Fatty liver disease a rising cause of liver problems in people with HIV

Slide from the study presented by Zobair Younossi at The International Liver Congress. Image from the EASL livestream.

Now that hepatitis C can be successfully treated, non-alcoholic fatty liver disease (NAFLD) is becoming an increasingly important cause of serious liver problems and liver-related death among people living with HIV in the US, according to a report at the EASL International Liver Congress this month in Vienna.

Dr Zobair Younossi of Inova Fairfax Medical Campus in Falls Church, Virginia, who presented the findings at a press conference, said that given the increasing impact of fatty liver disease among people with HIV, “clinicians must be vigilant in identifying and managing NAFLD in these individuals."

As people with HIV are living longer thanks to effective antiretroviral treatment, non-HIV-related conditions such as cardiovascular disease, non-AIDS cancers and liver disease account for a rising proportion of illness and death in this population. As HIV-positive people become healthier, they are also more likely to be overweight, Younossi noted.

Glossary

non-alcoholic fatty liver disease (NAFLD)

Non-alcoholic fatty liver disease (NAFLD) is a very common disorder and refers to a group of conditions where there is accumulation of excess fat in the liver of people who drink little or no alcohol. The most common form of NAFLD is a non-serious condition called fatty liver, by which fat accumulates in the liver cells. A small group of people with NAFLD may have a more serious condition named non-alcoholic steatohepatitis (NASH).

hepatitis B virus (HBV)

The hepatitis B virus can be spread through sexual contact, sharing of contaminated needles and syringes, needlestick injuries and during childbirth. Hepatitis B infection may be either short-lived and rapidly cleared in less than six months by the immune system (acute infection) or lifelong (chronic). The infection can lead to serious illnesses such as cirrhosis and liver cancer. A vaccine is available to prevent the infection.

non-alcoholic steatohepatitis (NASH)

In NASH, fat accumulation is associated with liver cell inflammation and different degrees of scarring. NASH is a potentially serious condition that may lead to severe liver scarring and cirrhosis. It sometimes affects older people living with HIV.

fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is a very common disorder and refers to a group of conditions where there is accumulation of excess fat in the liver of people who drink little or no alcohol. The most common form of NAFLD is a non-serious condition called fatty liver, by which fat accumulates in the liver cells. A small group of people with NAFLD may have a more serious condition named non-alcoholic steatohepatitis (NASH).

fibrosis

Thickening and scarring of connective tissue. Often refers to fibrosis of the liver, which can be caused by an inflammatory reaction to long-term hepatitis infection. See also ‘cirrhosis’, which is more severe scarring.

Non-alcoholic fatty liver disease and its more severe form, non-alcoholic steatohepatitis (NASH), are characterised by the accumulation of fat in the liver. This triggers inflammation, which over time can lead to the development of fibrosis, cirrhosis and liver cancer. There are currently no effective treatments for NAFLD and NASH, and management relies on lifestyle changes such as weight loss and exercise.

Many people living with HIV also have hepatitis B virus (HBV) or hepatitis C virus (HCV). An effective HBV vaccine has been available since the late 1980s, antiviral medications like tenofovir disoproxil fumarate (Viread) and entecavir (Baraclude) can keep hepatitis B under control and hepatitis C can now be cured with direct-acting antivirals. Among HIV-positive people in the US – like that country's population as a whole – viral hepatitis is falling as a cause of serious liver disease while NAFLD is rising.

Younossi and colleagues looked at the prevalence and mortality trends of NAFLD, viral hepatitis and other liver diseases among HIV-positive people receiving Medicare, which generally is available to those age 65 or older and some younger people with disabilities.

Searching medical records of more than 47,000 HIV-positive people, the researchers identified 10,474, or 22.3%, with liver disease. Hepatitis C was the most common cause, accounting for 5628 cases (53.7%), followed by NAFLD, at 2629 cases (25.1%). Other causes were less common, including 1374 with hepatitis B (13.1%t), 645 with HBV and HCV co-infection (6.2%) and 198 with other liver diseases (1.9%).

Between 2006 and 2016, the prevalence of viral hepatitis among people with HIV decreased from 27.8 to 24.1 per 100,000 population (an annual percentage change of -0.9%), while the NAFLD rate more than doubled from 5.3 to 11.6 per 100,000 (an annual percentage change of +7.2%).

A similar pattern was observed for mortality. Of the 2882 total deaths during the study period, just over a third (36.2%) were related to liver disease. Of these, half were attributable to HCV, 20.3% to NAFLD, 14.4% to HBV, 11.9% to HBV/HCV co-infection and 3.9% to other liver diseases.

During the same decade, mortality related to viral hepatitis fell from 3.8 to 2.6 per 100,000 (an annual percentage change of -5.2%), while deaths related to NAFLD rose from 0.2 to 0.8 per 100,000 (an annual percentage change of +8.9%).

In a multivariate analysis that took multiple risk factors into account, HIV-positive people with liver disease had longer hospital stays, higher inpatient and outpatient costs, and a higher risk of dying within a year compared to those without liver disease.

A related study at the conference looked at NAFLD in two cohorts of people living with HIV in Canada and Italy who did not drink to excess and did not have hepatitis B or C. Among 1228 people whose records were reviewed, 31.8% had NAFLD. Of these, 25.2% were considered at risk for liver disease progression based on elevated ALT levels or the presence of significant fibrosis.

"These studies indicate the changing profile of liver disease in patients with HIV. Whilst viral hepatitis is still the major cause of liver disease in such groups, NAFLD is becoming a much commoner problem," EASL vice secretary Prof Philip Newsome of the University of Birmingham said in a conference press release. "This reinforces the need to study therapeutic agents in patients with NAFLD and HIV, an area which is seldom examined."

References

Paik J et al (Younossi Z presenting). The increasing importance of non-alcoholic fatty liver disease in human deficiency virus (HIV) positive patients. International Liver Congress, Vienna, abstract PS-062, 2019. Journal of Hepatology 70:e37, 2019.

Watch this presentation on the conference website.

Cocciolillo S et al. Application of guidelines for fatty liver in two prospective cohorts of human immunodeficiency virus positive patients
. International Liver Congress, Vienna, abstract SAT-286, 2019. Journal of Hepatology 70:e762, 2019.