- Journal List
- Indian J Sex Transm Dis AIDS
- v.44(1); Jan-Jun 2023
- PMC10343110
As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply endorsem*nt of, or agreement with, the contents by NLM or the National Institutes of Health.
Learn more: PMC Disclaimer | PMC Copyright Notice
Indian J Sex Transm Dis AIDS. 2023 Jan-Jun; 44(1): 66–68.
Published online 2022 Dec 9. doi:10.4103/ijstd.ijstd_73_22
PMCID: PMC10343110
PMID: 37457519
Manish Manrai, Rohit Vashisht, Balakrishnan Arivalagan, Puneet Baveja,1 Ahmed Waheed Kashif,1 and Anil Menon
Author information Article notes Copyright and License information PMC Disclaimer
Abstract
A wide spectrum of hepatobiliary manifestations occur in Human Immunodeficiency Virus (HIV)-infected patients. Among the common causes are the infectious hepatitis, drug-related hepatitis, opportunistic infections, non-alcoholic steatohepatitis, HIV cholangiopathy and neoplasm. Auto-immune hepatitis (AIH) is rarely reported in this setting. We present two different presentations of auto immune hepatitis in HIV positive patients. One developed jaundice and ascites as a consequence of liver decompensation and other exhibited cholestatic pattern. Their serology and liver biopsy confirmed autoimmune hepatitis as underlying aetiology. We would like to share the clinical improvement with simultaneous immunosuppressive therapy and combination Anti Retroviral Therapy (cART). There are no documented cases on this issue from the Indian subcontinent that we are aware of.
Keywords: AIH, antinuclear antibodies, cART, HIV, liver biopsy, steroids
Introduction
Autoimmune hepatitis is characterized by chronic, progressive inflammation of the liver caused by regulatory T-cells dysfunction.[1] HIV affects the native immunity of the individual. The existence of HIV and AIH in the same individual is a contrasting phenomenon, though recent epidemiologic studies revealed the presence of AIH in HIV positive individuals.[2,3] However, no correlation has been established between cluster of differentiation (CD4) count or HIV viral load and development of AIH. Hereby, we report two cases of AIH in the setting of HIV.
Case Reports
Case 1
A 49-year-old HIV-positive female on cART presented with jaundice and abdominal distension of 3-month duration along with easy fatigability and pruritus. There is no history suggestive of encephalopathy or coagulopathy. There was no history of fever, blood transfusions, or surgery in the past. There was no history suggestive of Wilson's disease or alcohol use. Ultrasound abdomen revealed coarse liver echo texture and endoscopy showed Grade I esophageal varices and severe portal hypertensive gastropathy. Paracentesis showed high serum ascites albumin gradient with low protein suggestive of portal hypertension.
Case 2
A 26-year-old HIV-positive male with no addictions presented with easy fatigability and generalized weakness with no abdominal pain, fever, or any symptoms of liver cell failure. His evaluation revealed raised alkaline phosphate (ALP) and gamma-glutamyl transferase (GGT) with mild elevation in bilirubin and transaminases. He was managed with tablet ursodeoxycholic acid and observed for few days. His bilirubin levels and liver enzymes showed a declining trend, but his ALP and GGT were persistently elevated. His HIV load was undetectable on his existing cART. Magnetic resonance cholangiography was essentially normal.
In both the cases, the etiology investigation for infections, Wilson's disease, nonalcoholic steatohepatitis and hepatic malignancy were all negative. Their investigations profile is given in detail in Table 1.
Table 1
Investigations of cases
| Investigations | Case 1 | Case 2 | Reference |
|---|---|---|---|
| On admission | |||
| Hemoglobin | 11.7 | 12.8 | 12.5–16.5 g % |
| White blood count | 7600 | 4900 | 4000–11,000 cells/µL |
| Neutrophil | 58% | 67% | 60%–70% |
| Lymphocyte | 27% | 22% | 25%–30% |
| Platelet | 168,000 | 274,000 | 1.5–4.5 lakhs/mm3 |
| PT/INR | 18.2/1.22 | 17.6/1.1 | 10–14 s |
| BUN/creatinine | 08/0.6 | 29/0.97 | 10–50/0.7–1.3 mg/dL |
| Serum bilirubin (total)/(direct) | 0.8/0.2 | 3.9/2.5 | T: 0.2–1.0/D: 0–0.2 mg/dL |
| Total protein | 8.6 | 7.5 | 6.4–8.2 g/dL |
| Serum albumin | 2.3 | 3.6 | 3.4–5.0 g/dL |
| AST | 136 | 87 | 16–63 IU/L |
| ALT | 89 | 52 | 15–37 IU/L |
| ALP | 160 | 740 | 46–116 IU/L |
| GGT | 42 | 467 | 5–85 IU/L |
| Serum ceruloplasmin | 17.9 | 27.3 | 20–60 |
| 24 h urine copper | 27.76 | 18.6 | 3–50 µg/day |
| Serum ferritin | 22.3 | 72.6 | Female: 25–280 µg/dL Male: 70–435 µg/dL |
| FBS/PPBS | 84/98 | 83/117 | 80–110/140 mg/dL |
| Total IgG | 4837 | 1610 | 700–1600 mg/dL |
| ANA | 1: 320 | 1:160 | 1:80 |
| AMA | Negative | Negative | |
| SMA | Negative | Negative | |
| Anti-LKM | Negative | Negative | |
| Total Anti HBc Ab | 0.02 | 0.06 | <0.1 |
| CD count | 469 | 177 | 448–1611 cells/µL |
| HIV load | TND | TND | TND |
| HBsAg/anti-HCV | Negative | Negative | |
| Ascitic fluid protein | Negative for malignant cells | No ascites | |
| Upper gastrointestinal endoscopy | Portal hypertension | Not undergone | |
| Fibroscan (kPA) | 17.6 | 10.1 | |
| Follow up after 3 months | |||
| Serum bilirubin - Total/direct | 0.5/0.2 | 1.8/0.2 | 0.2–1.0/0–0.2 mg/dL |
| Total protein | 8.1 | 7.5 | 6.4–8.2 g/dL |
| Serum albumin | 3.8 | 3.6 | 3.4–5.0 g/dL |
| AST | 34 | 36 | 16–63 IU/L |
| ALT | 36 | 49 | 15–37 IU/L |
| ALP | 48 | 138 | 46–116 U/L |
| GGT | 40 | 132 | 5–85 IU/L |
Open in a separate window
PT=Prothrombin time; INR=International normalized ratio; BUN=Blood urea nitrogen; AST=Aspartate transaminase; ALT=Alanine transaminase; ALP=Alkaline phosphatase; GGT=Gamma glutamyl transferase; FBS=Fasting blood sugar; PPBS=Post prandial blood sugar; ANA=Antinuclear antibodies; AMA=Antimitochondrial antibodies; SMA=Smooth muscle antibodies; LKM=Liver kidney microsomal; HBc Ab=Hepatitis B core antibody; CD=Cluster of differentiation; HIV=Human Immunodeficiency Virus; HBsAg=Hepatitis B surface antigen; HCV=Hepatitis C virus; TND=Target not detected
Their autoimmune hepatitis screening revealed antinuclear antibodies (ANA) positivity by immunofluorescence method with elevated immunoglobulin G (IgG) levels. We did liver biopsy in both the cases, which showed findings consistent with autoimmune hepatitis as shown in Figure 1.
Figure 1
Liver biopsy: (a) H and E, ×100: Dense inflammation in portal tracts infiltrating into lobules. (b) H and E, ×400: Mononuclear inflammatory infiltrate in portal tract consisting of lymphocytes and plasma cells, plasma cells are shown by arrows (↑). (c) Mason trichrome stain, ×100: highlights fibrosis with nodule formation. (d) Immunohistochemistry (CD38): Highlights plasma cells
We continued cART in both the cases and simultaneously started them on oral prednisolone 40 mg once a day followed by azathioprine therapy. Our female patient responded very well; hence, steroid was tapered to 10 mg along with tablet azathioprine 50 mg once a day. At present, she is compensated in Child Pugh A with Model for End Stage Liver Disease–Sodium score of 12. The male patient was started on steroid monotherapy and showed an inadequate response initially, as evidenced by a minimal drop in ALP and GGT levels. During treatment, he developed herpes zoster over trunk and was managed with acyclovir. Simultaneously, his CD4 count also dropped to 69 cells/mm3. His steroids were tapered and tablet azathioprine 50 mg once a day was added. A gradual improvement was noticed thereafter as his CD4 count recovered to 112 cells/mm3 and ALP and GGT levels demonstrated a decreasing trend. The follow-up investigations for both the cases are mentioned in Table 1.
Discussion
The existence of AIH among HIV-positive individuals is a rare entity. The common causes for deranged liver functions in HIV-positive patients are drug associated, chronic hepatitis B or C, opportunistic infections, but AIH should also be kept as one of the differential diagnoses.[3,4] Pathophysiology of liver damage in these patients can be explained either by the cell-mediated cytotoxic response against liver antigens or autoreactive CD4 or CD8 T-cells response post immune reconstitution phase following initiation of cART.[4,5] The clinical phenotype and the histological findings of liver biopsy in HIV-AIH patient are similar to those having AIH only. However, till now, no correlation has been established between CD4 count or HIV viral load and development of AIH.
A meta-analysis of 35 patients of AIH in HIV by Mubder et al.[2] showed female preponderance (75%) with a mean age of 45.7 years. In our case series, we reported two cases, one in a middle-aged female and the other in a young male. Most cases develop AIH with an undetectable HIV viral load as seen in our case series also. Other autoimmune diseases coexisted in 6 patients (17.1%); however, we report none in our series. Liver enzymes were predominantly raised in males. However, our cases did show elevated transaminases. We noticed persistently elevated ALP in our male patient against Mubder et al.'s analysis, where the mean level was about 80 IU/L. Liver biopsy was performed in both the cases for diagnosing AIH, as in the meta-analysis. Patients were managed successfully with steroids and a regime of tapering steroids with the addition of azathioprine. We also managed both the patients with the combination regime.
Chaiteerakij et al. also studied 13 cases having both HIV and AIH.[5] All patients reported stable viral loads with a mean CD4 count of 557 cells/uL, whereas in our study, the male patient had a CD4 count of <200. Most of their cases presented with persistently elevated transaminases; however, our cases showed transient elevated transaminases which might be due to varied disease manifestation of AIH. Total IgG levels and ANA titers were raised in our study, which is in line with their case series. One patient presented with acute hepatitis and the other patient presented with jaundice in that case series, whereas in our study, one presented with ascites and jaundice and the other had cholestatic disease. Our study highlights that the cholestatic pattern is also an important part of the clinical spectrum in HIV-AIH patients.
Treatment is challenging in this subset of patients. It is evident from previous cases that there is no difference in treatment approach among HIV-AIH patients and patients having AIH alone. Immunosuppressive agents remain the mainstay of the treatment and prevent further hepatocellular damage and cirrhosis development. The response is characterized by normalization of serum aminotransferase and IgG levels and histological remission. The drug compliance is must to prevent frequent relapses and long-term maintenance with low-dose immunosuppressive drugs is required.[5]
Conclusion
AIH is an emerging entity occurring in patients with well-controlled HIV with liver dysfunction. Histological findings of liver biopsy in HIV-AIH are similar to those having AIH alone. Liver biopsy is mandatory in all suspected cases. Immunosuppressive therapy is the mainstay of treatment and it should be individualized. The patients should be closely monitored for CD4 count decline or viral rebound and emergence of opportunistic infections.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
1. Linzay CD, Sharma B, Pandit S. In: Stat Pearls. Treasure Island (FL): StatPearls Publishing; 2022. Autoimmune Hepatitis. [PubMed] [Google Scholar]
2. Mubder M, Azab M, Jayaraj M, Cross C, Lankarani D, Dhindsa B, et al. Autoimmune hepatitis in patients with human immunodeficiency virus infection: A systematic review of the published literature. Medicine (Baltimore) 2019;98:e17094. [PMC free article] [PubMed] [Google Scholar]
3. Kia L, Beattie A, Green RM. Autoimmune hepatitis in patients with Human Immunodeficiency Virus (HIV): Case reports of a rare, but important diagnosis with therapeutic implications. Medicine (Baltimore) 2017;96:e6011. [PMC free article] [PubMed] [Google Scholar]
4. Ofori E, Ramai D, Ona MA, Reddy M. Autoimmune hepatitis in the setting of human immunodeficiency virus infection: A case series. World J Hepatol. 2017;9:1367–71. [PMC free article] [PubMed] [Google Scholar]
5. Chaiteerakij R, Sanpawat A, Avihingsanon A, Treeprasertsuk S. Autoimmune hepatitis in human immunodeficiency virus-infected patients: A case series and review of the literature. World J Gastroenterol. 2019;25:5388–402. [PMC free article] [PubMed] [Google Scholar]
Articles from Indian Journal of Sexually Transmitted Diseases and AIDS are provided here courtesy of Wolters Kluwer -- Medknow Publications
