Liver Diseases, Epidemiology, Presentations, Diagnosis, and Integrated Treatment

Liver Diseases, Epidemiology, Presentations, Diagnosis, and Integrated Treatment  

A paper “Chronic Viral Hepatitis in Malaysia: "Where are we now?" was published online by Ruksana Raihan, Rosmawati Mohamed, Muhammad Radzi Abu Hassan, and Rosaida Md Said here:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5663777/

We shall discuss this further and separately with different other views:

Pathophysiology:

Chronic hepatitis is not confined only to Malaysia but is a worldwide problem. This disease is characterized by hepatic-necrosis and inflammatory cell infiltration which is most commonly caused by viral and toxic agents. Deemed chronic when persisting for longer than 6 months. Hepatitis triggers an ongoing inflammation that oftens leads to fibrosis and eventually cirrhosis, with a concomitant increased risk of hepatocellular carcinoma. 

Chronic hepatitis may develop due to a variety of aetiology, either in isolation or in combination such as: 

hepatitis viruses causing hepatitis B (+ / - hepatitis D), and hepatitis C. It can also be caused by toxins and medications such as ethanol, methyldopa, isoniazid, nitrofurantoin, amiodaron, or even by aflatoxins especially from mouldy peanuts where aflatoxins are produced by the micro fungi Aspergillus flavus especially in hot humid countries like Malaysia, Africa, and other tropical countries. Constant ingestion of contaminated peanuts or peanut sauce or their products can lead to cancer of the liver.   The majority of individuals develop chronic hepatitis without a recent recognizable acute clinical illness or obvious symptoms. The condition is typically insidious and slowly progressive, declaring itself clinically only after cirrhosis develops with accompanying signs and symptoms. 

Hepatitis C is the most common cause of chronic viral hepatitis in Malaysia and elsewhere in the world accounting to approximately 3/4 of all cases.^1,2 Given its high prevalence and clinical implications, chronic hepatitis C (CHC) is the focus of this article. Integrative treatment aimed at controlling hepatitis inflammation and its sequelae underlying the pathogenesis of CHC are applicable to other liver disorders that share a similar pathophysiology. 

The hepatitis C virus (HCV) is hepatotropic but minimally cytopathic. The detrimental effects of chronic infection arise predominantly from the ongoing inflammation, which causes marked oxidative stress. In the presence of ongoing hepatic necrosis, connective tissues are laid down as the body attempts repair. Accumulation of extracellular connective tissues lead to fibrosis which progresses predictably, in stage 0 where there is no fibrosis, stage 1, confines to enlarged portal zone, stage 2, periportal or portal-portal septa with intact architecture, stage 3, architectural distortion (septal fibrosis bridging) without obvious cirrhosis, and lastly, stage 4 with probable or definite cirrhosis. 

Cirrhosis is the final stage of the fibrotic process, characterized by diffused hepatocyte damage, nodular regeneration, and aberrant architecture accompanied by impaired hepatocyte function and impeded portal blood flow. The histopathological hallmarks of chronic hepatitis are hepatic necrosis, mononuclear infiltration, and fibrosis, which serves as the primary indicator of hepatic injury. Fibrosis and cirrhosis are assessed directly with liver biopsy or indirectly with non-invasive testing, including transient elastography and blood markers, such as platelet count, hyaluronic acid, procollagen type 3 N-terminal peptide, and tissue inhibitor of matrix metalloproteinase. ^1,3

 Chronic inflammation due to hepatic infection results in free radical production, fibrosis, cirrhosis, and hepatocellular carcinoma. Advanced fibrosis and cirrhosis are associated with increased risk of hepatocellular carcinoma (HCC). CHC is the leading cause of HCC worldwide with approximately 5 % to 12 % incidence per year among individuals with HCV-related cirrhosis. ⁴   Liver cancer incidence in developed countries like in the United States tripled between 1975 and 2005 and doubled that in 2023. We have no statistics for Malaysia.  Although the 1-year-cause-specific for HCC has increased from 25 % in 1992 to 47 % in 2004.^3, overall, 3-year survival remains approximately 17 %.⁷

With the recent introduction of direct-acting antivirals (DAAs), curative-intent treatment is recommended for all adults with CHC.⁸ Fibrotic stage, however, is a primary consideration in determining the relative urgency of antiviral treatment.  Approximately 5 % to 20 % of individuals with CHC develop cirrhosis over 20 - 30 years.^{9 - 11} The result s of prospective observational studies and outcome modelling projection indicates the risk of CHC disease progression to severe fibrosis or cirrhosis is minimal at 10 to 15 years in individuals with persistently normal alanine aminotransferase (ALT) levels, but greater than 30 % to 40 % in those with elevated serum ALT levels and portal fibrosis.^{9 ,12} Because clinical findings and liver enzymes levels do not predictably correlate with hepatic histological features, cirrhosis cannot be ruled out based on clinical and laboratory assessment alone. ^13,14 Non-histological factors associated with accelerated CHC progression in genotype males are: age > 40 years at the time of the time of initial infection, heavy alcoholism, daily marijuana use, obesity, and or insulin resistance, genotype 3 infection, coinfection with HIV and or, HBV, organ transplant.  Viral load is notably absent as it has not been found to correlate with disease progression. 

We shall discuss this further along with free radicals, liver detoxification enhancing therapy,  the use of pharmaceuticals, direct-acting HCV antivirals, clinical factors that increase priority for antiviral hepatitis C treatment, ribavirin, treatment response, hepatitis A and B vaccination, nutritional supplements such as glutathione, vitamins C, E, selenium, and S-Adenosylmethionine, herbal medicines such as Schizandra (Schisandra chinensis) that has long been used in Traditional Chinese Medicine, and other traditional Chinese botanical medicines, together with mind-body therapy, lifestyle interventions such as reducing dietary toxin exposures.

However, may take an estimated of another 60,000 words to complete this article. This would amount to almost writing out an MSc dissertation in nutritional and medical toxicology, and may not be worthwhile my efforts, unless readers request for this. 

I have also left typing out all the cited references as this is not a research paper, but meant only for clinicians, scientifically oriented readers and other interested readers.