Cause of Cirrhosis Other Than Alcohol

Liver cirrhosis is a chronic liver disease distinguished by the degeneration of cells in the liver, causing fibrosis and malfunctioning regenerating nodules that lead to complications due to portal hypertension ¹. In 2015, liver cirrhosis and liver neoplasms accounted for 3.5% of worldwide deaths ². About 1 million annual deaths are accounted for by liver cirrhosis, making it the 11^th cause of death and 4^th in the cause of disability-adjusted lives worldwide ². Cirrhosis is more prevalent in developing countries like Pakistan than in developed countries like Europe ¹. Europe is prevalently the country with the most liver disease in the world, with about 26 cases per 100000 inhabitants ². The major cause of cirrhosis in Europe is an alcoholic liver disease which causes about (9.2 deaths per 100,000) inhabitants, with hepatitis C virus (HCV) following with about (5.3 deaths per 100,000) inhabitants and thirdly hepatitis B virus (HBV) with( 3.9 per 100,000) inhabitants ². However, in Pakistan, the Hepatitis C and Hepatitis B virus are the leading causes of cirrhosis respectively ¹. A study in 2009 in Pakistan revealed that the most commonly affected age group was 40-60 years ¹. With the severity and alarming rate of death caused by cirrhosis, there has been the invention of noninvasive biomarkers that investigate and predict the stages of liver fibrosis ³. This literature review aims at examining the different causes of liver cirrhosis other than alcohol.

Causes of liver cirrhosis other than alcohol

Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV)

HBV and HCV both may lead to increased morbidity and mortality in patients as a result of chronic liver infections that may cause liver cirrhosis, heap-tocellular carcinoma, and other liver cirrhosis complications ¹. Hepatitis c virus often leads to more chronic stages than hepatitis B virus¹ and similarly confer a greater risk of hepatocellular carcinoma than other causes ⁵. Out of the approximate 4.1 million people who showed a history of HCV exposure, 2.5 million resulted in chronic stages ⁴. A one-time HCV opt-out screening for individuals above 18 years is recommended ⁴. Early care and treatment of patients with chronic hepatitis C may prevent the progress to liver cirrhosis and the late stage of liver diseases ⁴. Due to the advancement and simplified management of hepatitis C, physicians can now follow up and provide treatment to more individuals ⁴. In healthy blood donors, HCV prevalence indicated a 15.6% in Africa, 0.34% in Canada, 1.5% in Japan, 0.64%in US, 0.075% in the United Kingdom, and 00-20.89% in Pakistan ⁴. Only about 15% of the HCV-infected patients are able to overcome the acute viral infection leaving about 85% being unable to control it ⁶. While the prevalence of HCV is 27.7%, only about 8% are carriers of HBV in developing countries ⁶.

Non-alcoholic fatty liver disease.

Non-alcoholic liver disease (NAFLD) is one of the major causes of liver cirrhosis and it affects about one-third of the western population ⁸. NAFLD is mainly characterized by the liver cells storing excessive fat ⁹. However, there are no proven facts as to why some individuals tend to have fat accumulate in the liver and others don’t ⁹. Similarly, little to no knowledge as to why some of the affected fatty livers lead to liver cirrhosis ⁹. Some of the patients with NAFD may acquire Nonalcoholic steatohepatitis (NASH), which is a belligerent result of fatty liver diseases⁹. NASH is characterized by inflammation of the liver and is likely to result in cirrhosis in some liver failure ⁹. Both NAFLD and NASH’s possible causes include obesity, insulin resistance, high levels of triglycerides fats in the blood, and hyperglycemia ⁹. According to findings from the University of Health Sciences, NAFLD is a major problem in obese adolescents due to decreased levels of omentin-1 ⁸. Individuals with sleep apnea, metabolic syndrome, polycystic ovary syndrome, hypothyroidism, and hypopituitarism, are at risk of acquiring NAFLD⁹. Due to inflammation as a result of NASH, fibrosis occurs while the liver is trying to counteract the inflammation ⁹. As the inflammation continues, fibrosis spreads more in the liver tissues thus leading to cirrhosis ⁹. The risk of NASH and NAFLD progression to cirrhosis is between 5% and 12% ⁹.

Primary sclerosing cholangitis (PSC)

Primary sclerosing cholangitis (PSC) is a disease of the liver that is a result of continuous bile ducts inflammation and scarring ¹⁰. As a result, multifocal bile duct strictures are developed leading to fibrosis and later progressing to cirrhosis ¹¹. Despite PSC not being a common disease, it has an incidence of 0.8 to 1.3 per 100000 persons ¹¹. Although the PSC’s pathogenesis remains unknown, some evidence indicates that environmental, genetic, and immunologic factors are linked to it ¹¹. PSC just like most diseases has variants, classic PSC which is the major cause of PSC cases is characterized by cholangiography strictures in the bile ducts ¹². The large duct PSC which is predominant in males coexists with inflammatory bowel disease (IBD) and shows with cholestasis ¹². Despite most PSC patients having IBD only 5% of IBD patients develop PSC ¹². The small duct PSC patients, which is a small group, show a genetic link to PSC ¹². PSC cure is yet to be determined and patients who advance to chronic liver disease and cirrhosis undergo liver transplantation¹¹. Although PSC reoccurs in 23% of individuals after the liver transplantation¹¹, in most cases it is curative. The development of antiviral therapies for other chronic liver diseases like hepatitis C triggered the research for PSC treatments which are currently ongoing ¹².

Conclusion

Liver chemistries are used to determine the liver functions and identify any present diseases⁴. Liver enzymes, like alkaline phosphate (AP), are used to show the occurrence of hepatocellular damages or biliary obstruction⁴. Alanine aminotransferase (ALT) is more effective in determining liver injuries ⁴. Although aspartate aminotransferase also determines liver injuries, ALT is a better marker for the injuries ⁴.

Hepatitis C is the most common cause of liver cirrhosis worldwide after alcoholic liver disease ¹. While injection of drug use is the main risk factor for HCV infections with over 60% case attributes⁴, other factors like hemodialysis, parenteral exposure, incarceration also are risk factors. HBV genotype D characterized by distinct viral characteristics is the main attribute for HBV¹³. The hepatitis B e antigen is mainly detected in its negative phase which results in chronic HBV ¹³. NAFLD is majorly linked to the metabolic rate and genetics of individuals. Obese adolescents are at a higher risk of contracting NAFLD due to excessive fat storage. For PSC more research is ongoing to determine its pathogenesis and relation to IBP¹².

Newer investigations of the diagnosis of liver disease are ongoing due to the implicit disadvantage of liver biopsy being invasive hence making it difficult to assess repeated progressions ³. Non-invasive biomarkers are now being used to predict fibrosis stage³. These indirect markers are based on the effect of fibrogenic markers, unlike the direct fibrosis markers that rely on the basic mechanism of fibrosis³. Currently, Artificial intelligence (AI) is the most recent addition and it works by interpreting data from images with a convolutional neural network³. Additionally, the combination of the serological and radiographical methods while used stepwise could yield better results in the determination of chronic liver diseases including cirrhosis³.

References

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