Fatty liver, the beginning of the end

-Alice in Wonderland.

A journey back in time... One summer night, I was at the closing gala of a congress on the liver. It was carried out in a house of neoclassical architecture, typical of the nineteenth century. The night adventure began when I visited the toilet to touch up my makeup.

The unusual porcelain has survived, like the entire property, to the deterioration of the urban beauty of Paseo de Montejo Avenue. A silent property aroused my interest in its historical presence, from a time of splendor of the magical times of hene-quen, not only of the state but of the country. A mysterious, romantic, cozy place, as if the house whispered a pamper and hugged you. From the garden, delimited by columns of Ionic style, a portico, and a beautiful piano in the basement of French style could be observed.

I will confess that I did not miss the opportunity to entertain the night with the piece that my husband fell in love with when I met him, Fur Elise; the place’s acoustics are perfect despite my rusty fingers. Suddenly, when touching a molding on the wall, like Alice in Wonderland, a secret door opened. I could illuminate with the lamp of my mobile some dark stairs, spiral, with small vents. I climbed each of the irregular steps, my heart in full paroxysmal supraventricular tachycardia was heard more than the bustle of the party. I traveled back in time; suddenly, I was in a dome with rich interior decoration. I felt like in the Almoravid Qubba, in Marrakech.

Then I contemplated the calm of the starriest night I have ever seen, sitting in a viewpoint of Moorish influence; the wind played with my hair, and I started writing. The floors of that terrace of expensive building materials resembled the Saadian tombs of Marrakech; the sunrise surprised me in the Minaret. I received the first rays of the sun as a gift of time; it was the same sun that illuminated the Porfiriato. Suddenly on my mobile screen, as a time machine, I hear a “trin” notification of my iCal 5K NASH. I teleport, and again is 7:00 am in the city, the first race for liver health and against obesity, five kilometers that arose thanks to the efforts of the Mexican Association of Hepatology on July 16, 2022, in Merida, Yucatan; I toured all of Paseo de Montejo with great colleagues and friends.

The following week, already back to reality to commemorate the #WorldHepatitisDay, I placed a post on my social networks, inviting all my patients to participate in a marathon of timely detection of hepatocellular cancer.

A few minutes later, I received a funny audio from two friends, Laura and Jorge, in the chat we have in common with my husband. The audio said something like that:

Jorge: “Good morning, you know what, Dr.? you don’t need to invite me to a marathon, I know what the state of my liver is... my liver is fucked.”

Laura: “I don’t know, Dr., how do you invite me to run a marathon to know the health of my liver? If I don’t have a liver to run. What’s more, Dr., I already sent a memo to my liver, I said: “Liver, get ready; today, you have a talent test.” Also, I don’t know how you do it, in the morning, you run a marathon, and then you do many studies.”

-Jorge interrupts: “My life, Dr., convoked a marathon of studies. She will do many studies; that’s why it’s a marathon.”

After attacking myself with laughter for a few minutes, I realized that my friends and family have no fear of God nor the remotest idea of where the liver is located and less of what it is for. As is evident, they have all the metabolic risk factors to start as DM2 and being critical drivers of chronic liver disease, including fatty liver, I decided to write the following lines:

Hepatocytes are the parenchymal cells of the liver, are polygon-shaped, and perform metabolic functions. The liver is the most talented organ in the human body. The ancient Greeks linked it to pleasure: it is believed that the words hepatic and hedonistic share the same root. The Elizabethans referred to their monarch not as the head of state but as the nation’s liver: beware of anyone who dared to make him angry.

Since ancient times, Roman writers such as Cicero and Livy, in several passages of their works, describe the practice of hepatoscopy (etymologically: examination of the liver), a prediction by examining the liver coming from an animal sacrificed to the gods. It was one of the earliest popular divinatory techniques among

the Mesopotamian peoples, for both the Assyrians and the Babylonians. For them and their medical-religious knowledge, the liver was the generator of blood, the seat of emotions, feelings, and desires, that is, life’s seat organ 1 .

Metabolism consists of a series of reactions that occur within the cells of living organisms to sustain life. The metabolism process involves many interconnected cellular pathways to ultimately provide cells with the energy needed to perform their function.

These pathways’ importance and evolutionary advantage are visible, as many remain unchanged by animals, plants, fungi, and bacteria. In eukaryotes, metabolic pathways occur within the cytosol and mitochondria of cells, and the utilization of glucose or fatty acids provides most of the cellular energy in animals. Metabolism is organized into metabolic pathways to maximize energy capture or minimize its use. Metabolism can be divided into a series of chemical reactions comprising the synthesis and degradation of complex macromolecules known as anabolism or catabolism.

The basic principles of energy consumption and production are discussed, along with the biochemical pathways that constitute the metabolic process-es fundamental to life(3). Our liver gets sick when metabolic processes start, which are inadequate for the intended purpose.

Currently, risk factors for fatty liver disease are common in the Mexican population, and available studies seem to underestimate their prevalence. Nonalcoholic steatohepatitis (NASH) is the inflammatory subtype of nonalcoholic fatty liver

disease (NAFLD); it can be considered as: “the beginning of the end, a prelude to tragedy,” as it is associated with the progression of chronic liver disease and the development of cirrhosis; 5% will develop hepatocellular cancer and the likely need for a liver transplant. Reflection is required on distributive justice around this issue in Mexico.

Despite its importance, NAFLD is little recognized in clinical practice. Nonalcoholic fatty liver disease (NAFLD) affects approximately 3% to 6% of the U.S. population, and the prevalence is increasing. NASH is strongly associated with obesity, dyslipidemia, type 2 diabetes, and metabolic syndrome.

Although several non-invasive tests and scoring systems characterize NAFLD and NASH, liver biopsy is the only accepted method for diagnosing NASH (fortunately indicated only in a few patients or clinical trials).

In Mexico, Bernal-Reyes et al. studied 585 volunteers, resulting in a prevalence of NAFLD of 41.3%, predominance of men over 50 years, poor eating habits, and a sedentary lifestyle. Males, obesity, metabolic syndrome, and elevated ALT were risk factors for the disease, and 40% of those affected had advanced fibrosis. They concluded that the prevalence of NAFLD in our population is among the highest in the world2. The U.S. Food and Drug Administration has not approved any specific therapies for NASH. Lifestyle modification is the mainstay of treatment, including changes in diet and exercise, with the primary goal of losing 7% of total weight to eliminate fatty liver and 10% of weight to try to reverse liver fibrosis. Substantial improvement in histological outcomes, including fibrosis, directly correlates with increased weight loss.

In some cases, bariatric surgery may be indicated to achieve and maintain the degree of weight loss necessary for the therapeutic effect. An estimated 20% of patients with NASH will develop cirrhosis, and NASH is predicted to become the leading indication for liver transplants in the U.S. The mortality rate among patients with NASH is substantially higher than the general population or patients without this inflammatory subtype of NAFLD, with an annual all-cause mortality rate of 25.56 per 1000 person-years and a liverspecific mortality rate of 11.77 per 1000 person-years.

The conditions of the disease can be modified. It occurs to me that the urgent need for the teamwork of two branches of medicine, such as hepatology and endocrinology may arise, as well as the close relationship of medical practice based on scientific evidence. Public policies are needed that favor actions to reduce the current trend of the Mexican population.

Dr. Ana Villaseñor-Todd

Sources:

1. Abel Fernando Martínez Martín, Doctor of Medicine and Surgery, Magister and Doctor of History. Research group Historia de la Salud en Boyacá-Universidad Pedagógica y Tecnológica de Colombia (UPTC).

2. Bernal-Reyes R, Icaza-Chávez ME, Chi-Cervera LA, Remes-Troche JM, Amieva-Balmori M, Priego-Parra BA, Martínez-Vázquez S, Méndez-Guerrero IO, Martínez-Rodríguez L, Barranca-Enríquez A, Palmeros-Exsome C, Cano-Contreras AD, Triana-Romero A. Prevalence and clinical-epidemiologic characteristics of a Mexican population with metabolic (dysfunction) associated fatty liver disease: An open population study. Rev Gastroenterol Mex (Engl Ed). 2022 May 7:S2255-534X(22)00026-3. doi: 10.1016/j.rgmxen.2022.04.001. Epub ahead of print. PMID: 35537911.

3. Judge A, Dodd MS. Metabolism. Essays Biochem. 2020 Oct 8;64(4):607-647. doi: 10.1042/EBC20190041. PMID: 32830223; PM- CID: PMC7545035.