Role of Alcohol Explored in Hepatitis B Review

April 8, 2020
Kenny Walter

Approximately 1.5 billion patients had chronic liver disease in 2017, with 29% resulting from a hepatitis B viral infection.

Murali Ganesan, PhD

More research is needed to explore the role of alcohol in the pathogenesis of hepatitis B viral (HBV) infections.

A team, led by Murali Ganesan, PhD, an assistant professor in the Department of Internal Medicine, Division of Gastroenterology and Hepatology at the University of Nebraska Medical Center, examined the factors associated with the higher risk of liver diseases in alcohol-induced HBV pathogenies that could lead to future treatment.

HBV and alcohol abuse often contribute to the development of end-stage liver disease, where the alcohol abuse can cause a rapid progression of liver disease in HBV infected patients. This also allows the HBV to persist chronically.

However, the mechanism by which alcohol promotes the progression of HBV-associated liver disease is not completely understood.

Some of the potential mechanisms for this interaction include a suppressed immune response, oxidative stress, endoplasmic reticulum and Golgi apparatus stresses, and increased HBV replication.

The investigators examined recent findings on the combined effects of alcohol and hepatitis B virus-infection in the progression of liver diseases, including steatosis, fibrosis, cirrhosis, and hepatocellular carcinoma.

The hepatic steatosis induced by HBV infection is mainly caused by HBx protein by increasing the mitochondrial reactive oxygen species levels, oxidative stress, and through the interaction with liver-enriched transcription factors, hepatocyte nuclear factor 3-β, CCAAT/enhancer-binding protein α, peroxisome proliferator-activated receptor α axis, and fatty acid—binding protein 1.

The interaction between viral proteins in the liver and immune system induces hepatocyte damage, followed by tissue repair, which may cause deposition of extracellular matrix leading to progression of liver fibrosis.

Chronic alcohol intake alters the architecture and compromises the functional capacity of the liver, where alcohol metabolism is catalyzed by alcohol dehydrogenase and cytochrome P450 2E1 (CYP2E1) to acetaldehyde and this major metabolite is the culprit for the majority of the toxic effects associated with alcohol use.

Acetaldehyde is both highly toxic and carcinogenic, while CYP2E1 is involved in the induction of ROS, which interacts with fat molecules causing lipid peroxidation.

“Overall, the effect of alcohol metabolism on protein function, DNA, changes to the immune system and oxidative stress affect both hepatocytes and other liver cells,” the authors wrote. “They take place under both acute and chronic exposure to alcohol and induce significant functional impairments resulting in cell death, tumorigenesis, altered cell to cell communication, and become more prone to viral infections.”

Approximately 1.5 billion people had chronic liver disease in 2017. Of this patient population, 29% resulted from HBV, while only 2% resulted from alcoholic liver disease.

About 2 billion people are infected with HBV worldwide, including 257 million chronic carriers globally and 2.2 million chronic infection cases in the US.

However, many patients living with HBV are unaware of their infection and patients with acute hepatitis B clear HBV from their blood and liver within 6 months.

More research is needed before investigators better understand these mechanisms to develop treatment options to prevent rapid liver disease progression in alcohol-abusing patients with hepatitis B.

“While many potential mechanisms for the synergistic effects of HBV and alcohol abuse exist, most of them have not been explicitly studied and characterized,” the authors wrote. “More research is required to understand the complex interactions between alcohol consumption and HBV infection. Once elucidated, these mechanisms could aid in the development of new treatments to prevent the progression of end-stage liver disease in alcohol abusing HBV patients.”

The study, “Role of alcohol in pathogenesis of hepatitis B virus infection,” was published online in the World Journal of Gastroenterology.


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