A CASE REPORT ON ALCOHOL INDUCED HEPATITIS WITH HIV INFECTION

A CASE REPORT ON ALCOHOL INDUCED HEPATITIS WITH HIV INFECTION

INTRODUCTION:

HEPATITIS:

·       Hepatitis refers to an inflammatory condition of the liver that results from a variety of causes, both infectious and non-infectious.

·       Infectious agents that cause hepatitis include viruses such as hepatitis b virus (HBV) whereas non-infectious causes include certain drugs (eg: Isoniazid, Methotrexate) and toxic agents (eg: alcohol).

SIGNS AND SYMPTOMS:

•        Anorexia
•        Jaundice
•        Dark urine
•        Pale colour stools
•        Pain in the right side of the abdomen
•        Fatigue
•        Nausea and vomiting

COMPLICATIONS OF HEPATITIS:

• Cirrhosis
• Acute or subacute hepatic necrosis.
• Hepatic failure
• Hepatocellular carcinoma

HIV (HUMAN IMMUNODEFICIENCY VIRUS):

·       It is the virus that can lead to acquired immunodeficiency syndrome or AIDS if not treated. HIV attacks the body’s immune system, specifically the CD4 cells (T cells), which are involved in immune function thereby making the person prone to opportunistic infections.

·       HIV is a retrovirus that belongs to genus lenti virus and it is a single stranded RNA virus.

·       Two types of HIV virus have been recognized i.e HIV-1 and HIV-2, HIV-1 is more virulent than HIV-2 and is cause of majority of HIV infections globally.

·       HIV is transmitted through blood, sexual fluids such as semen and breast milk.

STAGES OF HIV:

• Acute HIV infection
• Clinical latency or dormant period
• AIDS

SIGNS AND SYMPTOMS OF HIV INFECTION:

SYMPTOMS OF ACUTE HIV INFECTION	SYMPTOMS OF AIDS
Ø  Fever Ø  Weight loss Ø  Myalgia Ø  Skin rashes Ø  Malaise Ø  Nausea and vomiting Ø  Liver and spleen enlargement	Ø  Encephalitis Ø  Meningitis Ø  Pneumonia Ø  Tuberculosis Ø  Skin tumors Ø  Chronic diarrhoea Ø  Retinitis

TREATMENT FOR HIV INFECTED INDIVIDUALS:

•   ART (Anti-Retroviral Therapy) is recommended for all the HIV infected individuals irrespective of CD4 cell count.

•        This helps in prevention of transmission and progression of disease as well as reduces the morbidity and mortality associated with HIV infection.

•        Standard ART consists of 2 NRTI (Nucleoside reverse transcriptase inhibitors) in combination with an NNRTI (Non-Nucleoside reverse transcriptase inhibitors), PI (Protease inhibitors) or integrase inhibitors.

•        Some of the preferred regimens include

1. Efavirenz+tenofovir+Emtricitabine
2. Atazanavir+ tenofovir+Emtricitabine
3. Raltegravir+ tenofovir+Emtricitabine

•        Some of the commercially available FDC’s are

1. Efavirenz+tenofovir+Emtricitabine---ATRIPLA
2. Zidovudine+Lamivudine+abacavir----TRIZIVIR

•        Hepatitis, Liver toxicity, Lactic acidosis and Lipoatrophy are some of the SAE reported with the ART treatment.

•        As there is significant reduction in the mortality due to HIV infection, non-AIDS illnesses are becoming increasingly important sources of morbidity and mortality in the HIV-infected population.

•        In particular, liver-related diseases are becoming increasingly prominent in HIV-infected patients. 

Figure 1 ANTI-RETROVIRAL DRUGS- SITES OF ACTION

•        The liver-related disease has been estimated to account for 13-18%of all-cause mortality in HIV-infected patients and is one of the leading causes of non-AIDS-related death.

•        Typical mechanisms of liver disease in HIV infected patients include oxidative stress, mitochondrial injury, lipotoxicity, immune-mediated injury, cytotoxicity, toxic metabolite accumulation, gut microbial translocation, systemic inflammation, senescence, and nodular regenerative hyperplasia.

CASE REPORT:

·       A 35-year-old male patient with greater than a 7-year history of alcohol misuse was presented to the hospital with a 10-day history of generalized weakness.

·       Social history was remarkable for drinking whiskey and beer very often. Physical examination shows a pale color of the skin especially on the face and palms which has occurred due to illness and anemia.

·       The laboratory findings on admission revealed that the patient has Microcytic Hypochromic Anemia with mild Leucopenia which indicates that the patient has iron deficiency Anemia. Liver function tests showed an increase in Bilirubin levels and liver transaminases.

·       Abdominal sonography revealed an enlarged liver showing mild hepatomegaly with gallbladder wall edema and minimal ascites.

·       A rapid HIV TRI-DOT test has been done to the patient which gave a positive result which means that the patient has been infected with the HIV virus. CD 4 cell count laboratory reports show a decline in CD 4 Immune cells.

Parameter	Observed value	Reference
Total bilirubin	5.2 mg/dl	0.3-1.0mg/dl
Direct bilirubin	1.3 mg/dl	<0.3mg/dl
Indirect bilirubin	3.9 mg/dl	0.2-0.7mg/dl
SGOT	200 IU/L	5-40IU/L
SGPT	158 IU/L	5-35IU/L
ALP	146IU/L	35-130IU/L

Table- 1 LIVER FUNCTION TEST

Parameter	Observed value	Reference value
Haemoglobin	7.9 gm/dl	13-18 gm/dl
Total RBC	3.0 mill/cumm	4.0-6.5 mill/cumm
Total WBC	3,700 cells/cumm	4000-1100 cells/cumm
Neutrophil	59%	35-75%
Lymphocytes	32%	20-45%
Eosinophils	05%	01-08%
Monocytes	04%	01-06%
Basophils	00%	0-1%
Platelets	4.2 lakhs/cumm	1.5-4.5 lakhs/cumm
CD 4 cell count	320 cells/cumm	500-1200 cells/cumm

Table-2 HAEMATOLOGY REPORT

DISCUSSION:

MECHANISMS OF LIVER INJURY IN ART DRUGS:
Nucleoside Reverse Transcriptase Inhibitors:

Mitochondrial toxicity is a prevailing explanation for hepatotoxicity among patients treated with NRTIs, especially stavudine, didanosine, and zalcitabine. Mitochondrial toxicity results in lactic acidosis, which may present with or without hepatic microsteatosis.

Non-nucleoside Reverse Transcriptase Inhibitors:

Several mechanisms have been suggested. These include hypersensitivity reaction, direct cholestatic injury or mediation of immune reconstitution syndromes such as IRIS (Immune Reconstitution Inflammatory Syndrome). Although rare, the use of both efavirenz and nevirapine has been associated with the development of fulminant hepatic failure and/or toxic hepatitis.

Protease Inhibitors:

Protease inhibitors also may have other direct and indirect effects on the liver. These drugs suppress the breakdown of nuclear sterol-regulatory element binding proteins in liver and adipose tissues which leads to an excess of fatty acid and cholesterol biosynthesis in the liver.

MECHANISM OF ALCOHOL INDUCED HEPATIC DAMAGE:

Figure 2 MECHANISMS OF ALCOHOL INDUCED HEPATIC DAMAGE

MECHANISM OF ANEMIA IN ALCOHOLIC PATIENTS:

·       Managing liver disease is an increasingly important component to the care of individuals infected with human immunodeficiency virus -1.

·       In some studies, nearly half of deaths among hospitalized HIV- infected patients in the ART- era have been attributed to liver disease.

·       In patients infected with human immunodeficiency virus type-1 (HIV-1), Liver toxicity is one of the most relevant adverse effects of antiretroviral therapy (ART)

• Most patients with hepatic alterations due to ART are asymptomatic, and liver disease may unexpectedly be diagnosed during the evaluation of unexplained persistent elevations of serum liver enzymes
• Given the potential impact of hepatotoxic reactions in patients undergoing treatment for HIV, monitoring of liver enzymes, especially during the initiation of ART is necessary.
• Clinical manifestations of hepatotoxicity such as elevated transaminases often will spontaneously resolve without interrupting antiretroviral therapy.
• If, after thorough clinical assessment, one or more antiretroviral drugs is believed to be a causative factor in severe hepatotoxicity, discontinuation of the agent may be necessary. In this case, it may be advantageous to completely stop all antiretroviral therapy rather than just one or two agents, so as to minimize the potential for development of individual drug-resistant strains.
• Frequent assessment of disease progression (eg, CD4 count) is necessary in patients discontinued from antiretroviral therapy.

CONCLUSION:

·       Establishing a balance between efficacy and toxicity is an essential consideration in the design of any drug regimen.

·       Long-term HAART is necessary to prevent disease recurrence and/or exacerbation in HIV-infected individuals and is effective in prolonging survival. Life-long antiretroviral therapy, however, is limited by several significant tolerability issues, including hepatotoxicity.

·       Frequent monitoring for drug-related side effects is necessary, especially in the early phases of treatment. All classes of antiretroviral drugs have the potential to cause hepatotoxic reactions through one or more mechanisms.

·       Coinfection with hepatitis B or C virus and baseline elevations in liver enzymes appear to be relatively consistent risk factors for antiretroviral therapy-associated hepatotoxicity in some studies.

·       In summary, this is a case of anemia and hepatitis with newly diagnosed HIV infection for which patient is advised with ART therapy for further treatment.

·       So, the patient has to be properly counseled about adverse effects of ART therapy advise them to report as soon as possible if they experience any signs and symptoms of hepatitis such as yellowish discoloration of skin, anorexia & vomitings.

DIETARY COUNSELING POINTS FOR ANEMIC PATIENTS:

·       Consumption of vitamin B₁₂ rich foods such as meat, eggs, fish and almonds.z

·       Consumption of iron rich foods such as spinach, chicken liver.

·       Consumption of vitamin c rich fruits such as lemon, orange which helps in increasing the iron absorption.

·       Drink copper infused water as copper is essential in building haemoglobin. Store water in a copper glass overnight and drink it in the morning.

·       Avoid tea, coffee and soda as they interfere with iron absorption.

·       Foods rich in insoluble fibre such as whole grains, beans should be avoided as they may interfere with the absorption of iron.

 POLUDASARI SHRAVAN KUMAR