Source: It is leaves obatined from the plant, Cosmostigma racemosum (Roxb.) Wight

Family:  Apocynaceae

Synonym: Periploca cordata Dennst.

Taxonomy

1. Kingdom: Plantae
2. Phylum: Tracheophytes
3. Class: Magnoliopsida
4. Order: Gentianales
5. Family: Apocynaceae
6. Subfamily: Asclepiadoideae
7. Genus: Cosmostigma
8. Species: racemosum