Cirrhosis is a complication that is caused by various liver diseases. It is characterized by irregular structures – and thus abnormal function – of the liver. The liver's atypical structure and function is set off by the development of scar tissue within the liver, which replaces healthy tissue. It is generally developed slowly, sometimes over the years. Thus, scarring can begin early in the first phase of disease progression, but the actual cirrhosis disease can occur in the late stages.
Scarring is caused by attempts by the liver to repair damaged cells. This scarring causes the creation of a large amount of scarred cells, which creates fibrosis. The main cause of damage to liver cells that leads to fibrosis is excessive consumption of alcohol. However, other sources of damage are hemochromatosis, hepatitis, non-alcoholic steatohepatitis, and biliary obstruction.
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Disease Progression
Cirrhosis develops in two main phases. The first stage is the compensated phase. During this period, the liver is able to retain the ability to carry out its essential functions. This phase can last for several years, even while scarring is taking place. Furthermore, the patient developing the scarring shows no symptoms of liver damage or failure. At this stage, despite the lack of symptoms, the liver is becoming inflamed. If the cause of inflammation is not eliminated at this stage of the disease progression, cirrhosis develops into the second stage: the decompensated stage. In the second phase, several symptoms make themselves known. These symptoms include issues such as ascites, jaundice, variceal hemorrhage, and encephalopathy (Nusrat et al., 2014). This phase of the disease is the most widely known. Patients at the decompensated stage have a median survival rate of 2 years (Nusrat et al., 2014). The second stage’s survival rate is low compared to the median survival rate of patients with compensated cirrhosis, which stands at 9 years. The severity of the disease is, therefore, extremely exacerbated in the decompensated stage. Best practices for managing cirrhosis while in the compensated stage is focusing the therapy on eliminating etiology.
Overview
Prevalence and Associated Complications
Liver cirrhosis was ranked the 11 th most deadly disease in the United States in 2017. In 2017, it accounted for 41, 743 deaths (CDC, 2019). Cirrhosis is commonly associated with complications such as ascites, varices, encephalopathy, and hepatopulmonary hypertension (Berzigotti, 2017). The most common complication is ascites. It is also a fatal complication associated with liver cirrhosis. Ascites kills around 15 % of patients with liver cirrhosis annually. Every five years, it kills an average of 44 % of these patients. Another prevalent complication is the formation of gastroesophageal varices. These occur in around half of the cirrhosis patients. It usually develops into variceal hemorrhage as the condition worsens with time. Variceal bleeding is often deadly, and more than 20 % of patients who develop this hemorrhage die six weeks into its development. The only treatment for variceal bleeding is a liver transplant, which can increase cirrhosis patients' survival rate from 23% to 63 % (CDC, 2019)
Other, less prevalent, complications are bacterial peritonitis, coagulation, hepatocellular carcinoma, and hepatorenal syndrome . Bacterial peritonitis and hepatorenal syndrome are even less fatal than other complications and are more treatable (Nusrat et al., 2014).. Bacterial peritonitis can be combated through antibiotic therapy. Hepatorenal syndrome, on the other hand, can be treated through hemodialysis. The various types of treatments for the symptoms that these associated complications create characterize cirrhosis treatment.
Demographics
Data from the CDC in 2017 states that liver cirrhosis is one of the most deadly diseases in the US. Four years prior to the 2017 CDC report, cirrhosis was the 12 th most fatal disease, responsible for more than 36,000 deaths (CDC 2013). The increase in prevalence and fatality indicates not only the severity and prevalence of the disease, but also that it is gaining momentum.
The most common causes of developing liver cirrhosis are hepatitis C, alcoholism, in addition to Non-Alcoholic Fatty Liver Disease – NAFLD. Liver cirrhosis as a result of developing NAFLD is on the rise recently, as data from the National Health and Nutrition Examination Survey (NHANES) displays that there was a jump in its development between the years of 1988 and 2008 (Setiawan et al., 2016). NAFLD is now the second most prevalent source of liver cirrhosis, a close second after hepatitis C (Setiawan et al., 2016). From 2004 to 2013, the total number of patients receiving a liver transplant due to NAFLD-associated cirrhosis increased by 170 %. These numbers mean that any interventions regarding liver cirrhosis must now include considerations for patients with NAFLD more than ever before.
Ethnic Factors
A study conducted by Setiawan et al. in 2016 investigated the prevalence and causes of cirrhosis among different ethnic groups. This study drew on Medicare data collected between 1999 and 2012. The results showed that 3.9 % of African-Americans on Medicare during this time suffered from liver cirrhosis. Comparatively, the proportion of Hawaiians was 4.1%, the proportion of whites was 6.7 % and the proportion of American Japanese was 6.9 % These numbers place Caucasians and Asian-Americans at the top of the disease prevalence list as far as liver cirrhosis is concerned. Fifty-two % of all the cases were accounted for by NAFLD, while 21 % were accounted for by alcoholism.
Regional Data
The National Centre for Health Statistics (NCHS) report from 2018 ranked states based on death rates from liver cirrhosis. New Mexico has the highest death rate, with 25.5 % of the liver cirrhosis deaths in the United States. Next was South Dakota, with 19.8 %, Wyoming with 19.1 %, Alaska with 15.6 %, and Oklahoma in 15.4 %. These are the states with the highest death rates in the US. The rest of the states fell below 10 %, including Vermont, Hawaii, New York, Maryland, and Connecticut. Men are more 40 % more likely to die from cirrhosis than women.
Age
Cirrhosis affects adults that are generally between 65 and 74 years old, according to a report from the CDC in 2018. Of the total deaths that year, the cohort aged between 65 and 74 accounted for 3 %. The age range for 45 to 64 and 18 to 44 had the second and third highest death rates, respectively. The cohort aged 75 and above accounted for 1.4 % of the deaths.
Another factor to consider associated with cirrhosis death rates is education. The majority of people that died from cirrhosis were individuals with education below high school diploma level. The rest were distributed among those with high school diplomas, college diplomas, and Bachelor's degrees, with proportions lowering as education levels got higher. Economic factors have also been considered by research, and reports by the CDC have found that among the total deaths in the US in 2018, 4.2 % of were attributed to liver cirrhosis in low-income individuals, 2.1 % were for those close to low income, and 1.3 % were individuals who were not poor.
Causes and Symptoms
Cirrhosis is caused by scarring that occurs as the liver tries to patch-up damaged cells. This scarring limits liver function and causes the symptoms of cirrhosis that are most commonly associated with the disease (Berzigotti, 2017). Scarring is the product of liver inflammation that remains untreated when the disease is still in the primary compensated stage. As liver function becomes compromised, the patient will suffer from malnutrition, loss of appetite, itchy skin, fatigue, and nausea.
Once the second stage – the decompensated stage – begins, the patient develops a visible pattern of blood vessels under the skin with a spider-web like appearance. Their palms also become red, and their feet, ankles, and legs become swollen (Nishikawa & Osaki, 2015). Jaundice is also common and characterized by a yellow tinge in the eyes and skin. There are also sex-differentiated symptoms (Nishikawa & Osaki, 2015). For women who have not yet experienced menopause, there is a loss of monthly periods. For men, there is a loss of sex drive (Nishikawa & Osaki, 2015). Fatal complications during the final stage of the decompensated stage are variceal bleeding, ascites, hepatorenal syndrome, portal hypertension, and encephalopathy (Nishikawa & Osaki, 2015).
Ascites is the most prevalent and fatal complication. The accumulation of abdominal fluid characterizes it. Hepatic portal hypertension is another common complication and leads to variceal bleeding, which is another common fatal complication. Hepatic portal hypertension is caused by blood flow resistance. This resistance leads to scarring and eventual hemorrhage in the gastric or esophageal varix. As a result, the patient develops variceal bleeding. Another complication associated with cirrhosis is compromised immunity. One common opportunistic disease caused by this is bacterial peritonitis (Nishikawa & Osaki, 2015). If it is caught early, this disease can be treated through the use of antibiotics.
Treatment and Proliferation
Cirrhosis is managed primarily through alleviating symptoms and improving liver function. Thus, the therapies that health practitioners engaged in for treatment are targeted towards these two main goals. Therapies that are used include nitric oxide inhibitors, oxygen, garlic, methylene blue, beta-blockers, and somatostatin (Nusrat et al., 2014). One therapy explicitly used for improving gaseous exchange is transjugular intrahepatic shunt (TIPS) (Nusrat et al., 2014). Another therapy aimed at connecting the left and right shunts is intra-arterial coil embolization.
Treatment also includes the prevention of the development of more liver diseases. Thus, patients undergoing treatment are immunized against Hepatitis A and B, and HPV. Patients are also immunized against diseases affecting other essential organs, including pneumonia, tetanus, zoster, and influenza (Nishikawa & Osaki, 2015). Diet is another essential part of treatment, as patients are prohibited from ingesting substances that can damage liver cells, including NSAIDs, alcohol, and hepatotoxic drugs.
Recent advances in cirrhosis treatment focus on regenerating tissues using cell therapy, or organ engineering (Setiawan et al., 2016). They are generally applied after procedural therapy has proven to be ineffective. Regeneration is facilitated through cell transplants, as undifferentiated cells are implanted to facilitate regeneration. However, research and trials are still underway in determining their efficacy (Nusrat et al., 2014). These trials, aimed at improving proliferation within damaged livers, will allow patients’ outcomes to be bettered through the use of cells from allogeneic sources (Nusrat et al., 2014).
Conclusion
For the most part, liver cirrhosis remains irreversible, and the scarring that the liver receives is permanent. The treatments that are available focus on alleviating the symptoms of the disease, and improving the liver function that is still present. Associated risk factors for cirrhosis are viral hepatitis infections, NAFLD, alcoholism, and unhealthy lifestyles. Poor cirrhosis treatment means that it is best controlled using prevention methods such as immunization against viral liver diseases, avoiding alcoholism, and utilizing a proper diet. Future research on cirrhosis focuses on new therapies, medications, and treatment procedures that can regenerate liver cells, and better alleviate symptoms. Attention with regards to prevention remains on early detection and encouraging healthy lifestyle change. The main idea behind these research efforts is devising methods that allow early detection of scarring, and medicine to halt or reverse the scarring.
References
Berzigotti, A. (2017). Advances and challenges in cirrhosis and portal hypertension. BMC medicine, 15(1), 200.
CDC. (2019, October 11). FastStats . Centers for Disease Control and Prevention. https://www.cdc.gov/nchs/fastats/liver-disease.htm
Nishikawa, H., & Osaki, Y. (2015). Liver cirrhosis: evaluation, nutritional status, and prognosis. Mediators of inflammation , 2015.
Nusrat, S., Khan, M. S., Fazili, J., & Madhoun, M. F. (2014). Cirrhosis and its complications: evidence-based treatment. World Journal of Gastroenterology : WJG, 20(18), 5442.
Setiawan, V. W., Stram, D. O., Porcel, J., Lu, S. C., Le Marchand, L., & Noureddin, M. (2016). Prevalence of chronic liver disease and cirrhosis by underlying cause in understudied ethnic groups: the multiethnic cohort. Hepatology, 64(6), 1969-1977.
