Liver diseases in patients with HIV infection Aung Zayar Paing

Introduction

�  Abnormal liver function tests can be seen frequently in HIV patients. (prevalence as high as 30%)

�  Liver disease is the second commonest cause of mortality in HIV patients.

�  Hepatitis virus coinfections represent the most significant cause of liver disease in HIV patients.

�  Some other conditions also play their role to cause liver injury in HIV patients.

Lancet 2011; 377: 1198–1209

AIDS Rev. 2013; 15:25-31

Lancet 2011; 377: 1198–1209

Different causes of hepatitis in HIV infected patients

HAIVN M2-08-Hepatic Toxicity in Patients Taking ARVs-EN

HAIVN M2-08-Hepatic Toxicity in Patients Taking ARVs-EN

Hepatitis Coinfections

AIDS Rev. 2013; 15:25-31

HBV coinfection

�  ARVs like Tenofovir (TDF), Lamivudine (3TC) and Emtricitabine (FTC) are active against HIV as well as HBV.

�  WHO guideline 2013 recommends to start ART for HIV-HBV coinfected patients with evidence of severe chronic liver disease.

�  US DHHS guideline advises to start ART for all patients who need anti-HBV treatment.

Hepatic flare up after HAART in HBV coinfected patients

�  Some patients with HIV-HBV coinfection experience hepatic flare up having high ALT levels.

�  Like IRIS associated with OIs, high antigen burden (high HBV DNA level) (ID 2009:199, Crane et al. http://jid.oxfordjournals.org/)

ALT and HBV DNA values in HF and non-HF subjects over 1st 12 weeks after HAART initiation. x-axis: Weeks after HAART initiation. y-axis 1: HBV DNA log 10 c/ml. y-axis 2: ALT IU/L. Avihingsanon et al. AIDS Research and Therapy 2012 9:6 doi:10.1186/1742-6405-9-6

HCV coinfection

�  Nearly 1/3 of HCV patients progress to cirrhosis at a median time of less than 20 years.

�  Compared to HCV monoinfected patients, HIV-HCV coinfected patients have 3 times greater risk of progression to cirrhosis or decompensated liver disease.

�  Peginterferon + Ribavirin is the mainstay treatment.

�  Interferon sparing regimens are possible for some genotypes recently after the introduction of new directly active antiviral (DAA) Sofosbuvir.

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Drug interaction and toxicities

�  AZT + RBV - increased risk of anemia

�  ddI + RBV – life threatening ddI-associated mitochondrial toxicity including hepatomegaly/steatosis, pancreatitis, and lactic acidosis

�  ABC - decreased response to PegIFN/RBV ???

�  Other DAAs, Boceprevir and telaprevir interacts significantly with EFV.

Hepatitis E virus infection in HIV patients

�  Some studies showed that HIV infected patients have increased susceptibility to hepatitis E virus infection.

�  Acute HEV infection can mimic drug induced liver injury.

�  HIV patients have risk of chronic HEV infection. (HEV RNA in serum or stools for 6 months or more)

�  Myanmar is one of the countries with high prevalence of HEV infection.

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Source and route of HEV1–4 infection HEV1 and HEV2 are waterborne only, with possible human-to-human transmission, including vertical transmission.

Hepatotoxicity of drugs

HAIVN M2-08-Hepatic Toxicity in Patients Taking ARVs-EN

HAIVN M2-08-Hepatic Toxicity in Patients Taking ARVs-EN

Martin Fisher’s presentation: ICVH 2013

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Martin Fisher’s presentation: ICVH 2013

Hyperbilirubinemia due to some PIs

Liver metabolism of bilirubin and potential mechanisms of interference of atazanavir (ATV) and indinavir (IDV). Uridine diphosphate glucuronosyltransferase 1A1 is the liver enzyme that conjugates the bilirubin. The insertion of an extra dinucleotide (TA) on the promoter gene of the UGT1A1 results in a decreased enzyme activity. Atazanavir and IDV inhibit the UGT1A1, which in turn result in hyperbilirubinemia.

http://www.nature.com/tpj/journal/v6/n4/fig_tab/6500374f6.html

ACTG grading system for hepatotoxicity

Grade 1 Grade 2 Grade 3 Grade 4 ALT* ≤ 2.5 x ULN 2.6 – 5.0 x ULN 5.1-10.0 x ULN 10.0 x ULN

If  Grade  1  or  2  hepatotoxicity  occurs  during  NVP  lead-­‐in  dose,  lead-­‐in  dose  can  extend    next  2  weeks  (maximum).  If  ALT  sFll  raised  and  <  grade  2  stop  NVP  and  start  EFV.  

Other conditions

Alcoholic hepatitis

�  Alcoholism is common in HIV patients and alcoholic hepatitis sometimes complicate HIV treatment.

�  Abrupt stopping of alcohol in chronic drinker is dangerous and the patient may suffer from alcohol withdrawal. (mild to sever manifestation like Delirium Tremens)

Signs and symptoms

CCO HIV inPractice

�  AST/ALT ratio - usually > 1

�  GGT - may be increased (low sensitivity/specificity for alcohol abuse

�  Bilirubin may be increased

�  INR - raised

�  PT - prolonged

Nonalcoholic Fatty Liver Disease (NAFLD)

�  NAFLD is the condition caused by accumulation of Triglycerides in hepatocytes associated with obesity, diabetes mellitus and hyperlipidemia.

�  Non-alcoholic steatohepatitis is the progressive form of NAFLD.

�  40-70% HIV-HCV coinfected patients are found to have hepatic steatosis.

�  The risk is higher in patients taking ddI or d4T

�  AST/ALT ration is usually < 1

http://dx.doi.org/10.1155/2013/493413

Thank you