Understanding the Canvas of Hepatitis for Improving Healthcare Access and Outcomes – Dr. Varsha Narayanan, Dr. Manish Bhatnagar

Abstract

Hepatitis represents a large canvas of types and aetiologies of liver inflammation of both infectious and non-infectious causes. While acute hepatitis presents symptomatically and is managed timely, chronic hepatitis may progress silently causing long-term liver damage and fibrosis. The healthcare foundation of our country rests on general practitioners and family physicians and therefore knowledge, diagnosis and referral are the three important cornerstones of improving hepatitis management in the community and reducing its complications and sequelae.

Keywords: Hepatitis, Fibrosis, Cirrhosis, Liver function, MAFLD, MASLD, ALD

Introduction

World Hepatitis Day is observed on 28^th July annually to raise awareness on hepatitis for both physicians and the community. Though often handled by super-speciality gastro-hepatologists, it is important for general practitioners and consultant physicians to be fully updated and equipped to manage acute hepatitis and have good clinical suspicion for super-speciality referral for chronic and severe acute cases.

Hepatitis is the inflammation of the liver (hepa-liver; itis-inflammation). As we know, inflammation is the response and damage caused in the body due to any injurious agent.The injuring agent can be infectious organisms like bacteria, viruses, parasites and fungi; noxious substances like alcohol, tobacco, certain medicines/drugs and toxins; deposition of fats or iron and copper that can cause long-term injury to the liver; lack of blood (oxygen) supply; or rarely an autoimmune cause. (Table1)

The word ‘hepatitis’ is often taken to mean infectious hepatitis due to hepatitis virus but it is important to understand the large canvas of other causes^1,2. Inflammation can occur over a short period of time (acute hepatitis) or over a long period of time (chronic hepatitis) causing long-term liver damage and loss of function. (Table 2)

Table 1 – Causes and Types of Hepatitis

Table 2: Acute and Chronic Hepatitis

MANAGEMENT OF HEPATITIS

Prevention – Vaccines 

Preventive vaccines are now available for viral hepatitis A and B and are regularly given to children as part of the immunization schedule and to high-risk adults with comorbidities or those prone to needle injuries like doctors and lab workers.

A recombinant vaccine for hepatitis E is available in China and is likely to soon be available in other countries³. Vaccine for hepatitis C is still in the research stages.

Diagnosis

There are specific antigen (HbsAg, HBV-DNA) and IgM/IgG antibody tests available for hepatitis viruses that help establish the causative virus and also the stage of the disease.

There are also blood tests available for malaria, typhoid and other infections causing hepatitis.

Liver function tests (LFT) are blood tests that help to assess the amount of liver inflammation, the functioning of the liver and also help to monitor disease progression/improvement.

These include liver enzymes (SGOT or AST, SGPT or ALT, ALP and GGT, the latter 2 being especially increased in cholestatic disease), bilirubin, proteins (albumin and globulin) and prothrombin time (PT-INR).

Blood tests including those for fasting and postprandial sugar, complete blood counts including platelets, lipid profile, thyroid and renal function may also be performed.

Based on tests, risk scores are also assessed. For example, MASLD risk score based on age, BMI, impaired fasting glucose, albumin, AST-ALT and platelet count is an indirect marker for the amount of liver damage and fibrosis.

Fibroscan

Fatty liver (steatosis), inflammation due to fatty deposition (steatohepatitis), and fibrosis/cirrhosis are usually diagnosed by the ultrasound test called FibroScan, and it is confirmed and staged by performing a liver biopsy. Since there are usually no specific symptoms in the early stages of chronic hepatitis, people with the mentioned risk factors for MASLD (MAFLD) and those with alcohol history, should be screened by FibroScan⁴.

The FibroScan measures 2 parameters: (Table 3a & b)

1. Controlled Attenuation Parameter (CAP): indicates and grades the amount of fat deposited in the liver – measured in dB/m. CAP score grading is based on the amount (%) of liver involved.
2. Liver Stiffness Measurement (LSM) by Transient Elastography: indicates and grades the amount of fibrosis- measured in kPa. Normal values for liver stiffness range from 2-7 kPa, while in cirrhosis it can go to 15 or more up to a maximum of 75 kPa. CAP score grading is based on the amount (%) of liver involved.  

Table 3a – CAP score and % Liver with Fatty change

Table 3b: Fibrosis stage according to LSM by Transient Elastography

HBV: Hepatitis B virus, HCV: Hepatitis C virus, HIV: Human Immunodeficiency virus, MASH: Metabolic Associated Steatohepatitis, MAFLD: Metabolic Associated Fatty Liver Disease, ALD: Alcoholic Liver Disease, CLD: Cholestatic Liver Disease, LSM: Liver Stiffness Measurement

APRI

The APRI score estimates the amount of fibrosis in the liver by dividing the AST level by the upper limit of normal for AST, then dividing that result by the platelet count (PLT). An APRI score above a certain threshold (0.7) suggests significant fibrosis. A higher APRI score generally indicates more severe fibrosis. APRI is used as a screening tool to identify individuals who may need further evaluation for liver fibrosis, particularly those with chronic liver diseases like hepatitis C or non-alcoholic fatty liver disease⁴.

Fib4

The FIB-4 index is a simple non-invasive approach using selected laboratory measures (AST, ALT, platelet count PLT) in combination with patient age to assess if an individual is at higher risk for advanced liver fibrosis (F3-F4)⁴.

The formula for FIB-4 is: Age ([yr] x AST [U/L]) / ((PLT [10⁹/L]) x (ALT [U/L])(1/2)).

Treatment

Acute hepatitis (mainly due to HVA and HVE common with water and food contamination), is managed with rest, adequate fluids, dietary fat and alcohol restriction and no drugs/medicines. It usually shows a full recovery in 3-4 weeks. Rarely it may present as a severe form spiralling quickly into liver failure. Adults especially the migrating population, and pregnant women are most at risk for complications and fatality due to hepatitis A and E.

Chronic hepatitis if due to HBV is managed with medicines.Tenofovir and Entecavir are first-line oral treatments due to their potency and low resistance rates. Treatment is long term, several years and even sometimes for life. Lamivudine, adefovir, and telbivudine are used less commonly second-line options. Injectable interferon is another treatment option, though it may have more side effects.

The updated guidelines expand eligibility for treatment, with four options for meeting treatment eligibility that apply to all adults with chronic hepatitis B and now also adolescents (≥12 years)⁵.

• Option 1: Treat all individuals with significant fibrosis (≥F2) based on revised thresholds of non-invasive tests for staging of liver disease (APRI score >0.5 or transient elastography [if available] >7 kPa), or cirrhosis based on clinical criteria (or an APRI score >1.0 or transient elastography >12.5 kPa), regardless of HBV DNA or alanine aminotransferase (ALT) levels.
• Option 2: Treat if HBV DNA is over 2000 IU/mL (previously >20,000 IU/mL) and ALT is above the upper limit of normal.
• Option 3: Treat if there is the presence of any of the following: co-infections (eg, HIV, HCV, HDV); a family history of liver cancer or cirrhosis; immune suppression, diabetes or MASLD; or extrahepatic manifestations (eg, glomerulonephritis or vasculitis), regardless of HBV DNA or ALT levels.
• Option 4: In settings where there is no access to HBV DNA testing, treat on the basis of persistently abnormal ALT levels alone.

Chronic hepatitis C is also treated with direct-acting antiviral (DAA) medications sofosbuvir, ledipasvir, daclatasvir and velpatasvir with other drugs ribavarinand Interferon injections where needed. In 2024, Hepatitis C treatment continues to be highly effective with the mentioned direct-acting antiviral (DAA) medications achieving sustained virologic response (SVR), meaning no detectable virus in the blood rates exceeding 95% in many cases. Treatment typically involves 8-12 weeks of oral medication and is generally well-tolerated⁶. Even after long-term treatment and recovery, monitoring continues for life as the increased risk of developing liver cancer remains.

Autoimmune hepatitis is managed with immunosuppressive medicines.

For DILI treatment rests on recognition of the disorder and stopping of the incriminating drug along with supportive care. N- Acetylcysteine (NAC) is used in paracetamol poisoning and sometimes also in other drug related liver damage though more evidence is needed⁷.

ALD and MASLD currently have no specific medicines, though supportive therapy with tonics, nutritional supplements and antioxidants are often prescribed. Research on specific drugs are in progress. Saroglitazar has recently been approved in India as a specific drug for MASH⁸. Resmetirom, a THR-β agonist, that helps to reduce lipogenesis, increase the breakdown of fatty acids (beta oxidation), and decrease liver fat content, was approved by FDA in March 2024 for MASH and liver scarring due to steatosis⁹. Antidiabetic drugs and vitamin E are also used in managing various stages of MASLD^10,11. Treatment and management of underlying risk factors is the cornerstone.

Cholestatic liver disease is treated by firstly addressing the cause, like changing medicines, treating infection with appropriate antibiotics or antivirals and using procedures like endoscopy (ERCP – Endoscopic retrograde cholangiopancreatography) to remove blockages and bile duct stones and open up narrowed passages with stents¹².

In chronic cases, lifestyle-diet changes with medicines like ursodeoxycholic acid (UDCA) and cholestyramine which help relieve bile stasis are used.

Once cirrhosis is advanced, liver transplant should be considered.

Conclusion

Understanding the various types and presentations of hepatitis, as well as management of non-infectious and infectious hepatitis can lead to better access and outcomes of hepatitis management across socioeconomic strata and rural-urban healthcare services. General practitioners, family physicians and consultant physicians forming the back bone of Indian healthcare when updated and equipped with knowledge and guidelines, can manage acute hepatitis and develop good clinical suspicion, thereby also providing appropriate and timely super-speciality referral for chronic and severe acute cases.

References

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Corresponding Author: ¹Chief Editor, The Indian Practitioner and Medical Director, Dr. Varsha’s Health Solutions, Mumbai. Email: info@drvarsha.com
²Consultant Gastroenterologist and Hepatologist, Director – ICON Hospital, Ahmedabad.