Hepatitis B

 Hepatitis B is a chronic liver infection, caused by the hepatitis B virus. This is prevalent in Asia and the Eastern Mediterranean region as in West Africa and the South Pacific but can be found in Europe and the Americas, too. It has been markedly decreased since vaccination was introduced thirty years ago but not all areas of the world are evenly vaccinated.

Hepatitis B can be transmitted with bodily fluids. Transfusion used to be a significant way but donor screening has been universal, especially in developed countries. It is easily transmitted sexually and with shared needles. A special form is mother-to-fetus transmission at the time of birth. There is mandatory testing and perinatal vaccination in the US and this form of transmission is exceedingly rare. Unfortunately, it is not so in many Asian countries.

Acute hepatitis B is mostly asymptomatic and is missed. Chronic disease is also rarely diagnosed because of symptoms but mostly on routine blood tests.

There are different phases of chronic hepatitis B, ranging from decades long immune tolerance, when the virus replicates but the body does not attack the infected liver cells (hence no hepatitis) to different immune active and inactive (carrier) phases. Infection may resolve spontaneously, more so in Caucasian than Asian patients.

In contrast to hepatitis C, the genetic material of the hepatitis B virus can be integrated into the liver cell’s DNA and this can cause liver cancer, even in patients, whose disease resolved, albeit to a much lesser extent.

 

Hepatitis B may also cause disease outside of the liver, the so-called extrahepatic manifestations: kidney disease, polyarteritis nodosa and aplastic anemia.

 

Vaccination is the most important way to fight hepatitis B. The newer, recombinant vaccines are well tolerated and very effective. In many places, vaccination is mandatory before age 14 and this strategy has been remarkably effective.

Treatment is effective mostly in suppressing the virus but is not curative in many patients. There are several oral medications, which are safe and effective and have been shown to prevent progression of the disease, stabilize even advanced disease and reduce the recurrence of liver cancer after its eradication by other means. They can also reduce the rate of transmission from mother to fetus and are used safely during pregnancy. These medications are used for very long times, frequently indefinitely. Interferon, an injectable drug, is used for about a year, alone or in combination with oral antivirals, but is also rarely curative and has many more side effects.

New therapeutics are being actively researched, aimed not only at viral suppression but also at elimination of the disease, by priming the body’s own immune cells to preferentially attack infected liver cells.

New Oral Treatments for Inflammatory Bowel Disease

 Biologics have been mainstay of treatment for moderate-to-severe IBD for the last two decades, gaining prominence and wide acceptance since the introduction of Remicade in the late 1990s. They have revolutionized IBD therapy and are still growing in numbers. There are three main groups : anti-TNFs ( Remicade, Humira, Simponi, Cimzia), anti-Integrins (Entyvio, Tysabri) and anti- IL 12/23 ( Stelara). They are all so-called monoclonal antibodies and need to be given as injection, some intravenously, some subcutaneously. They work, but not universally and all can provoke an immune reaction against themselves in the human body. They are also expensive and cumbersome to administer. I have been closely involved with their development as a clinical researcher.

The last few years brought oral medications for IBD to supplement, and maybe one day to supplant, the current biologics. First came Xeljanz ( Tofacitinib) and more recently Zeposia  (Ozanimod).

Xeljanz is a JAK inhibitor. This mechanism of action is similar to that of biologics: it disrupts one step of the cellular inflammatory response. It is rapidly effective in many patients. While it is generally safe, there have been serious side effects, such as the development of shingles and pulmonary embolism. Also, Xeljanz  is not active for Crohn’s Disease, although second generation JAK inhibitors show promise. Rinvoq, a selective JAK inhibitor, has just been approved for Ulcerative Colitis patients, who failed treatment with an anti-TNF agent.

Zeposia works differently. It captures the inflammatory cells before they can enter the tissue and traps them in lymph nodes. It seems safer and it shows promise for Crohn’s Disease, too. Other companies are working on newer versions of it.

The epidemic of liver disease due to obesity

 Americans are overweight and obese in alarming numbers. This leads to several chronic health problems : Diabetes, High Blood Pressure, Heart Disease and Fatty Liver Disease.

 

Fatty liver occurs when there is accumulation of fat in the liver tissue. This can stay relatively benign but the fat in the liver cells may also give rise to inflammation. Alcohol consumption is a frequent cause but many times it is not due to alcohol. These are Non- Alcoholic Fatty Liver (NAFL) and Non-Alcoholic Steatohepatitis (NASH), which is the inflammatory form. NASH can lead to scarring of the liver, leading to full-blown cirrhosis and, once cirrhosis has been established, to cancer of the liver (Hepatocellular Carcinoma, HCC).

I have been part of several research studies in this arena and am currently working with Altimmune, a biopharmaceutical company active in this arena.

At this point the best way to get rid of fat in the liver and to reverse to process is to lose weight. This is easier said and done. There are a few, not very effective weight loss medications, and they all should be used as part of a comprehensive weight management program. The most effective way to lose weight and to reverse to process leading to cirrhosis is bariatric surgery.

There are newer medications: the injectables Victosa (Luraglutide) and Rybelsus (Semaglutide). These are more effective and Rybelsus can be administered once weekly. They are GLP-1 agonists. Whena GLP-1 agonist is combined in one molecule with a glucagon receptor agonist, even better results might be achievable with fewer side effects. These promising drug candidates are in clinical trials at this time.