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CASE STUDY REPORT

Acute Hepatitis B and Chronic Heptatits C in a 28 twelvemonth old male – A Case Study

1. Introduction-

1.1 An Introduction to Liver and Liver Diseases-

The liver is the largest solid organ in the human organic structure and is indispensable for life. It is said to the chief metabolizing and detoxicating chamber of our organic structure. It has a important function of metabolising foods from the bowels, detoxicating ammonium hydroxide incorporating waste merchandises, filtrating drugs and toxic substances in our blood. Apart from these, it has besides a function to assist modulate blood- glucose and triglyceride degrees, and endocrines in our circulatory system, every bit good as take parting in our immune defence against infection. Hepatocyte is the cellular and functional unit of the liver, and about 60 per cent of the liver is made up hepatocytes. ( 1 ) The liver besides has bile-duct cells, macrophages and reticulo-endothelial cells apart from hepatocytes, which aid the liver in transporting out all its maps. The detoxicating chamber of our organic structure, the liver, can defy a great trade of maltreatment and failure of the liver means that there is irreversible harm beyond fix to its construction and map. ( 1 ) Persons who develop liver failure can decease with no warning within months of diagnosing. There are legion causes of liver diseases, toxic consequence of drugs, inordinate ingestion of intoxicant, viruses, familial defects or exposure to toxic chemicals. Some common symptoms and marks associated with liver disease include sickness, emesis, reduced appetency, icterus, low-grade febrility, abdominal hurting and weariness. Many liver diseases coexist with chronic nephritic disease, because many systemic conditions affect both the liver and the kidneys. ( FlorenceA Wong, 2011 ) . The morbidity of these diseases has necessitated a drawn-out hunt for effectual therapy.A ( Dusheiko,2003 ) .

1.2 Hepatitis B and C –

Presently, the most common cause of liver failure is viral hepatitis and HBV and HCV i.e. hepatitis B and hepatitis C viruses are the most common causes of chronic diseases worldwide. ( Rocio Torres Ibarra, 2006 ) . Chronic liver disease further when left untreated may perplex affairs and lead to liver cirrhosis or hepatocellular carcinoma ( HCC ) . ( Rocio Torres Ibarra, 2006 ) . Harmonizing to the World wellness organisation an estimated 350 million people are infected with HBV and about 170 million individuals have HCV. ( Sannat GmbH,2008, Rocio Torres Ibarra, 2006 ) . The hepatitis B virus ( HBV ) and the hepatitis C virus ( HCV ) portion common transmittal tracts. ( Mitre and Mendonca, 2007 ) . Therefore, co-infection can be expected. However the exact figure of HBV-HCV co-infectied persons is unknown. But it is estimated that it is between 9 % and 30 % , depending on the geographical part. ( Rocio Torres Ibarra, 2006 ) . Although a figure of surveies have evaluated little Numberss of co-infected persons. But due to non uniformity of appraisal standards, inclusion standards, viral genotypes, epidemiology and ethnicity, the findings of these stray surveies can non be used as conclusive grounds ( Mitre and Mendonca, 2007 ) . A co-infection with HBV – HCV is a more serious disease, and the hazard of developing HCC is besides increased than HCV infection entirely. ( Rocio Torres Ibarra, 2006 ) .

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2. Case presentation –

A 28-year-old male old male patient was presented to the accident and exigency ( A & A ; E ) section with terrible abdominal hurting, icterus, and mental confusion. From his medical history, it was revealed that this individual had history of endovenous drug maltreatment for many old ages. A physical scrutiny of this patient revealed needle path Markss on both weaponries. Indicative of an drawn-out and inordinate tegument puncture with acerate leafs due to drug maltreatment ( Center for Substance Abuse Treatment-USA, 2002 ) .

Hepatitis serological trials were carried out on this patient as portion of clinical probe and the patient was admitted instantly. Serologic trials were performed for HAV, HBV, and HCV. The consequences of the viral hepatitis proving were as follows:

Sex – Male, Age – 28 old ages

HBsAg

– Positive

IgM anti-HBc

– Positive

IgM anti-HAV

– Negative

Anti-HCV

– Positive by enzyme immunoassay

HCV RNA

– Positive

Table 2.1- The diagnostic hepatitis serological trial carried out on the patient and the consequences obtained. The assorted immunological trials carried out are HBsAg- Hepatitis B surface antigen trial, IgM anti-HBc- Hepatitis B Virus Core Antibody- IgM a Qualitative CIA i.e. Chemiluminescent Immunoassay, IgM anti-HAV- Hepatitis A Virus Antibody-IgM a Qualitaitve CIA, Anti-HCV- Hepatitis C Virus Antibody by EIA i.e. Enzyme Immunoassay, HCV RNA- Hepatitis C Virus RNA Qualitative PCR ) ( Baweja et al, 2003 )

His status improved bit by bit and he was given a discharged from the infirmary with scheduled assignments. The discharge diagnosing was HBV infection and chronic HCV infection. ( Table 2.1 )

The patient after a period of eight months had a follow-up visit with the physician. A hepatic diagnostic trial was carried out once more to look into if the patient has shown marks of recovery. The consequences of trial carried out at this visit were as follows:

HBsAg

– Negative

Anti-HBs

– 500 mIU/mL

HCV RNA

– Positive

Table 2.2- The diagnostic hepatitis serological trial carried out on the patient on the follow up visit and the consequences obtained. ( HBsAg- Hepatitis B surface antigen trial, Anti-HBs- Antibody to Hepatitis B Virus Surface antigen-a Quantative CIA, mlU/ml- milli International unity/ milli litre, HCV RNA- Hepatitis C Virus RNA Qualitative PCR ) ( Baweja et al, 2003 )

3. Laboratory Analysis-

Liver disease is frequently diagnosed by look intoing liver enzymes ( LFT trial ) , degrees of hematoidin or perturbations in blood curdling. For the diagnosing of hepatitis virus, a hepatitis virus panel with a series of blood trials used to observe current or past infection byA hepatitis A, A hepatitis B, orA hepatitis C. It can test blood samples for more than one sort of hepatitis virus at the same clip. Antigen andA antibodyA trials can assist in the sensing of each of the different hepatitis viruses. ( saloon med wellness ) . The initial research lab rating for our patient was neither LFT nor blood trials but straight a research lab analysis of his serum for hepatitis virus antigens was selected due to the exigency that the patient was brought into and the scope of clinical marks shown by the patient and the fact that the patient had a history of drug maltreatment. ( Garfein RS et al,2004 )

3.1 Serum Hepatitis trial for proving antigens for HBV and HCV-

HBsAg was detected in topic ‘s serum on executing ELISA on the patient ‘s serum and the consequence was positive. ( Washington Web instance surveies ) . The positive consequence for IgM anti-HBc by qualitative CIA i.e. Chemiluminescent Immunoassay, indicate the presence of nucleus antigens of hepatitis virus. The initial testing regulations out hepatitis A ( HAV ) in acute presentation ; by executing the HAV antibody IgM trial a qualitative CIA i.e. Chemiluminescent Immunoassay, which gave a negative consequence. The consequences for Anti-HCV antibody trial done utilizing EIA was positive once more, declarative mood of presence of antibody for HCV in the serum. As a consequence of the positive HCV antibody consequence, the sera samples were farther tested and a HCV RNA PCR for qualitative finding corroborating presence of HCV, by RT-PCR testing, and the consequences were positive once more corroborating that the sera was infected with HCV.

3.2 Laboratory analysis carried after eight months-

Lab analysis for trials carried out on the patient after eight months was as follows, proving surface antigen of HBV- HBsAg by ELISA on the patient ‘s serum and the consequence was negative. Proposing the serum was cleared of the HBV surface antigens. Anti-HBs- Hepatitis B Virus Surface antibody a quantative CIA was performed and the consequence was 500 mIU/mL. This consequence idicates that the virus is cleared form the organic structure and anti organic structures have already been detected along with the entire remotion of surface antigens. A HCV RNA PCR for qualitative PCR was performed and it once more confirmed the presence of HCV.

4. Pathophysiology-

HBV belonging to the hepadnavirus household, is a non-cytopathic virus and contains a partly double-stranded DNA genome. ( Joe Sasadeusz et Al, 2011 ) . This virus preponderantly infects hepatocytes. HBV has two chief antigens, an outer envelope incorporating hepatitis B surface antigen ( HBsAg ) and a nucleus containing hepatitis B nucleus antigen ( HBcAg ) . The surplus of HBsAg is produced as sub-viral atoms which circulate in the blood and license diagnosing of HBV in patient sera. A 3rd antigen produced by HBV is hepatitis B ‘e ‘ antigen or HBeAg. This is secreted into the blood. HCV belonging to the flavivirus household, is a single-stranded, enveloped RNA virus. HCV RNA is translated by the host cell following infection of the hepatocyte and internalization of the virus. ( Joe Sasadeusz et Al, 2011 ) . In a co- infection, the nucleus antigen of the HCV seems to impact the written text of HBV and, as a consequence, its reproduction. This can be seen by old studies. ( Mitre and Mendonca, 2007 ) After clearance of HBV, HCV can prevail, ensuing in chronic hepatitis. Further doing an aggravated disease and increasing the hazard of decease. The chronologies of the infections besides play a function in make up one’s minding which virus dominantes over the other. ( Mitre and Mendonca, 2007 ) . An inactive HBV and active HCV infection was seen in our patient after the 2nd scrutiny. This was due to undetectable HBsAg and noticeable HCV RNA. ( Mitre and Mendonca, 2007 ) .

4.1 Serologic Response to Acute HBV Infection and Resolved HBV Infection –

The incubation period of HBV, is typically about eight to twelve hebdomads. Infection by HBV, there is a typical host response created to the virologic antigenic markers ( Figure 4.1 ) . The first marker to look in the serum is HBsAg, which can ab initio be detected in serum from one to twelve hebdomads after infection. ( Hoofnagle, 1981 ) About the clip that the patient starts demoing clinical symptoms, anti-HBc ( antibody to hepatitis B nucleus antigen ) appears, chiefly noticeable as the IgM classA ( IgM anti-HBc ) . ( Hoofnagle, 1981 ) . With the oncoming of clinical symptoms, patients will hold additions in serum transaminase degrees that reflect hepatic hurt. Higher the energy of the immune response observed, greater the hepatic harm caused ( Lee, 1997 ) . The IgM antibodies to the HBV nucleus antigen bit by bit decline to untraceable sums within six months, but the IgG antibodies persists indefinitely as a marker of earlier HBV infection. The consequences of laboratory analysis, show that the HBV infection was resolved. The HBsAg disappeares at approximately 3 to 6 months, frequently merely prior to the sensing of antibodies to hepatitis B surface antigen ( anti-HBs ) . The presence of anti-HBs following acute infection by and large indicates recovery and protective unsusceptibility against re-infection. ( Aldershvile et al, 1980 ) .

Figure 4.1- Graphical representation of visual aspect of virological markers of HBV and their serum titre concentrations. ( Courtesy- David Spach et al,2006 )

4.2 Serologic Response to Acute – Chronic HCV Infection –

After an exposure to HCV, it takes about 6-8 hebdomads to develop antibodies against it. Therefore, the HCV EIA can neglect to observe acute HCVA infection ( Stramer, et al 2004 ) . The diagnosing of the infection is infrequently made, chiefly because more than 70 % of patients holding acute infections are symptomless. Though the clinical symptoms are non usually observed in acute phases in this infection, approximately 25 % of all patients with acute HCV nowadays with icterus, and about 10-20 % develop GI symptoms like abdominalA hurting, sickness, or purging. ( Busch and Shafer, 2005 ) . When a patient has a positive consequence for HCV EIA trial, the primary aim is to find whether they have chronic hepatitis C, this can be achieved by making by proving for HCV RNA or by RIBA i.e. recombinant immunoblot check. ( Chevaliez S, Pawlotsky JM,2005 ) ( Strader et al, 2004 ) ( NIH Consensus Development Program for the direction of Hep.C-2002 ) . The normal class of algorithm used in the diagnosing of HCV is shown in Figure4.3. The HCV RNA trial is more normally used and sooner performed quantative check. The positive trial confirms the nowadays of retroflexing virus in the organic structure and provides the footing for promt initation of pre- intervention rating, reding and future class of action. ( Figure 4.2 – serologic Pattern of Acute HCV Infection With ProgressionA to Chronic Infection. )

Figure 4.2-Serologic Pattern of Acute HCV Infection With ProgressionA to Chronic Infection. ( Courtesy- Abbott nosologies, A 2011 Abbott Laboratories, U.S.A. )

A HCV RNA trial sensible when a individual has HCV hazard factors, such as endovenous drug usage, or they have an elevated ALT, as in the instance presented above, since these people are really likely to hold a positive HCV RNA trial. Another advantage of RNA testing is that when positive, it besides confirms the diagnosing of chronic hepatitis C.

Figure 4.3- Logarithm followed for the testing of HCV and Chronic HCV. ( Courtesy- Pawlotsky,2002 )

5. Treatment Options-

The harm caused to the liver and the hepatocytes can non be repaired immediately. The infection from the organic structure needs to be taken attention of by halting down or decelerating down the reproduction of the virus. The pillar of therapy for patients with a co-infection include is complex due to the interaction between both viruses, and between the host immune system. IFN is an immunomodulating drug, with antiviral and anti-proliferative consequence, it is effectual against HBV and HCV. It is besides the most widely studied curative option. The first survey in co-infected persons, carried out in the1990s, suggests that higher doses ( 9 MU 3 times a hebdomad ) are more effectual for the clearance of HBV or HCV. ( Mitre and Mendonca, 2007 ) .

Many practicians prefer the wait-and-see attack others justifies intervention in most instances. Recurrence in this disease is common and remittal is hard to accomplish. However, the consequences of two recent surveies suggest that prolonged IFN therapy may hold viral reproduction and bring on a high per centum of sustained response in patients. ( Kaufman, 1997 )

The suggestions on effectual intervention for glandular fever infected persons and among others, have been defined by professional associations of liver research workers, such as the Asian-Pacific Association for the Study of the Liver, the European Association for the Study of the Liver, and the American Association for the Study of Liver Diseases. ( Mitre and Mendonca, 2007 ) .

Previous surveies sing assorted parametric quantities indicate that patients without cirrhosis are more antiphonal to interferon. Improved responses have been observed in patients with lower degrees of go arounding hepatitis C virus RNA. ( Dusheiko,2003 ) A intervention of Interferon with ribaverin i.e. IFN + RBV, it is the intervention of choice.Co-infected persons have a higher hazard of development to cirrhosis if compared with mono-infected persons ( 44 % and 21 % , severally ) every bit good as a higher hazard of chronic hepatitis decompensation. ( Mitre and Mendonca, 2007 ) . A

The Food and Drug Administration ( FDA ) of USA has approved a 2nd antiviral drug, adefovir, to handle HBV infection. Adefovir, is a nucleotide parallel, is a pro-drug that undergoes phosphorylations twice in the cell to give the active drug, it is an effectual inhibitor of the viral polymerase. . ( Mitre and Mendonca, 2007 ) . A Interferon, for many old ages, disposal of interferon alfa ( 5 million to 10 million units subcutaneously three times per hebdomad, for at least three months ) has been the pillar of therapy, but due to legion side effects its usage has been replaced with utilizing it with an antiviral drug like ribaverin or 3TC. In instance of farther complications in the patient, a liver graft with a proper HLA lucifer would be a better option.

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